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chebi_nactem

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[ { "id": "201", "type": "", "text": [ "The 55-kDa receptor for tumor necrosis factor (TR55) triggers multiple signaling cascades initiated by adapter proteins like TRADD and FAN. By use of the primary amine monodansylcadaverine (MDC), we addressed the functional role of tumor necrosis factor (TNF) receptor internalization for intracellular signal distribution. We show that MDC does not prevent the interaction of the p55 TNF receptor (TR55) with FAN and TRADD. Furthermore, the activation of plasmamembrane-associated neutral sphingomyelinase activation as well as the stimulation of proline-directed protein kinases were not affected in MDC-treated cells. In contrast, activation of signaling enzymes that are linked to the \"death domain\" of TR55, like acid sphingomyelinase and c-Jun-N-terminal protein kinase as well as TNF signaling of apoptosis in U937 and L929 cells, are blocked in the presence of MDC. The results of our study suggest a role of TR55 internalization for the activation of select TR55 death domain signaling pathways including those leading to apoptosis. \n" ], "offsets": [ [ 0, 1048 ] ] } ]

[ { "id": "201_T1", "type": "Protein", "text": [ "receptor for tumor necrosis factor" ], "offsets": [ [ 11, 45 ] ], "normalized": [] }, { "id": "201_T2", "type": "Protein", "text": [ "TR55" ], "offsets": [ [ 47, 51 ] ], "normalized": [] }, { "id": "201_T3", "type": "Protein", "text": [ "TRADD" ], "offsets": [ [ 126, 131 ] ], "normalized": [] }, { "id": "201_T4", "type": "Protein", "text": [ "FAN" ], "offsets": [ [ 136, 139 ] ], "normalized": [] }, { "id": "201_T5", "type": "Protein", "text": [ "adapter proteins" ], "offsets": [ [ 104, 120 ] ], "normalized": [] }, { "id": "201_T6", "type": "Chemical", "text": [ "primary amine" ], "offsets": [ [ 155, 169 ] ], "normalized": [] }, { "id": "201_T7", "type": "Chemical", "text": [ "monodansylcadaverine" ], "offsets": [ [ 170, 190 ] ], "normalized": [] }, { "id": "201_T8", "type": "Chemical", "text": [ "MDC" ], "offsets": [ [ 192, 195 ] ], "normalized": [] }, { "id": "201_T9", "type": "Protein", "text": [ "tumor necrosis factor", "receptor" ], "offsets": [ [ 234, 255 ], [ 262, 270 ] ], "normalized": [] }, { "id": "201_T10", "type": "Protein", "text": [ "TNF", "receptor" ], "offsets": [ [ 257, 260 ], [ 262, 270 ] ], "normalized": [] }, { "id": "201_T11", "type": "Chemical", "text": [ "MDC" ], "offsets": [ [ 339, 342 ] ], "normalized": [] }, { "id": "201_T12", "type": "Protein", "text": [ "p55 TNF receptor" ], "offsets": [ [ 383, 399 ] ], "normalized": [] }, { "id": "201_T13", "type": "Protein", "text": [ "TR55" ], "offsets": [ [ 401, 405 ] ], "normalized": [] }, { "id": "201_T14", "type": "Protein", "text": [ "FAN" ], "offsets": [ [ 412, 415 ] ], "normalized": [] }, { "id": "201_T15", "type": "Protein", "text": [ "TRADD" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "201_T16", "type": "Chemical", "text": [ "MDC" ], "offsets": [ [ 604, 607 ] ], "normalized": [] }, { "id": "201_T17", "type": "Protein", "text": [ "neutral sphingomyelinase" ], "offsets": [ [ 484, 508 ] ], "normalized": [] }, { "id": "201_T18", "type": "Biological_Activity", "text": [ "activation" ], "offsets": [ [ 509, 519 ] ], "normalized": [] }, { "id": "201_T19", "type": "Protein", "text": [ "proline-directed protein kinases" ], "offsets": [ [ 550, 582 ] ], "normalized": [] }, { "id": "201_T20", "type": "Biological_Activity", "text": [ "stimulation" ], "offsets": [ [ 535, 546 ] ], "normalized": [] }, { "id": "201_T21", "type": "Protein", "text": [ "signaling enzymes" ], "offsets": [ [ 651, 668 ] ], "normalized": [] }, { "id": "201_T22", "type": "Biological_Activity", "text": [ "activation" ], "offsets": [ [ 637, 647 ] ], "normalized": [] }, { "id": "201_T23", "type": "Protein", "text": [ "TR55" ], "offsets": [ [ 710, 714 ] ], "normalized": [] }, { "id": "201_T24", "type": "Protein", "text": [ "acid sphingomyelinase" ], "offsets": [ [ 721, 742 ] ], "normalized": [] }, { "id": "201_T25", "type": "Protein", "text": [ "c-Jun-N-terminal protein kinase" ], "offsets": [ [ 747, 778 ] ], "normalized": [] }, { "id": "201_T26", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 790, 793 ] ], "normalized": [] }, { "id": "201_T27", "type": "Biological_Activity", "text": [ "signaling" ], "offsets": [ [ 794, 803 ] ], "normalized": [] }, { "id": "201_T28", "type": "Chemical", "text": [ "MDC" ], "offsets": [ [ 873, 876 ] ], "normalized": [] }, { "id": "201_T31", "type": "Protein", "text": [ "TR55" ], "offsets": [ [ 921, 925 ] ], "normalized": [] }, { "id": "201_T35", "type": "Protein", "text": [ "TR55" ], "offsets": [ [ 972, 976 ] ], "normalized": [] }, { "id": "201_T36", "type": "Biological_Activity", "text": [ "activation" ], "offsets": [ [ 951, 961 ] ], "normalized": [] }, { "id": "201_T37", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 1036, 1045 ] ], "normalized": [] }, { "id": "201_T38", "type": "Biological_Activity", "text": [ "intracellular signal distribution" ], "offsets": [ [ 291, 324 ] ], "normalized": [] }, { "id": "201_T39", "type": "Biological_Activity", "text": [ "signaling" ], "offsets": [ [ 71, 82 ] ], "normalized": [] }, { "id": "201_T40", "type": "Biological_Activity", "text": [ "activation" ], "offsets": [ [ 444, 454 ] ], "normalized": [] }, { "id": "201_T29", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 807, 816 ] ], "normalized": [] } ]

[]

[]

[ { "id": "201_R1", "type": "Associated_With", "arg1_id": "201_T28", "arg2_id": "201_T27", "normalized": [] }, { "id": "201_R2", "type": "Binds_With", "arg1_id": "201_T28", "arg2_id": "201_T24", "normalized": [] }, { "id": "201_R3", "type": "Binds_With", "arg1_id": "201_T28", "arg2_id": "201_T25", "normalized": [] }, { "id": "201_R7", "type": "Binds_With", "arg1_id": "201_T28", "arg2_id": "201_T26", "normalized": [] } ]

[ { "id": "203", "type": "", "text": [ "Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms, and as a consequence, they induce different profiles of effects. For example, in utero treatment with the androgen receptor (AR) antagonist, flutamide, produces ventral prostate agenesis and testicular nondescent, while in contrast, finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT) synthesis, rarely, if ever, induces such malformations. In this regard, it was recently proposed that dibutyl phthalate (DBP) alters reproductive development by a different mechanism of action than flutamide or vinclozolin (V), which are AR antagonists, because the male offsprings display an unusually high incidence of testicular and epididymal alterations--effects rarely seen after in utero flutamide or V treatment. In this study, we present original data describing the reproductive effects of 10 known or suspected anti-androgens, including a Leydig cell toxicant ethane dimethane sulphonate (EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day-1), p,p'-DDE (100 mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone (P, 100 mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1 day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1 day-1), and polychlorinated biphenyl (PCB) congener no. 169 (single dose of 1.8 mg kg-1). Our analysis indicates that the chemicals discussed here can be clustered into three or four separate groups, based on the resulting profiles of reproductive effects. Vinclozolin, P, and DDE, known AR ligands, produce similar profiles of toxicity. However, p,p'-DDE is less potent in this regard. DBP and DEHP produce a profile distinct from the above AR ligands. Male offsprings display a higher incidence of epididymal and testicular lesions than generally seen with flutamide, P, or V even at high dosage levels. Linuron treatment induced a level of external effects consistent with its low affinity for AR [reduced anogenital distance (AGD), retained nipples, and a low incidence of hypospadias]. However, L treatment also induced an unanticipated degree of malformed epididymides and testis atrophy. In fact, the profile of effects induced by L was similar to that seen with DBP. These results suggest that L may display several mechanisms of endocrine toxicity, one of which involves AR binding. Chlozolinate and iprodione did not produce any signs of maternal or fetal endocrine toxicity at 100 mg kg-1 day-1. EDS produced severe maternal toxicity and a 45% reduction in size at birth, which resulted in the death of all neonates by 5 days of age. However, EDS only reduced AGD in male pups by 15%. Ketoconazole did not demasculinize or feminize males but rather displayed anti-hormonal activities, apparently by inhibiting ovarian hormone synthesis, which resulted in delayed delivery and whole litter loss. In summary, the above in vivo data suggest that the chemicals we studied alter male sexual differentiation via different mechanisms. The anti-androgens V, P, and p,p'-DDE produce flutamide-like profiles that are distinct from those seen with DBP, DEHP, and L. The effects of PCB 169 bear little resemblance to those of any known anti-androgen. Only in depth in vitro studies will reveal the degree to which one can rely upon in vivo studies, like those presented here, to predict the cellular and molecular mechanisms of developmental toxicity. \n" ], "offsets": [ [ 0, 3427 ] ] } ]

[ { "id": "203_T1", "type": "Biological_Activity", "text": [ "Antiandrogenic" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "203_T2", "type": "Chemical", "text": [ "Antiandrogenic chemicals" ], "offsets": [ [ 0, 24 ] ], "normalized": [] }, { "id": "203_T4", "type": "Protein", "text": [ "androgen receptor" ], "offsets": [ [ 189, 206 ] ], "normalized": [] }, { "id": "203_T6", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 208, 210 ] ], "normalized": [] }, { "id": "203_T8", "type": "Biological_Activity", "text": [ "antagonist" ], "offsets": [ [ 212, 222 ] ], "normalized": [] }, { "id": "203_T9", "type": "Chemical", "text": [ "flutamide" ], "offsets": [ [ 224, 233 ] ], "normalized": [] }, { "id": "203_T10", "type": "Biological_Activity", "text": [ "agenesis" ], "offsets": [ [ 261, 269 ] ], "normalized": [] }, { "id": "203_T12", "type": "Chemical", "text": [ "finasteride" ], "offsets": [ [ 316, 327 ] ], "normalized": [] }, { "id": "203_T13", "type": "Chemical", "text": [ "5 alpha-dihydrotestosterone" ], "offsets": [ [ 345, 372 ] ], "normalized": [] }, { "id": "203_T14", "type": "Chemical", "text": [ "DHT" ], "offsets": [ [ 374, 377 ] ], "normalized": [] }, { "id": "203_T15", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 332, 341 ] ], "normalized": [] }, { "id": "203_T16", "type": "Chemical", "text": [ "dibutyl phthalate" ], "offsets": [ [ 481, 498 ] ], "normalized": [] }, { "id": "203_T17", "type": "Chemical", "text": [ "DBP" ], "offsets": [ [ 500, 503 ] ], "normalized": [] }, { "id": "203_T19", "type": "Chemical", "text": [ "flutamide" ], "offsets": [ [ 577, 586 ] ], "normalized": [] }, { "id": "203_T20", "type": "Chemical", "text": [ "vinclozolin" ], "offsets": [ [ 590, 601 ] ], "normalized": [] }, { "id": "203_T22", "type": "Biological_Activity", "text": [ "antagonists" ], "offsets": [ [ 620, 631 ] ], "normalized": [] }, { "id": "203_T23", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 617, 619 ] ], "normalized": [] }, { "id": "203_T26", "type": "Chemical", "text": [ "flutamide" ], "offsets": [ [ 775, 784 ] ], "normalized": [] }, { "id": "203_T27", "type": "Chemical", "text": [ "V" ], "offsets": [ [ 788, 789 ] ], "normalized": [] }, { "id": "203_T28", "type": "Chemical", "text": [ "V" ], "offsets": [ [ 603, 604 ] ], "normalized": [] }, { "id": "203_T29", "type": "Chemical", "text": [ "anti-androgens" ], "offsets": [ [ 902, 916 ] ], "normalized": [] }, { "id": "203_T30", "type": "Biological_Activity", "text": [ "anti-androgen" ], "offsets": [ [ 902, 915 ] ], "normalized": [] }, { "id": "203_T31", "type": "Biological_Activity", "text": [ "toxicant" ], "offsets": [ [ 942, 950 ] ], "normalized": [] }, { "id": "203_T32", "type": "Chemical", "text": [ "ethane dimethane sulphonate" ], "offsets": [ [ 951, 978 ] ], "normalized": [] }, { "id": "203_T33", "type": "Chemical", "text": [ "EDS" ], "offsets": [ [ 980, 983 ] ], "normalized": [] }, { "id": "203_T35", "type": "Chemical", "text": [ "linuron" ], "offsets": [ [ 1004, 1011 ] ], "normalized": [] }, { "id": "203_T36", "type": "Chemical", "text": [ "L" ], "offsets": [ [ 1013, 1014 ] ], "normalized": [] }, { "id": "203_T37", "type": "Chemical", "text": [ "p,p'-DDE" ], "offsets": [ [ 1036, 1044 ] ], "normalized": [] }, { "id": "203_T38", "type": "Chemical", "text": [ "ketoconazole" ], "offsets": [ [ 1066, 1078 ] ], "normalized": [] }, { "id": "203_T39", "type": "Chemical", "text": [ "procymidone" ], "offsets": [ [ 1102, 1113 ] ], "normalized": [] }, { "id": "203_T40", "type": "Chemical", "text": [ "P" ], "offsets": [ [ 1115, 1116 ] ], "normalized": [] }, { "id": "203_T41", "type": "Chemical", "text": [ "chlozolinate" ], "offsets": [ [ 1138, 1150 ] ], "normalized": [] }, { "id": "203_T42", "type": "Chemical", "text": [ "iprodione" ], "offsets": [ [ 1172, 1181 ] ], "normalized": [] }, { "id": "203_T43", "type": "Chemical", "text": [ "DBP" ], "offsets": [ [ 1203, 1206 ] ], "normalized": [] }, { "id": "203_T44", "type": "Chemical", "text": [ "diethylhexyl phthalate" ], "offsets": [ [ 1228, 1250 ] ], "normalized": [] }, { "id": "203_T45", "type": "Chemical", "text": [ "DEHP" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "203_T46", "type": "Chemical", "text": [ "polychlorinated biphenyl", "congener no. 169" ], "offsets": [ [ 1282, 1306 ], [ 1313, 1329 ] ], "normalized": [] }, { "id": "203_T47", "type": "Chemical", "text": [ "PCB", "congener no. 169" ], "offsets": [ [ 1308, 1311 ], [ 1313, 1329 ] ], "normalized": [] }, { "id": "203_T48", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 1561, 1563 ] ], "normalized": [] }, { "id": "203_T50", "type": "Chemical", "text": [ "Vinclozolin" ], "offsets": [ [ 1530, 1541 ] ], "normalized": [] }, { "id": "203_T51", "type": "Chemical", "text": [ "P" ], "offsets": [ [ 1543, 1544 ] ], "normalized": [] }, { "id": "203_T52", "type": "Chemical", "text": [ "DDE" ], "offsets": [ [ 1550, 1553 ] ], "normalized": [] }, { "id": "203_T54", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 1602, 1610 ] ], "normalized": [] }, { "id": "203_T55", "type": "Chemical", "text": [ "p,p'-DDE" ], "offsets": [ [ 1621, 1629 ] ], "normalized": [] }, { "id": "203_T56", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 1716, 1718 ] ], "normalized": [] }, { "id": "203_T58", "type": "Chemical", "text": [ "DBP" ], "offsets": [ [ 1661, 1664 ] ], "normalized": [] }, { "id": "203_T59", "type": "Chemical", "text": [ "DEHP" ], "offsets": [ [ 1669, 1673 ] ], "normalized": [] }, { "id": "203_T62", "type": "Chemical", "text": [ "flutamide" ], "offsets": [ [ 1833, 1842 ] ], "normalized": [] }, { "id": "203_T63", "type": "Chemical", "text": [ "P" ], "offsets": [ [ 1844, 1845 ] ], "normalized": [] }, { "id": "203_T64", "type": "Chemical", "text": [ "V" ], "offsets": [ [ 1850, 1851 ] ], "normalized": [] }, { "id": "203_T65", "type": "Chemical", "text": [ "Linuron" ], "offsets": [ [ 1880, 1887 ] ], "normalized": [] }, { "id": "203_T66", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 1971, 1973 ] ], "normalized": [] }, { "id": "203_T67", "type": "Chemical", "text": [ "L" ], "offsets": [ [ 2074, 2075 ] ], "normalized": [] }, { "id": "203_T69", "type": "Biological_Activity", "text": [ "atrophy" ], "offsets": [ [ 2160, 2167 ] ], "normalized": [] }, { "id": "203_T70", "type": "Chemical", "text": [ "L" ], "offsets": [ [ 2212, 2213 ] ], "normalized": [] }, { "id": "203_T71", "type": "Chemical", "text": [ "DBP" ], "offsets": [ [ 2244, 2247 ] ], "normalized": [] }, { "id": "203_T72", "type": "Chemical", "text": [ "L" ], "offsets": [ [ 2276, 2277 ] ], "normalized": [] }, { "id": "203_T73", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 2323, 2331 ] ], "normalized": [] }, { "id": "203_T74", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 2355, 2357 ] ], "normalized": [] }, { "id": "203_T77", "type": "Chemical", "text": [ "Chlozolinate" ], "offsets": [ [ 2367, 2379 ] ], "normalized": [] }, { "id": "203_T78", "type": "Chemical", "text": [ "iprodione" ], "offsets": [ [ 2384, 2393 ] ], "normalized": [] }, { "id": "203_T80", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 2451, 2459 ] ], "normalized": [] }, { "id": "203_T81", "type": "Chemical", "text": [ "EDS" ], "offsets": [ [ 2482, 2485 ] ], "normalized": [] }, { "id": "203_T82", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 2511, 2519 ] ], "normalized": [] }, { "id": "203_T84", "type": "Biological_Activity", "text": [ "death" ], "offsets": [ [ 2580, 2585 ] ], "normalized": [] }, { "id": "203_T85", "type": "Chemical", "text": [ "EDS" ], "offsets": [ [ 2629, 2632 ] ], "normalized": [] }, { "id": "203_T91", "type": "Chemical", "text": [ "Ketoconazole" ], "offsets": [ [ 2671, 2683 ] ], "normalized": [] }, { "id": "203_T94", "type": "Biological_Activity", "text": [ "anti-hormonal" ], "offsets": [ [ 2745, 2758 ] ], "normalized": [] }, { "id": "203_T95", "type": "Biological_Activity", "text": [ "inhibiting" ], "offsets": [ [ 2785, 2795 ] ], "normalized": [] }, { "id": "203_T99", "type": "Chemical", "text": [ "V" ], "offsets": [ [ 3033, 3034 ] ], "normalized": [] }, { "id": "203_T100", "type": "Chemical", "text": [ "P" ], "offsets": [ [ 3036, 3037 ] ], "normalized": [] }, { "id": "203_T101", "type": "Chemical", "text": [ "p,p'-DDE" ], "offsets": [ [ 3043, 3051 ] ], "normalized": [] }, { "id": "203_T102", "type": "Biological_Activity", "text": [ "anti-androgen" ], "offsets": [ [ 3018, 3031 ] ], "normalized": [] }, { "id": "203_T103", "type": "Chemical", "text": [ "flutamide" ], "offsets": [ [ 3060, 3069 ] ], "normalized": [] }, { "id": "203_T104", "type": "Chemical", "text": [ "DBP" ], "offsets": [ [ 3123, 3126 ] ], "normalized": [] }, { "id": "203_T105", "type": "Chemical", "text": [ "DEHP" ], "offsets": [ [ 3128, 3132 ] ], "normalized": [] }, { "id": "203_T106", "type": "Chemical", "text": [ "L" ], "offsets": [ [ 3138, 3139 ] ], "normalized": [] }, { "id": "203_T107", "type": "Chemical", "text": [ "PCB 169" ], "offsets": [ [ 3156, 3163 ] ], "normalized": [] }, { "id": "203_T108", "type": "Biological_Activity", "text": [ "anti-androgen" ], "offsets": [ [ 3210, 3223 ] ], "normalized": [] }, { "id": "203_T109", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 3416, 3424 ] ], "normalized": [] }, { "id": "203_T110", "type": "Species", "text": [ "pups" ], "offsets": [ [ 2658, 2662 ] ], "normalized": [] }, { "id": "203_T111", "type": "Biological_Activity", "text": [ "synthesis" ], "offsets": [ [ 379, 388 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "205", "type": "", "text": [ "Amiodarone (AD) is an effective antidysrythmic drug, however, there can be serious side effects, such as hepatic and neurological alterations, as well as skin photosensitization, as seen in porphyrias. Clinical signs in porphyrias might be triggered by the so-called porphyrinogenic drugs. Without sound basis, Amiodarone has been classified as an unsafe drug for porphyric patients. The aim of this work has been to study the effect of AD, both in vivo and in vitro, on heme metabolism. In the in vivo assays, the activities of 5-aminolevulinate synthetase (ALA-S), ALA dehydratase (ALA-D), porphobilinogenase (PBGase) and PBG-deaminase (PBG-D) in blood, liver, and kidney; hepatic and fecal porphyrins, urinary ALA, PBG and porphyrins in male mice strain CF1 treated with AD (100 mg i.p. daily) for 1 week and 1 month, were measured. No significanat differences were found for any of these parameters in the AD treated animals as compared to controls. In the in vitro experiments human blood, and mice blood, liver, and kidney, were used to measure the activities of ALA-S, ALA-D, PBGase, PBG-D and uroporphyrinogen decarboxylase, in the presence of varying concentrations of AD (0.0172-4.304 mM). AD did not modify any of the enzyme activities. All of the above biochemical parameters were studied in 17 cardiac patients under AD treatment for 3 to 20 years. Neither the activities of the heme enzymes, nor the levels of precursors and porphyrins in urine and plasma were altered. These findings clearly demonstrate that AD is a pharmacologically safe drug and can be used for the treatment of associated pathologies in porphyrias. \n" ], "offsets": [ [ 0, 1640 ] ] } ]

[ { "id": "205_T1", "type": "Chemical", "text": [ "Amiodarone" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "205_T2", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 12, 14 ] ], "normalized": [] }, { "id": "205_T3", "type": "Biological_Activity", "text": [ "antidysrythmic" ], "offsets": [ [ 32, 46 ] ], "normalized": [] }, { "id": "205_T6", "type": "Biological_Activity", "text": [ "photosensitization" ], "offsets": [ [ 159, 177 ] ], "normalized": [] }, { "id": "205_T9", "type": "Biological_Activity", "text": [ "porphyrinogenic" ], "offsets": [ [ 267, 282 ] ], "normalized": [] }, { "id": "205_T10", "type": "Chemical", "text": [ "Amiodarone" ], "offsets": [ [ 311, 321 ] ], "normalized": [] }, { "id": "205_T11", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 438, 440 ] ], "normalized": [] }, { "id": "205_T12", "type": "Protein", "text": [ "5-aminolevulinate synthetase" ], "offsets": [ [ 530, 558 ] ], "normalized": [] }, { "id": "205_T13", "type": "Protein", "text": [ "ALA-S" ], "offsets": [ [ 560, 565 ] ], "normalized": [] }, { "id": "205_T14", "type": "Protein", "text": [ "5-aminolevulinate", "dehydratase" ], "offsets": [ [ 530, 547 ], [ 572, 583 ] ], "normalized": [] }, { "id": "205_T15", "type": "Protein", "text": [ "ALA dehydratase" ], "offsets": [ [ 568, 583 ] ], "normalized": [] }, { "id": "205_T16", "type": "Protein", "text": [ "ALA-D" ], "offsets": [ [ 585, 590 ] ], "normalized": [] }, { "id": "205_T17", "type": "Protein", "text": [ "porphobilinogenase" ], "offsets": [ [ 593, 611 ] ], "normalized": [] }, { "id": "205_T18", "type": "Protein", "text": [ "porphobilinogen", "deaminase" ], "offsets": [ [ 593, 608 ], [ 629, 638 ] ], "normalized": [] }, { "id": "205_T19", "type": "Protein", "text": [ "PBGase" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "205_T20", "type": "Protein", "text": [ "PBG-deaminase" ], "offsets": [ [ 625, 638 ] ], "normalized": [] }, { "id": "205_T21", "type": "Protein", "text": [ "PBG-D" ], "offsets": [ [ 640, 645 ] ], "normalized": [] }, { "id": "205_T22", "type": "Chemical", "text": [ "porphyrins" ], "offsets": [ [ 694, 704 ] ], "normalized": [] }, { "id": "205_T23", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "205_T24", "type": "Chemical", "text": [ "PBG" ], "offsets": [ [ 720, 723 ] ], "normalized": [] }, { "id": "205_T25", "type": "Chemical", "text": [ "porphyrins" ], "offsets": [ [ 728, 738 ] ], "normalized": [] }, { "id": "205_T26", "type": "Species", "text": [ "mice strain CF1" ], "offsets": [ [ 747, 762 ] ], "normalized": [] }, { "id": "205_T27", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 776, 778 ] ], "normalized": [] }, { "id": "205_T28", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 912, 914 ] ], "normalized": [] }, { "id": "205_T29", "type": "Species", "text": [ "human" ], "offsets": [ [ 984, 989 ] ], "normalized": [] }, { "id": "205_T30", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1001, 1005 ] ], "normalized": [] }, { "id": "205_T31", "type": "Protein", "text": [ "ALA-S" ], "offsets": [ [ 1071, 1076 ] ], "normalized": [] }, { "id": "205_T32", "type": "Protein", "text": [ "ALA-D" ], "offsets": [ [ 1078, 1083 ] ], "normalized": [] }, { "id": "205_T33", "type": "Protein", "text": [ "PBGase" ], "offsets": [ [ 1085, 1091 ] ], "normalized": [] }, { "id": "205_T34", "type": "Protein", "text": [ "PBG-D" ], "offsets": [ [ 1093, 1098 ] ], "normalized": [] }, { "id": "205_T35", "type": "Protein", "text": [ "uroporphyrinogen decarboxylase" ], "offsets": [ [ 1103, 1133 ] ], "normalized": [] }, { "id": "205_T36", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 1180, 1182 ] ], "normalized": [] }, { "id": "205_T37", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 1202, 1204 ] ], "normalized": [] }, { "id": "205_T38", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1317, 1325 ] ], "normalized": [] }, { "id": "205_T39", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 1332, 1334 ] ], "normalized": [] }, { "id": "205_T41", "type": "Chemical", "text": [ "AD" ], "offsets": [ [ 1527, 1529 ] ], "normalized": [] }, { "id": "205_T43", "type": "Species", "text": [ "patients" ], "offsets": [ [ 374, 382 ] ], "normalized": [] }, { "id": "205_T45", "type": "Protein", "text": [ "heme enzymes" ], "offsets": [ [ 1394, 1406 ] ], "normalized": [] }, { "id": "205_T7", "type": "Chemical", "text": [ "heme" ], "offsets": [ [ 472, 476 ] ], "normalized": [] }, { "id": "205_T8", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 477, 487 ] ], "normalized": [] }, { "id": "205_T40", "type": "Biological_Activity", "text": [ "enzyme activities" ], "offsets": [ [ 1231, 1248 ] ], "normalized": [] }, { "id": "205_T46", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1231, 1237 ] ], "normalized": [] }, { "id": "205_T44", "type": "Chemical", "text": [ "porphyrins" ], "offsets": [ [ 1442, 1452 ] ], "normalized": [] }, { "id": "205_T4", "type": "Chemical", "text": [ "drug" ], "offsets": [ [ 1558, 1562 ] ], "normalized": [] } ]

[]

[]

[ { "id": "205_R1", "type": "Associated_With", "arg1_id": "205_T1", "arg2_id": "205_T3", "normalized": [] }, { "id": "205_R2", "type": "Associated_With", "arg1_id": "205_T2", "arg2_id": "205_T3", "normalized": [] }, { "id": "205_R7", "type": "Associated_With", "arg1_id": "205_T1", "arg2_id": "205_T6", "normalized": [] }, { "id": "205_R8", "type": "Associated_With", "arg1_id": "205_T2", "arg2_id": "205_T6", "normalized": [] } ]

[ { "id": "207", "type": "", "text": [ "Lysine clonixinate (LC) is a drug of antiinflammatory antipyretic and analgesic activity that produces minor digestive side-effects. This fact induced us to think that LC is possibly a weak COX-1 inhibitor. In order to investigate our hypothesis we inhibited cyclooxygenase activity with LC or indomethacin (INDO) in rat lung and stomach obtained from rats treated with lipopolysacharide (LPS) and control rats. Rat lung preparations incubated with 14C-arachidonic acid synthesise mainly PGE2. LC at 2.5 and 4.1 x 10(-5) M does not modify the basal production of PGE2 (probably COX-1) but at 6.8 x 10(-5) M significantly inhibited PGE2 production (approximately 48.5% inhibition, P<0.001). On the other hand, INDO at 10(-6) inhibited the basal production of PGE2 by around 73%. In LPS-treated rats, the production of PGE2 was significantly higher than in the lungs of control rats, probably due to the induction of COX-2. The addition of LC at 2.7 and 4.1 x 10(-5) M recovered the control values of PGE2 inhibiting, probably only from COX-2 activity. LC at higher concentrations (6.8 x 10(-5) M) and INDO 10(-6) M inhibited PGE2 formed by COX-2 and also partly by COX-1 activity. \n" ], "offsets": [ [ 0, 1182 ] ] } ]

[ { "id": "207_T1", "type": "Chemical", "text": [ "Lysine clonixinate" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "207_T2", "type": "Chemical", "text": [ "LC" ], "offsets": [ [ 20, 22 ] ], "normalized": [] }, { "id": "207_T3", "type": "Biological_Activity", "text": [ "antiinflammatory" ], "offsets": [ [ 37, 53 ] ], "normalized": [] }, { "id": "207_T4", "type": "Biological_Activity", "text": [ "antipyretic" ], "offsets": [ [ 54, 65 ] ], "normalized": [] }, { "id": "207_T5", "type": "Biological_Activity", "text": [ "analgesic" ], "offsets": [ [ 70, 79 ] ], "normalized": [] }, { "id": "207_T7", "type": "Chemical", "text": [ "LC" ], "offsets": [ [ 168, 170 ] ], "normalized": [] }, { "id": "207_T8", "type": "Protein", "text": [ "COX-1" ], "offsets": [ [ 190, 195 ] ], "normalized": [] }, { "id": "207_T9", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 196, 205 ] ], "normalized": [] }, { "id": "207_T10", "type": "Protein", "text": [ "cyclooxygenase" ], "offsets": [ [ 259, 273 ] ], "normalized": [] }, { "id": "207_T11", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 249, 258 ] ], "normalized": [] }, { "id": "207_T12", "type": "Chemical", "text": [ "LC" ], "offsets": [ [ 288, 290 ] ], "normalized": [] }, { "id": "207_T13", "type": "Chemical", "text": [ "indomethacin" ], "offsets": [ [ 294, 306 ] ], "normalized": [] }, { "id": "207_T14", "type": "Chemical", "text": [ "INDO" ], "offsets": [ [ 308, 312 ] ], "normalized": [] }, { "id": "207_T16", "type": "Species", "text": [ "rat" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "207_T17", "type": "Species", "text": [ "rats" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "207_T18", "type": "Species", "text": [ "Rat" ], "offsets": [ [ 413, 416 ] ], "normalized": [] }, { "id": "207_T19", "type": "Chemical", "text": [ "14C-arachidonic acid" ], "offsets": [ [ 450, 470 ] ], "normalized": [] }, { "id": "207_T20", "type": "Chemical", "text": [ "arachidonic acid" ], "offsets": [ [ 454, 470 ] ], "normalized": [] }, { "id": "207_T21", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "207_T22", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "207_T23", "type": "Chemical", "text": [ "LC" ], "offsets": [ [ 495, 497 ] ], "normalized": [] }, { "id": "207_T24", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 564, 568 ] ], "normalized": [] }, { "id": "207_T25", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 564, 568 ] ], "normalized": [] }, { "id": "207_T26", "type": "Protein", "text": [ "COX-1" ], "offsets": [ [ 579, 584 ] ], "normalized": [] }, { "id": "207_T27", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "207_T29", "type": "Chemical", "text": [ "INDO" ], "offsets": [ [ 710, 714 ] ], "normalized": [] }, { "id": "207_T31", "type": "Species", "text": [ "rats" ], "offsets": [ [ 794, 798 ] ], "normalized": [] }, { "id": "207_T34", "type": "Chemical", "text": [ "lipopolysacharide" ], "offsets": [ [ 370, 387 ] ], "normalized": [] }, { "id": "207_T35", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 389, 392 ] ], "normalized": [] }, { "id": "207_T36", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 782, 785 ] ], "normalized": [] }, { "id": "207_T37", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 916, 921 ] ], "normalized": [] }, { "id": "207_T38", "type": "Chemical", "text": [ "LC" ], "offsets": [ [ 939, 941 ] ], "normalized": [] }, { "id": "207_T39", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 1000, 1004 ] ], "normalized": [] }, { "id": "207_T40", "type": "Biological_Activity", "text": [ "inhibiting" ], "offsets": [ [ 1005, 1015 ] ], "normalized": [] }, { "id": "207_T41", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1036, 1041 ] ], "normalized": [] }, { "id": "207_T42", "type": "Chemical", "text": [ "LC" ], "offsets": [ [ 1052, 1054 ] ], "normalized": [] }, { "id": "207_T43", "type": "Chemical", "text": [ "INDO" ], "offsets": [ [ 1101, 1105 ] ], "normalized": [] }, { "id": "207_T44", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 1125, 1129 ] ], "normalized": [] }, { "id": "207_T45", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1140, 1145 ] ], "normalized": [] }, { "id": "207_T46", "type": "Protein", "text": [ "COX-1" ], "offsets": [ [ 1165, 1170 ] ], "normalized": [] }, { "id": "207_T48", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 1115, 1124 ] ], "normalized": [] }, { "id": "207_T50", "type": "Species", "text": [ "rats" ], "offsets": [ [ 407, 411 ] ], "normalized": [] }, { "id": "207_T52", "type": "Species", "text": [ "rats" ], "offsets": [ [ 877, 881 ] ], "normalized": [] }, { "id": "207_T6", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 759, 763 ] ], "normalized": [] }, { "id": "207_T28", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 759, 763 ] ], "normalized": [] }, { "id": "207_T30", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 818, 822 ] ], "normalized": [] }, { "id": "207_T32", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 818, 822 ] ], "normalized": [] }, { "id": "207_T15", "type": "Biological_Activity", "text": [ "cyclooxygenase" ], "offsets": [ [ 259, 273 ] ], "normalized": [] } ]

[]

[]

[ { "id": "207_R1", "type": "Associated_With", "arg1_id": "207_T1", "arg2_id": "207_T3", "normalized": [] }, { "id": "207_R2", "type": "Associated_With", "arg1_id": "207_T2", "arg2_id": "207_T3", "normalized": [] }, { "id": "207_R3", "type": "Associated_With", "arg1_id": "207_T1", "arg2_id": "207_T4", "normalized": [] }, { "id": "207_R4", "type": "Associated_With", "arg1_id": "207_T2", "arg2_id": "207_T4", "normalized": [] }, { "id": "207_R5", "type": "Associated_With", "arg1_id": "207_T1", "arg2_id": "207_T5", "normalized": [] }, { "id": "207_R7", "type": "Associated_With", "arg1_id": "207_T2", "arg2_id": "207_T5", "normalized": [] }, { "id": "207_R9", "type": "Associated_With", "arg1_id": "207_T13", "arg2_id": "207_T11", "normalized": [] }, { "id": "207_R10", "type": "Associated_With", "arg1_id": "207_T14", "arg2_id": "207_T11", "normalized": [] }, { "id": "207_R13", "type": "Metabolite_Of", "arg1_id": "207_T22", "arg2_id": "207_T20", "normalized": [] }, { "id": "207_R14", "type": "Isolated_From", "arg1_id": "207_T22", "arg2_id": "207_T18", "normalized": [] }, { "id": "207_R21", "type": "Associated_With", "arg1_id": "207_T42", "arg2_id": "207_T48", "normalized": [] }, { "id": "207_R22", "type": "Associated_With", "arg1_id": "207_T43", "arg2_id": "207_T48", "normalized": [] }, { "id": "207_R23", "type": "Associated_With", "arg1_id": "207_T7", "arg2_id": "207_T9", "normalized": [] }, { "id": "207_R8", "type": "Binds_With", "arg1_id": "207_T7", "arg2_id": "207_T8", "normalized": [] }, { "id": "207_R16", "type": "Binds_With", "arg1_id": "207_T13", "arg2_id": "207_T10", "normalized": [] }, { "id": "207_R17", "type": "Binds_With", "arg1_id": "207_T12", "arg2_id": "207_T10", "normalized": [] }, { "id": "207_R18", "type": "Binds_With", "arg1_id": "207_T14", "arg2_id": "207_T10", "normalized": [] }, { "id": "207_R6", "type": "Binds_With", "arg1_id": "207_T43", "arg2_id": "207_T45", "normalized": [] }, { "id": "207_R11", "type": "Binds_With", "arg1_id": "207_T43", "arg2_id": "207_T46", "normalized": [] }, { "id": "207_R12", "type": "Binds_With", "arg1_id": "207_T42", "arg2_id": "207_T45", "normalized": [] }, { "id": "207_R15", "type": "Binds_With", "arg1_id": "207_T42", "arg2_id": "207_T46", "normalized": [] } ]

[ { "id": "209", "type": "", "text": [ "The purpose of this study was to determine the antimutagenicity of WR-1065 added after irradiation of cells of cell lines differing in their ability to rejoin radiation-induced DNA double-strand breaks (DSBs). The postirradiation antimutagenicity of WR-1065 at the thymidine kinase locus was demonstrated for L5178Y (LY)-S1 cells that are deficient in repair of DNA DSBs. Less postirradiation antimutagenicity of WR-1065 was observed in LY-R16 and LY-SR1 cells, which are relatively efficient in DSB repair. Postirradiation treatment with WR-1065 had only a small stimulatory effect on DSB rejoining. A 3-h incubation of irradiated LY cells with WR-1065 caused slight changes in the distribution of cells in the phases of the cell cycle that differed between LY-S1 and LY-SR1 cells. Both LY-S1 and LY-SR1 cells were protected against the cytotoxic and mutagenic effects of radiation when WR-1065 was present 30 min before and during the irradiation. We conclude that the differential postirradiation effects of WR-1065 in the LY-S1 and LY-SR1 cells are not caused by differences in cellular uptake of the radioprotector or in its radical scavenging activity. Possible mechanisms for the postirradiation antimutagenicity of WR-1065 are discussed. \n" ], "offsets": [ [ 0, 1248 ] ] } ]

[ { "id": "209_T1", "type": "Biological_Activity", "text": [ "antimutagenicity" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "209_T2", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 67, 74 ] ], "normalized": [] }, { "id": "209_T4", "type": "Species", "text": [ "L5178Y" ], "offsets": [ [ 310, 316 ] ], "normalized": [] }, { "id": "209_T6", "type": "Biological_Activity", "text": [ "antimutagenicity" ], "offsets": [ [ 231, 247 ] ], "normalized": [] }, { "id": "209_T7", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 251, 258 ] ], "normalized": [] }, { "id": "209_T8", "type": "Protein", "text": [ "thymidine kinase" ], "offsets": [ [ 266, 282 ] ], "normalized": [] }, { "id": "209_T9", "type": "Biological_Activity", "text": [ "antimutagenicity" ], "offsets": [ [ 394, 410 ] ], "normalized": [] }, { "id": "209_T10", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "209_T11", "type": "Biological_Activity", "text": [ "DSB repair" ], "offsets": [ [ 497, 507 ] ], "normalized": [] }, { "id": "209_T12", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 540, 547 ] ], "normalized": [] }, { "id": "209_T13", "type": "Biological_Activity", "text": [ "DSB rejoining" ], "offsets": [ [ 587, 600 ] ], "normalized": [] }, { "id": "209_T14", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 647, 654 ] ], "normalized": [] }, { "id": "209_T17", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 889, 896 ] ], "normalized": [] }, { "id": "209_T18", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 1012, 1019 ] ], "normalized": [] }, { "id": "209_T19", "type": "Biological_Activity", "text": [ "radical scavenging" ], "offsets": [ [ 1131, 1149 ] ], "normalized": [] }, { "id": "209_T20", "type": "Biological_Activity", "text": [ "antimutagenicity" ], "offsets": [ [ 1204, 1220 ] ], "normalized": [] }, { "id": "209_T21", "type": "Chemical", "text": [ "WR-1065" ], "offsets": [ [ 1224, 1231 ] ], "normalized": [] }, { "id": "209_T22", "type": "Biological_Activity", "text": [ "radioprotector" ], "offsets": [ [ 1106, 1120 ] ], "normalized": [] }, { "id": "209_T3", "type": "Biological_Activity", "text": [ "protected" ], "offsets": [ [ 817, 826 ] ], "normalized": [] }, { "id": "209_T5", "type": "Biological_Activity", "text": [ "cytotoxic" ], "offsets": [ [ 839, 848 ] ], "normalized": [] }, { "id": "209_T15", "type": "Biological_Activity", "text": [ "mutagenic" ], "offsets": [ [ 853, 862 ] ], "normalized": [] } ]

[]

[]

[ { "id": "209_R1", "type": "Associated_With", "arg1_id": "209_T2", "arg2_id": "209_T1", "normalized": [] }, { "id": "209_R2", "type": "Associated_With", "arg1_id": "209_T7", "arg2_id": "209_T6", "normalized": [] }, { "id": "209_R3", "type": "Associated_With", "arg1_id": "209_T10", "arg2_id": "209_T9", "normalized": [] }, { "id": "209_R4", "type": "Associated_With", "arg1_id": "209_T12", "arg2_id": "209_T13", "normalized": [] }, { "id": "209_R7", "type": "Associated_With", "arg1_id": "209_T21", "arg2_id": "209_T20", "normalized": [] }, { "id": "209_R8", "type": "Associated_With", "arg1_id": "209_T18", "arg2_id": "209_T22", "normalized": [] }, { "id": "209_R5", "type": "Associated_With", "arg1_id": "209_T17", "arg2_id": "209_T3", "normalized": [] }, { "id": "209_R6", "type": "Associated_With", "arg1_id": "209_T18", "arg2_id": "209_T19", "normalized": [] } ]

[ { "id": "211", "type": "", "text": [ "The leaves of the composite Solidago canadensis (goldenrod) were shown to contain (-)-alpha-gurjunene synthase activity. This sesquiterpene is likely to be the precursor for cyclocolorenone, a sesquiterpene ketone present in high amounts in S. canadensis leaves. (-)-alpha-Gurjunene synthase was purified to apparent homogeneity (741-fold) by anion-exchange chromatography (on several matrices), dye ligand chromatography, hydroxylapatite chromatography, and gel filtration. Chromatography on a gel filtration matrix indicated a native molecular mass of 48 kDa, and SDS-PAGE showed the enzyme to be composed of one subunit with a denatured mass of 60 kDa. Its maximum activity was observed at pH 7.8 in the presence of 10 mM Mg2+ and the KM value for the substrate farnesyl diphosphate was 5.5 microM. Over a range of purification steps (-)-alpha-gurjunene and (+)-gamma-gurjunene synthase activities copurified. In addition, the product ratio of the enzyme activity under several different assay conditions was always 91% (-)-alpha-gurjunene and 9% (+)-gamma-gurjunene. This suggests that the formation of these two structurally related products is catalyzed by one enzyme. For further confirmation, we carried out a number of mechanistic studies with (-)-alpha-gurjunene synthase, in which an enzyme preparation was incubated with deuterated substrate analogues. Based on mass spectrometry analysis of the products formed, a cyclization mechanism was postulated which makes it plausible that the synthase catalyzes the formation of both sesquiterpenes. \n" ], "offsets": [ [ 0, 1560 ] ] } ]

[ { "id": "211_T1", "type": "Species", "text": [ "Solidago canadensis" ], "offsets": [ [ 28, 47 ] ], "normalized": [] }, { "id": "211_T2", "type": "Species", "text": [ "goldenrod" ], "offsets": [ [ 49, 58 ] ], "normalized": [] }, { "id": "211_T3", "type": "Protein", "text": [ "(-)-alpha-gurjunene synthase" ], "offsets": [ [ 82, 110 ] ], "normalized": [] }, { "id": "211_T4", "type": "Chemical", "text": [ "(-)-alpha-gurjunene" ], "offsets": [ [ 82, 101 ] ], "normalized": [] }, { "id": "211_T5", "type": "Biological_Activity", "text": [ "synthase" ], "offsets": [ [ 102, 110 ] ], "normalized": [] }, { "id": "211_T6", "type": "Chemical", "text": [ "sesquiterpene" ], "offsets": [ [ 126, 139 ] ], "normalized": [] }, { "id": "211_T7", "type": "Chemical", "text": [ "cyclocolorenone" ], "offsets": [ [ 174, 189 ] ], "normalized": [] }, { "id": "211_T8", "type": "Chemical", "text": [ "sesquiterpene ketone" ], "offsets": [ [ 193, 213 ] ], "normalized": [] }, { "id": "211_T9", "type": "Species", "text": [ "S. canadensis" ], "offsets": [ [ 242, 255 ] ], "normalized": [] }, { "id": "211_T10", "type": "Metabolite", "text": [ "cyclocolorenone" ], "offsets": [ [ 174, 189 ] ], "normalized": [] }, { "id": "211_T11", "type": "Metabolite", "text": [ "(-)-alpha-gurjunene" ], "offsets": [ [ 82, 101 ] ], "normalized": [] }, { "id": "211_T12", "type": "Protein", "text": [ "(-)-alpha-Gurjunene synthase" ], "offsets": [ [ 264, 292 ] ], "normalized": [] }, { "id": "211_T13", "type": "Chemical", "text": [ "hydroxylapatite" ], "offsets": [ [ 424, 439 ] ], "normalized": [] }, { "id": "211_T14", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 587, 593 ] ], "normalized": [] }, { "id": "211_T15", "type": "Chemical", "text": [ "Mg2+" ], "offsets": [ [ 726, 730 ] ], "normalized": [] }, { "id": "211_T16", "type": "Chemical", "text": [ "farnesyl diphosphate" ], "offsets": [ [ 766, 786 ] ], "normalized": [] }, { "id": "211_T17", "type": "Chemical", "text": [ "(-)-alpha-gurjunene" ], "offsets": [ [ 838, 857 ] ], "normalized": [] }, { "id": "211_T18", "type": "Chemical", "text": [ "(+)-gamma-gurjunene" ], "offsets": [ [ 862, 881 ] ], "normalized": [] }, { "id": "211_T19", "type": "Protein", "text": [ "(-)-alpha-gurjunene", "synthase" ], "offsets": [ [ 838, 857 ], [ 882, 890 ] ], "normalized": [] }, { "id": "211_T20", "type": "Protein", "text": [ "(+)-gamma-gurjunene synthase" ], "offsets": [ [ 862, 890 ] ], "normalized": [] }, { "id": "211_T22", "type": "Biological_Activity", "text": [ "synthase" ], "offsets": [ [ 882, 890 ] ], "normalized": [] }, { "id": "211_T23", "type": "Chemical", "text": [ "(-)-alpha-gurjunene" ], "offsets": [ [ 1025, 1044 ] ], "normalized": [] }, { "id": "211_T24", "type": "Chemical", "text": [ "(+)-gamma-gurjunene" ], "offsets": [ [ 1052, 1071 ] ], "normalized": [] }, { "id": "211_T25", "type": "Protein", "text": [ "(-)-alpha-gurjunene synthase" ], "offsets": [ [ 1256, 1284 ] ], "normalized": [] }, { "id": "211_T26", "type": "Spectral_Data", "text": [ "mass spectrometry analysis" ], "offsets": [ [ 1377, 1403 ] ], "normalized": [] }, { "id": "211_T27", "type": "Chemical", "text": [ "deuterated substrate analogues" ], "offsets": [ [ 1336, 1366 ] ], "normalized": [] }, { "id": "211_T28", "type": "Protein", "text": [ "synthase" ], "offsets": [ [ 1502, 1510 ] ], "normalized": [] }, { "id": "211_T29", "type": "Chemical", "text": [ "sesquiterpenes" ], "offsets": [ [ 1543, 1557 ] ], "normalized": [] }, { "id": "211_T30", "type": "Metabolite", "text": [ "farnesyl diphosphate" ], "offsets": [ [ 766, 786 ] ], "normalized": [] }, { "id": "211_T31", "type": "Metabolite", "text": [ "-)-alpha-gurjunene" ], "offsets": [ [ 1026, 1044 ] ], "normalized": [] }, { "id": "211_T32", "type": "Metabolite", "text": [ "(+)-gamma-gurjunene" ], "offsets": [ [ 1052, 1071 ] ], "normalized": [] }, { "id": "211_T33", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1169, 1175 ] ], "normalized": [] } ]

[]

[]

[ { "id": "211_R1", "type": "Metabolite_Of", "arg1_id": "211_T10", "arg2_id": "211_T4", "normalized": [] }, { "id": "211_R2", "type": "Isolated_From", "arg1_id": "211_T10", "arg2_id": "211_T9", "normalized": [] }, { "id": "211_R3", "type": "Isolated_From", "arg1_id": "211_T11", "arg2_id": "211_T1", "normalized": [] }, { "id": "211_R4", "type": "Isolated_From", "arg1_id": "211_T11", "arg2_id": "211_T2", "normalized": [] }, { "id": "211_R5", "type": "Metabolite_Of", "arg1_id": "211_T31", "arg2_id": "211_T16", "normalized": [] }, { "id": "211_R6", "type": "Metabolite_Of", "arg1_id": "211_T32", "arg2_id": "211_T16", "normalized": [] } ]

[ { "id": "213", "type": "", "text": [ "The stereochemistry of the alpha-oxidation of 3-methyl-branched fatty acids was studied in rat liver. R- and S-3-methylhexadecanoic acid were equally well alpha-oxidized in intact hepatocytes and homogenates. Subcellular fractionation studies showed that alpha-oxidation of both isomers is confined to peroxisomes. Dehydrogenation of 2-methylpentadecanal, the end-product of the peroxisomal alpha-oxidation of 3-methylhexadecanoic acid, to 2-methylpentadecanoic acid, followed by derivatization with R-1-phenylethylamine and subsequent separation of the stereoisomers by gas chromatography, revealed that the configuration of the methyl-branch is preserved throughout the whole alpha-oxidation process. Metabolism and formation of the 2-hydroxy-3-methylhexadecanoyl-CoA intermediate were also investigated. Separation of the methyl esters of the four isomers of 2-hydroxy-3-methylhexadecanoic acid was achieved by gas chromatography after derivatization of the hydroxy group with R-2-methoxy-2-trifluoromethylphenylacetic acid chloride and the absolute configuration of the four isomers was determined. Although purified peroxisomes are capable of metabolizing all four isomers of 2-hydroxy-3-methylhexadecanoyl-CoA, they can only form the (2S,3R) and the (2R,3S) isomers. Our experiments exclude the racemization of the 3-methyl branch during the alpha-oxidation process. The configuration of the 3-methyl branch does not influence the rate of alpha-oxidation, but determines the side of the 2-hydroxylation, hence the configuration of the 2-hydroxy-3-methylacyl-CoA intermediates formed during the process. \n" ], "offsets": [ [ 0, 1611 ] ] } ]

[ { "id": "213_T1", "type": "Chemical", "text": [ "3-methyl-branched fatty acids" ], "offsets": [ [ 46, 75 ] ], "normalized": [] }, { "id": "213_T2", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 33, 42 ] ], "normalized": [] }, { "id": "213_T3", "type": "Species", "text": [ "rat" ], "offsets": [ [ 91, 94 ] ], "normalized": [] }, { "id": "213_T4", "type": "Chemical", "text": [ "R-", "3-methylhexadecanoic acid" ], "offsets": [ [ 102, 104 ], [ 111, 136 ] ], "normalized": [] }, { "id": "213_T5", "type": "Chemical", "text": [ "S-3-methylhexadecanoic acid" ], "offsets": [ [ 109, 136 ] ], "normalized": [] }, { "id": "213_T6", "type": "Chemical", "text": [ "2-methylpentadecanal" ], "offsets": [ [ 334, 354 ] ], "normalized": [] }, { "id": "213_T7", "type": "Chemical", "text": [ "3-methylhexadecanoic acid" ], "offsets": [ [ 410, 435 ] ], "normalized": [] }, { "id": "213_T8", "type": "Metabolite", "text": [ "2-methylpentadecanal" ], "offsets": [ [ 334, 354 ] ], "normalized": [] }, { "id": "213_T9", "type": "Chemical", "text": [ "2-methylpentadecanoic acid" ], "offsets": [ [ 440, 466 ] ], "normalized": [] }, { "id": "213_T10", "type": "Chemical", "text": [ "R-1-phenylethylamine" ], "offsets": [ [ 500, 520 ] ], "normalized": [] }, { "id": "213_T11", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 397, 406 ] ], "normalized": [] }, { "id": "213_T12", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 684, 693 ] ], "normalized": [] }, { "id": "213_T13", "type": "Chemical", "text": [ "2-hydroxy-3-methylhexadecanoyl-CoA" ], "offsets": [ [ 735, 769 ] ], "normalized": [] }, { "id": "213_T14", "type": "Metabolite", "text": [ "2-hydroxy-3-methylhexadecanoyl-CoA" ], "offsets": [ [ 735, 769 ] ], "normalized": [] }, { "id": "213_T15", "type": "Chemical", "text": [ "methyl esters of", "2-hydroxy-3-methylhexadecanoic acid" ], "offsets": [ [ 825, 841 ], [ 862, 897 ] ], "normalized": [] }, { "id": "213_T16", "type": "Chemical", "text": [ "hydroxy group" ], "offsets": [ [ 961, 974 ] ], "normalized": [] }, { "id": "213_T17", "type": "Chemical", "text": [ "R-2-methoxy-2-trifluoromethylphenylacetic acid chloride" ], "offsets": [ [ 980, 1035 ] ], "normalized": [] }, { "id": "213_T18", "type": "Chemical", "text": [ "2-hydroxy-3-methylhexadecanoyl-CoA" ], "offsets": [ [ 1181, 1215 ] ], "normalized": [] }, { "id": "213_T19", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 1355, 1364 ] ], "normalized": [] }, { "id": "213_T20", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 1452, 1461 ] ], "normalized": [] }, { "id": "213_T21", "type": "Chemical", "text": [ "2-hydroxy-3-methylacyl-CoA" ], "offsets": [ [ 1542, 1568 ] ], "normalized": [] }, { "id": "213_T22", "type": "Metabolite", "text": [ "2-hydroxy-3-methylacyl-CoA" ], "offsets": [ [ 1542, 1568 ] ], "normalized": [] }, { "id": "213_T23", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 261, 270 ] ], "normalized": [] }, { "id": "213_T24", "type": "Biological_Activity", "text": [ "Metabolism" ], "offsets": [ [ 703, 713 ] ], "normalized": [] } ]

[]

[]

[ { "id": "213_R1", "type": "Metabolite_Of", "arg1_id": "213_T8", "arg2_id": "213_T7", "normalized": [] }, { "id": "213_R2", "type": "Metabolite_Of", "arg1_id": "213_T14", "arg2_id": "213_T7", "normalized": [] }, { "id": "213_R3", "type": "Metabolite_Of", "arg1_id": "213_T8", "arg2_id": "213_T13", "normalized": [] } ]

[ { "id": "215", "type": "", "text": [ "A methodology to determine the intrinsic capacities of a microflora to degrade gasoline was developed, in particular for assessing the potential of autochtonous populations of polluted and non polluted soils for natural attenuation and engineered bioremediation. A model mixture (GM23) constituted of the 23 most representative hydrocarbons of a commercial gasoline was used. The capacities of the microflorae (kinetics and extent of biodegradation) were assessed by chromatographic analysis of hydrocarbon consumption and of CO2 production. The degradation of the components of GM23 was assayed in separate incubations of each component and in the complete mixture. For the microflora of an unpolluted spruce forest soil, all hydrocarbons of GM23 except cyclohexane, 2,2,4- and 2,3,4-trimethylpentane isomers were degraded to below detection limit in 28 days. This microflora was reinforced with two mixed microbial communities selected from gasoline-polluted sites and shown to degrade cyclohexane and 2,2,4-trimethylpentane. With the reinforced microflora, complete degradation of GM23 was observed. The degradation patterns of individual components of GM23 were similar when the compounds were present individually or in the GM23 mixture, as long as the concentrations of 2-ethyltoluene and trimethylbenzene isomers were kept sufficiently low (< or = 35 mg.l-1) to remain below their inhibitory level. \n" ], "offsets": [ [ 0, 1408 ] ] } ]

[ { "id": "215_T1", "type": "Species", "text": [ "microflora" ], "offsets": [ [ 57, 67 ] ], "normalized": [] }, { "id": "215_T2", "type": "Chemical", "text": [ "gasoline" ], "offsets": [ [ 79, 87 ] ], "normalized": [] }, { "id": "215_T3", "type": "Chemical", "text": [ "hydrocarbons" ], "offsets": [ [ 328, 340 ] ], "normalized": [] }, { "id": "215_T4", "type": "Chemical", "text": [ "gasoline" ], "offsets": [ [ 357, 365 ] ], "normalized": [] }, { "id": "215_T5", "type": "Species", "text": [ "microflorae" ], "offsets": [ [ 399, 410 ] ], "normalized": [] }, { "id": "215_T6", "type": "Chemical", "text": [ "hydrocarbon" ], "offsets": [ [ 496, 507 ] ], "normalized": [] }, { "id": "215_T7", "type": "Metabolite", "text": [ "CO2" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "215_T8", "type": "Chemical", "text": [ "CO2" ], "offsets": [ [ 527, 530 ] ], "normalized": [] }, { "id": "215_T9", "type": "Species", "text": [ "microflora" ], "offsets": [ [ 676, 686 ] ], "normalized": [] }, { "id": "215_T10", "type": "Species", "text": [ "spruce" ], "offsets": [ [ 704, 710 ] ], "normalized": [] }, { "id": "215_T11", "type": "Chemical", "text": [ "hydrocarbons" ], "offsets": [ [ 728, 740 ] ], "normalized": [] }, { "id": "215_T12", "type": "Chemical", "text": [ "cyclohexane" ], "offsets": [ [ 756, 767 ] ], "normalized": [] }, { "id": "215_T13", "type": "Chemical", "text": [ "2,2,4-", "trimethylpentane" ], "offsets": [ [ 769, 775 ], [ 786, 802 ] ], "normalized": [] }, { "id": "215_T14", "type": "Chemical", "text": [ "2,3,4-trimethylpentane" ], "offsets": [ [ 780, 802 ] ], "normalized": [] }, { "id": "215_T15", "type": "Species", "text": [ "microflora" ], "offsets": [ [ 867, 877 ] ], "normalized": [] }, { "id": "215_T16", "type": "Chemical", "text": [ "gasoline" ], "offsets": [ [ 944, 952 ] ], "normalized": [] }, { "id": "215_T17", "type": "Chemical", "text": [ "cyclohexane" ], "offsets": [ [ 989, 1000 ] ], "normalized": [] }, { "id": "215_T18", "type": "Chemical", "text": [ "2,2,4-trimethylpentane" ], "offsets": [ [ 1005, 1027 ] ], "normalized": [] }, { "id": "215_T19", "type": "Species", "text": [ "microflora" ], "offsets": [ [ 1049, 1059 ] ], "normalized": [] }, { "id": "215_T20", "type": "Chemical", "text": [ "2-ethyltoluene" ], "offsets": [ [ 1277, 1291 ] ], "normalized": [] }, { "id": "215_T21", "type": "Chemical", "text": [ "trimethylbenzene isomers" ], "offsets": [ [ 1296, 1320 ] ], "normalized": [] }, { "id": "215_T22", "type": "Biological_Activity", "text": [ "biodegradation" ], "offsets": [ [ 435, 449 ] ], "normalized": [] }, { "id": "215_T23", "type": "Biological_Activity", "text": [ "degradation" ], "offsets": [ [ 1070, 1081 ] ], "normalized": [] }, { "id": "215_T24", "type": "Chemical", "text": [ "GM23" ], "offsets": [ [ 280, 284 ] ], "normalized": [] }, { "id": "215_T25", "type": "Chemical", "text": [ "GM23" ], "offsets": [ [ 580, 584 ] ], "normalized": [] }, { "id": "215_T26", "type": "Chemical", "text": [ "GM23" ], "offsets": [ [ 744, 748 ] ], "normalized": [] }, { "id": "215_T27", "type": "Chemical", "text": [ "GM23" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "215_T28", "type": "Chemical", "text": [ "GM23" ], "offsets": [ [ 1157, 1161 ] ], "normalized": [] }, { "id": "215_T29", "type": "Chemical", "text": [ "GM23" ], "offsets": [ [ 1230, 1234 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "217", "type": "", "text": [ "Nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) are the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (dehydrocostus lactone) isolated from the medicinal plant, Saussurea lappa, inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. This compound also decreased the TNF-alpha level in LPS-activated systems in vitro and in vivo. Thus, dehydrocostus lactone may be a possible candidate for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-alpha. \n" ], "offsets": [ [ 0, 716 ] ] } ]

[ { "id": "217_T1", "type": "Chemical", "text": [ "Nitric oxide" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "217_T2", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 14, 16 ] ], "normalized": [] }, { "id": "217_T3", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 22, 49 ] ], "normalized": [] }, { "id": "217_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 51, 60 ] ], "normalized": [] }, { "id": "217_T7", "type": "Chemical", "text": [ "sesquiterpene lactone" ], "offsets": [ [ 196, 217 ] ], "normalized": [] }, { "id": "217_T8", "type": "Chemical", "text": [ "dehydrocostus lactone" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "217_T9", "type": "Metabolite", "text": [ "dehydrocostus lactone" ], "offsets": [ [ 228, 249 ] ], "normalized": [] }, { "id": "217_T10", "type": "Species", "text": [ "Saussurea lappa" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "217_T11", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 303, 312 ] ], "normalized": [] }, { "id": "217_T12", "type": "Chemical", "text": [ "lipopolysaccharide" ], "offsets": [ [ 337, 355 ] ], "normalized": [] }, { "id": "217_T13", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 357, 360 ] ], "normalized": [] }, { "id": "217_T14", "type": "Species", "text": [ "RAW 264.7" ], "offsets": [ [ 372, 381 ] ], "normalized": [] }, { "id": "217_T15", "type": "Protein", "text": [ "nitric oxide synthase" ], "offsets": [ [ 413, 434 ] ], "normalized": [] }, { "id": "217_T16", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 435, 441 ] ], "normalized": [] }, { "id": "217_T17", "type": "Biological_Activity", "text": [ "suppressing" ], "offsets": [ [ 391, 402 ] ], "normalized": [] }, { "id": "217_T19", "type": "Chemical", "text": [ "dehydrocostus lactone" ], "offsets": [ [ 556, 577 ] ], "normalized": [] }, { "id": "217_T20", "type": "Metabolite", "text": [ "dehydrocostus lactone" ], "offsets": [ [ 556, 577 ] ], "normalized": [] }, { "id": "217_T5", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 331, 333 ] ], "normalized": [] }, { "id": "217_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 487, 496 ] ], "normalized": [] }, { "id": "217_T18", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 506, 509 ] ], "normalized": [] }, { "id": "217_T21", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 697, 699 ] ], "normalized": [] }, { "id": "217_T22", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 704, 713 ] ], "normalized": [] } ]

[]

[]

[ { "id": "217_R3", "type": "Isolated_From", "arg1_id": "217_T9", "arg2_id": "217_T10", "normalized": [] }, { "id": "217_R4", "type": "Associated_With", "arg1_id": "217_T8", "arg2_id": "217_T11", "normalized": [] }, { "id": "217_R5", "type": "Associated_With", "arg1_id": "217_T9", "arg2_id": "217_T11", "normalized": [] }, { "id": "217_R6", "type": "Associated_With", "arg1_id": "217_T8", "arg2_id": "217_T17", "normalized": [] }, { "id": "217_R7", "type": "Associated_With", "arg1_id": "217_T9", "arg2_id": "217_T17", "normalized": [] } ]

[ { "id": "219", "type": "", "text": [ "The stable prostacyclin analogue, iloprost relaxes a variety of blood vessels and increases cyclic AMP, although the relationship between adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and vasorelaxation remains unclear. We therefore investigated the effect of the adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) on iloprost-mediated relaxation and cyclic AMP elevation in endothelium-denuded aortic strips. Iloprost (1-1000 nM) caused a concentration-dependent inhibition of phenylephrine (1-6 microM) contractions, the responses being unaffected by pre-incubation with SQ22536 (100 microM) for 30 min. In other experiments 60 nM iloprost caused a 64% inhibition of phenylephrine contractions concomitant with a 3 fold rise in cyclic AMP. SQ22536 completely abolished the iloprost-induced elevation in cyclic AMP while having no significant effect on relaxation. Our results therefore strongly suggest that cyclic AMP-independent pathways are responsible for the vasorelaxant effects of iloprost in guinea-pig aorta. \n" ], "offsets": [ [ 0, 1057 ] ] } ]

[ { "id": "219_T1", "type": "Chemical", "text": [ "prostacyclin" ], "offsets": [ [ 11, 23 ] ], "normalized": [] }, { "id": "219_T2", "type": "Chemical", "text": [ "prostacyclin analogue" ], "offsets": [ [ 11, 32 ] ], "normalized": [] }, { "id": "219_T3", "type": "Chemical", "text": [ "iloprost" ], "offsets": [ [ 34, 42 ] ], "normalized": [] }, { "id": "219_T5", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 92, 102 ] ], "normalized": [] }, { "id": "219_T7", "type": "Chemical", "text": [ "adenosine 3': 5'-cyclic monophosphate" ], "offsets": [ [ 138, 175 ] ], "normalized": [] }, { "id": "219_T8", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 177, 187 ] ], "normalized": [] }, { "id": "219_T9", "type": "Biological_Activity", "text": [ "vasorelaxation" ], "offsets": [ [ 193, 207 ] ], "normalized": [] }, { "id": "219_T10", "type": "Protein", "text": [ "adenylyl cyclase" ], "offsets": [ [ 269, 285 ] ], "normalized": [] }, { "id": "219_T12", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 286, 295 ] ], "normalized": [] }, { "id": "219_T13", "type": "Chemical", "text": [ "9-(tetrahydro-2-furanyl)-9H-purin-6-amine" ], "offsets": [ [ 297, 338 ] ], "normalized": [] }, { "id": "219_T14", "type": "Chemical", "text": [ "SQ22536" ], "offsets": [ [ 340, 347 ] ], "normalized": [] }, { "id": "219_T15", "type": "Chemical", "text": [ "iloprost" ], "offsets": [ [ 352, 360 ] ], "normalized": [] }, { "id": "219_T16", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 385, 395 ] ], "normalized": [] }, { "id": "219_T19", "type": "Chemical", "text": [ "Iloprost" ], "offsets": [ [ 444, 452 ] ], "normalized": [] }, { "id": "219_T20", "type": "Biological_Activity", "text": [ "inhibition" ], "offsets": [ [ 498, 508 ] ], "normalized": [] }, { "id": "219_T21", "type": "Chemical", "text": [ "SQ22536" ], "offsets": [ [ 608, 615 ] ], "normalized": [] }, { "id": "219_T22", "type": "Chemical", "text": [ "iloprost" ], "offsets": [ [ 668, 676 ] ], "normalized": [] }, { "id": "219_T23", "type": "Biological_Activity", "text": [ "inhibition" ], "offsets": [ [ 690, 700 ] ], "normalized": [] }, { "id": "219_T25", "type": "Chemical", "text": [ "SQ22536" ], "offsets": [ [ 777, 784 ] ], "normalized": [] }, { "id": "219_T27", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 840, 850 ] ], "normalized": [] }, { "id": "219_T29", "type": "Biological_Activity", "text": [ "vasorelaxant" ], "offsets": [ [ 1002, 1014 ] ], "normalized": [] }, { "id": "219_T30", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 946, 956 ] ], "normalized": [] }, { "id": "219_T31", "type": "Chemical", "text": [ "iloprost" ], "offsets": [ [ 1026, 1034 ] ], "normalized": [] }, { "id": "219_T32", "type": "Species", "text": [ "guinea-pig" ], "offsets": [ [ 1038, 1048 ] ], "normalized": [] }, { "id": "219_T4", "type": "Metabolite", "text": [ "cyclic AMP" ], "offsets": [ [ 92, 102 ] ], "normalized": [] }, { "id": "219_T6", "type": "Metabolite", "text": [ "adenosine 3': 5'-cyclic monophosphate" ], "offsets": [ [ 138, 175 ] ], "normalized": [] }, { "id": "219_T33", "type": "Metabolite", "text": [ "cyclic AMP" ], "offsets": [ [ 177, 187 ] ], "normalized": [] }, { "id": "219_T18", "type": "Metabolite", "text": [ "cyclic AMP" ], "offsets": [ [ 385, 395 ] ], "normalized": [] }, { "id": "219_T17", "type": "Chemical", "text": [ "phenylephrine" ], "offsets": [ [ 512, 525 ] ], "normalized": [] }, { "id": "219_T34", "type": "Chemical", "text": [ "phenylephrine" ], "offsets": [ [ 704, 717 ] ], "normalized": [] }, { "id": "219_T24", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 765, 775 ] ], "normalized": [] }, { "id": "219_T35", "type": "Metabolite", "text": [ "cyclic AMP" ], "offsets": [ [ 765, 775 ] ], "normalized": [] }, { "id": "219_T26", "type": "Chemical", "text": [ "iloprost" ], "offsets": [ [ 810, 818 ] ], "normalized": [] }, { "id": "219_T36", "type": "Metabolite", "text": [ "cyclic AMP" ], "offsets": [ [ 840, 850 ] ], "normalized": [] }, { "id": "219_T28", "type": "Metabolite", "text": [ "cyclic AMP" ], "offsets": [ [ 946, 956 ] ], "normalized": [] } ]

[]

[]

[ { "id": "219_R3", "type": "Associated_With", "arg1_id": "219_T3", "arg2_id": "219_T9", "normalized": [] }, { "id": "219_R5", "type": "Associated_With", "arg1_id": "219_T13", "arg2_id": "219_T12", "normalized": [] }, { "id": "219_R6", "type": "Associated_With", "arg1_id": "219_T14", "arg2_id": "219_T12", "normalized": [] }, { "id": "219_R10", "type": "Associated_With", "arg1_id": "219_T19", "arg2_id": "219_T20", "normalized": [] }, { "id": "219_R11", "type": "Associated_With", "arg1_id": "219_T22", "arg2_id": "219_T23", "normalized": [] }, { "id": "219_R14", "type": "Associated_With", "arg1_id": "219_T31", "arg2_id": "219_T29", "normalized": [] }, { "id": "219_R1", "type": "Binds_With", "arg1_id": "219_T14", "arg2_id": "219_T10", "normalized": [] }, { "id": "219_R2", "type": "Binds_With", "arg1_id": "219_T13", "arg2_id": "219_T10", "normalized": [] } ]

[ { "id": "221", "type": "", "text": [ "The putative biosynthetic gene cluster for the alpha-glucosidase inhibitor acarbose was identified in the producer Actinoplanes sp. 50/110 by cloning a DNA segment containing the conserved gene for dTDP-D-glucose 4,6-dehydratase, acbB. The two flanking genes were acbA (dTDP-D-glucose synthase) and acbC, encoding a protein with significant similarity to 3-dehydroquinate synthases (AroB proteins). The acbC gene was overexpressed heterologously in Streptomyces lividans 66, and the product was shown to be a C7-cyclitol synthase using sedo-heptulose 7-phosphate, but not ido-heptulose 7-phosphate, as its substrate. The cyclization product, 2-epi-5-epi-valiolone ((2S,3S,4S,5R)-5-(hydroxymethyl)cyclohexanon-2,3,4,5-tetrol), is a precursor of the valienamine moiety of acarbose. A possible five-step reaction mechanism is proposed for the cyclization reaction catalyzed by AcbC based on the recent analysis of the three-dimensional structure of a eukaryotic 3-dehydroquinate synthase domain (Carpenter, E. P., Hawkins, A. R., Frost, J. W., and Brown, K. A. (1998) Nature 394, 299-302). \n" ], "offsets": [ [ 0, 1090 ] ] } ]

[ { "id": "221_T1", "type": "Protein", "text": [ "alpha-glucosidase" ], "offsets": [ [ 47, 64 ] ], "normalized": [] }, { "id": "221_T3", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 65, 74 ] ], "normalized": [] }, { "id": "221_T4", "type": "Chemical", "text": [ "acarbose" ], "offsets": [ [ 75, 83 ] ], "normalized": [] }, { "id": "221_T5", "type": "Metabolite", "text": [ "acarbose" ], "offsets": [ [ 75, 83 ] ], "normalized": [] }, { "id": "221_T6", "type": "Species", "text": [ "Actinoplanes sp. 50/110" ], "offsets": [ [ 115, 138 ] ], "normalized": [] }, { "id": "221_T7", "type": "Protein", "text": [ "3-dehydroquinate synthases" ], "offsets": [ [ 356, 382 ] ], "normalized": [] }, { "id": "221_T8", "type": "Species", "text": [ "Streptomyces lividans 66" ], "offsets": [ [ 450, 474 ] ], "normalized": [] }, { "id": "221_T9", "type": "Protein", "text": [ "C7-cyclitol synthase" ], "offsets": [ [ 510, 530 ] ], "normalized": [] }, { "id": "221_T10", "type": "Chemical", "text": [ "sedo-heptulose 7-phosphate" ], "offsets": [ [ 537, 563 ] ], "normalized": [] }, { "id": "221_T11", "type": "Chemical", "text": [ "ido-heptulose 7-phosphate" ], "offsets": [ [ 573, 598 ] ], "normalized": [] }, { "id": "221_T13", "type": "Chemical", "text": [ "(2S,3S,4S,5R)-5-(hydroxymethyl)cyclohexanon-2,3,4,5-tetrol" ], "offsets": [ [ 667, 725 ] ], "normalized": [] }, { "id": "221_T14", "type": "Chemical", "text": [ "valienamine" ], "offsets": [ [ 750, 761 ] ], "normalized": [] }, { "id": "221_T15", "type": "Metabolite", "text": [ "acarbose" ], "offsets": [ [ 772, 780 ] ], "normalized": [] }, { "id": "221_T16", "type": "Metabolite", "text": [ "(2S,3S,4S,5R)-5-(hydroxymethyl)cyclohexanon-2,3,4,5-tetrol" ], "offsets": [ [ 667, 725 ] ], "normalized": [] }, { "id": "221_T17", "type": "Chemical", "text": [ "acarbose" ], "offsets": [ [ 772, 780 ] ], "normalized": [] }, { "id": "221_T18", "type": "Protein", "text": [ "3-dehydroquinate synthase" ], "offsets": [ [ 961, 986 ] ], "normalized": [] }, { "id": "221_T19", "type": "Protein", "text": [ "dTDP-D-glucose 4,6-dehydratase" ], "offsets": [ [ 199, 229 ] ], "normalized": [] }, { "id": "221_T20", "type": "Protein", "text": [ "dTDP-D-glucose synthase" ], "offsets": [ [ 271, 294 ] ], "normalized": [] }, { "id": "221_T21", "type": "Protein", "text": [ "AroB proteins" ], "offsets": [ [ 384, 397 ] ], "normalized": [] }, { "id": "221_T22", "type": "Chemical", "text": [ "2-epi-5-epi-valiolone" ], "offsets": [ [ 644, 665 ] ], "normalized": [] }, { "id": "221_T23", "type": "Metabolite", "text": [ "2-epi-5-epi-valiolone" ], "offsets": [ [ 644, 665 ] ], "normalized": [] } ]

[]

[]

[ { "id": "221_R1", "type": "Isolated_From", "arg1_id": "221_T5", "arg2_id": "221_T6", "normalized": [] }, { "id": "221_R3", "type": "Metabolite_Of", "arg1_id": "221_T15", "arg2_id": "221_T13", "normalized": [] }, { "id": "221_R4", "type": "Metabolite_Of", "arg1_id": "221_T16", "arg2_id": "221_T10", "normalized": [] }, { "id": "221_R5", "type": "Associated_With", "arg1_id": "221_T4", "arg2_id": "221_T3", "normalized": [] }, { "id": "221_R6", "type": "Associated_With", "arg1_id": "221_T5", "arg2_id": "221_T3", "normalized": [] }, { "id": "221_R9", "type": "Metabolite_Of", "arg1_id": "221_T15", "arg2_id": "221_T22", "normalized": [] }, { "id": "221_R10", "type": "Metabolite_Of", "arg1_id": "221_T23", "arg2_id": "221_T10", "normalized": [] }, { "id": "221_R11", "type": "Binds_With", "arg1_id": "221_T5", "arg2_id": "221_T1", "normalized": [] }, { "id": "221_R12", "type": "Binds_With", "arg1_id": "221_T4", "arg2_id": "221_T1", "normalized": [] }, { "id": "221_R7", "type": "Binds_With", "arg1_id": "221_T10", "arg2_id": "221_T9", "normalized": [] } ]

[ { "id": "223", "type": "", "text": [ "The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesized following the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategies were designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC50) = 3. 5-3.7 micrograms/mL, cytotoxicity (CC50) >/= 40 micrograms/mL, MCC = 20 micrograms/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration. \n" ], "offsets": [ [ 0, 939 ] ] } ]

[ { "id": "223_T1", "type": "Chemical", "text": [ "acyclonucleosides" ], "offsets": [ [ 10, 27 ] ], "normalized": [] }, { "id": "223_T2", "type": "Chemical", "text": [ "benzothiadiazine dioxide" ], "offsets": [ [ 41, 65 ] ], "normalized": [] }, { "id": "223_T3", "type": "Chemical", "text": [ "acetoxyethoxymethyl", "groups" ], "offsets": [ [ 162, 181 ], [ 223, 229 ] ], "normalized": [] }, { "id": "223_T4", "type": "Chemical", "text": [ "benzyloxymethyl", "groups" ], "offsets": [ [ 183, 198 ], [ 223, 229 ] ], "normalized": [] }, { "id": "223_T5", "type": "Chemical", "text": [ "acyclic moieties" ], "offsets": [ [ 134, 150 ] ], "normalized": [] }, { "id": "223_T6", "type": "Chemical", "text": [ "propargyloxymethyl groups" ], "offsets": [ [ 204, 229 ] ], "normalized": [] }, { "id": "223_T7", "type": "Chemical", "text": [ "N-1", "derivatives" ], "offsets": [ [ 313, 316 ], [ 324, 335 ] ], "normalized": [] }, { "id": "223_T8", "type": "Chemical", "text": [ "N-3 derivatives" ], "offsets": [ [ 320, 335 ] ], "normalized": [] }, { "id": "223_T9", "type": "Protein", "text": [ "Lipase" ], "offsets": [ [ 337, 343 ] ], "normalized": [] }, { "id": "223_T11", "type": "Chemical", "text": [ "acyclonucleosides" ], "offsets": [ [ 402, 419 ] ], "normalized": [] }, { "id": "223_T12", "type": "Chemical", "text": [ "benzothiadiazine dioxide acyclonucleosides" ], "offsets": [ [ 433, 475 ] ], "normalized": [] }, { "id": "223_T14", "type": "Chemical", "text": [ "benzothiadiazine dioxide acyclonucleoside", "16" ], "offsets": [ [ 433, 474 ], [ 491, 493 ] ], "normalized": [] }, { "id": "223_T15", "type": "Chemical", "text": [ "ganciclovir" ], "offsets": [ [ 599, 610 ] ], "normalized": [] }, { "id": "223_T16", "type": "Biological_Activity", "text": [ "cytotoxicity" ], "offsets": [ [ 674, 686 ] ], "normalized": [] }, { "id": "223_T17", "type": "Chemical", "text": [ "compound 16" ], "offsets": [ [ 755, 766 ] ], "normalized": [] }, { "id": "223_T10", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 767, 776 ] ], "normalized": [] } ]

[]

[]

[ { "id": "223_R5", "type": "Associated_With", "arg1_id": "223_T14", "arg2_id": "223_T16", "normalized": [] }, { "id": "223_R1", "type": "Associated_With", "arg1_id": "223_T17", "arg2_id": "223_T10", "normalized": [] } ]

[ { "id": "225", "type": "", "text": [ "The photosynthetic organelles (cyanelles) of the protist Cyanophora paradoxa are surrounded by a peptidoglycan wall, modified through amidation with N-acetylputrescine. Cyanelle envelope membrane preparations were shown to catalyze the lipid-linked steps of peptidoglycan biosynthesis as well as the putrescinylation and subsequent acetylation, occurring at the stage of lipid I and/or lipid II. \n" ], "offsets": [ [ 0, 398 ] ] } ]

[ { "id": "225_T1", "type": "Species", "text": [ "Cyanophora paradoxa" ], "offsets": [ [ 57, 76 ] ], "normalized": [] }, { "id": "225_T2", "type": "Chemical", "text": [ "peptidoglycan" ], "offsets": [ [ 98, 111 ] ], "normalized": [] }, { "id": "225_T3", "type": "Chemical", "text": [ "N-acetylputrescine" ], "offsets": [ [ 150, 168 ] ], "normalized": [] }, { "id": "225_T4", "type": "Biological_Activity", "text": [ "biosynthesis" ], "offsets": [ [ 273, 285 ] ], "normalized": [] }, { "id": "225_T5", "type": "Biological_Activity", "text": [ "putrescinylation" ], "offsets": [ [ 301, 317 ] ], "normalized": [] }, { "id": "225_T6", "type": "Biological_Activity", "text": [ "acetylation" ], "offsets": [ [ 333, 344 ] ], "normalized": [] }, { "id": "225_T7", "type": "Chemical", "text": [ "lipid I" ], "offsets": [ [ 372, 379 ] ], "normalized": [] }, { "id": "225_T8", "type": "Chemical", "text": [ "lipid II" ], "offsets": [ [ 387, 395 ] ], "normalized": [] }, { "id": "225_T9", "type": "Chemical", "text": [ "lipid" ], "offsets": [ [ 237, 242 ] ], "normalized": [] }, { "id": "225_T10", "type": "Chemical", "text": [ "peptidoglycan" ], "offsets": [ [ 259, 272 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "227", "type": "", "text": [ "The purpose of the present study was to investigate the involvement of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and tyrosine kinase on prostaglandin E2 (PGE2) production in human gingival fibroblasts stimulated by interleukin-1beta (IL-1beta) and/or epidermal growth factor (EGF). The cytokine IL-1beta and to a lesser extent EGF, enhanced COX-2 mRNA levels in gingival fibroblasts. Simultaneous treatment with EGF and IL-1beta resulted in enhanced COX-2 mRNA levels accompanied by a synergistic stimulation of PGE2 biosynthesis compared to the cells treated with IL-1beta or EGF alone. Neither IL-1beta EGF nor the combination of IL-1beta and EGF enhanced COX-1 mRNA levels in gingival fibroblasts. The tyrosine kinase inhibitors, Herbimycin A and PD 153035 hydrochloride, reduced COX-2 mRNA levels as well as PGE2 production induced by IL-1beta or the combination of IL-1beta and EGF whereas COX-1 mRNA levels were not affected. Furthermore, the COX-2 specific inhibitor, NS-398, abolished the PGE2 production induced by IL-1beta, EGF, or the combination. These results indicate that the synergy between IL-1beta and EGF on PGE2 production is due to an enhanced gene expression of COX-2 and that tyrosine kinase(s) are involved in the signal transduction of COX-2 in gingival fibroblasts. \n" ], "offsets": [ [ 0, 1304 ] ] } ]

[ { "id": "227_T1", "type": "Protein", "text": [ "cyclooxygenase-1" ], "offsets": [ [ 71, 87 ] ], "normalized": [] }, { "id": "227_T2", "type": "Protein", "text": [ "COX-1" ], "offsets": [ [ 89, 94 ] ], "normalized": [] }, { "id": "227_T3", "type": "Protein", "text": [ "cyclooxygenase-2" ], "offsets": [ [ 97, 113 ] ], "normalized": [] }, { "id": "227_T4", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 115, 120 ] ], "normalized": [] }, { "id": "227_T5", "type": "Protein", "text": [ "tyrosine kinase" ], "offsets": [ [ 127, 142 ] ], "normalized": [] }, { "id": "227_T6", "type": "Chemical", "text": [ "prostaglandin E2" ], "offsets": [ [ 146, 162 ] ], "normalized": [] }, { "id": "227_T7", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 164, 168 ] ], "normalized": [] }, { "id": "227_T8", "type": "Metabolite", "text": [ "prostaglandin E2" ], "offsets": [ [ 146, 162 ] ], "normalized": [] }, { "id": "227_T9", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 164, 168 ] ], "normalized": [] }, { "id": "227_T10", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 225, 242 ] ], "normalized": [] }, { "id": "227_T11", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 244, 252 ] ], "normalized": [] }, { "id": "227_T12", "type": "Protein", "text": [ "epidermal growth factor" ], "offsets": [ [ 261, 284 ] ], "normalized": [] }, { "id": "227_T13", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 286, 289 ] ], "normalized": [] }, { "id": "227_T16", "type": "Species", "text": [ "human" ], "offsets": [ [ 184, 189 ] ], "normalized": [] }, { "id": "227_T17", "type": "Protein", "text": [ "cytokine IL-1beta" ], "offsets": [ [ 296, 313 ] ], "normalized": [] }, { "id": "227_T18", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 337, 340 ] ], "normalized": [] }, { "id": "227_T19", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 351, 356 ] ], "normalized": [] }, { "id": "227_T20", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 422, 425 ] ], "normalized": [] }, { "id": "227_T21", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 430, 438 ] ], "normalized": [] }, { "id": "227_T22", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 460, 465 ] ], "normalized": [] }, { "id": "227_T23", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 522, 526 ] ], "normalized": [] }, { "id": "227_T24", "type": "Biological_Activity", "text": [ "biosynthesis" ], "offsets": [ [ 527, 539 ] ], "normalized": [] }, { "id": "227_T25", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 575, 583 ] ], "normalized": [] }, { "id": "227_T26", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 587, 590 ] ], "normalized": [] }, { "id": "227_T27", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 606, 614 ] ], "normalized": [] }, { "id": "227_T28", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 615, 618 ] ], "normalized": [] }, { "id": "227_T29", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 642, 650 ] ], "normalized": [] }, { "id": "227_T30", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "227_T31", "type": "Protein", "text": [ "COX-1" ], "offsets": [ [ 668, 673 ] ], "normalized": [] }, { "id": "227_T32", "type": "Protein", "text": [ "tyrosine kinase" ], "offsets": [ [ 715, 730 ] ], "normalized": [] }, { "id": "227_T33", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 731, 740 ] ], "normalized": [] }, { "id": "227_T34", "type": "Chemical", "text": [ "Herbimycin A" ], "offsets": [ [ 743, 755 ] ], "normalized": [] }, { "id": "227_T35", "type": "Chemical", "text": [ "PD 153035 hydrochloride" ], "offsets": [ [ 760, 783 ] ], "normalized": [] }, { "id": "227_T36", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 793, 798 ] ], "normalized": [] }, { "id": "227_T39", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 822, 826 ] ], "normalized": [] }, { "id": "227_T41", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 849, 857 ] ], "normalized": [] }, { "id": "227_T42", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 880, 888 ] ], "normalized": [] }, { "id": "227_T43", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 893, 896 ] ], "normalized": [] }, { "id": "227_T44", "type": "Protein", "text": [ "COX-1" ], "offsets": [ [ 905, 910 ] ], "normalized": [] }, { "id": "227_T45", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 959, 964 ] ], "normalized": [] }, { "id": "227_T47", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 974, 983 ] ], "normalized": [] }, { "id": "227_T48", "type": "Chemical", "text": [ "NS-398" ], "offsets": [ [ 985, 991 ] ], "normalized": [] }, { "id": "227_T50", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "227_T51", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1034, 1042 ] ], "normalized": [] }, { "id": "227_T52", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 1044, 1047 ] ], "normalized": [] }, { "id": "227_T53", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1117, 1125 ] ], "normalized": [] }, { "id": "227_T54", "type": "Protein", "text": [ "EGF" ], "offsets": [ [ 1130, 1133 ] ], "normalized": [] }, { "id": "227_T55", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "227_T56", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 522, 526 ] ], "normalized": [] }, { "id": "227_T57", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "227_T59", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1194, 1199 ] ], "normalized": [] }, { "id": "227_T60", "type": "Protein", "text": [ "tyrosine kinase(s)" ], "offsets": [ [ 1209, 1227 ] ], "normalized": [] }, { "id": "227_T61", "type": "Protein", "text": [ "COX-2" ], "offsets": [ [ 1272, 1277 ] ], "normalized": [] }, { "id": "227_T64", "type": "Metabolite", "text": [ "PGE2" ], "offsets": [ [ 822, 826 ] ], "normalized": [] }, { "id": "227_T65", "type": "Chemical", "text": [ "PGE2" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "227_T14", "type": "Biological_Activity", "text": [ "stimulation" ], "offsets": [ [ 507, 518 ] ], "normalized": [] } ]

[]

[]

[ { "id": "227_R1", "type": "Associated_With", "arg1_id": "227_T34", "arg2_id": "227_T33", "normalized": [] }, { "id": "227_R2", "type": "Associated_With", "arg1_id": "227_T35", "arg2_id": "227_T33", "normalized": [] }, { "id": "227_R5", "type": "Binds_With", "arg1_id": "227_T34", "arg2_id": "227_T32", "normalized": [] }, { "id": "227_R10", "type": "Associated_With", "arg1_id": "227_T48", "arg2_id": "227_T47", "normalized": [] }, { "id": "227_R3", "type": "Binds_With", "arg1_id": "227_T35", "arg2_id": "227_T32", "normalized": [] }, { "id": "227_R4", "type": "Binds_With", "arg1_id": "227_T48", "arg2_id": "227_T45", "normalized": [] } ]

[ { "id": "229", "type": "", "text": [ "The mechanism of DNA damage induced by metabolites of nitrobenzene was investigated in relation to the carcinogenicity and reproductive toxicity of nitrobenzene. Nitrosobenzene, a nitrobenzene metabolite, induced NADH plus Cu(II)-mediated DNA cleavage frequently at thymine and cytosine residues. Catalase and bathocuproine inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). Typical free hydroxyl radical scavengers showed no inhibitory effects on DNA damage. Nitrosobenzene caused the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of NADH and Cu(II). ESR spectroscopic study has confirmed that nitrosobenzene is reduced by NADH to the phenylhydronitroxide radical even in the absence of Cu(II). These results suggest that nitrosobenzene can be reduced non-enzymatically by NADH, and the redox cycle reaction resulted in oxidative DNA damage due to the copper-oxygen complex, derived from the reaction of Cu(I) with H2O2. \n" ], "offsets": [ [ 0, 984 ] ] } ]

[ { "id": "229_T2", "type": "Metabolite", "text": [ "metabolites of nitrobenzene" ], "offsets": [ [ 39, 66 ] ], "normalized": [] }, { "id": "229_T3", "type": "Chemical", "text": [ "metabolites of nitrobenzene" ], "offsets": [ [ 39, 66 ] ], "normalized": [] }, { "id": "229_T4", "type": "Chemical", "text": [ "nitrobenzene" ], "offsets": [ [ 54, 66 ] ], "normalized": [] }, { "id": "229_T5", "type": "Biological_Activity", "text": [ "carcinogenicity" ], "offsets": [ [ 103, 118 ] ], "normalized": [] }, { "id": "229_T6", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 136, 144 ] ], "normalized": [] }, { "id": "229_T7", "type": "Chemical", "text": [ "nitrobenzene" ], "offsets": [ [ 148, 160 ] ], "normalized": [] }, { "id": "229_T8", "type": "Chemical", "text": [ "Nitrosobenzene" ], "offsets": [ [ 162, 176 ] ], "normalized": [] }, { "id": "229_T9", "type": "Chemical", "text": [ "nitrobenzene" ], "offsets": [ [ 180, 192 ] ], "normalized": [] }, { "id": "229_T10", "type": "Metabolite", "text": [ "Nitrosobenzene" ], "offsets": [ [ 162, 176 ] ], "normalized": [] }, { "id": "229_T12", "type": "Chemical", "text": [ "thymine", "residues" ], "offsets": [ [ 266, 273 ], [ 287, 295 ] ], "normalized": [] }, { "id": "229_T13", "type": "Chemical", "text": [ "cytosine residues" ], "offsets": [ [ 278, 295 ] ], "normalized": [] }, { "id": "229_T14", "type": "Protein", "text": [ "Catalase" ], "offsets": [ [ 297, 305 ] ], "normalized": [] }, { "id": "229_T15", "type": "Chemical", "text": [ "bathocuproine" ], "offsets": [ [ 310, 323 ] ], "normalized": [] }, { "id": "229_T16", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 324, 333 ] ], "normalized": [] }, { "id": "229_T17", "type": "Chemical", "text": [ "H2O2" ], "offsets": [ [ 380, 384 ] ], "normalized": [] }, { "id": "229_T18", "type": "Chemical", "text": [ "Cu(I)" ], "offsets": [ [ 389, 394 ] ], "normalized": [] }, { "id": "229_T19", "type": "Chemical", "text": [ "free hydroxyl radical" ], "offsets": [ [ 404, 425 ] ], "normalized": [] }, { "id": "229_T20", "type": "Biological_Activity", "text": [ "radical scavengers" ], "offsets": [ [ 418, 436 ] ], "normalized": [] }, { "id": "229_T22", "type": "Chemical", "text": [ "Nitrosobenzene" ], "offsets": [ [ 482, 496 ] ], "normalized": [] }, { "id": "229_T23", "type": "Metabolite", "text": [ "Nitrosobenzene" ], "offsets": [ [ 482, 496 ] ], "normalized": [] }, { "id": "229_T24", "type": "Chemical", "text": [ "8-oxo-7, 8-dihydro-2'-deoxyguanosine" ], "offsets": [ [ 521, 557 ] ], "normalized": [] }, { "id": "229_T25", "type": "Species", "text": [ "calf" ], "offsets": [ [ 561, 565 ] ], "normalized": [] }, { "id": "229_T26", "type": "Chemical", "text": [ "NADH" ], "offsets": [ [ 596, 600 ] ], "normalized": [] }, { "id": "229_T27", "type": "Chemical", "text": [ "Cu(II)" ], "offsets": [ [ 605, 611 ] ], "normalized": [] }, { "id": "229_T28", "type": "Spectral_Data", "text": [ "ESR spectroscopic study" ], "offsets": [ [ 613, 636 ] ], "normalized": [] }, { "id": "229_T29", "type": "Chemical", "text": [ "nitrosobenzene" ], "offsets": [ [ 656, 670 ] ], "normalized": [] }, { "id": "229_T30", "type": "Metabolite", "text": [ "nitrosobenzene" ], "offsets": [ [ 656, 670 ] ], "normalized": [] }, { "id": "229_T31", "type": "Chemical", "text": [ "NADH" ], "offsets": [ [ 685, 689 ] ], "normalized": [] }, { "id": "229_T32", "type": "Chemical", "text": [ "phenylhydronitroxide radical" ], "offsets": [ [ 697, 725 ] ], "normalized": [] }, { "id": "229_T33", "type": "Metabolite", "text": [ "phenylhydronitroxide radical" ], "offsets": [ [ 697, 725 ] ], "normalized": [] }, { "id": "229_T34", "type": "Chemical", "text": [ "Cu(II)" ], "offsets": [ [ 749, 755 ] ], "normalized": [] }, { "id": "229_T35", "type": "Chemical", "text": [ "nitrosobenzene" ], "offsets": [ [ 784, 798 ] ], "normalized": [] }, { "id": "229_T36", "type": "Metabolite", "text": [ "nitrosobenzene" ], "offsets": [ [ 784, 798 ] ], "normalized": [] }, { "id": "229_T37", "type": "Chemical", "text": [ "NADH" ], "offsets": [ [ 835, 839 ] ], "normalized": [] }, { "id": "229_T39", "type": "Chemical", "text": [ "copper-oxygen complex" ], "offsets": [ [ 914, 935 ] ], "normalized": [] }, { "id": "229_T40", "type": "Chemical", "text": [ "Cu(I)" ], "offsets": [ [ 966, 971 ] ], "normalized": [] }, { "id": "229_T41", "type": "Chemical", "text": [ "H2O2" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "229_T1", "type": "Chemical", "text": [ "NADH" ], "offsets": [ [ 213, 217 ] ], "normalized": [] }, { "id": "229_T11", "type": "Chemical", "text": [ "Cu(II)" ], "offsets": [ [ 223, 229 ] ], "normalized": [] } ]

[]

[]

[ { "id": "229_R1", "type": "Metabolite_Of", "arg1_id": "229_T10", "arg2_id": "229_T9", "normalized": [] }, { "id": "229_R5", "type": "Metabolite_Of", "arg1_id": "229_T33", "arg2_id": "229_T29", "normalized": [] }, { "id": "229_R6", "type": "Associated_With", "arg1_id": "229_T33", "arg2_id": "229_T28", "normalized": [] }, { "id": "229_R7", "type": "Associated_With", "arg1_id": "229_T32", "arg2_id": "229_T28", "normalized": [] }, { "id": "229_R10", "type": "Associated_With", "arg1_id": "229_T7", "arg2_id": "229_T5", "normalized": [] }, { "id": "229_R11", "type": "Associated_With", "arg1_id": "229_T7", "arg2_id": "229_T6", "normalized": [] } ]

[ { "id": "231", "type": "", "text": [ "Phosphorothioate oligonucleotides (S-oligos) are nucleic acid derivatives that are commonly used as antisense agents. These compounds, similar to bacterial DNA and CpG oligonucleotides, display a variety of immunological activities in vitro and in vivo. To assess further these activities, the antigenicity of a series of S-oligos was assessed in the solid phase using anti-DNA antibodies from sera of patients with systemic lupus erythematosus. By ELISA, S-oligos bound well to anti-DNA antibodies under the same conditions as calf thymus DNA antigen. The specificity for anti-DNA was established by competition assays showing cross-inhibition of binding by DNA and S-oligos. Reactivity with anti-DNA was observed with S-oligos varying in sequence, suggesting interaction with a conserved determinant not strictly dependent on the bases. Furthermore. in comparison with a phosphodiester oligomer of the same sequence, a phosphorothioate showed dramatically increased activity. These findings indicate that structural features associated with the S-oligo backbone promote specific binding to anti-DNA antibodies and influence the size requirement for antigenicity in the solid phase. These observations thus extend the immunological properties of S-oligos and suggest uses of these compounds in the diagnosis and treatment of autoimmune disease. \n" ], "offsets": [ [ 0, 1351 ] ] } ]

[ { "id": "231_T1", "type": "Chemical", "text": [ "Phosphorothioate oligonucleotides" ], "offsets": [ [ 0, 33 ] ], "normalized": [] }, { "id": "231_T2", "type": "Chemical", "text": [ "S-oligos" ], "offsets": [ [ 35, 43 ] ], "normalized": [] }, { "id": "231_T3", "type": "Chemical", "text": [ "nucleic acid derivatives" ], "offsets": [ [ 49, 73 ] ], "normalized": [] }, { "id": "231_T4", "type": "Biological_Activity", "text": [ "antisense" ], "offsets": [ [ 100, 109 ] ], "normalized": [] }, { "id": "231_T5", "type": "Chemical", "text": [ "oligonucleotides" ], "offsets": [ [ 169, 185 ] ], "normalized": [] }, { "id": "231_T6", "type": "Biological_Activity", "text": [ "immunological" ], "offsets": [ [ 208, 221 ] ], "normalized": [] }, { "id": "231_T7", "type": "Biological_Activity", "text": [ "antigenicity" ], "offsets": [ [ 296, 308 ] ], "normalized": [] }, { "id": "231_T8", "type": "Chemical", "text": [ "S-oligos" ], "offsets": [ [ 325, 333 ] ], "normalized": [] }, { "id": "231_T9", "type": "Protein", "text": [ "anti-DNA antibodies" ], "offsets": [ [ 372, 391 ] ], "normalized": [] }, { "id": "231_T10", "type": "Species", "text": [ "patients" ], "offsets": [ [ 405, 413 ] ], "normalized": [] }, { "id": "231_T12", "type": "Chemical", "text": [ "S-oligos" ], "offsets": [ [ 459, 467 ] ], "normalized": [] }, { "id": "231_T13", "type": "Protein", "text": [ "anti-DNA antibodies" ], "offsets": [ [ 482, 501 ] ], "normalized": [] }, { "id": "231_T14", "type": "Species", "text": [ "calf" ], "offsets": [ [ 531, 535 ] ], "normalized": [] }, { "id": "231_T15", "type": "Chemical", "text": [ "S-oligos" ], "offsets": [ [ 670, 678 ] ], "normalized": [] }, { "id": "231_T16", "type": "Chemical", "text": [ "S-oligos" ], "offsets": [ [ 723, 731 ] ], "normalized": [] }, { "id": "231_T17", "type": "Chemical", "text": [ "phosphodiester oligomer" ], "offsets": [ [ 876, 899 ] ], "normalized": [] }, { "id": "231_T18", "type": "Chemical", "text": [ "phosphorothioate" ], "offsets": [ [ 924, 940 ] ], "normalized": [] }, { "id": "231_T19", "type": "Chemical", "text": [ "S-oligo" ], "offsets": [ [ 1051, 1058 ] ], "normalized": [] }, { "id": "231_T20", "type": "Biological_Activity", "text": [ "binding" ], "offsets": [ [ 1085, 1092 ] ], "normalized": [] }, { "id": "231_T21", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 1105, 1115 ] ], "normalized": [] }, { "id": "231_T22", "type": "Chemical", "text": [ "S-oligos" ], "offsets": [ [ 1251, 1259 ] ], "normalized": [] }, { "id": "231_T11", "type": "Biological_Activity", "text": [ "antigenicity" ], "offsets": [ [ 1155, 1167 ] ], "normalized": [] }, { "id": "231_T23", "type": "Biological_Activity", "text": [ "bound" ], "offsets": [ [ 468, 473 ] ], "normalized": [] } ]

[]

[]

[ { "id": "231_R1", "type": "Associated_With", "arg1_id": "231_T1", "arg2_id": "231_T4", "normalized": [] }, { "id": "231_R2", "type": "Associated_With", "arg1_id": "231_T2", "arg2_id": "231_T4", "normalized": [] }, { "id": "231_R3", "type": "Associated_With", "arg1_id": "231_T1", "arg2_id": "231_T6", "normalized": [] }, { "id": "231_R4", "type": "Associated_With", "arg1_id": "231_T2", "arg2_id": "231_T6", "normalized": [] }, { "id": "231_R7", "type": "Associated_With", "arg1_id": "231_T8", "arg2_id": "231_T7", "normalized": [] }, { "id": "231_R5", "type": "Binds_With", "arg1_id": "231_T12", "arg2_id": "231_T13", "normalized": [] } ]

[ { "id": "233", "type": "", "text": [ "1. The urinary metabolic fate of 4-fluoroaniline (4-FA) and 1-[13C]-4-fluoroacetanilide (4-FAA) has been studied using NMR-based methods after 50 and 100 mg kg(-1) i.p. doses respectively to the male Sprague-Dawley rat. 2. 4-FA was both ortho- and para-hydroxylated. The major metabolite produced by ortho-hydroxylation was 2-amino-5-fluorophenylsulphate accounting for approximately 30% of the dose. Of the dose, approximately 10% was excreted via para-hydroxylation and the resulting defluorinated metabolites were N-acetylated and excreted as sulphate (major), glucuronide (minor) and N-acetyl-cysteinyl (minor) conjugates of 4-acetamidophenol (paracetamol). 3. The major route of metabolism of 1-[13C]-4-FAA was N-deacetylation and the metabolites excreted in the urine were qualitatively identical to 4-FA. The paracetamol metabolites produced via para-hydroxylation were also a product of N-deacetylation and reacetylation, as the [13C]-label was not retained. 4. These studies demonstrate the value of [13C]-labelling in understanding the contribution of N-acetylation, and futile deacetylation-reacetylation reactions, in aniline metabolism. In addition, this work sheds new light on the metabolic lability of certain aromatic fluorine substituents. \n" ], "offsets": [ [ 0, 1262 ] ] } ]

[ { "id": "233_T1", "type": "Chemical", "text": [ "4-fluoroaniline" ], "offsets": [ [ 33, 48 ] ], "normalized": [] }, { "id": "233_T2", "type": "Chemical", "text": [ "4-FA" ], "offsets": [ [ 50, 54 ] ], "normalized": [] }, { "id": "233_T3", "type": "Chemical", "text": [ "1-[13C]-4-fluoroacetanilide" ], "offsets": [ [ 60, 87 ] ], "normalized": [] }, { "id": "233_T4", "type": "Chemical", "text": [ "4-FAA" ], "offsets": [ [ 89, 94 ] ], "normalized": [] }, { "id": "233_T5", "type": "Species", "text": [ "Sprague-Dawley rat" ], "offsets": [ [ 200, 218 ] ], "normalized": [] }, { "id": "233_T6", "type": "Chemical", "text": [ "4-FA" ], "offsets": [ [ 223, 227 ] ], "normalized": [] }, { "id": "233_T7", "type": "Chemical", "text": [ "2-amino-5-fluorophenylsulphate" ], "offsets": [ [ 324, 354 ] ], "normalized": [] }, { "id": "233_T8", "type": "Metabolite", "text": [ "2-amino-5-fluorophenylsulphate" ], "offsets": [ [ 324, 354 ] ], "normalized": [] }, { "id": "233_T9", "type": "Chemical", "text": [ "sulphate", "conjugates of 4-acetamidophenol" ], "offsets": [ [ 547, 555 ], [ 616, 647 ] ], "normalized": [] }, { "id": "233_T10", "type": "Chemical", "text": [ "4-acetamidophenol" ], "offsets": [ [ 630, 647 ] ], "normalized": [] }, { "id": "233_T11", "type": "Metabolite", "text": [ "sulphate", "conjugates of 4-acetamidophenol" ], "offsets": [ [ 547, 555 ], [ 616, 647 ] ], "normalized": [] }, { "id": "233_T12", "type": "Chemical", "text": [ "glucuronide", "conjugates of 4-acetamidophenol" ], "offsets": [ [ 565, 576 ], [ 616, 647 ] ], "normalized": [] }, { "id": "233_T13", "type": "Metabolite", "text": [ "glucuronide", "conjugates of 4-acetamidophenol" ], "offsets": [ [ 565, 576 ], [ 616, 647 ] ], "normalized": [] }, { "id": "233_T14", "type": "Chemical", "text": [ "N-acetyl-cysteinyl", "conjugates of 4-acetamidophenol" ], "offsets": [ [ 589, 607 ], [ 616, 647 ] ], "normalized": [] }, { "id": "233_T15", "type": "Metabolite", "text": [ "N-acetyl-cysteinyl", "conjugates of 4-acetamidophenol" ], "offsets": [ [ 589, 607 ], [ 616, 647 ] ], "normalized": [] }, { "id": "233_T16", "type": "Metabolite", "text": [ "defluorinated metabolites" ], "offsets": [ [ 486, 511 ] ], "normalized": [] }, { "id": "233_T17", "type": "Chemical", "text": [ "1-[13C]-4-FAA" ], "offsets": [ [ 699, 712 ] ], "normalized": [] }, { "id": "233_T18", "type": "Metabolite", "text": [ "4-fluoroaniline" ], "offsets": [ [ 33, 48 ] ], "normalized": [] }, { "id": "233_T19", "type": "Chemical", "text": [ "4-FA" ], "offsets": [ [ 807, 811 ] ], "normalized": [] }, { "id": "233_T20", "type": "Metabolite", "text": [ "4-FA" ], "offsets": [ [ 807, 811 ] ], "normalized": [] }, { "id": "233_T21", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 649, 660 ] ], "normalized": [] }, { "id": "233_T22", "type": "Chemical", "text": [ "aniline" ], "offsets": [ [ 1133, 1140 ] ], "normalized": [] }, { "id": "233_T23", "type": "Chemical", "text": [ "aromatic fluorine substituents" ], "offsets": [ [ 1229, 1259 ] ], "normalized": [] }, { "id": "233_T24", "type": "Chemical", "text": [ "13C" ], "offsets": [ [ 1012, 1015 ] ], "normalized": [] }, { "id": "233_T25", "type": "Spectral_Data", "text": [ "NMR-based methods" ], "offsets": [ [ 119, 136 ] ], "normalized": [] }, { "id": "233_T35", "type": "Chemical", "text": [ "paracetamol metabolites" ], "offsets": [ [ 817, 840 ] ], "normalized": [] }, { "id": "233_T36", "type": "Metabolite", "text": [ "paracetamol metabolites" ], "offsets": [ [ 817, 840 ] ], "normalized": [] }, { "id": "233_T26", "type": "Chemical", "text": [ "13C" ], "offsets": [ [ 939, 942 ] ], "normalized": [] }, { "id": "233_T27", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 685, 695 ] ], "normalized": [] }, { "id": "233_T28", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1141, 1151 ] ], "normalized": [] } ]

[]

[]

[ { "id": "233_R1", "type": "Metabolite_Of", "arg1_id": "233_T8", "arg2_id": "233_T1", "normalized": [] }, { "id": "233_R2", "type": "Metabolite_Of", "arg1_id": "233_T8", "arg2_id": "233_T2", "normalized": [] }, { "id": "233_R3", "type": "Metabolite_Of", "arg1_id": "233_T11", "arg2_id": "233_T6", "normalized": [] }, { "id": "233_R4", "type": "Metabolite_Of", "arg1_id": "233_T13", "arg2_id": "233_T6", "normalized": [] }, { "id": "233_R5", "type": "Metabolite_Of", "arg1_id": "233_T15", "arg2_id": "233_T6", "normalized": [] }, { "id": "233_R6", "type": "Metabolite_Of", "arg1_id": "233_T18", "arg2_id": "233_T17", "normalized": [] }, { "id": "233_R7", "type": "Metabolite_Of", "arg1_id": "233_T20", "arg2_id": "233_T17", "normalized": [] }, { "id": "233_R8", "type": "Metabolite_Of", "arg1_id": "233_T8", "arg2_id": "233_T17", "normalized": [] }, { "id": "233_R9", "type": "Metabolite_Of", "arg1_id": "233_T11", "arg2_id": "233_T17", "normalized": [] }, { "id": "233_R10", "type": "Metabolite_Of", "arg1_id": "233_T13", "arg2_id": "233_T17", "normalized": [] } ]

[ { "id": "235", "type": "", "text": [ "Synthetic benzamide derivatives were investigated for their ability to inhibit histone deacetylase (HDA). In this study, one of the most active benzamide derivatives, MS-27-275, was examined with regard to its biological properties and antitumor efficacy. MS-27-275 inhibited partially purified human HDA and caused hyperacetylation of nuclear histones in various tumor cell lines. It behaved in a manner similar to other HDA inhibitors, such as sodium butyrate and trichostatin A; MS-27-275 induced p21(WAF1/CIP1) and gelsolin and changed the cell cycle distribution, decrease of S-phase cells, and increase of G1-phase cells. The in vitro sensitivity spectrum of MS-27-275 against various human tumor cell lines showed a pattern different than that of a commonly used antitumor agent, 5-fluorouracil, and, of interest, the accumulation of p21(WAF1/CIP1) tended to be faster and greater in the cell lines sensitive to MS-27-275. MS-27-275 administered orally strongly inhibited the growth in seven of eight tumor lines implanted into nude mice, although most of these did not respond to 5-fluorouracil. A structurally analogous compound to MS-27-275 without HDA-inhibiting activity showed neither the biological effects in cell culture nor the in vivo therapeutic efficacy. These results suggest that MS-27-275 acts as an antitumor agent through HDA inhibition and may provide a novel chemotherapeutic strategy for cancers insensitive to traditional antitumor agents. \n" ], "offsets": [ [ 0, 1471 ] ] } ]

[ { "id": "235_T1", "type": "Chemical", "text": [ "benzamide derivatives" ], "offsets": [ [ 10, 31 ] ], "normalized": [] }, { "id": "235_T2", "type": "Protein", "text": [ "histone deacetylase" ], "offsets": [ [ 79, 98 ] ], "normalized": [] }, { "id": "235_T3", "type": "Protein", "text": [ "HDA" ], "offsets": [ [ 100, 103 ] ], "normalized": [] }, { "id": "235_T4", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 71, 78 ] ], "normalized": [] }, { "id": "235_T6", "type": "Chemical", "text": [ "benzamide derivatives" ], "offsets": [ [ 144, 165 ] ], "normalized": [] }, { "id": "235_T7", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 167, 176 ] ], "normalized": [] }, { "id": "235_T8", "type": "Biological_Activity", "text": [ "antitumor" ], "offsets": [ [ 236, 245 ] ], "normalized": [] }, { "id": "235_T9", "type": "Species", "text": [ "human" ], "offsets": [ [ 295, 300 ] ], "normalized": [] }, { "id": "235_T10", "type": "Protein", "text": [ "HDA" ], "offsets": [ [ 301, 304 ] ], "normalized": [] }, { "id": "235_T12", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 266, 275 ] ], "normalized": [] }, { "id": "235_T13", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 256, 265 ] ], "normalized": [] }, { "id": "235_T14", "type": "Biological_Activity", "text": [ "hyperacetylation" ], "offsets": [ [ 316, 332 ] ], "normalized": [] }, { "id": "235_T15", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 426, 435 ] ], "normalized": [] }, { "id": "235_T16", "type": "Protein", "text": [ "HDA" ], "offsets": [ [ 422, 425 ] ], "normalized": [] }, { "id": "235_T18", "type": "Chemical", "text": [ "sodium butyrate" ], "offsets": [ [ 446, 461 ] ], "normalized": [] }, { "id": "235_T19", "type": "Chemical", "text": [ "trichostatin A" ], "offsets": [ [ 466, 481 ] ], "normalized": [] }, { "id": "235_T20", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 483, 492 ] ], "normalized": [] }, { "id": "235_T21", "type": "Protein", "text": [ "gelsolin" ], "offsets": [ [ 520, 528 ] ], "normalized": [] }, { "id": "235_T22", "type": "Protein", "text": [ "p21(WAF1/CIP1)" ], "offsets": [ [ 501, 515 ] ], "normalized": [] }, { "id": "235_T28", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 666, 675 ] ], "normalized": [] }, { "id": "235_T29", "type": "Species", "text": [ "human" ], "offsets": [ [ 692, 697 ] ], "normalized": [] }, { "id": "235_T30", "type": "Biological_Activity", "text": [ "antitumor" ], "offsets": [ [ 771, 780 ] ], "normalized": [] }, { "id": "235_T31", "type": "Chemical", "text": [ "5-fluorouracil" ], "offsets": [ [ 788, 802 ] ], "normalized": [] }, { "id": "235_T32", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 920, 929 ] ], "normalized": [] }, { "id": "235_T33", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 931, 940 ] ], "normalized": [] }, { "id": "235_T34", "type": "Species", "text": [ "nude mice" ], "offsets": [ [ 1036, 1045 ] ], "normalized": [] }, { "id": "235_T35", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 970, 979 ] ], "normalized": [] }, { "id": "235_T36", "type": "Chemical", "text": [ "5-fluorouracil" ], "offsets": [ [ 1089, 1103 ] ], "normalized": [] }, { "id": "235_T37", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 1142, 1151 ] ], "normalized": [] }, { "id": "235_T38", "type": "Biological_Activity", "text": [ "inhibiting" ], "offsets": [ [ 1164, 1174 ] ], "normalized": [] }, { "id": "235_T39", "type": "Chemical", "text": [ "structurally analogous compound to MS-27-275" ], "offsets": [ [ 1107, 1151 ] ], "normalized": [] }, { "id": "235_T40", "type": "Chemical", "text": [ "MS-27-275" ], "offsets": [ [ 1303, 1312 ] ], "normalized": [] }, { "id": "235_T41", "type": "Biological_Activity", "text": [ "antitumor" ], "offsets": [ [ 1324, 1333 ] ], "normalized": [] }, { "id": "235_T42", "type": "Biological_Activity", "text": [ "inhibition" ], "offsets": [ [ 1352, 1362 ] ], "normalized": [] }, { "id": "235_T43", "type": "Biological_Activity", "text": [ "antitumor" ], "offsets": [ [ 1452, 1461 ] ], "normalized": [] }, { "id": "235_T46", "type": "Protein", "text": [ "HDA" ], "offsets": [ [ 1160, 1163 ] ], "normalized": [] }, { "id": "235_T47", "type": "Protein", "text": [ "HDA" ], "offsets": [ [ 1348, 1351 ] ], "normalized": [] }, { "id": "235_T49", "type": "Chemical", "text": [ "antitumor agents" ], "offsets": [ [ 1452, 1468 ] ], "normalized": [] } ]

[]

[]

[ { "id": "235_R2", "type": "Associated_With", "arg1_id": "235_T13", "arg2_id": "235_T12", "normalized": [] }, { "id": "235_R3", "type": "Associated_With", "arg1_id": "235_T13", "arg2_id": "235_T14", "normalized": [] }, { "id": "235_R6", "type": "Associated_With", "arg1_id": "235_T18", "arg2_id": "235_T15", "normalized": [] }, { "id": "235_R7", "type": "Associated_With", "arg1_id": "235_T19", "arg2_id": "235_T15", "normalized": [] }, { "id": "235_R23", "type": "Associated_With", "arg1_id": "235_T31", "arg2_id": "235_T30", "normalized": [] }, { "id": "235_R24", "type": "Associated_With", "arg1_id": "235_T7", "arg2_id": "235_T8", "normalized": [] }, { "id": "235_R25", "type": "Associated_With", "arg1_id": "235_T28", "arg2_id": "235_T30", "normalized": [] }, { "id": "235_R26", "type": "Associated_With", "arg1_id": "235_T37", "arg2_id": "235_T38", "normalized": [] }, { "id": "235_R27", "type": "Associated_With", "arg1_id": "235_T40", "arg2_id": "235_T41", "normalized": [] }, { "id": "235_R28", "type": "Associated_With", "arg1_id": "235_T40", "arg2_id": "235_T42", "normalized": [] }, { "id": "235_R31", "type": "Associated_With", "arg1_id": "235_T1", "arg2_id": "235_T4", "normalized": [] }, { "id": "235_R8", "type": "Associated_With", "arg1_id": "235_T33", "arg2_id": "235_T35", "normalized": [] }, { "id": "235_R9", "type": "Binds_With", "arg1_id": "235_T1", "arg2_id": "235_T2", "normalized": [] }, { "id": "235_R10", "type": "Binds_With", "arg1_id": "235_T1", "arg2_id": "235_T3", "normalized": [] }, { "id": "235_R11", "type": "Binds_With", "arg1_id": "235_T13", "arg2_id": "235_T10", "normalized": [] }, { "id": "235_R1", "type": "Binds_With", "arg1_id": "235_T18", "arg2_id": "235_T16", "normalized": [] }, { "id": "235_R12", "type": "Binds_With", "arg1_id": "235_T19", "arg2_id": "235_T16", "normalized": [] }, { "id": "235_R4", "type": "Binds_With", "arg1_id": "235_T37", "arg2_id": "235_T46", "normalized": [] }, { "id": "235_R5", "type": "Binds_With", "arg1_id": "235_T40", "arg2_id": "235_T47", "normalized": [] } ]

[ { "id": "237", "type": "", "text": [ "Mechanisms leading to down-regulation of activated microglia and astrocytes are poorly understood, in spite of the potentially detrimental role of activated glia in neurodegeneration. Prostaglandins, produced both by neurons and glia, may serve as mediators of glial and neuronal functions. We examined the influence of cyclopentenone prostaglandins and their precursors on activated glia. As models of glial activation, production of inducible nitric-oxide synthase (iNOS) was studied in lipopolysaccharide-stimulated rat microglia, a murine microglial cell line BV-2, and IL-1beta-stimulated rat astrocytes. Cyclopentenone prostaglandins were potent inhibitors of iNOS induction and were more effective than their precursors, prostaglandins E2 and D2. 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) was the most potent prostaglandin among those tested. In activated microglia, 15d-PGJ2 suppressed iNOS promoter activity, iNOS mRNA, and protein levels. The action of 15d-PGJ2 does not appear to involve its nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) because troglitazone, a specific ligand of PPARgamma, was unable to inhibit iNOS induction, and neither troglitazone nor 15d-PGJ2 could stimulate the activity of a PPAR-dependent promoter in the absence of cotransfected PPARgamma. 15d-PGJ2 did not block nuclear translocation or DNA-binding activity of the transcription factor NFkappaB, but it did inhibit the activity of an NFkappaB reporter construct, suggesting that the mechanism of suppression of microglial iNOS by 15d-PGJ2 may involve interference with NFkappaB transcriptional activity in the nucleus. Thus, our data suggest the existence of a novel pathway mediated by cyclopentenone prostaglandins, which may represent part of a feedback mechanism leading to the cessation of inflammatory glial responses in the brain. \n" ], "offsets": [ [ 0, 1872 ] ] } ]

[ { "id": "237_T1", "type": "Biological_Activity", "text": [ "neurodegeneration" ], "offsets": [ [ 165, 182 ] ], "normalized": [] }, { "id": "237_T2", "type": "Chemical", "text": [ "Prostaglandins" ], "offsets": [ [ 184, 198 ] ], "normalized": [] }, { "id": "237_T3", "type": "Metabolite", "text": [ "Prostaglandins" ], "offsets": [ [ 184, 198 ] ], "normalized": [] }, { "id": "237_T4", "type": "Metabolite", "text": [ "cyclopentenone prostaglandins" ], "offsets": [ [ 321, 350 ] ], "normalized": [] }, { "id": "237_T5", "type": "Chemical", "text": [ "cyclopentenone prostaglandin", "precursors" ], "offsets": [ [ 321, 349 ], [ 361, 371 ] ], "normalized": [] }, { "id": "237_T7", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 469, 473 ] ], "normalized": [] }, { "id": "237_T8", "type": "Species", "text": [ "rat" ], "offsets": [ [ 520, 523 ] ], "normalized": [] }, { "id": "237_T9", "type": "Species", "text": [ "rat" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "237_T10", "type": "Protein", "text": [ "inducible nitric-oxide synthase" ], "offsets": [ [ 436, 467 ] ], "normalized": [] }, { "id": "237_T6", "type": "Chemical", "text": [ "lipopolysaccharide" ], "offsets": [ [ 490, 508 ] ], "normalized": [] }, { "id": "237_T13", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 576, 584 ] ], "normalized": [] }, { "id": "237_T14", "type": "Chemical", "text": [ "Cyclopentenone prostaglandins" ], "offsets": [ [ 612, 641 ] ], "normalized": [] }, { "id": "237_T15", "type": "Biological_Activity", "text": [ "inhibitors" ], "offsets": [ [ 655, 665 ] ], "normalized": [] }, { "id": "237_T16", "type": "Chemical", "text": [ "prostaglandin", "D2" ], "offsets": [ [ 731, 744 ], [ 753, 755 ] ], "normalized": [] }, { "id": "237_T17", "type": "Chemical", "text": [ "prostaglandin", "E2" ], "offsets": [ [ 731, 744 ], [ 746, 748 ] ], "normalized": [] }, { "id": "237_T18", "type": "Chemical", "text": [ "cyclopentenone prostaglandins" ], "offsets": [ [ 321, 350 ] ], "normalized": [] }, { "id": "237_T19", "type": "Chemical", "text": [ "15-Deoxy-Delta12,14-prostaglandin J2" ], "offsets": [ [ 757, 793 ] ], "normalized": [] }, { "id": "237_T20", "type": "Chemical", "text": [ "15d-PGJ2" ], "offsets": [ [ 795, 803 ] ], "normalized": [] }, { "id": "237_T21", "type": "Chemical", "text": [ "prostaglandin" ], "offsets": [ [ 825, 838 ] ], "normalized": [] }, { "id": "237_T22", "type": "Chemical", "text": [ "15d-PGJ2" ], "offsets": [ [ 883, 891 ] ], "normalized": [] }, { "id": "237_T24", "type": "Biological_Activity", "text": [ "suppress" ], "offsets": [ [ 892, 900 ] ], "normalized": [] }, { "id": "237_T26", "type": "Chemical", "text": [ "15d-PGJ2" ], "offsets": [ [ 972, 980 ] ], "normalized": [] }, { "id": "237_T27", "type": "Protein", "text": [ "peroxisome proliferator-activated receptor gamma" ], "offsets": [ [ 1029, 1077 ] ], "normalized": [] }, { "id": "237_T28", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 1079, 1088 ] ], "normalized": [] }, { "id": "237_T29", "type": "Chemical", "text": [ "troglitazone" ], "offsets": [ [ 1098, 1110 ] ], "normalized": [] }, { "id": "237_T30", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 1133, 1142 ] ], "normalized": [] }, { "id": "237_T32", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 1158, 1165 ] ], "normalized": [] }, { "id": "237_T33", "type": "Chemical", "text": [ "troglitazone" ], "offsets": [ [ 1194, 1206 ] ], "normalized": [] }, { "id": "237_T34", "type": "Chemical", "text": [ "15d-PGJ2" ], "offsets": [ [ 1211, 1219 ] ], "normalized": [] }, { "id": "237_T35", "type": "Protein", "text": [ "PPAR" ], "offsets": [ [ 1255, 1259 ] ], "normalized": [] }, { "id": "237_T36", "type": "Protein", "text": [ "PPARgamma" ], "offsets": [ [ 1311, 1320 ] ], "normalized": [] }, { "id": "237_T37", "type": "Chemical", "text": [ "15d-PGJ2" ], "offsets": [ [ 1322, 1330 ] ], "normalized": [] }, { "id": "237_T38", "type": "Protein", "text": [ "NFkappaB" ], "offsets": [ [ 1419, 1427 ] ], "normalized": [] }, { "id": "237_T39", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 1440, 1447 ] ], "normalized": [] }, { "id": "237_T41", "type": "Protein", "text": [ "NFkappaB" ], "offsets": [ [ 1602, 1610 ] ], "normalized": [] }, { "id": "237_T42", "type": "Chemical", "text": [ "cyclopentenone prostaglandins" ], "offsets": [ [ 1720, 1749 ] ], "normalized": [] }, { "id": "237_T43", "type": "Metabolite", "text": [ "cyclopentenone prostaglandins" ], "offsets": [ [ 1720, 1749 ] ], "normalized": [] }, { "id": "237_T44", "type": "Metabolite", "text": [ "Cyclopentenone prostaglandins" ], "offsets": [ [ 612, 641 ] ], "normalized": [] }, { "id": "237_T45", "type": "Metabolite", "text": [ "15-Deoxy-Delta12,14-prostaglandin J2" ], "offsets": [ [ 757, 793 ] ], "normalized": [] }, { "id": "237_T46", "type": "Metabolite", "text": [ "15d-PGJ2" ], "offsets": [ [ 795, 803 ] ], "normalized": [] }, { "id": "237_T47", "type": "Metabolite", "text": [ "15d-PGJ2" ], "offsets": [ [ 972, 980 ] ], "normalized": [] }, { "id": "237_T48", "type": "Metabolite", "text": [ "15d-PGJ2" ], "offsets": [ [ 1322, 1330 ] ], "normalized": [] }, { "id": "237_T49", "type": "Metabolite", "text": [ "15d-PGJ2" ], "offsets": [ [ 883, 891 ] ], "normalized": [] }, { "id": "237_T50", "type": "Metabolite", "text": [ "15d-PGJ2" ], "offsets": [ [ 1211, 1219 ] ], "normalized": [] }, { "id": "237_T53", "type": "Species", "text": [ "murine" ], "offsets": [ [ 537, 543 ] ], "normalized": [] }, { "id": "237_T51", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 669, 673 ] ], "normalized": [] }, { "id": "237_T11", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 1166, 1170 ] ], "normalized": [] }, { "id": "237_T12", "type": "Protein", "text": [ "NFkappaB" ], "offsets": [ [ 1467, 1475 ] ], "normalized": [] }, { "id": "237_T23", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 1555, 1559 ] ], "normalized": [] }, { "id": "237_T25", "type": "Chemical", "text": [ "15d-PGJ2" ], "offsets": [ [ 1563, 1571 ] ], "normalized": [] }, { "id": "237_T40", "type": "Metabolite", "text": [ "15d-PGJ2" ], "offsets": [ [ 1563, 1571 ] ], "normalized": [] }, { "id": "237_T52", "type": "Biological_Activity", "text": [ "inflammatory" ], "offsets": [ [ 1828, 1840 ] ], "normalized": [] }, { "id": "237_T31", "type": "Biological_Activity", "text": [ "promoter" ], "offsets": [ [ 908, 916 ] ], "normalized": [] }, { "id": "237_T54", "type": "Biological_Activity", "text": [ "binding" ], "offsets": [ [ 1374, 1381 ] ], "normalized": [] }, { "id": "237_T55", "type": "Biological_Activity", "text": [ "transcriptional" ], "offsets": [ [ 1611, 1626 ] ], "normalized": [] }, { "id": "237_T56", "type": "Biological_Activity", "text": [ "induction" ], "offsets": [ [ 674, 683 ] ], "normalized": [] }, { "id": "237_T57", "type": "Biological_Activity", "text": [ "induction" ], "offsets": [ [ 1171, 1180 ] ], "normalized": [] }, { "id": "237_T58", "type": "Biological_Activity", "text": [ "stimulate" ], "offsets": [ [ 1226, 1235 ] ], "normalized": [] }, { "id": "237_T59", "type": "Biological_Activity", "text": [ "suppression" ], "offsets": [ [ 1529, 1540 ] ], "normalized": [] } ]

[]

[]

[ { "id": "237_R1", "type": "Associated_With", "arg1_id": "237_T14", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R2", "type": "Associated_With", "arg1_id": "237_T17", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R3", "type": "Associated_With", "arg1_id": "237_T16", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R4", "type": "Metabolite_Of", "arg1_id": "237_T4", "arg2_id": "237_T5", "normalized": [] }, { "id": "237_R5", "type": "Associated_With", "arg1_id": "237_T19", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R6", "type": "Associated_With", "arg1_id": "237_T20", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R11", "type": "Associated_With", "arg1_id": "237_T37", "arg2_id": "237_T39", "normalized": [] }, { "id": "237_R12", "type": "Metabolite_Of", "arg1_id": "237_T44", "arg2_id": "237_T16", "normalized": [] }, { "id": "237_R13", "type": "Metabolite_Of", "arg1_id": "237_T44", "arg2_id": "237_T17", "normalized": [] }, { "id": "237_R18", "type": "Associated_With", "arg1_id": "237_T45", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R19", "type": "Associated_With", "arg1_id": "237_T46", "arg2_id": "237_T15", "normalized": [] }, { "id": "237_R7", "type": "Associated_With", "arg1_id": "237_T49", "arg2_id": "237_T24", "normalized": [] }, { "id": "237_R8", "type": "Associated_With", "arg1_id": "237_T22", "arg2_id": "237_T24", "normalized": [] }, { "id": "237_R9", "type": "Binds_With", "arg1_id": "237_T29", "arg2_id": "237_T30", "normalized": [] } ]

[ { "id": "239", "type": "", "text": [ "This ongoing study evaluates the efficacy of oral 9-nitrocamptothecin (9NC), or RFS-2000, in the treatment of advanced pancreatic cancer. Patients received 9NC orally for 5 days/week; 8 weeks of therapy is required to achieve minimum effective dose. Starting dose was 1.5 mg/m2/day, with adjustments made as necessary. Patients were analyzed for changes in tumor size by CT scan, changes in serum CA 19-9 tumor marker levels, quality of life, and survival. 107 consecutive patients with advanced adenocarcinoma of the pancreas were enrolled before November 3, 1997. Of this group, 47 patients did not receive the minimum 2 courses of treatment necessary to induce response, leaving 60 evaluable patients. Primary dose-limiting toxicities were myelosuppression and interstitial cystitis. No deaths were attributed to 9NC. Median survival was 6.5 months for the 107 total patients and 8.7 months for the 60 evaluable patients, with one patient surviving at 44+ months. Of the 60 evaluable patients, 31.7% were responders (median survival 18.6 months; range 6.5-44.7+ months), 31.7% were stable (median survival 9.7 months), and 36.6% were non-responders (median survival 6.8 months). Fifty-seven previously untreated patients had a median survival of 7.3 months compared to 4.7 months for the 50 previously treated patients. Thirty-three patients who failed gemcitabine therapy prior to 9NC treatment had a median survival of 4.7 months. 9NC is safe and efficacious as first-line therapy for the treatment of advanced pancreatic cancer. It also shows some modest success as second-line therapy in treating gemcitabine failures. \n" ], "offsets": [ [ 0, 1628 ] ] } ]

[ { "id": "239_T1", "type": "Chemical", "text": [ "9-nitrocamptothecin" ], "offsets": [ [ 50, 69 ] ], "normalized": [] }, { "id": "239_T2", "type": "Chemical", "text": [ "9NC" ], "offsets": [ [ 71, 74 ] ], "normalized": [] }, { "id": "239_T3", "type": "Chemical", "text": [ "RFS-2000" ], "offsets": [ [ 80, 88 ] ], "normalized": [] }, { "id": "239_T5", "type": "Species", "text": [ "Patients" ], "offsets": [ [ 138, 146 ] ], "normalized": [] }, { "id": "239_T6", "type": "Chemical", "text": [ "9NC" ], "offsets": [ [ 156, 159 ] ], "normalized": [] }, { "id": "239_T9", "type": "Chemical", "text": [ "9NC" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "239_T10", "type": "Biological_Activity", "text": [ "myelosuppression" ], "offsets": [ [ 743, 759 ] ], "normalized": [] }, { "id": "239_T12", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 1357, 1368 ] ], "normalized": [] }, { "id": "239_T13", "type": "Chemical", "text": [ "9NC" ], "offsets": [ [ 1386, 1389 ] ], "normalized": [] }, { "id": "239_T14", "type": "Chemical", "text": [ "9NC" ], "offsets": [ [ 1437, 1440 ] ], "normalized": [] }, { "id": "239_T16", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 1605, 1616 ] ], "normalized": [] }, { "id": "239_T17", "type": "Species", "text": [ "Patients" ], "offsets": [ [ 319, 327 ] ], "normalized": [] }, { "id": "239_T18", "type": "Species", "text": [ "patients" ], "offsets": [ [ 473, 481 ] ], "normalized": [] }, { "id": "239_T19", "type": "Species", "text": [ "patients" ], "offsets": [ [ 584, 592 ] ], "normalized": [] }, { "id": "239_T20", "type": "Species", "text": [ "patients" ], "offsets": [ [ 870, 878 ] ], "normalized": [] }, { "id": "239_T21", "type": "Species", "text": [ "patients" ], "offsets": [ [ 915, 923 ] ], "normalized": [] }, { "id": "239_T22", "type": "Species", "text": [ "patients" ], "offsets": [ [ 987, 995 ] ], "normalized": [] }, { "id": "239_T23", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1216, 1224 ] ], "normalized": [] }, { "id": "239_T24", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1314, 1322 ] ], "normalized": [] }, { "id": "239_T25", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1337, 1345 ] ], "normalized": [] }, { "id": "239_T26", "type": "Species", "text": [ "patient" ], "offsets": [ [ 934, 941 ] ], "normalized": [] }, { "id": "239_T27", "type": "Biological_Activity", "text": [ "toxicities" ], "offsets": [ [ 727, 737 ] ], "normalized": [] } ]

[]

[]

[ { "id": "239_R1", "type": "Associated_With", "arg1_id": "239_T9", "arg2_id": "239_T10", "normalized": [] } ]

[ { "id": "241", "type": "", "text": [ "An efficient solid-phase synthesis of benzisothiazolone-1,1-dioxide-based serine protease inhibitors involving alkylation of carboxylic acids with N-(bromomethyl)benzisothiazolone-1,1-dioxide has been developed. An example using this procedure for preparation of a library of human mast cell tryptase inhibitors is described. \n" ], "offsets": [ [ 0, 328 ] ] } ]

[ { "id": "241_T1", "type": "Chemical", "text": [ "benzisothiazolone-1,1-dioxide" ], "offsets": [ [ 38, 67 ] ], "normalized": [] }, { "id": "241_T3", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 91, 100 ] ], "normalized": [] }, { "id": "241_T4", "type": "Chemical", "text": [ "carboxylic acids" ], "offsets": [ [ 126, 142 ] ], "normalized": [] }, { "id": "241_T5", "type": "Chemical", "text": [ "N-(bromomethyl)benzisothiazolone-1,1-dioxide" ], "offsets": [ [ 148, 192 ] ], "normalized": [] }, { "id": "241_T6", "type": "Protein", "text": [ "human mast cell tryptase" ], "offsets": [ [ 277, 301 ] ], "normalized": [] }, { "id": "241_T8", "type": "Biological_Activity", "text": [ "inhibitors" ], "offsets": [ [ 302, 312 ] ], "normalized": [] }, { "id": "241_T9", "type": "Protein", "text": [ "serine protease" ], "offsets": [ [ 74, 90 ] ], "normalized": [] }, { "id": "241_T10", "type": "Species", "text": [ "human" ], "offsets": [ [ 277, 282 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "243", "type": "", "text": [ "We compared effects of alpha-galactosylceramide (alpha-GalCer) and its 3alpha- or 3beta-galactosylated derivatives on the proliferation of murine spleen cells. The 3alpha-galactosylated alpha-GalCer showed stronger proliferative response than the parental alpha-GalCer, but the 3beta-galactosylated alpha-GalCer possessed weaker activity than the alpha-GalCer. In addition, alpha-Gal-3-Cer did not show immunostimulatory activity. \n" ], "offsets": [ [ 0, 433 ] ] } ]

[ { "id": "243_T1", "type": "Chemical", "text": [ "alpha-galactosylceramide", "3beta-galactosylated derivative" ], "offsets": [ [ 23, 47 ], [ 82, 113 ] ], "normalized": [] }, { "id": "243_T2", "type": "Chemical", "text": [ "alpha-GalCer" ], "offsets": [ [ 49, 61 ] ], "normalized": [] }, { "id": "243_T3", "type": "Chemical", "text": [ "alpha-galactosylceramide", "3alpha", "-galactosylated derivative" ], "offsets": [ [ 23, 47 ], [ 71, 77 ], [ 87, 113 ] ], "normalized": [] }, { "id": "243_T4", "type": "Chemical", "text": [ "alpha-GalCer", "3alpha-", "galactosylated derivative" ], "offsets": [ [ 49, 61 ], [ 71, 78 ], [ 88, 113 ] ], "normalized": [] }, { "id": "243_T5", "type": "Chemical", "text": [ "alpha-galactosylceramide" ], "offsets": [ [ 23, 47 ] ], "normalized": [] }, { "id": "243_T6", "type": "Chemical", "text": [ "alpha-GalCer", "3beta-galactosylated derivative" ], "offsets": [ [ 49, 61 ], [ 82, 113 ] ], "normalized": [] }, { "id": "243_T7", "type": "Species", "text": [ "murine" ], "offsets": [ [ 139, 145 ] ], "normalized": [] }, { "id": "243_T9", "type": "Chemical", "text": [ "3alpha-galactosylated alpha-GalCer" ], "offsets": [ [ 164, 198 ] ], "normalized": [] }, { "id": "243_T10", "type": "Chemical", "text": [ "alpha-GalCer" ], "offsets": [ [ 256, 268 ] ], "normalized": [] }, { "id": "243_T11", "type": "Chemical", "text": [ "3beta-galactosylated alpha-GalCer" ], "offsets": [ [ 278, 311 ] ], "normalized": [] }, { "id": "243_T12", "type": "Biological_Activity", "text": [ "immunostimulatory" ], "offsets": [ [ 404, 421 ] ], "normalized": [] }, { "id": "243_T13", "type": "Chemical", "text": [ "alpha-Gal-3-Cer" ], "offsets": [ [ 374, 389 ] ], "normalized": [] }, { "id": "243_T8", "type": "Chemical", "text": [ "alpha-GalCer" ], "offsets": [ [ 347, 359 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "245", "type": "", "text": [ "Zonal elution and high-performance affinity chromatography were used to examine interactions of the drugs digitoxin and acetyldigitoxin with the protein human serum albumin (HSA). This was done by injecting small amounts of digitoxin and acetyldigitoxin onto an immobilized HSA column in the presence of mobile phases that contained various concentrations of digitoxin, acetyldigitoxin or other solutes as competing agents. A fixed concentration of beta-cyclodextrin was also present in the mobile phase as a solubilising agent. It was found that digitoxin and acetyldigitoxin each had strong interactions at a single common binding site on HSA, but with slightly different equilibrium constants for this region. Neither compound showed any competition with warfarin or L-tryptophan, which were used as probes for binding at the warfarin-azapropazone and indole-benzodiazepine sites of HSA. These results confirmed the presence of a separate binding region on HSA for digitoxin-related compounds. \n" ], "offsets": [ [ 0, 1001 ] ] } ]

[ { "id": "245_T1", "type": "Chemical", "text": [ "digitoxin" ], "offsets": [ [ 106, 115 ] ], "normalized": [] }, { "id": "245_T2", "type": "Chemical", "text": [ "acetyldigitoxin" ], "offsets": [ [ 120, 135 ] ], "normalized": [] }, { "id": "245_T3", "type": "Protein", "text": [ "human serum albumin" ], "offsets": [ [ 153, 172 ] ], "normalized": [] }, { "id": "245_T4", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 174, 177 ] ], "normalized": [] }, { "id": "245_T5", "type": "Chemical", "text": [ "digitoxin" ], "offsets": [ [ 224, 233 ] ], "normalized": [] }, { "id": "245_T6", "type": "Chemical", "text": [ "acetyldigitoxin" ], "offsets": [ [ 238, 253 ] ], "normalized": [] }, { "id": "245_T7", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 274, 277 ] ], "normalized": [] }, { "id": "245_T8", "type": "Chemical", "text": [ "digitoxin" ], "offsets": [ [ 359, 368 ] ], "normalized": [] }, { "id": "245_T9", "type": "Chemical", "text": [ "acetyldigitoxin" ], "offsets": [ [ 370, 385 ] ], "normalized": [] }, { "id": "245_T10", "type": "Chemical", "text": [ "beta-cyclodextrin" ], "offsets": [ [ 449, 466 ] ], "normalized": [] }, { "id": "245_T11", "type": "Biological_Activity", "text": [ "solubilising" ], "offsets": [ [ 510, 522 ] ], "normalized": [] }, { "id": "245_T12", "type": "Chemical", "text": [ "digitoxin" ], "offsets": [ [ 548, 559 ] ], "normalized": [] }, { "id": "245_T13", "type": "Chemical", "text": [ "acetyldigitoxin" ], "offsets": [ [ 563, 578 ] ], "normalized": [] }, { "id": "245_T18", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 644, 647 ] ], "normalized": [] }, { "id": "245_T19", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 761, 769 ] ], "normalized": [] }, { "id": "245_T20", "type": "Chemical", "text": [ "L-tryptophan" ], "offsets": [ [ 773, 785 ] ], "normalized": [] }, { "id": "245_T21", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 889, 892 ] ], "normalized": [] }, { "id": "245_T23", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 832, 840 ] ], "normalized": [] }, { "id": "245_T24", "type": "Chemical", "text": [ "azapropazone" ], "offsets": [ [ 841, 853 ] ], "normalized": [] }, { "id": "245_T25", "type": "Chemical", "text": [ "indole" ], "offsets": [ [ 858, 864 ] ], "normalized": [] }, { "id": "245_T26", "type": "Chemical", "text": [ "benzodiazepine" ], "offsets": [ [ 865, 879 ] ], "normalized": [] }, { "id": "245_T28", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 963, 966 ] ], "normalized": [] }, { "id": "245_T29", "type": "Chemical", "text": [ "digitoxin" ], "offsets": [ [ 971, 980 ] ], "normalized": [] }, { "id": "245_T30", "type": "Chemical", "text": [ "digitoxin-related compounds" ], "offsets": [ [ 971, 998 ] ], "normalized": [] }, { "id": "245_T31", "type": "Chemical", "text": [ "drugs" ], "offsets": [ [ 100, 105 ] ], "normalized": [] } ]

[]

[]

[ { "id": "245_R1", "type": "Associated_With", "arg1_id": "245_T10", "arg2_id": "245_T11", "normalized": [] }, { "id": "245_R4", "type": "Binds_With", "arg1_id": "245_T19", "arg2_id": "245_T21", "normalized": [] }, { "id": "245_R7", "type": "Binds_With", "arg1_id": "245_T12", "arg2_id": "245_T18", "normalized": [] }, { "id": "245_R8", "type": "Binds_With", "arg1_id": "245_T13", "arg2_id": "245_T18", "normalized": [] }, { "id": "245_R2", "type": "Binds_With", "arg1_id": "245_T20", "arg2_id": "245_T21", "normalized": [] }, { "id": "245_R3", "type": "Binds_With", "arg1_id": "245_T30", "arg2_id": "245_T28", "normalized": [] } ]

[ { "id": "247", "type": "", "text": [ "The cellular responses of plants to numerous extracellular stimuli are mediated by transient elevations in the concentration of cytosolic free calcium ([Ca2+]cyt). We have addressed the question of how cells can use this apparently ubiquitous system to initiate so many specific and appropriate end responses. We show that the pollutant gas ozone elicits a biphasic Ca2+ response in intact Arabidopsis plants and a subsequent increase in expression of the gene encoding the antioxidant defence enzyme glutathione-S-transferase (GST). The second of the two [Ca2+]cyt peaks, but not the first, could be eliminated either by pre-treatment of plants with lanthanum chloride, or by reducing the duration of ozone fumigation. Under these conditions, ozone-induced GST expression was abolished. These data provide a functional dissection of the ozone Ca2+ signalling pathway and indicate that the second ozone-induced [Ca2+]cyt peak provides the necessary information to direct expression of GST. \n" ], "offsets": [ [ 0, 993 ] ] } ]

[ { "id": "247_T1", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 143, 150 ] ], "normalized": [] }, { "id": "247_T3", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 343, 348 ] ], "normalized": [] }, { "id": "247_T4", "type": "Species", "text": [ "Arabidopsis" ], "offsets": [ [ 392, 403 ] ], "normalized": [] }, { "id": "247_T5", "type": "Protein", "text": [ "glutathione-S-transferase" ], "offsets": [ [ 503, 528 ] ], "normalized": [] }, { "id": "247_T6", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 530, 533 ] ], "normalized": [] }, { "id": "247_T9", "type": "Biological_Activity", "text": [ "antioxidant" ], "offsets": [ [ 476, 487 ] ], "normalized": [] }, { "id": "247_T11", "type": "Chemical", "text": [ "lanthanum chloride" ], "offsets": [ [ 653, 671 ] ], "normalized": [] }, { "id": "247_T12", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 704, 709 ] ], "normalized": [] }, { "id": "247_T14", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 746, 751 ] ], "normalized": [] }, { "id": "247_T15", "type": "Chemical", "text": [ "Ca2+" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "247_T16", "type": "Chemical", "text": [ "Ca2+" ], "offsets": [ [ 153, 157 ] ], "normalized": [] }, { "id": "247_T17", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 840, 845 ] ], "normalized": [] }, { "id": "247_T18", "type": "Chemical", "text": [ "Ca2+" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "247_T19", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 899, 904 ] ], "normalized": [] }, { "id": "247_T20", "type": "Chemical", "text": [ "Ca2+" ], "offsets": [ [ 914, 918 ] ], "normalized": [] }, { "id": "247_T21", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 987, 990 ] ], "normalized": [] }, { "id": "247_T7", "type": "Species", "text": [ "plants" ], "offsets": [ [ 26, 32 ] ], "normalized": [] }, { "id": "247_T2", "type": "Chemical", "text": [ "Ca2+" ], "offsets": [ [ 368, 372 ] ], "normalized": [] }, { "id": "247_T8", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 760, 763 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "249", "type": "", "text": [ "Masoprocol (nordihydroguaiaretic acid) is a lipoxygenase inhibitor isolated from the creosote bush and used by native healers to treat type 2 diabetes. It has been recently shown to decrease serum glucose, free fatty acid (FFA), and triglyceride (TG) concentrations in rodent models of type 2 diabetes. The current study was initiated to quantify the effects of masoprocol incubation of adipocytes isolated from normal rats. The results indicate that masoprocol significantly increased glucose uptake by adipocytes in both the absence and presence of insulin. In addition, the maximal rate of insulin-stimulated glucose transport was increased in adipocytes incubated with masoprocol and the insulin concentration resulting in a half-maximal glucose transport rate (ED50) decreased. Finally, isoproterenol-stimulated increases in FFA and glycerol release were significantly decreased in the presence of masoprocol. These results provide an explanation at the cellular level for the observation that masoprocol decreases serum glucose, insulin, and FFA concentrations in rodent models of type 2 diabetes. \n" ], "offsets": [ [ 0, 1108 ] ] } ]

[ { "id": "249_T1", "type": "Chemical", "text": [ "Masoprocol" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "249_T2", "type": "Chemical", "text": [ "nordihydroguaiaretic acid" ], "offsets": [ [ 12, 37 ] ], "normalized": [] }, { "id": "249_T4", "type": "Protein", "text": [ "lipoxygenase" ], "offsets": [ [ 44, 56 ] ], "normalized": [] }, { "id": "249_T5", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 57, 66 ] ], "normalized": [] }, { "id": "249_T6", "type": "Species", "text": [ "creosote bush" ], "offsets": [ [ 86, 99 ] ], "normalized": [] }, { "id": "249_T7", "type": "Metabolite", "text": [ "Masoprocol" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "249_T8", "type": "Metabolite", "text": [ "nordihydroguaiaretic acid" ], "offsets": [ [ 12, 37 ] ], "normalized": [] }, { "id": "249_T12", "type": "Chemical", "text": [ "fatty acid" ], "offsets": [ [ 212, 222 ] ], "normalized": [] }, { "id": "249_T14", "type": "Species", "text": [ "rodent" ], "offsets": [ [ 270, 276 ] ], "normalized": [] }, { "id": "249_T16", "type": "Metabolite", "text": [ "masoprocol" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "249_T17", "type": "Chemical", "text": [ "masoprocol" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "249_T18", "type": "Species", "text": [ "rats" ], "offsets": [ [ 420, 424 ] ], "normalized": [] }, { "id": "249_T19", "type": "Metabolite", "text": [ "masoprocol" ], "offsets": [ [ 452, 462 ] ], "normalized": [] }, { "id": "249_T20", "type": "Chemical", "text": [ "masoprocol" ], "offsets": [ [ 452, 462 ] ], "normalized": [] }, { "id": "249_T22", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 552, 559 ] ], "normalized": [] }, { "id": "249_T24", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 594, 601 ] ], "normalized": [] }, { "id": "249_T25", "type": "Chemical", "text": [ "masoprocol" ], "offsets": [ [ 675, 685 ] ], "normalized": [] }, { "id": "249_T26", "type": "Metabolite", "text": [ "masoprocol" ], "offsets": [ [ 675, 685 ] ], "normalized": [] }, { "id": "249_T27", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 694, 701 ] ], "normalized": [] }, { "id": "249_T29", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 794, 807 ] ], "normalized": [] }, { "id": "249_T31", "type": "Metabolite", "text": [ "masoprocol" ], "offsets": [ [ 905, 915 ] ], "normalized": [] }, { "id": "249_T33", "type": "Chemical", "text": [ "masoprocol" ], "offsets": [ [ 905, 915 ] ], "normalized": [] }, { "id": "249_T34", "type": "Chemical", "text": [ "masoprocol" ], "offsets": [ [ 1001, 1013 ] ], "normalized": [] }, { "id": "249_T35", "type": "Metabolite", "text": [ "masoprocol" ], "offsets": [ [ 1001, 1013 ] ], "normalized": [] }, { "id": "249_T39", "type": "Species", "text": [ "rodent" ], "offsets": [ [ 1073, 1079 ] ], "normalized": [] }, { "id": "249_T9", "type": "Chemical", "text": [ "glucose" ], "offsets": [ [ 198, 205 ] ], "normalized": [] }, { "id": "249_T10", "type": "Chemical", "text": [ "triglyceride" ], "offsets": [ [ 234, 246 ] ], "normalized": [] }, { "id": "249_T11", "type": "Chemical", "text": [ "FFA" ], "offsets": [ [ 224, 227 ] ], "normalized": [] }, { "id": "249_T13", "type": "Chemical", "text": [ "TG" ], "offsets": [ [ 248, 250 ] ], "normalized": [] }, { "id": "249_T15", "type": "Chemical", "text": [ "glucose" ], "offsets": [ [ 613, 622 ] ], "normalized": [] }, { "id": "249_T21", "type": "Chemical", "text": [ "glucose" ], "offsets": [ [ 744, 751 ] ], "normalized": [] }, { "id": "249_T23", "type": "Chemical", "text": [ "FFA" ], "offsets": [ [ 832, 835 ] ], "normalized": [] }, { "id": "249_T28", "type": "Chemical", "text": [ "FFA" ], "offsets": [ [ 1051, 1054 ] ], "normalized": [] }, { "id": "249_T3", "type": "Chemical", "text": [ "glucose" ], "offsets": [ [ 487, 494 ] ], "normalized": [] }, { "id": "249_T30", "type": "Chemical", "text": [ "glucose" ], "offsets": [ [ 1029, 1036 ] ], "normalized": [] }, { "id": "249_T32", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 1038, 1045 ] ], "normalized": [] } ]

[]

[]

[ { "id": "249_R3", "type": "Associated_With", "arg1_id": "249_T1", "arg2_id": "249_T5", "normalized": [] }, { "id": "249_R4", "type": "Associated_With", "arg1_id": "249_T2", "arg2_id": "249_T5", "normalized": [] }, { "id": "249_R5", "type": "Isolated_From", "arg1_id": "249_T7", "arg2_id": "249_T6", "normalized": [] }, { "id": "249_R6", "type": "Isolated_From", "arg1_id": "249_T8", "arg2_id": "249_T6", "normalized": [] }, { "id": "249_R7", "type": "Associated_With", "arg1_id": "249_T7", "arg2_id": "249_T5", "normalized": [] }, { "id": "249_R8", "type": "Associated_With", "arg1_id": "249_T8", "arg2_id": "249_T5", "normalized": [] }, { "id": "249_R11", "type": "Binds_With", "arg1_id": "249_T7", "arg2_id": "249_T4", "normalized": [] }, { "id": "249_R12", "type": "Binds_With", "arg1_id": "249_T1", "arg2_id": "249_T4", "normalized": [] }, { "id": "249_R13", "type": "Binds_With", "arg1_id": "249_T8", "arg2_id": "249_T4", "normalized": [] }, { "id": "249_R14", "type": "Binds_With", "arg1_id": "249_T2", "arg2_id": "249_T4", "normalized": [] } ]

[ { "id": "251", "type": "", "text": [ "Dipiperon drops 30-180 mg/day were given for eight weeks to 29 children with character neuroses and behavioural disorders. A 16-item rating-scale covering several features of behaviour disorder was completed by a psychologist and a teacher independent from each other. The individual number of pathological scores showed a decrease already within the first treatment week and a further decrease by the end of the trial, especially for the items of capriciousness, obstinacy, irritability and restlessness. The therapeutic benefit was not accompanied by an adverse effect on the school performance of the children. No side-effects were reported or observed. \n" ], "offsets": [ [ 0, 660 ] ] } ]

[ { "id": "251_T1", "type": "Chemical", "text": [ "Dipiperon" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "251_T2", "type": "Species", "text": [ "children" ], "offsets": [ [ 63, 71 ] ], "normalized": [] }, { "id": "251_T10", "type": "Species", "text": [ "psychologist" ], "offsets": [ [ 213, 225 ] ], "normalized": [] }, { "id": "251_T11", "type": "Species", "text": [ "teacher" ], "offsets": [ [ 232, 239 ] ], "normalized": [] }, { "id": "251_T12", "type": "Species", "text": [ "children" ], "offsets": [ [ 606, 614 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "253", "type": "", "text": [ "In starfish oocytes, maturation is induced by a hormone, 1-methyladenine (1-MA), that binds to the receptors exposed to the outer surface of the plasma membrane. The signal of 1-MA stimulates the heterotrimeric G protein, resulting in dissociation of the betagamma subunit of G protein (Gbetagamma) from a pertussis toxin-sensitive Gi-type alpha subunit. To investigate the targets for Gbetagamma, we analyzed 1-MA- or Gbetagamma-dependent phosphorylation using in vivo and in vitro systems. A 62-kDa protein was phosphorylated immediately after 1-MA treatment in intact oocytes. In the cell-free preparations, the 62-kDa protein was also phosphorylated on serine residue(s) immediately after addition of 1-MA or Gbetagamma. The Gbetagamma-dependent phosphorylation of the 62-kDa protein was inhibited by wortmannin or LY294002, which are mechanistically different inhibitors of phosphatidylinositol 3-kinase (PI3K). LY294002 also inhibited Gbetagamma- as well as 1-MA-induced maturation of oocytes. Taken together, these results indicate that the 62-kDa protein functions downstream of Gbetagamma and PI3K in the early signaling pathway of 1-MA-induced starfish oocyte maturation. The phosphorylation of the 62-kDa protein may be required for the activation of maturation-promoting factor. \n" ], "offsets": [ [ 0, 1296 ] ] } ]

[ { "id": "253_T1", "type": "Species", "text": [ "starfish" ], "offsets": [ [ 3, 11 ] ], "normalized": [] }, { "id": "253_T2", "type": "Biological_Activity", "text": [ "hormone" ], "offsets": [ [ 48, 55 ] ], "normalized": [] }, { "id": "253_T3", "type": "Chemical", "text": [ "1-methyladenine" ], "offsets": [ [ 57, 72 ] ], "normalized": [] }, { "id": "253_T4", "type": "Metabolite", "text": [ "1-methyladenine" ], "offsets": [ [ 57, 72 ] ], "normalized": [] }, { "id": "253_T5", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 74, 78 ] ], "normalized": [] }, { "id": "253_T6", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 74, 78 ] ], "normalized": [] }, { "id": "253_T7", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 100, 109 ] ], "normalized": [] }, { "id": "253_T9", "type": "Biological_Activity", "text": [ "binds" ], "offsets": [ [ 87, 92 ] ], "normalized": [] }, { "id": "253_T10", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 178, 182 ] ], "normalized": [] }, { "id": "253_T11", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 178, 182 ] ], "normalized": [] }, { "id": "253_T12", "type": "Biological_Activity", "text": [ "stimulates" ], "offsets": [ [ 183, 193 ] ], "normalized": [] }, { "id": "253_T13", "type": "Protein", "text": [ "G protein" ], "offsets": [ [ 213, 222 ] ], "normalized": [] }, { "id": "253_T14", "type": "Protein", "text": [ "G protein" ], "offsets": [ [ 278, 287 ] ], "normalized": [] }, { "id": "253_T15", "type": "Protein", "text": [ "pertussis toxin" ], "offsets": [ [ 308, 324 ] ], "normalized": [] }, { "id": "253_T16", "type": "Protein", "text": [ "betagamma subunit of G protein" ], "offsets": [ [ 257, 287 ] ], "normalized": [] }, { "id": "253_T17", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 289, 299 ] ], "normalized": [] }, { "id": "253_T18", "type": "Protein", "text": [ "Gi-type alpha subunit" ], "offsets": [ [ 335, 356 ] ], "normalized": [] }, { "id": "253_T19", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 389, 399 ] ], "normalized": [] }, { "id": "253_T22", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 422, 432 ] ], "normalized": [] }, { "id": "253_T23", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 413, 417 ] ], "normalized": [] }, { "id": "253_T24", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 413, 417 ] ], "normalized": [] }, { "id": "253_T26", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 504, 511 ] ], "normalized": [] }, { "id": "253_T28", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 549, 553 ] ], "normalized": [] }, { "id": "253_T29", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 549, 553 ] ], "normalized": [] }, { "id": "253_T30", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 783, 790 ] ], "normalized": [] }, { "id": "253_T31", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 625, 632 ] ], "normalized": [] }, { "id": "253_T33", "type": "Chemical", "text": [ "serine residue" ], "offsets": [ [ 660, 674 ] ], "normalized": [] }, { "id": "253_T34", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "253_T35", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "253_T36", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 716, 726 ] ], "normalized": [] }, { "id": "253_T37", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 732, 742 ] ], "normalized": [] }, { "id": "253_T39", "type": "Chemical", "text": [ "wortmannin" ], "offsets": [ [ 808, 818 ] ], "normalized": [] }, { "id": "253_T40", "type": "Chemical", "text": [ "LY294002" ], "offsets": [ [ 822, 830 ] ], "normalized": [] }, { "id": "253_T41", "type": "Protein", "text": [ "phosphatidylinositol 3-kinase" ], "offsets": [ [ 882, 911 ] ], "normalized": [] }, { "id": "253_T43", "type": "Protein", "text": [ "PI3K" ], "offsets": [ [ 913, 917 ] ], "normalized": [] }, { "id": "253_T47", "type": "Chemical", "text": [ "LY294002" ], "offsets": [ [ 920, 928 ] ], "normalized": [] }, { "id": "253_T48", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 944, 954 ] ], "normalized": [] }, { "id": "253_T51", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 967, 971 ] ], "normalized": [] }, { "id": "253_T52", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 967, 971 ] ], "normalized": [] }, { "id": "253_T53", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1059, 1066 ] ], "normalized": [] }, { "id": "253_T54", "type": "Protein", "text": [ "Gbetagamma" ], "offsets": [ [ 1091, 1101 ] ], "normalized": [] }, { "id": "253_T55", "type": "Protein", "text": [ "PI3K" ], "offsets": [ [ 1106, 1110 ] ], "normalized": [] }, { "id": "253_T56", "type": "Chemical", "text": [ "1-MA" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "253_T57", "type": "Metabolite", "text": [ "1-MA" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "253_T58", "type": "Species", "text": [ "starfish" ], "offsets": [ [ 1158, 1166 ] ], "normalized": [] }, { "id": "253_T62", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1220, 1227 ] ], "normalized": [] }, { "id": "253_T21", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 795, 804 ] ], "normalized": [] }, { "id": "253_T25", "type": "Biological_Activity", "text": [ "inhibitors" ], "offsets": [ [ 868, 878 ] ], "normalized": [] }, { "id": "253_T27", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 934, 943 ] ], "normalized": [] }, { "id": "253_T8", "type": "Biological_Activity", "text": [ "maturation-promoting" ], "offsets": [ [ 1266, 1286 ] ], "normalized": [] } ]

[]

[]

[ { "id": "253_R1", "type": "Isolated_From", "arg1_id": "253_T4", "arg2_id": "253_T1", "normalized": [] }, { "id": "253_R2", "type": "Isolated_From", "arg1_id": "253_T6", "arg2_id": "253_T1", "normalized": [] }, { "id": "253_R7", "type": "Associated_With", "arg1_id": "253_T4", "arg2_id": "253_T9", "normalized": [] }, { "id": "253_R8", "type": "Associated_With", "arg1_id": "253_T3", "arg2_id": "253_T9", "normalized": [] }, { "id": "253_R9", "type": "Associated_With", "arg1_id": "253_T6", "arg2_id": "253_T9", "normalized": [] }, { "id": "253_R10", "type": "Associated_With", "arg1_id": "253_T5", "arg2_id": "253_T9", "normalized": [] }, { "id": "253_R25", "type": "Associated_With", "arg1_id": "253_T4", "arg2_id": "253_T2", "normalized": [] }, { "id": "253_R26", "type": "Associated_With", "arg1_id": "253_T3", "arg2_id": "253_T2", "normalized": [] }, { "id": "253_R27", "type": "Associated_With", "arg1_id": "253_T11", "arg2_id": "253_T12", "normalized": [] }, { "id": "253_R28", "type": "Associated_With", "arg1_id": "253_T10", "arg2_id": "253_T12", "normalized": [] }, { "id": "253_R11", "type": "Associated_With", "arg1_id": "253_T39", "arg2_id": "253_T21", "normalized": [] }, { "id": "253_R12", "type": "Associated_With", "arg1_id": "253_T40", "arg2_id": "253_T21", "normalized": [] }, { "id": "253_R13", "type": "Associated_With", "arg1_id": "253_T39", "arg2_id": "253_T25", "normalized": [] }, { "id": "253_R14", "type": "Associated_With", "arg1_id": "253_T40", "arg2_id": "253_T25", "normalized": [] }, { "id": "253_R15", "type": "Associated_With", "arg1_id": "253_T47", "arg2_id": "253_T27", "normalized": [] }, { "id": "253_R16", "type": "Binds_With", "arg1_id": "253_T4", "arg2_id": "253_T7", "normalized": [] }, { "id": "253_R21", "type": "Binds_With", "arg1_id": "253_T3", "arg2_id": "253_T7", "normalized": [] }, { "id": "253_R22", "type": "Binds_With", "arg1_id": "253_T6", "arg2_id": "253_T7", "normalized": [] }, { "id": "253_R23", "type": "Binds_With", "arg1_id": "253_T5", "arg2_id": "253_T7", "normalized": [] }, { "id": "253_R3", "type": "Binds_With", "arg1_id": "253_T39", "arg2_id": "253_T41", "normalized": [] }, { "id": "253_R4", "type": "Binds_With", "arg1_id": "253_T39", "arg2_id": "253_T43", "normalized": [] }, { "id": "253_R5", "type": "Binds_With", "arg1_id": "253_T40", "arg2_id": "253_T41", "normalized": [] }, { "id": "253_R6", "type": "Binds_With", "arg1_id": "253_T40", "arg2_id": "253_T43", "normalized": [] } ]

[ { "id": "255", "type": "", "text": [ "The flavoenzyme d-aspartate oxidase from beef kidney (DASPO, EC 1.4. 3.1) has been overexpressed in Escherichia coli. A purification procedure, faster than the one used for the enzyme from the natural source (bDASPO), has been set up yielding about 2 mg of pure recombinant protein (rDASPO) per each gram of wet E. coli paste. rDASPO has been shown to possess the same general biochemical properties of bDASPO, except that the former contains only FAD, while the latter is a mixture of two forms, one active containing FAD and one inactive containing 6-OH-FAD (9-20% depending on the preparation). This results in a slightly higher specific activity (about 15%) for rDASPO compared to bDASPO and in facilitated procedures for apoprotein preparation and reconstitution. Redox potentials of -97 mV and -157 mV were determined for free and l-(+)-tartrate complexed DASPO, respectively, in 0.1 M KPi, pH 7.0, 25 degrees C. The large positive shift in the redox potential of the coenzyme compared to free FAD (-207 mV) is in agreement with similar results obtained with other flavooxidases. rDASPO has been used to assess a possible oxidative activity of the enzyme towards a number of compounds used as agonists or antagonists of neurotransmitters, including d-aspartatic acid, d-glutamic acid, N-methyl-d-aspartic acid, d,l-cysteic acid, d-homocysteic acid, d, l-2-amino-3-phosphonopropanoic acid, d-alpha-aminoadipic acid, d-aspartic acid-beta-hydroxamate, glycyl-d-aspartic acid and cis-2, 3-piperidine dicarboxylic acid. Kinetic parameters for each substrate in 50 mM KPi, pH 7.4, 25 degrees C are reported. \n" ], "offsets": [ [ 0, 1616 ] ] } ]

[ { "id": "255_T1", "type": "Protein", "text": [ "flavoenzyme" ], "offsets": [ [ 4, 15 ] ], "normalized": [] }, { "id": "255_T2", "type": "Protein", "text": [ "d-aspartate oxidase" ], "offsets": [ [ 16, 35 ] ], "normalized": [] }, { "id": "255_T3", "type": "Species", "text": [ "beef" ], "offsets": [ [ 41, 45 ] ], "normalized": [] }, { "id": "255_T4", "type": "Protein", "text": [ "DASPO" ], "offsets": [ [ 54, 59 ] ], "normalized": [] }, { "id": "255_T5", "type": "Protein", "text": [ "EC 1.4. 3.1" ], "offsets": [ [ 61, 72 ] ], "normalized": [] }, { "id": "255_T6", "type": "Species", "text": [ "Escherichia coli" ], "offsets": [ [ 100, 116 ] ], "normalized": [] }, { "id": "255_T7", "type": "Protein", "text": [ "bDASPO" ], "offsets": [ [ 209, 215 ] ], "normalized": [] }, { "id": "255_T8", "type": "Protein", "text": [ "rDASPO" ], "offsets": [ [ 283, 289 ] ], "normalized": [] }, { "id": "255_T9", "type": "Species", "text": [ "E. coli" ], "offsets": [ [ 312, 320 ] ], "normalized": [] }, { "id": "255_T10", "type": "Protein", "text": [ "rDASPO" ], "offsets": [ [ 328, 334 ] ], "normalized": [] }, { "id": "255_T11", "type": "Protein", "text": [ "bDASPO" ], "offsets": [ [ 404, 410 ] ], "normalized": [] }, { "id": "255_T12", "type": "Chemical", "text": [ "FAD" ], "offsets": [ [ 449, 452 ] ], "normalized": [] }, { "id": "255_T13", "type": "Chemical", "text": [ "FAD" ], "offsets": [ [ 521, 524 ] ], "normalized": [] }, { "id": "255_T14", "type": "Chemical", "text": [ "6-OH-FAD" ], "offsets": [ [ 554, 562 ] ], "normalized": [] }, { "id": "255_T15", "type": "Metabolite", "text": [ "FAD" ], "offsets": [ [ 449, 452 ] ], "normalized": [] }, { "id": "255_T16", "type": "Metabolite", "text": [ "FAD" ], "offsets": [ [ 521, 524 ] ], "normalized": [] }, { "id": "255_T17", "type": "Metabolite", "text": [ "6-OH-FAD" ], "offsets": [ [ 554, 562 ] ], "normalized": [] }, { "id": "255_T18", "type": "Protein", "text": [ "rDASPO" ], "offsets": [ [ 670, 676 ] ], "normalized": [] }, { "id": "255_T19", "type": "Protein", "text": [ "bDASPO" ], "offsets": [ [ 689, 695 ] ], "normalized": [] }, { "id": "255_T20", "type": "Chemical", "text": [ "l-(+)-tartrate" ], "offsets": [ [ 841, 855 ] ], "normalized": [] }, { "id": "255_T21", "type": "Protein", "text": [ "DASPO" ], "offsets": [ [ 866, 871 ] ], "normalized": [] }, { "id": "255_T22", "type": "Chemical", "text": [ "coenzyme" ], "offsets": [ [ 978, 986 ] ], "normalized": [] }, { "id": "255_T23", "type": "Chemical", "text": [ "FAD" ], "offsets": [ [ 1004, 1007 ] ], "normalized": [] }, { "id": "255_T24", "type": "Metabolite", "text": [ "FAD" ], "offsets": [ [ 1004, 1007 ] ], "normalized": [] }, { "id": "255_T25", "type": "Protein", "text": [ "flavooxidases" ], "offsets": [ [ 1075, 1088 ] ], "normalized": [] }, { "id": "255_T26", "type": "Protein", "text": [ "rDASPO" ], "offsets": [ [ 1090, 1096 ] ], "normalized": [] }, { "id": "255_T27", "type": "Biological_Activity", "text": [ "oxidative" ], "offsets": [ [ 1132, 1141 ] ], "normalized": [] }, { "id": "255_T28", "type": "Biological_Activity", "text": [ "agonists or antagonists" ], "offsets": [ [ 1204, 1227 ] ], "normalized": [] }, { "id": "255_T29", "type": "Chemical", "text": [ "d-aspartatic acid" ], "offsets": [ [ 1260, 1277 ] ], "normalized": [] }, { "id": "255_T30", "type": "Chemical", "text": [ "d-glutamic acid" ], "offsets": [ [ 1279, 1294 ] ], "normalized": [] }, { "id": "255_T31", "type": "Chemical", "text": [ "N-methyl-d-aspartic acid" ], "offsets": [ [ 1296, 1320 ] ], "normalized": [] }, { "id": "255_T32", "type": "Chemical", "text": [ "d,l-cysteic acid" ], "offsets": [ [ 1322, 1338 ] ], "normalized": [] }, { "id": "255_T33", "type": "Chemical", "text": [ "d-homocysteic acid" ], "offsets": [ [ 1340, 1359 ] ], "normalized": [] }, { "id": "255_T34", "type": "Chemical", "text": [ "d, l-2-amino-3-phosphonopropanoic acid" ], "offsets": [ [ 1361, 1399 ] ], "normalized": [] }, { "id": "255_T35", "type": "Chemical", "text": [ "d-alpha-aminoadipic acid" ], "offsets": [ [ 1401, 1425 ] ], "normalized": [] }, { "id": "255_T36", "type": "Chemical", "text": [ "d-aspartic acid-beta-hydroxamate" ], "offsets": [ [ 1427, 1459 ] ], "normalized": [] }, { "id": "255_T37", "type": "Chemical", "text": [ "glycyl-d-aspartic acid" ], "offsets": [ [ 1461, 1483 ] ], "normalized": [] }, { "id": "255_T38", "type": "Chemical", "text": [ "cis-2, 3-piperidine dicarboxylic acid" ], "offsets": [ [ 1488, 1526 ] ], "normalized": [] } ]

[]

[]

[ { "id": "255_R1", "type": "Isolated_From", "arg1_id": "255_T15", "arg2_id": "255_T3", "normalized": [] }, { "id": "255_R2", "type": "Isolated_From", "arg1_id": "255_T16", "arg2_id": "255_T6", "normalized": [] }, { "id": "255_R3", "type": "Isolated_From", "arg1_id": "255_T17", "arg2_id": "255_T6", "normalized": [] }, { "id": "255_R4", "type": "Associated_With", "arg1_id": "255_T29", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R5", "type": "Associated_With", "arg1_id": "255_T30", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R6", "type": "Associated_With", "arg1_id": "255_T31", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R7", "type": "Associated_With", "arg1_id": "255_T32", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R8", "type": "Associated_With", "arg1_id": "255_T33", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R9", "type": "Associated_With", "arg1_id": "255_T34", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R10", "type": "Associated_With", "arg1_id": "255_T35", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R11", "type": "Associated_With", "arg1_id": "255_T36", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R12", "type": "Associated_With", "arg1_id": "255_T37", "arg2_id": "255_T28", "normalized": [] }, { "id": "255_R13", "type": "Associated_With", "arg1_id": "255_T38", "arg2_id": "255_T28", "normalized": [] } ]

[ { "id": "257", "type": "", "text": [ "LD50 of karminomycin, rubomycin and adriamycin were determined after their single administration or 3-, 5-, 10- and 15-fold administration once a day to 540 hybrid male mice F1(C57B1 X CBA). Comparison of the cumulative indices for these antibiotics showed that after injections they were close. After 5 injections the cumulative properties were more pronounced for adriamycin. After 10 or 15 injections the cumulative properties were less pronounced for karminomycin. \n" ], "offsets": [ [ 0, 471 ] ] } ]

[ { "id": "257_T1", "type": "Chemical", "text": [ "karminomycin" ], "offsets": [ [ 8, 20 ] ], "normalized": [] }, { "id": "257_T2", "type": "Chemical", "text": [ "rubomycin" ], "offsets": [ [ 22, 31 ] ], "normalized": [] }, { "id": "257_T3", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 36, 46 ] ], "normalized": [] }, { "id": "257_T4", "type": "Species", "text": [ "mice F1(C57B1 X CBA)" ], "offsets": [ [ 169, 189 ] ], "normalized": [] }, { "id": "257_T5", "type": "Biological_Activity", "text": [ "antibiotic" ], "offsets": [ [ 238, 248 ] ], "normalized": [] }, { "id": "257_T6", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 367, 377 ] ], "normalized": [] }, { "id": "257_T7", "type": "Chemical", "text": [ "karminomycin" ], "offsets": [ [ 456, 468 ] ], "normalized": [] } ]

[]

[]

[ { "id": "257_R1", "type": "Associated_With", "arg1_id": "257_T1", "arg2_id": "257_T5", "normalized": [] }, { "id": "257_R2", "type": "Associated_With", "arg1_id": "257_T2", "arg2_id": "257_T5", "normalized": [] }, { "id": "257_R3", "type": "Associated_With", "arg1_id": "257_T3", "arg2_id": "257_T5", "normalized": [] } ]

[ { "id": "259", "type": "", "text": [ "The cardiotoxic effect of karminomycin and adriamycin administered intravenously for 5 times in equitoxic doses constituting equal portions of LD50 of the respective antibiotic on its single intravenous administration was studied on albino mice. Histological examination of the heart showed that almost identical damages of the myocardium occured after administration of karminomycin and adriamycin in doses of 0.45 of LD50 (1.5 mg/kg) and 0.3 of LD50 (6.3 mg/kg) respectively. The character of the damages due to the antibiotics was close, the most significant changes were observed when the animals were sacrificed 1 month after the last administration of the drug. The histological method is of value in estimation of the cardiotoxic effect of the drugs, using mice as the model suitable for the investigation. Adriamycin had more pronounced cumulative properties as compared to karminomycin: suppression of the weight gain in the mice and their death rate were higher with the use of adriamycin. \n" ], "offsets": [ [ 0, 1003 ] ] } ]

[ { "id": "259_T1", "type": "Biological_Activity", "text": [ "cardiotoxic" ], "offsets": [ [ 4, 15 ] ], "normalized": [] }, { "id": "259_T2", "type": "Chemical", "text": [ "karminomycin" ], "offsets": [ [ 26, 38 ] ], "normalized": [] }, { "id": "259_T3", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 43, 53 ] ], "normalized": [] }, { "id": "259_T4", "type": "Biological_Activity", "text": [ "antibiotic" ], "offsets": [ [ 167, 177 ] ], "normalized": [] }, { "id": "259_T5", "type": "Species", "text": [ "albino mice" ], "offsets": [ [ 234, 245 ] ], "normalized": [] }, { "id": "259_T7", "type": "Chemical", "text": [ "karminomycin" ], "offsets": [ [ 372, 384 ] ], "normalized": [] }, { "id": "259_T8", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 389, 399 ] ], "normalized": [] }, { "id": "259_T9", "type": "Biological_Activity", "text": [ "antibiotics" ], "offsets": [ [ 519, 530 ] ], "normalized": [] }, { "id": "259_T10", "type": "Biological_Activity", "text": [ "cardiotoxic" ], "offsets": [ [ 727, 738 ] ], "normalized": [] }, { "id": "259_T11", "type": "Species", "text": [ "mice" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "259_T12", "type": "Chemical", "text": [ "Adriamycin" ], "offsets": [ [ 816, 826 ] ], "normalized": [] }, { "id": "259_T13", "type": "Chemical", "text": [ "karminomycin" ], "offsets": [ [ 884, 896 ] ], "normalized": [] }, { "id": "259_T16", "type": "Species", "text": [ "mice" ], "offsets": [ [ 936, 940 ] ], "normalized": [] }, { "id": "259_T17", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 990, 1000 ] ], "normalized": [] }, { "id": "259_T18", "type": "Chemical", "text": [ "antibiotics" ], "offsets": [ [ 519, 530 ] ], "normalized": [] }, { "id": "259_T19", "type": "Chemical", "text": [ "antibiotic" ], "offsets": [ [ 167, 177 ] ], "normalized": [] }, { "id": "259_T20", "type": "Chemical", "text": [ "drug" ], "offsets": [ [ 664, 668 ] ], "normalized": [] }, { "id": "259_T21", "type": "Chemical", "text": [ "drugs" ], "offsets": [ [ 753, 758 ] ], "normalized": [] } ]

[]

[]

[ { "id": "259_R1", "type": "Associated_With", "arg1_id": "259_T3", "arg2_id": "259_T4", "normalized": [] }, { "id": "259_R2", "type": "Associated_With", "arg1_id": "259_T2", "arg2_id": "259_T4", "normalized": [] }, { "id": "259_R3", "type": "Associated_With", "arg1_id": "259_T2", "arg2_id": "259_T1", "normalized": [] }, { "id": "259_R4", "type": "Associated_With", "arg1_id": "259_T3", "arg2_id": "259_T1", "normalized": [] } ]

[ { "id": "261", "type": "", "text": [ "We have compared the minimum local analgesic concentrations (MLAC) of levobupivacaine relative to racemic bupivacaine in a prospective, randomized, double-blind, sequential allocation study. Women in labour were given a 20-ml bolus of epidural levobupivacaine or bupivacaine diluted to a concentration determined by up-down sequential allocation. The initial concentration was 0.07% w/v for both drugs. Efficacy was defined using a visual analogue pain score (VAPS) at 10 mm or less within 30 min. The MLAC of levobupivacaine was 0.083% w/v (95% CI 0.065-0.101) and the MLAC of bupivacaine 0.081% w/v (95% CI 0.055-0.108). In molar terms, the MLAC of levobupivacaine was 2.87 mmol litre-1 (95% CI 2.25-3.49) and the MLAC of bupivacaine 2.49 mmol litre-1 (95% CI 1.69-3.32). With regard to the commercial preparations, the potency ratio levobupivacaine: bupivacaine was 0.98 (95% CI 0.67-1.41), and this is unlikely to be of clinical relevance. In molar terms, the ratio was 0.87 (95% CI 0.60-1.25). With regard to toxicity, the evidence should be evaluated in the light of a possible 13% potency difference in molar concentration in favour of racemic bupivacaine. \n" ], "offsets": [ [ 0, 1167 ] ] } ]

[ { "id": "261_T1", "type": "Biological_Activity", "text": [ "analgesic" ], "offsets": [ [ 35, 44 ] ], "normalized": [] }, { "id": "261_T2", "type": "Chemical", "text": [ "levobupivacaine" ], "offsets": [ [ 70, 85 ] ], "normalized": [] }, { "id": "261_T3", "type": "Chemical", "text": [ "racemic bupivacaine" ], "offsets": [ [ 98, 117 ] ], "normalized": [] }, { "id": "261_T4", "type": "Species", "text": [ "Women" ], "offsets": [ [ 191, 196 ] ], "normalized": [] }, { "id": "261_T5", "type": "Chemical", "text": [ "levobupivacaine" ], "offsets": [ [ 244, 259 ] ], "normalized": [] }, { "id": "261_T6", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 263, 274 ] ], "normalized": [] }, { "id": "261_T7", "type": "Chemical", "text": [ "drugs" ], "offsets": [ [ 397, 402 ] ], "normalized": [] }, { "id": "261_T8", "type": "Chemical", "text": [ "levobupivacaine" ], "offsets": [ [ 511, 526 ] ], "normalized": [] }, { "id": "261_T9", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 579, 590 ] ], "normalized": [] }, { "id": "261_T10", "type": "Chemical", "text": [ "levobupivacaine" ], "offsets": [ [ 652, 667 ] ], "normalized": [] }, { "id": "261_T11", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 725, 736 ] ], "normalized": [] }, { "id": "261_T12", "type": "Chemical", "text": [ "levobupivacaine" ], "offsets": [ [ 837, 852 ] ], "normalized": [] }, { "id": "261_T13", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 854, 865 ] ], "normalized": [] }, { "id": "261_T14", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 1016, 1024 ] ], "normalized": [] }, { "id": "261_T15", "type": "Chemical", "text": [ "racemic bupivacaine" ], "offsets": [ [ 1145, 1164 ] ], "normalized": [] }, { "id": "261_T16", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 1153, 1164 ] ], "normalized": [] }, { "id": "261_T17", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 106, 117 ] ], "normalized": [] } ]

[]

[]

[ { "id": "261_R1", "type": "Associated_With", "arg1_id": "261_T2", "arg2_id": "261_T1", "normalized": [] }, { "id": "261_R2", "type": "Associated_With", "arg1_id": "261_T3", "arg2_id": "261_T1", "normalized": [] } ]

[ { "id": "263", "type": "", "text": [ "Three sialosylated and three neutral glycosphingolipids sharing a common iso-neolacto core were isolated from porcine kidney cortex. They were purified by preparative HPTLC, and were characterized by partial exoglycosidase hydrolysis followed by thin layer chromatography and immunostaining with anti-Galalpha1-->3Gal, anti-type 2 lactosamine and anti-Lewis(x) antibodies, methylation analysis, MALDI-TOF mass spectrometry and 1H-NMR spectroscopy. Among neutral glycolipids, one was a known structure, VI3VI'3(alphaGal)2-iso-nLc8Cer, and two were novel structures differing by the number of Galalpha3Lewis(x) determinants: VI3VI'3(alphaGal)2V'3alphaFuc-iso-nLc8, and VI3VI'3(alphaGal)2 V3V'3(alphaFuc)2-iso-nLc8. The single Galalpha3Lewis(x) determinant was found on the 6-linked antenna. Among sialosylated glycolipids, two had been previously found in other species and tissues, VI3VI'3(NeuAc)2-iso-nLc8, and VI3NeuAcVI'3alphaGal-iso-nLc8. A novel structure was discovered presenting a Galalpha3Lewis(x) determinant on the 6-linked antenna and a N-acetylneuraminic acid on the 3-linked antenna, VI3NeuAcVI'3alphaGalV'3alphaFuc-iso-nLc8. These results indicate that, in vivo, the porcine kidney alpha3fucosyltransferase synthesizes the Gala3Lewis(x) determinant, acting on the 6-linked before the 3-linked Galalpha3neolactosamine, and appears unable to synthesize the sialosylated Lewis(x) determinant on neolactoseries glycolipids. \n" ], "offsets": [ [ 0, 1437 ] ] } ]

[ { "id": "263_T1", "type": "Chemical", "text": [ "glycosphingolipids" ], "offsets": [ [ 37, 55 ] ], "normalized": [] }, { "id": "263_T2", "type": "Chemical", "text": [ "glycosphingolipids", "sialosylated" ], "offsets": [ [ 37, 55 ], [ 6, 18 ] ], "normalized": [] }, { "id": "263_T3", "type": "Chemical", "text": [ "iso-neolacto" ], "offsets": [ [ 73, 85 ] ], "normalized": [] }, { "id": "263_T4", "type": "Species", "text": [ "porcine" ], "offsets": [ [ 110, 117 ] ], "normalized": [] }, { "id": "263_T5", "type": "Metabolite", "text": [ "glycosphingolipids", "sialosylated" ], "offsets": [ [ 37, 55 ], [ 6, 18 ] ], "normalized": [] }, { "id": "263_T6", "type": "Metabolite", "text": [ "glycosphingolipids" ], "offsets": [ [ 37, 55 ] ], "normalized": [] }, { "id": "263_T7", "type": "Protein", "text": [ "exoglycosidase" ], "offsets": [ [ 208, 222 ] ], "normalized": [] }, { "id": "263_T10", "type": "Protein", "text": [ "anti-Galalpha1-->3Gal", "antibodies" ], "offsets": [ [ 296, 317 ], [ 361, 371 ] ], "normalized": [] }, { "id": "263_T11", "type": "Protein", "text": [ "anti-type 2 lactosamine", "antibodies" ], "offsets": [ [ 319, 342 ], [ 361, 371 ] ], "normalized": [] }, { "id": "263_T12", "type": "Protein", "text": [ "anti-Lewis(x) antibodies" ], "offsets": [ [ 347, 371 ] ], "normalized": [] }, { "id": "263_T13", "type": "Spectral_Data", "text": [ "MALDI-TOF mass spectrometry" ], "offsets": [ [ 395, 422 ] ], "normalized": [] }, { "id": "263_T14", "type": "Spectral_Data", "text": [ "1H-NMR spectroscopy" ], "offsets": [ [ 427, 446 ] ], "normalized": [] }, { "id": "263_T15", "type": "Chemical", "text": [ "VI3VI'3(alphaGal)2-iso-nLc8Cer" ], "offsets": [ [ 503, 533 ] ], "normalized": [] }, { "id": "263_T16", "type": "Metabolite", "text": [ "VI3VI'3(alphaGal)2-iso-nLc8Cer" ], "offsets": [ [ 503, 533 ] ], "normalized": [] }, { "id": "263_T17", "type": "Chemical", "text": [ "glycolipids" ], "offsets": [ [ 463, 474 ] ], "normalized": [] }, { "id": "263_T18", "type": "Chemical", "text": [ "VI3VI'3(alphaGal)2V'3alphaFuc-iso-nLc8" ], "offsets": [ [ 624, 662 ] ], "normalized": [] }, { "id": "263_T19", "type": "Metabolite", "text": [ "VI3VI'3(alphaGal)2V'3alphaFuc-iso-nLc8" ], "offsets": [ [ 624, 662 ] ], "normalized": [] }, { "id": "263_T20", "type": "Metabolite", "text": [ "VI3VI'3(alphaGal)2 V3V'3(alphaFuc)2-iso-nLc8" ], "offsets": [ [ 668, 712 ] ], "normalized": [] }, { "id": "263_T21", "type": "Chemical", "text": [ "VI3VI'3(alphaGal)2 V3V'3(alphaFuc)2-iso-nLc8" ], "offsets": [ [ 668, 712 ] ], "normalized": [] }, { "id": "263_T22", "type": "Chemical", "text": [ "Galalpha3Lewis(x)" ], "offsets": [ [ 592, 609 ] ], "normalized": [] }, { "id": "263_T23", "type": "Chemical", "text": [ "Galalpha3Lewis(x)" ], "offsets": [ [ 725, 742 ] ], "normalized": [] }, { "id": "263_T24", "type": "Chemical", "text": [ "sialosylated glycolipids" ], "offsets": [ [ 797, 821 ] ], "normalized": [] }, { "id": "263_T25", "type": "Metabolite", "text": [ "sialosylated glycolipids" ], "offsets": [ [ 797, 821 ] ], "normalized": [] }, { "id": "263_T26", "type": "Chemical", "text": [ "VI3VI'3(NeuAc)2-iso-nLc8" ], "offsets": [ [ 883, 907 ] ], "normalized": [] }, { "id": "263_T27", "type": "Chemical", "text": [ "VI3NeuAcVI'3alphaGal-iso-nLc8" ], "offsets": [ [ 913, 942 ] ], "normalized": [] }, { "id": "263_T28", "type": "Metabolite", "text": [ "VI3VI'3(NeuAc)2-iso-nLc8" ], "offsets": [ [ 883, 907 ] ], "normalized": [] }, { "id": "263_T29", "type": "Metabolite", "text": [ "VI3NeuAcVI'3alphaGal-iso-nLc8" ], "offsets": [ [ 913, 942 ] ], "normalized": [] }, { "id": "263_T30", "type": "Chemical", "text": [ "Galalpha3Lewis(x)" ], "offsets": [ [ 990, 1007 ] ], "normalized": [] }, { "id": "263_T31", "type": "Chemical", "text": [ "N-acetylneuraminic acid" ], "offsets": [ [ 1050, 1073 ] ], "normalized": [] }, { "id": "263_T32", "type": "Metabolite", "text": [ "VI3NeuAcVI'3alphaGalV'3alphaFuc-iso-nLc8" ], "offsets": [ [ 1099, 1139 ] ], "normalized": [] }, { "id": "263_T33", "type": "Chemical", "text": [ "VI3NeuAcVI'3alphaGalV'3alphaFuc-iso-nLc8" ], "offsets": [ [ 1099, 1139 ] ], "normalized": [] }, { "id": "263_T34", "type": "Species", "text": [ "porcine" ], "offsets": [ [ 1183, 1190 ] ], "normalized": [] }, { "id": "263_T35", "type": "Protein", "text": [ "porcine kidney alpha3fucosyltransferase" ], "offsets": [ [ 1183, 1222 ] ], "normalized": [] }, { "id": "263_T36", "type": "Chemical", "text": [ "Gala3Lewis(x)" ], "offsets": [ [ 1239, 1252 ] ], "normalized": [] }, { "id": "263_T37", "type": "Chemical", "text": [ "6-linked", "Galalpha3neolactosamine" ], "offsets": [ [ 1280, 1288 ], [ 1309, 1332 ] ], "normalized": [] }, { "id": "263_T38", "type": "Chemical", "text": [ "3-linked Galalpha3neolactosamine" ], "offsets": [ [ 1300, 1332 ] ], "normalized": [] }, { "id": "263_T39", "type": "Chemical", "text": [ "sialosylated Lewis(x)" ], "offsets": [ [ 1371, 1392 ] ], "normalized": [] }, { "id": "263_T40", "type": "Chemical", "text": [ "neolactoseries glycolipids" ], "offsets": [ [ 1408, 1434 ] ], "normalized": [] }, { "id": "263_T41", "type": "Chemical", "text": [ "glycolipids" ], "offsets": [ [ 1423, 1434 ] ], "normalized": [] } ]

[]

[]

[ { "id": "263_R1", "type": "Isolated_From", "arg1_id": "263_T6", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R2", "type": "Isolated_From", "arg1_id": "263_T5", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R3", "type": "Associated_With", "arg1_id": "263_T16", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R4", "type": "Associated_With", "arg1_id": "263_T15", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R5", "type": "Isolated_From", "arg1_id": "263_T16", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R6", "type": "Isolated_From", "arg1_id": "263_T19", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R7", "type": "Isolated_From", "arg1_id": "263_T20", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R8", "type": "Associated_With", "arg1_id": "263_T19", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R9", "type": "Associated_With", "arg1_id": "263_T18", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R10", "type": "Associated_With", "arg1_id": "263_T20", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R11", "type": "Associated_With", "arg1_id": "263_T21", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R12", "type": "Associated_With", "arg1_id": "263_T16", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R13", "type": "Associated_With", "arg1_id": "263_T15", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R14", "type": "Associated_With", "arg1_id": "263_T19", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R15", "type": "Associated_With", "arg1_id": "263_T18", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R16", "type": "Associated_With", "arg1_id": "263_T20", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R17", "type": "Associated_With", "arg1_id": "263_T21", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R18", "type": "Isolated_From", "arg1_id": "263_T28", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R19", "type": "Isolated_From", "arg1_id": "263_T29", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R20", "type": "Isolated_From", "arg1_id": "263_T32", "arg2_id": "263_T4", "normalized": [] }, { "id": "263_R21", "type": "Associated_With", "arg1_id": "263_T28", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R22", "type": "Associated_With", "arg1_id": "263_T26", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R23", "type": "Associated_With", "arg1_id": "263_T29", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R24", "type": "Associated_With", "arg1_id": "263_T27", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R25", "type": "Associated_With", "arg1_id": "263_T28", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R26", "type": "Associated_With", "arg1_id": "263_T26", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R27", "type": "Associated_With", "arg1_id": "263_T29", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R28", "type": "Associated_With", "arg1_id": "263_T27", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R29", "type": "Associated_With", "arg1_id": "263_T32", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R30", "type": "Associated_With", "arg1_id": "263_T33", "arg2_id": "263_T13", "normalized": [] }, { "id": "263_R31", "type": "Associated_With", "arg1_id": "263_T32", "arg2_id": "263_T14", "normalized": [] }, { "id": "263_R32", "type": "Associated_With", "arg1_id": "263_T33", "arg2_id": "263_T14", "normalized": [] } ]

[ { "id": "265", "type": "", "text": [ "The expression of the sialyl Lewis x antigen (sLe(x)) on surgical specimens of primary gastric cancer correlates with the degree of differentiation and synchronous and metachronous liver metastasis. Multivariate analysis by means of Quantification theory II revealed that sLe(x) expression was an independent risk factor for liver metastasis from gastric cancer. \n" ], "offsets": [ [ 0, 366 ] ] } ]

[ { "id": "265_T1", "type": "Chemical", "text": [ "sialyl Lewis x antigen" ], "offsets": [ [ 22, 44 ] ], "normalized": [] }, { "id": "265_T2", "type": "Chemical", "text": [ "sLe(x)" ], "offsets": [ [ 46, 52 ] ], "normalized": [] }, { "id": "265_T5", "type": "Chemical", "text": [ "sLe(x)" ], "offsets": [ [ 273, 279 ] ], "normalized": [] }, { "id": "265_T7", "type": "Biological_Activity", "text": [ "metastasis" ], "offsets": [ [ 187, 197 ] ], "normalized": [] }, { "id": "265_T3", "type": "Biological_Activity", "text": [ "differentiation" ], "offsets": [ [ 132, 147 ] ], "normalized": [] }, { "id": "265_T4", "type": "Biological_Activity", "text": [ "metastasis" ], "offsets": [ [ 333, 343 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "267", "type": "", "text": [ "Novel as well as known 5'-N-substituted carboxamidoadenosines were prepared via new routes that provided shorter reaction times and good yields. Binding affinities were determined for rat A1 and A2A receptors and human A3 receptors. EC50 values were determined for cyclic AMP production in CHO cells expressing human A2B receptors. On all receptor subtypes relatively small substituents on the carboxamido moiety were optimal. Selectivity for the A3 receptor was found for several analogues (1a, 1d, 1h, and 1k). On A1 receptors a number of compounds, but not 5'-N-ethylcarboxamidoadenosine (NECA, 1b), showed small GTP shifts, which could be indicative of lower intrinsic activities at the A1 receptor. At the A2B receptor, derivatives 1i-k with modified ethyl substituents had reduced activities compared to the A2B reference agonist NECA (1b). Thiocarboxamido derivatives (8b and 8c) displayed considerable although decreased A2B receptor activity. The X-ray structure determination of compound 8b was carried out. Due to intramolecular hydrogen bonding between the carboxamido NH and the purine N3 in the crystal structure, the ribose moiety of this compound is in a syn conformation. However, theoretical calculations support that NECA (1b), and less so 8b, can readily adopt both the syn and the anti conformation, therefore not excluding the proposed anti mode of binding to the receptor. \n" ], "offsets": [ [ 0, 1399 ] ] } ]

[ { "id": "267_T1", "type": "Chemical", "text": [ "5'-N-substituted carboxamidoadenosines" ], "offsets": [ [ 23, 61 ] ], "normalized": [] }, { "id": "267_T2", "type": "Species", "text": [ "rat" ], "offsets": [ [ 184, 187 ] ], "normalized": [] }, { "id": "267_T3", "type": "Species", "text": [ "human" ], "offsets": [ [ 213, 218 ] ], "normalized": [] }, { "id": "267_T4", "type": "Protein", "text": [ "A1", "receptors" ], "offsets": [ [ 188, 190 ], [ 199, 208 ] ], "normalized": [] }, { "id": "267_T5", "type": "Protein", "text": [ "A2A receptors" ], "offsets": [ [ 195, 208 ] ], "normalized": [] }, { "id": "267_T6", "type": "Protein", "text": [ "A3 receptors" ], "offsets": [ [ 219, 231 ] ], "normalized": [] }, { "id": "267_T10", "type": "Species", "text": [ "human" ], "offsets": [ [ 311, 316 ] ], "normalized": [] }, { "id": "267_T11", "type": "Protein", "text": [ "A2B receptors" ], "offsets": [ [ 317, 330 ] ], "normalized": [] }, { "id": "267_T13", "type": "Chemical", "text": [ "cyclic AMP" ], "offsets": [ [ 265, 275 ] ], "normalized": [] }, { "id": "267_T15", "type": "Species", "text": [ "CHO cells" ], "offsets": [ [ 290, 299 ] ], "normalized": [] }, { "id": "267_T16", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 339, 347 ] ], "normalized": [] }, { "id": "267_T17", "type": "Chemical", "text": [ "carboxamido" ], "offsets": [ [ 394, 405 ] ], "normalized": [] }, { "id": "267_T18", "type": "Protein", "text": [ "A3 receptor" ], "offsets": [ [ 447, 458 ] ], "normalized": [] }, { "id": "267_T21", "type": "Chemical", "text": [ "analogue", "1a" ], "offsets": [ [ 481, 489 ], [ 492, 494 ] ], "normalized": [] }, { "id": "267_T22", "type": "Chemical", "text": [ "analogue", "1d" ], "offsets": [ [ 481, 489 ], [ 496, 498 ] ], "normalized": [] }, { "id": "267_T23", "type": "Chemical", "text": [ "analogue", "1h" ], "offsets": [ [ 481, 489 ], [ 500, 502 ] ], "normalized": [] }, { "id": "267_T24", "type": "Chemical", "text": [ "analogue", "1k" ], "offsets": [ [ 481, 489 ], [ 508, 510 ] ], "normalized": [] }, { "id": "267_T25", "type": "Protein", "text": [ "A1 receptors" ], "offsets": [ [ 516, 528 ] ], "normalized": [] }, { "id": "267_T27", "type": "Chemical", "text": [ "5'-N-ethylcarboxamidoadenosine" ], "offsets": [ [ 560, 590 ] ], "normalized": [] }, { "id": "267_T28", "type": "Chemical", "text": [ "NECA" ], "offsets": [ [ 592, 596 ] ], "normalized": [] }, { "id": "267_T29", "type": "Chemical", "text": [ "1b" ], "offsets": [ [ 598, 600 ] ], "normalized": [] }, { "id": "267_T30", "type": "Protein", "text": [ "A2B receptor" ], "offsets": [ [ 711, 723 ] ], "normalized": [] }, { "id": "267_T32", "type": "Chemical", "text": [ "derivatives 1i-k" ], "offsets": [ [ 725, 741 ] ], "normalized": [] }, { "id": "267_T33", "type": "Chemical", "text": [ "modified ethyl substituents" ], "offsets": [ [ 747, 774 ] ], "normalized": [] }, { "id": "267_T34", "type": "Protein", "text": [ "A2B" ], "offsets": [ [ 815, 818 ] ], "normalized": [] }, { "id": "267_T36", "type": "Biological_Activity", "text": [ "agonist" ], "offsets": [ [ 829, 836 ] ], "normalized": [] }, { "id": "267_T37", "type": "Chemical", "text": [ "NECA" ], "offsets": [ [ 837, 841 ] ], "normalized": [] }, { "id": "267_T38", "type": "Chemical", "text": [ "1b" ], "offsets": [ [ 843, 845 ] ], "normalized": [] }, { "id": "267_T39", "type": "Chemical", "text": [ "Thiocarboxamido derivative", "8c" ], "offsets": [ [ 848, 874 ], [ 884, 886 ] ], "normalized": [] }, { "id": "267_T40", "type": "Chemical", "text": [ "Thiocarboxamido derivative", "8b" ], "offsets": [ [ 848, 874 ], [ 877, 879 ] ], "normalized": [] }, { "id": "267_T41", "type": "Protein", "text": [ "A2B receptor" ], "offsets": [ [ 930, 942 ] ], "normalized": [] }, { "id": "267_T44", "type": "Spectral_Data", "text": [ "X-ray structure determination" ], "offsets": [ [ 957, 986 ] ], "normalized": [] }, { "id": "267_T45", "type": "Chemical", "text": [ "compound 8b" ], "offsets": [ [ 990, 1001 ] ], "normalized": [] }, { "id": "267_T46", "type": "Chemical", "text": [ "carboxamido NH" ], "offsets": [ [ 1070, 1084 ] ], "normalized": [] }, { "id": "267_T47", "type": "Chemical", "text": [ "purine N3" ], "offsets": [ [ 1093, 1102 ] ], "normalized": [] }, { "id": "267_T48", "type": "Chemical", "text": [ "ribose moiety" ], "offsets": [ [ 1133, 1146 ] ], "normalized": [] }, { "id": "267_T49", "type": "Chemical", "text": [ "NECA" ], "offsets": [ [ 1237, 1241 ] ], "normalized": [] }, { "id": "267_T50", "type": "Chemical", "text": [ "1b" ], "offsets": [ [ 1243, 1245 ] ], "normalized": [] }, { "id": "267_T51", "type": "Chemical", "text": [ "8b" ], "offsets": [ [ 1261, 1263 ] ], "normalized": [] }, { "id": "267_T52", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 1388, 1396 ] ], "normalized": [] }, { "id": "267_T54", "type": "Protein", "text": [ "A1 receptor" ], "offsets": [ [ 691, 702 ] ], "normalized": [] } ]

[]

[]

[ { "id": "267_R1", "type": "Binds_With", "arg1_id": "267_T1", "arg2_id": "267_T4", "normalized": [] }, { "id": "267_R13", "type": "Associated_With", "arg1_id": "267_T37", "arg2_id": "267_T36", "normalized": [] }, { "id": "267_R14", "type": "Associated_With", "arg1_id": "267_T38", "arg2_id": "267_T36", "normalized": [] }, { "id": "267_R21", "type": "Associated_With", "arg1_id": "267_T45", "arg2_id": "267_T44", "normalized": [] }, { "id": "267_R22", "type": "Associated_With", "arg1_id": "267_T40", "arg2_id": "267_T44", "normalized": [] }, { "id": "267_R5", "type": "Binds_With", "arg1_id": "267_T1", "arg2_id": "267_T5", "normalized": [] }, { "id": "267_R6", "type": "Binds_With", "arg1_id": "267_T1", "arg2_id": "267_T6", "normalized": [] }, { "id": "267_R2", "type": "Binds_With", "arg1_id": "267_T21", "arg2_id": "267_T18", "normalized": [] }, { "id": "267_R3", "type": "Binds_With", "arg1_id": "267_T22", "arg2_id": "267_T18", "normalized": [] }, { "id": "267_R4", "type": "Binds_With", "arg1_id": "267_T23", "arg2_id": "267_T18", "normalized": [] }, { "id": "267_R7", "type": "Binds_With", "arg1_id": "267_T24", "arg2_id": "267_T18", "normalized": [] }, { "id": "267_R8", "type": "Binds_With", "arg1_id": "267_T37", "arg2_id": "267_T34", "normalized": [] }, { "id": "267_R9", "type": "Binds_With", "arg1_id": "267_T38", "arg2_id": "267_T34", "normalized": [] }, { "id": "267_R10", "type": "Binds_With", "arg1_id": "267_T40", "arg2_id": "267_T41", "normalized": [] }, { "id": "267_R11", "type": "Binds_With", "arg1_id": "267_T39", "arg2_id": "267_T41", "normalized": [] } ]

[ { "id": "269", "type": "", "text": [ "\n" ], "offsets": [ [ 0, 1 ] ] } ]

[]

[]

[]

[]

[ { "id": "271", "type": "", "text": [ "\n" ], "offsets": [ [ 0, 1 ] ] } ]

[]

[]

[]

[]

[ { "id": "273", "type": "", "text": [ "A monoclonal antibody (MAb) was produced against the p-nitrophenylphosphate derivative of 3 alpha, 5 beta-lithocholic acid, a transition-state analog for hydrolysis of a steroidal p-nitrophenylcarbonate. The indicated reaction was catalyzed by this Ab with kinetic constants kcat = 4.0 x 10(-2)/min and K(m) = 3.3 microM at pH 9.0 and 35 degrees C. The Ab also hydrolyzed the isomeric p-nitrophenylcarbonate of 3 beta, 5 beta-lithocholic acid with kcat = 8.4 x 10(-2)/min and K(m) = 1.0 microM. Bovine serum albumin (BSA) was found to catalyze the same reactions with similar turnover rates and Michaelis constants of 15 and 14 microM, respectively. Although the BSA-catalyzed reaction was only weakly inhibited by the phosphate ester TSA (IC50 ca. 40 microM), the Ab-catalyzed reaction was completely inhibited at less than 1 microM of the TSA. The relative rates and efficiencies of the MAb-catalyzed and BSA-catalyzed reactions are discussed in the context of the hydrophobic sites and intrinsic reactivity of the protein surfaces, and the induction of groups on the Ab to enhance the enzymatic function. \n" ], "offsets": [ [ 0, 1110 ] ] } ]

[ { "id": "273_T2", "type": "Protein", "text": [ "MAb" ], "offsets": [ [ 23, 26 ] ], "normalized": [] }, { "id": "273_T3", "type": "Chemical", "text": [ "p-nitrophenylphosphate derivative of 3 alpha, 5 beta-lithocholic acid" ], "offsets": [ [ 53, 122 ] ], "normalized": [] }, { "id": "273_T4", "type": "Chemical", "text": [ "steroidal p-nitrophenylcarbonate" ], "offsets": [ [ 170, 202 ] ], "normalized": [] }, { "id": "273_T5", "type": "Protein", "text": [ "Ab" ], "offsets": [ [ 249, 251 ] ], "normalized": [] }, { "id": "273_T7", "type": "Protein", "text": [ "monoclonal antibody" ], "offsets": [ [ 2, 21 ] ], "normalized": [] }, { "id": "273_T8", "type": "Chemical", "text": [ "p-nitrophenylcarbonate of 3 beta, 5 beta-lithocholic acid" ], "offsets": [ [ 385, 442 ] ], "normalized": [] }, { "id": "273_T9", "type": "Species", "text": [ "Bovine" ], "offsets": [ [ 495, 501 ] ], "normalized": [] }, { "id": "273_T11", "type": "Protein", "text": [ "BSA" ], "offsets": [ [ 517, 520 ] ], "normalized": [] }, { "id": "273_T13", "type": "Protein", "text": [ "Ab" ], "offsets": [ [ 353, 355 ] ], "normalized": [] }, { "id": "273_T15", "type": "Chemical", "text": [ "p-nitrophenylcarbonate", "3 alpha, 5 beta-lithocholic acid" ], "offsets": [ [ 180, 202 ], [ 90, 122 ] ], "normalized": [] }, { "id": "273_T18", "type": "Protein", "text": [ "BSA" ], "offsets": [ [ 663, 666 ] ], "normalized": [] }, { "id": "273_T19", "type": "Protein", "text": [ "Ab" ], "offsets": [ [ 765, 767 ] ], "normalized": [] }, { "id": "273_T20", "type": "Chemical", "text": [ "phosphate ester" ], "offsets": [ [ 719, 734 ] ], "normalized": [] }, { "id": "273_T21", "type": "Chemical", "text": [ "TSA" ], "offsets": [ [ 735, 738 ] ], "normalized": [] }, { "id": "273_T23", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 702, 711 ] ], "normalized": [] }, { "id": "273_T24", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 802, 811 ] ], "normalized": [] }, { "id": "273_T25", "type": "Chemical", "text": [ "TSA" ], "offsets": [ [ 841, 844 ] ], "normalized": [] }, { "id": "273_T26", "type": "Protein", "text": [ "MAb" ], "offsets": [ [ 890, 893 ] ], "normalized": [] }, { "id": "273_T27", "type": "Protein", "text": [ "BSA" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "273_T28", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1018, 1025 ] ], "normalized": [] }, { "id": "273_T29", "type": "Protein", "text": [ "Ab" ], "offsets": [ [ 1071, 1073 ] ], "normalized": [] }, { "id": "273_T30", "type": "Protein", "text": [ "enzymatic" ], "offsets": [ [ 1089, 1098 ] ], "normalized": [] }, { "id": "273_T32", "type": "Protein", "text": [ "Bovine serum albumin" ], "offsets": [ [ 495, 515 ] ], "normalized": [] } ]

[]

[]

[ { "id": "273_R13", "type": "Associated_With", "arg1_id": "273_T21", "arg2_id": "273_T23", "normalized": [] }, { "id": "273_R14", "type": "Associated_With", "arg1_id": "273_T3", "arg2_id": "273_T24", "normalized": [] }, { "id": "273_R15", "type": "Associated_With", "arg1_id": "273_T25", "arg2_id": "273_T24", "normalized": [] }, { "id": "273_R16", "type": "Binds_With", "arg1_id": "273_T3", "arg2_id": "273_T7", "normalized": [] }, { "id": "273_R17", "type": "Binds_With", "arg1_id": "273_T3", "arg2_id": "273_T2", "normalized": [] }, { "id": "273_R1", "type": "Binds_With", "arg1_id": "273_T15", "arg2_id": "273_T7", "normalized": [] }, { "id": "273_R2", "type": "Binds_With", "arg1_id": "273_T15", "arg2_id": "273_T2", "normalized": [] }, { "id": "273_R3", "type": "Binds_With", "arg1_id": "273_T8", "arg2_id": "273_T7", "normalized": [] }, { "id": "273_R4", "type": "Binds_With", "arg1_id": "273_T8", "arg2_id": "273_T2", "normalized": [] }, { "id": "273_R5", "type": "Binds_With", "arg1_id": "273_T15", "arg2_id": "273_T5", "normalized": [] }, { "id": "273_R6", "type": "Binds_With", "arg1_id": "273_T15", "arg2_id": "273_T11", "normalized": [] }, { "id": "273_R7", "type": "Binds_With", "arg1_id": "273_T3", "arg2_id": "273_T11", "normalized": [] }, { "id": "273_R11", "type": "Binds_With", "arg1_id": "273_T8", "arg2_id": "273_T5", "normalized": [] }, { "id": "273_R8", "type": "Binds_With", "arg1_id": "273_T8", "arg2_id": "273_T32", "normalized": [] }, { "id": "273_R12", "type": "Binds_With", "arg1_id": "273_T8", "arg2_id": "273_T11", "normalized": [] } ]

[ { "id": "275", "type": "", "text": [ "To clarify the relationship between the occurrence of unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid (UCA), and omega-muricholic acid (omega-MCA) in urine and liver disease severity, urinary bile acids were analyzed by gas-liquid chromatography in acute and late phases of acute hepatitis and before and after ursodeoxycholic acid (UDCA) loading in healthy adults and liver cirrhosis patients. In 11 patients with acute hepatitis, the occurrence rates and amounts of unusual trihydroxy bile acids were increased in the late (recovery) phase, as compared with those in the early phase. In 10 patients with severe acute hepatitis who had prothrombin times exceeding 16 seconds, these bile acids had completely disappeared from the urine in the early phase but reappeared in the late phase in those who had a good outcome, though never in a patient who died. After UDCA administration for a week, the amounts of unusual bile acids, especially UCA and omega-MCA, which are thought to be synthesized through 12 alpha- and 6 alpha-hydroxylations, respectively, from UDCA, were clearly increased in 10 healthy adults but only slightly changed in 10 patients with liver cirrhosis. In conclusion, hepatic hydroxylations of dihydroxy bile acids as a detoxification reaction were impaired in severe liver diseases, which may play a role in the intensification and perpetuation of hepatocellular injuries. \n" ], "offsets": [ [ 0, 1421 ] ] } ]

[ { "id": "275_T1", "type": "Chemical", "text": [ "trihydroxy bile acids" ], "offsets": [ [ 62, 83 ] ], "normalized": [] }, { "id": "275_T2", "type": "Chemical", "text": [ "hyocholic acid" ], "offsets": [ [ 92, 106 ] ], "normalized": [] }, { "id": "275_T3", "type": "Chemical", "text": [ "ursocholic acid" ], "offsets": [ [ 108, 123 ] ], "normalized": [] }, { "id": "275_T4", "type": "Metabolite", "text": [ "trihydroxy bile acids" ], "offsets": [ [ 62, 83 ] ], "normalized": [] }, { "id": "275_T5", "type": "Metabolite", "text": [ "hyocholic acid" ], "offsets": [ [ 92, 106 ] ], "normalized": [] }, { "id": "275_T6", "type": "Metabolite", "text": [ "ursocholic acid" ], "offsets": [ [ 108, 123 ] ], "normalized": [] }, { "id": "275_T7", "type": "Chemical", "text": [ "UCA" ], "offsets": [ [ 125, 128 ] ], "normalized": [] }, { "id": "275_T8", "type": "Metabolite", "text": [ "UCA" ], "offsets": [ [ 125, 128 ] ], "normalized": [] }, { "id": "275_T9", "type": "Chemical", "text": [ "omega-muricholic acid" ], "offsets": [ [ 135, 156 ] ], "normalized": [] }, { "id": "275_T10", "type": "Metabolite", "text": [ "omega-muricholic acid" ], "offsets": [ [ 135, 156 ] ], "normalized": [] }, { "id": "275_T11", "type": "Chemical", "text": [ "omega-MCA" ], "offsets": [ [ 158, 167 ] ], "normalized": [] }, { "id": "275_T12", "type": "Metabolite", "text": [ "omega-MCA" ], "offsets": [ [ 158, 167 ] ], "normalized": [] }, { "id": "275_T14", "type": "Chemical", "text": [ "bile acids" ], "offsets": [ [ 214, 224 ] ], "normalized": [] }, { "id": "275_T17", "type": "Chemical", "text": [ "ursodeoxycholic acid" ], "offsets": [ [ 333, 353 ] ], "normalized": [] }, { "id": "275_T18", "type": "Chemical", "text": [ "UDCA" ], "offsets": [ [ 355, 359 ] ], "normalized": [] }, { "id": "275_T19", "type": "Species", "text": [ "adults" ], "offsets": [ [ 380, 386 ] ], "normalized": [] }, { "id": "275_T21", "type": "Species", "text": [ "patients" ], "offsets": [ [ 424, 432 ] ], "normalized": [] }, { "id": "275_T22", "type": "Species", "text": [ "patients" ], "offsets": [ [ 615, 623 ] ], "normalized": [] }, { "id": "275_T24", "type": "Chemical", "text": [ "trihydroxy bile acids" ], "offsets": [ [ 499, 520 ] ], "normalized": [] }, { "id": "275_T25", "type": "Metabolite", "text": [ "trihydroxy bile acids" ], "offsets": [ [ 499, 520 ] ], "normalized": [] }, { "id": "275_T15", "type": "Species", "text": [ "patients" ], "offsets": [ [ 408, 416 ] ], "normalized": [] }, { "id": "275_T27", "type": "Chemical", "text": [ "bile acids" ], "offsets": [ [ 706, 716 ] ], "normalized": [] }, { "id": "275_T28", "type": "Metabolite", "text": [ "bile acids" ], "offsets": [ [ 706, 716 ] ], "normalized": [] }, { "id": "275_T30", "type": "Chemical", "text": [ "UDCA" ], "offsets": [ [ 887, 891 ] ], "normalized": [] }, { "id": "275_T31", "type": "Chemical", "text": [ "bile acids" ], "offsets": [ [ 942, 952 ] ], "normalized": [] }, { "id": "275_T32", "type": "Chemical", "text": [ "UCA" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "275_T33", "type": "Metabolite", "text": [ "bile acids" ], "offsets": [ [ 942, 952 ] ], "normalized": [] }, { "id": "275_T34", "type": "Metabolite", "text": [ "UCA" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "275_T35", "type": "Chemical", "text": [ "omega-MCA" ], "offsets": [ [ 973, 982 ] ], "normalized": [] }, { "id": "275_T36", "type": "Metabolite", "text": [ "omega-MCA" ], "offsets": [ [ 973, 982 ] ], "normalized": [] }, { "id": "275_T37", "type": "Chemical", "text": [ "UDCA" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "275_T38", "type": "Metabolite", "text": [ "UDCA" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "275_T39", "type": "Species", "text": [ "adults" ], "offsets": [ [ 1128, 1134 ] ], "normalized": [] }, { "id": "275_T40", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1167, 1175 ] ], "normalized": [] }, { "id": "275_T46", "type": "Species", "text": [ "patient" ], "offsets": [ [ 863, 870 ] ], "normalized": [] }, { "id": "275_T47", "type": "Protein", "text": [ "prothrombin" ], "offsets": [ [ 660, 671 ] ], "normalized": [] }, { "id": "275_T48", "type": "Chemical", "text": [ "dihydroxy bile acids" ], "offsets": [ [ 1239, 1259 ] ], "normalized": [] }, { "id": "275_T13", "type": "Biological_Activity", "text": [ "detoxification" ], "offsets": [ [ 1265, 1279 ] ], "normalized": [] } ]

[]

[]

[ { "id": "275_R1", "type": "Isolated_From", "arg1_id": "275_T5", "arg2_id": "275_T19", "normalized": [] }, { "id": "275_R2", "type": "Isolated_From", "arg1_id": "275_T6", "arg2_id": "275_T19", "normalized": [] }, { "id": "275_R3", "type": "Isolated_From", "arg1_id": "275_T8", "arg2_id": "275_T19", "normalized": [] }, { "id": "275_R4", "type": "Isolated_From", "arg1_id": "275_T10", "arg2_id": "275_T19", "normalized": [] }, { "id": "275_R5", "type": "Isolated_From", "arg1_id": "275_T12", "arg2_id": "275_T19", "normalized": [] }, { "id": "275_R6", "type": "Metabolite_Of", "arg1_id": "275_T36", "arg2_id": "275_T37", "normalized": [] }, { "id": "275_R7", "type": "Metabolite_Of", "arg1_id": "275_T34", "arg2_id": "275_T37", "normalized": [] } ]

[ { "id": "277", "type": "", "text": [ "1. Bioactivation of sulphamethoxazole (SMX) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity. We have therefore examined the cellular metabolism, disposition and conjugation of SMX and its metabolites in vitro. 2. Flow cytometry revealed binding of N-hydroxy (SMX-NHOH) and nitroso (SMX-NO) metabolites of SMX, but not of SMX itself, to the surface of viable white blood cells. Cellular haptenation by SMX-NO was reduced by exogenous glutathione (GSH). 3. SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine (CYS), GSH, human peripheral blood cells and plasma, suggesting that this is an important and ubiquitous bioinactivation mechanism. 4. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer, and to a lesser extent, in cells and plasma. 5. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability, with SMX having no effect. Lymphocytes were significantly (P<0.05) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils. 6. Partitioning of SMX-NHOH into red blood cells was significantly (P<0.05) lower than with the hydroxylamine of dapsone. 7. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism. If an imbalance exists, haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur, and may result in drug hypersensitivity. \n" ], "offsets": [ [ 0, 1636 ] ] } ]

[ { "id": "277_T1", "type": "Biological_Activity", "text": [ "Bioactivation" ], "offsets": [ [ 3, 16 ] ], "normalized": [] }, { "id": "277_T2", "type": "Chemical", "text": [ "sulphamethoxazole" ], "offsets": [ [ 20, 37 ] ], "normalized": [] }, { "id": "277_T3", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 39, 42 ] ], "normalized": [] }, { "id": "277_T4", "type": "Metabolite", "text": [ "metabolites" ], "offsets": [ [ 67, 78 ] ], "normalized": [] }, { "id": "277_T5", "type": "Chemical", "text": [ "metabolites" ], "offsets": [ [ 67, 78 ] ], "normalized": [] }, { "id": "277_T7", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 143, 146 ] ], "normalized": [] }, { "id": "277_T12", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 248, 251 ] ], "normalized": [] }, { "id": "277_T13", "type": "Chemical", "text": [ "SMX", "metabolites" ], "offsets": [ [ 248, 251 ], [ 260, 271 ] ], "normalized": [] }, { "id": "277_T14", "type": "Metabolite", "text": [ "SMX", "metabolites" ], "offsets": [ [ 248, 251 ], [ 260, 271 ] ], "normalized": [] }, { "id": "277_T15", "type": "Chemical", "text": [ "N-hydroxy", "metabolites of SMX" ], "offsets": [ [ 320, 329 ], [ 362, 380 ] ], "normalized": [] }, { "id": "277_T16", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "277_T17", "type": "Metabolite", "text": [ "N-hydroxy", "metabolites of SMX" ], "offsets": [ [ 320, 329 ], [ 362, 380 ] ], "normalized": [] }, { "id": "277_T18", "type": "Chemical", "text": [ "SMX-NHOH" ], "offsets": [ [ 331, 339 ] ], "normalized": [] }, { "id": "277_T19", "type": "Metabolite", "text": [ "SMX-NHOH" ], "offsets": [ [ 331, 339 ] ], "normalized": [] }, { "id": "277_T20", "type": "Chemical", "text": [ "nitroso", "metabolites of SMX" ], "offsets": [ [ 345, 352 ], [ 362, 380 ] ], "normalized": [] }, { "id": "277_T21", "type": "Metabolite", "text": [ "nitroso", "metabolites of SMX" ], "offsets": [ [ 345, 352 ], [ 362, 380 ] ], "normalized": [] }, { "id": "277_T22", "type": "Chemical", "text": [ "SMX-NO" ], "offsets": [ [ 354, 360 ] ], "normalized": [] }, { "id": "277_T23", "type": "Metabolite", "text": [ "SMX-NO" ], "offsets": [ [ 354, 360 ] ], "normalized": [] }, { "id": "277_T24", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 394, 397 ] ], "normalized": [] }, { "id": "277_T25", "type": "Biological_Activity", "text": [ "binding" ], "offsets": [ [ 309, 316 ] ], "normalized": [] }, { "id": "277_T27", "type": "Chemical", "text": [ "SMX-NO" ], "offsets": [ [ 474, 480 ] ], "normalized": [] }, { "id": "277_T28", "type": "Metabolite", "text": [ "SMX-NO" ], "offsets": [ [ 474, 480 ] ], "normalized": [] }, { "id": "277_T29", "type": "Chemical", "text": [ "glutathione" ], "offsets": [ [ 506, 517 ] ], "normalized": [] }, { "id": "277_T30", "type": "Chemical", "text": [ "GSH" ], "offsets": [ [ 519, 522 ] ], "normalized": [] }, { "id": "277_T31", "type": "Chemical", "text": [ "SMX-NHOH" ], "offsets": [ [ 528, 536 ] ], "normalized": [] }, { "id": "277_T32", "type": "Metabolite", "text": [ "SMX-NHOH" ], "offsets": [ [ 528, 536 ] ], "normalized": [] }, { "id": "277_T33", "type": "Chemical", "text": [ "SMX-NO" ], "offsets": [ [ 541, 547 ] ], "normalized": [] }, { "id": "277_T34", "type": "Metabolite", "text": [ "SMX-NO" ], "offsets": [ [ 541, 547 ] ], "normalized": [] }, { "id": "277_T35", "type": "Biological_Activity", "text": [ "haptenation" ], "offsets": [ [ 459, 470 ] ], "normalized": [] }, { "id": "277_T36", "type": "Chemical", "text": [ "cysteine" ], "offsets": [ [ 600, 608 ] ], "normalized": [] }, { "id": "277_T37", "type": "Chemical", "text": [ "CYS" ], "offsets": [ [ 610, 613 ] ], "normalized": [] }, { "id": "277_T38", "type": "Chemical", "text": [ "GSH" ], "offsets": [ [ 616, 619 ] ], "normalized": [] }, { "id": "277_T44", "type": "Chemical", "text": [ "SMX-NHOH" ], "offsets": [ [ 774, 782 ] ], "normalized": [] }, { "id": "277_T45", "type": "Metabolite", "text": [ "SMX-NHOH" ], "offsets": [ [ 774, 782 ] ], "normalized": [] }, { "id": "277_T46", "type": "Chemical", "text": [ "SMX-NO" ], "offsets": [ [ 787, 793 ] ], "normalized": [] }, { "id": "277_T47", "type": "Metabolite", "text": [ "SMX-NO" ], "offsets": [ [ 787, 793 ] ], "normalized": [] }, { "id": "277_T48", "type": "Chemical", "text": [ "CYS" ], "offsets": [ [ 803, 806 ] ], "normalized": [] }, { "id": "277_T49", "type": "Chemical", "text": [ "GSH" ], "offsets": [ [ 811, 814 ] ], "normalized": [] }, { "id": "277_T50", "type": "Chemical", "text": [ "buffer" ], "offsets": [ [ 818, 824 ] ], "normalized": [] }, { "id": "277_T52", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 885, 894 ] ], "normalized": [] }, { "id": "277_T53", "type": "Biological_Activity", "text": [ "inhibition" ], "offsets": [ [ 899, 909 ] ], "normalized": [] }, { "id": "277_T54", "type": "Chemical", "text": [ "SMX-NHOH" ], "offsets": [ [ 973, 981 ] ], "normalized": [] }, { "id": "277_T55", "type": "Metabolite", "text": [ "SMX-NHOH" ], "offsets": [ [ 973, 981 ] ], "normalized": [] }, { "id": "277_T56", "type": "Chemical", "text": [ "SMX-NO" ], "offsets": [ [ 986, 992 ] ], "normalized": [] }, { "id": "277_T57", "type": "Metabolite", "text": [ "SMX-NO" ], "offsets": [ [ 986, 992 ] ], "normalized": [] }, { "id": "277_T58", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 1046, 1049 ] ], "normalized": [] }, { "id": "277_T59", "type": "Chemical", "text": [ "SMX-NO" ], "offsets": [ [ 1159, 1165 ] ], "normalized": [] }, { "id": "277_T60", "type": "Metabolite", "text": [ "SMX-NO" ], "offsets": [ [ 1159, 1165 ] ], "normalized": [] }, { "id": "277_T61", "type": "Biological_Activity", "text": [ "cytotoxic" ], "offsets": [ [ 1138, 1147 ] ], "normalized": [] }, { "id": "277_T62", "type": "Chemical", "text": [ "SMX-NHOH" ], "offsets": [ [ 1203, 1211 ] ], "normalized": [] }, { "id": "277_T63", "type": "Metabolite", "text": [ "SMX-NHOH" ], "offsets": [ [ 1203, 1211 ] ], "normalized": [] }, { "id": "277_T64", "type": "Chemical", "text": [ "hydroxylamine of dapsone" ], "offsets": [ [ 1280, 1304 ] ], "normalized": [] }, { "id": "277_T66", "type": "Chemical", "text": [ "SMX" ], "offsets": [ [ 1367, 1370 ] ], "normalized": [] }, { "id": "277_T68", "type": "Chemical", "text": [ "SMX", "metabolites" ], "offsets": [ [ 1367, 1370 ], [ 1384, 1395 ] ], "normalized": [] }, { "id": "277_T69", "type": "Metabolite", "text": [ "SMX", "metabolites" ], "offsets": [ [ 1367, 1370 ], [ 1384, 1395 ] ], "normalized": [] }, { "id": "277_T71", "type": "Biological_Activity", "text": [ "haptenation" ], "offsets": [ [ 1488, 1499 ] ], "normalized": [] }, { "id": "277_T72", "type": "Metabolite", "text": [ "metabolites" ], "offsets": [ [ 1513, 1524 ] ], "normalized": [] }, { "id": "277_T73", "type": "Chemical", "text": [ "metabolites" ], "offsets": [ [ 1513, 1524 ] ], "normalized": [] }, { "id": "277_T74", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 1535, 1543 ] ], "normalized": [] }, { "id": "277_T78", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 94, 101 ] ], "normalized": [] }, { "id": "277_T6", "type": "Chemical", "text": [ "drug" ], "offsets": [ [ 1612, 1616 ] ], "normalized": [] }, { "id": "277_T8", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 205, 215 ] ], "normalized": [] }, { "id": "277_T9", "type": "Biological_Activity", "text": [ "toxic" ], "offsets": [ [ 1378, 1383 ] ], "normalized": [] }, { "id": "277_T10", "type": "Biological_Activity", "text": [ "reduction" ], "offsets": [ [ 1406, 1415 ] ], "normalized": [] }, { "id": "277_T11", "type": "Biological_Activity", "text": [ "toxic" ], "offsets": [ [ 1507, 1512 ] ], "normalized": [] } ]

[]

[]

[ { "id": "277_R1", "type": "Metabolite_Of", "arg1_id": "277_T14", "arg2_id": "277_T2", "normalized": [] }, { "id": "277_R2", "type": "Metabolite_Of", "arg1_id": "277_T14", "arg2_id": "277_T12", "normalized": [] }, { "id": "277_R3", "type": "Associated_With", "arg1_id": "277_T19", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R4", "type": "Associated_With", "arg1_id": "277_T18", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R5", "type": "Associated_With", "arg1_id": "277_T17", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R6", "type": "Associated_With", "arg1_id": "277_T15", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R7", "type": "Associated_With", "arg1_id": "277_T21", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R8", "type": "Associated_With", "arg1_id": "277_T20", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R9", "type": "Associated_With", "arg1_id": "277_T22", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R10", "type": "Associated_With", "arg1_id": "277_T23", "arg2_id": "277_T25", "normalized": [] }, { "id": "277_R14", "type": "Metabolite_Of", "arg1_id": "277_T23", "arg2_id": "277_T24", "normalized": [] }, { "id": "277_R15", "type": "Metabolite_Of", "arg1_id": "277_T19", "arg2_id": "277_T24", "normalized": [] }, { "id": "277_R13", "type": "Metabolite_Of", "arg1_id": "277_T21", "arg2_id": "277_T24", "normalized": [] }, { "id": "277_R16", "type": "Metabolite_Of", "arg1_id": "277_T17", "arg2_id": "277_T24", "normalized": [] }, { "id": "277_R17", "type": "Associated_With", "arg1_id": "277_T27", "arg2_id": "277_T35", "normalized": [] }, { "id": "277_R18", "type": "Associated_With", "arg1_id": "277_T28", "arg2_id": "277_T35", "normalized": [] }, { "id": "277_R43", "type": "Associated_With", "arg1_id": "277_T55", "arg2_id": "277_T52", "normalized": [] }, { "id": "277_R44", "type": "Associated_With", "arg1_id": "277_T54", "arg2_id": "277_T52", "normalized": [] }, { "id": "277_R45", "type": "Associated_With", "arg1_id": "277_T57", "arg2_id": "277_T53", "normalized": [] }, { "id": "277_R46", "type": "Associated_With", "arg1_id": "277_T56", "arg2_id": "277_T53", "normalized": [] }, { "id": "277_R47", "type": "Associated_With", "arg1_id": "277_T60", "arg2_id": "277_T61", "normalized": [] }, { "id": "277_R48", "type": "Associated_With", "arg1_id": "277_T59", "arg2_id": "277_T61", "normalized": [] }, { "id": "277_R53", "type": "Metabolite_Of", "arg1_id": "277_T4", "arg2_id": "277_T2", "normalized": [] }, { "id": "277_R54", "type": "Metabolite_Of", "arg1_id": "277_T4", "arg2_id": "277_T3", "normalized": [] } ]

[ { "id": "279", "type": "", "text": [ "Calcitriol, also known as 1,25-dihydroxy-vitamin D3, is a steroid hormone that has been shown to have effects on cytokine production and lymphocyte proliferation. Coadministration of calcitriol with trivalent influenza vaccine in mice enhanced both mucosal and systemic antibody responses. We studied the effects of calcitriol coadministered with a commercially available influenza vaccine in 175 human volunteers in this double-blind, placebo controlled clinical trial. Subjects that received calcitriol experienced more pain at the injection site compared with placebo recipients. No significant differences in hemagglutination inhibition titers against H1N1, H3N2, or influenza B antigens were detected at 1 or 3 months postvaccination. We conclude that coadministration of 1.0 microg of calcitriol at a site adjacent to influenza vaccination does not enhance humoral immunity in human volunteers. \n" ], "offsets": [ [ 0, 903 ] ] } ]

[ { "id": "279_T1", "type": "Chemical", "text": [ "Calcitriol" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "279_T2", "type": "Chemical", "text": [ "1,25-dihydroxy-vitamin D3" ], "offsets": [ [ 26, 51 ] ], "normalized": [] }, { "id": "279_T3", "type": "Chemical", "text": [ "steroid" ], "offsets": [ [ 58, 65 ] ], "normalized": [] }, { "id": "279_T4", "type": "Biological_Activity", "text": [ "hormone" ], "offsets": [ [ 66, 73 ] ], "normalized": [] }, { "id": "279_T7", "type": "Chemical", "text": [ "calcitriol" ], "offsets": [ [ 183, 193 ] ], "normalized": [] }, { "id": "279_T8", "type": "Species", "text": [ "mice" ], "offsets": [ [ 230, 234 ] ], "normalized": [] }, { "id": "279_T9", "type": "Protein", "text": [ "antibody" ], "offsets": [ [ 270, 278 ] ], "normalized": [] }, { "id": "279_T13", "type": "Chemical", "text": [ "calcitriol" ], "offsets": [ [ 316, 326 ] ], "normalized": [] }, { "id": "279_T14", "type": "Species", "text": [ "human" ], "offsets": [ [ 397, 402 ] ], "normalized": [] }, { "id": "279_T15", "type": "Species", "text": [ "volunteers" ], "offsets": [ [ 403, 413 ] ], "normalized": [] }, { "id": "279_T16", "type": "Chemical", "text": [ "calcitriol" ], "offsets": [ [ 494, 504 ] ], "normalized": [] }, { "id": "279_T17", "type": "Biological_Activity", "text": [ "inhibition" ], "offsets": [ [ 630, 640 ] ], "normalized": [] }, { "id": "279_T18", "type": "Chemical", "text": [ "influenza B antigens" ], "offsets": [ [ 671, 691 ] ], "normalized": [] }, { "id": "279_T19", "type": "Chemical", "text": [ "H1N1", "antigens" ], "offsets": [ [ 656, 660 ], [ 683, 691 ] ], "normalized": [] }, { "id": "279_T20", "type": "Chemical", "text": [ "H3N2", "antigens" ], "offsets": [ [ 662, 666 ], [ 683, 691 ] ], "normalized": [] }, { "id": "279_T21", "type": "Chemical", "text": [ "calcitriol" ], "offsets": [ [ 791, 801 ] ], "normalized": [] }, { "id": "279_T23", "type": "Species", "text": [ "human" ], "offsets": [ [ 884, 889 ] ], "normalized": [] }, { "id": "279_T24", "type": "Species", "text": [ "volunteers" ], "offsets": [ [ 890, 900 ] ], "normalized": [] }, { "id": "279_T5", "type": "Protein", "text": [ "cytokine" ], "offsets": [ [ 113, 121 ] ], "normalized": [] } ]

[]

[]

[ { "id": "279_R5", "type": "Associated_With", "arg1_id": "279_T1", "arg2_id": "279_T4", "normalized": [] }, { "id": "279_R6", "type": "Associated_With", "arg1_id": "279_T2", "arg2_id": "279_T4", "normalized": [] } ]

[ { "id": "281", "type": "", "text": [ "To examine the stereospecific effects of lipoic compounds on pyruvate metabolism, the effects of R-lipoic acid (R-LA), S-lipoic acid (S-LA) and 1,2-diselenolane-3-pentanoic acid (Se-LA) on the activities of the mammalian pyruvate dehydrogenase complex (PDC) and its catalytic components were investigated. Both S-LA and R-LA markedly inhibited PDC activity; whereas Se-LA displayed inhibition only at higher concentrations. Examination of the effects on the individual catalytic components indicated that Se-LA inhibited the pyruvate dehydrogenase component; whereas R-LA and S-LA inhibited the dihydrolipoamide acetyltransferase component. The three lipoic compounds lowered dihydrolipoamide dehydrogrenase (E3) activity in the forward reaction by about 30 to 45%. The kinetic data of E3 showed that both R-LA and Se-LA are used as substrates by E3 for the reverse reaction. Decarboxylation of [1-14C]pyruvate via PDC by cultured HepG2 cells was not affected by R-LA, but moderately decreased with S-LA and Se-LA. These findings indicate that (i) purified PDC and its catalytic components are affected by lipoic compounds based on their stereoselectivity; and (ii) the oxidation of pyruvate by intact HepG2 cells is not inhibited by R-LA. The later finding with the intact cells is in support of therapeutic role of R-LA as an antioxidant. \n" ], "offsets": [ [ 0, 1344 ] ] } ]

[ { "id": "281_T1", "type": "Chemical", "text": [ "pyruvate" ], "offsets": [ [ 61, 69 ] ], "normalized": [] }, { "id": "281_T2", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 70, 80 ] ], "normalized": [] }, { "id": "281_T3", "type": "Chemical", "text": [ "lipoic compounds" ], "offsets": [ [ 41, 57 ] ], "normalized": [] }, { "id": "281_T4", "type": "Chemical", "text": [ "R-lipoic acid" ], "offsets": [ [ 97, 110 ] ], "normalized": [] }, { "id": "281_T5", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "281_T6", "type": "Chemical", "text": [ "S-lipoic acid" ], "offsets": [ [ 119, 132 ] ], "normalized": [] }, { "id": "281_T7", "type": "Chemical", "text": [ "S-LA" ], "offsets": [ [ 134, 138 ] ], "normalized": [] }, { "id": "281_T8", "type": "Chemical", "text": [ "1,2-diselenolane-3-pentanoic acid" ], "offsets": [ [ 144, 177 ] ], "normalized": [] }, { "id": "281_T9", "type": "Chemical", "text": [ "Se-LA" ], "offsets": [ [ 179, 184 ] ], "normalized": [] }, { "id": "281_T10", "type": "Species", "text": [ "mammalian" ], "offsets": [ [ 211, 220 ] ], "normalized": [] }, { "id": "281_T11", "type": "Protein", "text": [ "pyruvate dehydrogenase complex" ], "offsets": [ [ 221, 251 ] ], "normalized": [] }, { "id": "281_T12", "type": "Protein", "text": [ "PDC" ], "offsets": [ [ 253, 256 ] ], "normalized": [] }, { "id": "281_T13", "type": "Chemical", "text": [ "S-LA" ], "offsets": [ [ 311, 315 ] ], "normalized": [] }, { "id": "281_T14", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "281_T15", "type": "Protein", "text": [ "PDC" ], "offsets": [ [ 344, 347 ] ], "normalized": [] }, { "id": "281_T16", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 334, 343 ] ], "normalized": [] }, { "id": "281_T17", "type": "Chemical", "text": [ "Se-LA" ], "offsets": [ [ 366, 371 ] ], "normalized": [] }, { "id": "281_T18", "type": "Chemical", "text": [ "Se-LA" ], "offsets": [ [ 505, 510 ] ], "normalized": [] }, { "id": "281_T19", "type": "Protein", "text": [ "pyruvate dehydrogenase" ], "offsets": [ [ 525, 547 ] ], "normalized": [] }, { "id": "281_T21", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 511, 520 ] ], "normalized": [] }, { "id": "281_T22", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 567, 571 ] ], "normalized": [] }, { "id": "281_T23", "type": "Chemical", "text": [ "S-LA" ], "offsets": [ [ 576, 580 ] ], "normalized": [] }, { "id": "281_T24", "type": "Protein", "text": [ "dihydrolipoamide acetyltransferase" ], "offsets": [ [ 595, 629 ] ], "normalized": [] }, { "id": "281_T26", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 581, 590 ] ], "normalized": [] }, { "id": "281_T27", "type": "Chemical", "text": [ "lipoic compounds" ], "offsets": [ [ 651, 667 ] ], "normalized": [] }, { "id": "281_T28", "type": "Protein", "text": [ "dihydrolipoamide dehydrogrenase" ], "offsets": [ [ 676, 708 ] ], "normalized": [] }, { "id": "281_T29", "type": "Protein", "text": [ "E3" ], "offsets": [ [ 710, 712 ] ], "normalized": [] }, { "id": "281_T34", "type": "Protein", "text": [ "E3" ], "offsets": [ [ 787, 789 ] ], "normalized": [] }, { "id": "281_T36", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 807, 811 ] ], "normalized": [] }, { "id": "281_T37", "type": "Chemical", "text": [ "Se-LA" ], "offsets": [ [ 816, 821 ] ], "normalized": [] }, { "id": "281_T39", "type": "Chemical", "text": [ "[1-14C]pyruvate" ], "offsets": [ [ 896, 911 ] ], "normalized": [] }, { "id": "281_T40", "type": "Chemical", "text": [ "pyruvate" ], "offsets": [ [ 903, 911 ] ], "normalized": [] }, { "id": "281_T41", "type": "Protein", "text": [ "PDC" ], "offsets": [ [ 916, 919 ] ], "normalized": [] }, { "id": "281_T42", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 965, 969 ] ], "normalized": [] }, { "id": "281_T43", "type": "Chemical", "text": [ "S-LA" ], "offsets": [ [ 1001, 1005 ] ], "normalized": [] }, { "id": "281_T44", "type": "Chemical", "text": [ "Se-LA" ], "offsets": [ [ 1010, 1015 ] ], "normalized": [] }, { "id": "281_T46", "type": "Protein", "text": [ "PDC" ], "offsets": [ [ 1059, 1062 ] ], "normalized": [] }, { "id": "281_T47", "type": "Chemical", "text": [ "lipoic compounds" ], "offsets": [ [ 1108, 1124 ] ], "normalized": [] }, { "id": "281_T48", "type": "Chemical", "text": [ "pyruvate" ], "offsets": [ [ 1185, 1193 ] ], "normalized": [] }, { "id": "281_T50", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 1236, 1240 ] ], "normalized": [] }, { "id": "281_T51", "type": "Chemical", "text": [ "R-LA" ], "offsets": [ [ 1319, 1323 ] ], "normalized": [] }, { "id": "281_T52", "type": "Biological_Activity", "text": [ "antioxidant" ], "offsets": [ [ 1330, 1341 ] ], "normalized": [] }, { "id": "281_T20", "type": "Biological_Activity", "text": [ "dehydrogrenase" ], "offsets": [ [ 694, 708 ] ], "normalized": [] }, { "id": "281_T25", "type": "Biological_Activity", "text": [ "oxidation" ], "offsets": [ [ 1172, 1181 ] ], "normalized": [] } ]

[]

[]

[ { "id": "281_R1", "type": "Associated_With", "arg1_id": "281_T13", "arg2_id": "281_T16", "normalized": [] }, { "id": "281_R2", "type": "Associated_With", "arg1_id": "281_T14", "arg2_id": "281_T16", "normalized": [] }, { "id": "281_R3", "type": "Associated_With", "arg1_id": "281_T17", "arg2_id": "281_T16", "normalized": [] }, { "id": "281_R4", "type": "Associated_With", "arg1_id": "281_T18", "arg2_id": "281_T21", "normalized": [] }, { "id": "281_R7", "type": "Associated_With", "arg1_id": "281_T23", "arg2_id": "281_T26", "normalized": [] }, { "id": "281_R28", "type": "Associated_With", "arg1_id": "281_T51", "arg2_id": "281_T52", "normalized": [] }, { "id": "281_R32", "type": "Binds_With", "arg1_id": "281_T13", "arg2_id": "281_T15", "normalized": [] }, { "id": "281_R33", "type": "Binds_With", "arg1_id": "281_T14", "arg2_id": "281_T15", "normalized": [] }, { "id": "281_R29", "type": "Binds_With", "arg1_id": "281_T17", "arg2_id": "281_T15", "normalized": [] }, { "id": "281_R30", "type": "Binds_With", "arg1_id": "281_T18", "arg2_id": "281_T19", "normalized": [] }, { "id": "281_R5", "type": "Binds_With", "arg1_id": "281_T23", "arg2_id": "281_T24", "normalized": [] }, { "id": "281_R31", "type": "Binds_With", "arg1_id": "281_T22", "arg2_id": "281_T24", "normalized": [] }, { "id": "281_R6", "type": "Associated_With", "arg1_id": "281_T22", "arg2_id": "281_T26", "normalized": [] }, { "id": "281_R9", "type": "Binds_With", "arg1_id": "281_T18", "arg2_id": "281_T29", "normalized": [] }, { "id": "281_R8", "type": "Binds_With", "arg1_id": "281_T18", "arg2_id": "281_T28", "normalized": [] }, { "id": "281_R16", "type": "Binds_With", "arg1_id": "281_T22", "arg2_id": "281_T28", "normalized": [] }, { "id": "281_R17", "type": "Binds_With", "arg1_id": "281_T23", "arg2_id": "281_T28", "normalized": [] }, { "id": "281_R18", "type": "Binds_With", "arg1_id": "281_T22", "arg2_id": "281_T29", "normalized": [] }, { "id": "281_R20", "type": "Binds_With", "arg1_id": "281_T23", "arg2_id": "281_T29", "normalized": [] }, { "id": "281_R19", "type": "Binds_With", "arg1_id": "281_T36", "arg2_id": "281_T34", "normalized": [] }, { "id": "281_R21", "type": "Binds_With", "arg1_id": "281_T37", "arg2_id": "281_T34", "normalized": [] } ]

[ { "id": "283", "type": "", "text": [ "A highly sensitive pre-column HPLC method for simultaneous determination of prolyl dipeptides, Pro and Hyp in urine was developed. The analytes were labelled with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70 degrees C for 20 min. The derivatives separated on tandem reversed-phase columns by a gradient elution and were monitored with fluorescence detection at 318 nm (excitation) and 392 nm (emission). The detection limits for prolyl dipeptides, Pro and Hyp were 1-5 fmol/injection (S/N = 3). Urine samples were treated with o-phthalaldehyde, followed by purification on a Bond Elut C18 column before conducting the labelling reaction. Pro-Hyp, Pro-Gly and Pro-Pro were identified as prolyl dipeptides in urine. The within-day and between-day relative standard deviations were 1.5-4.8 and 1.7-5.8%, respectively. The concentrations of Pro-Hyp, Pro-Gly, Pro-Pro, Pro and Hyp in normal human urine were 97.6 +/- 28.2, 2.74 +/- 1.48, 2.08 +/- 1.13, 6.71 +/- 3.34 and 2.30 +/- 1.59 nmol/mg creatinine, respectively. \n" ], "offsets": [ [ 0, 1046 ] ] } ]

[ { "id": "283_T1", "type": "Chemical", "text": [ "prolyl dipeptides" ], "offsets": [ [ 76, 93 ] ], "normalized": [] }, { "id": "283_T2", "type": "Chemical", "text": [ "Pro" ], "offsets": [ [ 95, 98 ] ], "normalized": [] }, { "id": "283_T3", "type": "Species", "text": [ "Hyp" ], "offsets": [ [ 103, 106 ] ], "normalized": [] }, { "id": "283_T4", "type": "Chemical", "text": [ "analytes" ], "offsets": [ [ 135, 143 ] ], "normalized": [] }, { "id": "283_T5", "type": "Chemical", "text": [ "4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride" ], "offsets": [ [ 163, 230 ] ], "normalized": [] }, { "id": "283_T6", "type": "Chemical", "text": [ "derivatives" ], "offsets": [ [ 263, 274 ] ], "normalized": [] }, { "id": "283_T7", "type": "Chemical", "text": [ "prolyl dipeptides" ], "offsets": [ [ 459, 476 ] ], "normalized": [] }, { "id": "283_T8", "type": "Chemical", "text": [ "Pro" ], "offsets": [ [ 478, 481 ] ], "normalized": [] }, { "id": "283_T9", "type": "Chemical", "text": [ "Hyp" ], "offsets": [ [ 486, 489 ] ], "normalized": [] }, { "id": "283_T10", "type": "Metabolite", "text": [ "prolyl dipeptides" ], "offsets": [ [ 76, 93 ] ], "normalized": [] }, { "id": "283_T11", "type": "Metabolite", "text": [ "Pro" ], "offsets": [ [ 95, 98 ] ], "normalized": [] }, { "id": "283_T12", "type": "Metabolite", "text": [ "Hyp" ], "offsets": [ [ 103, 106 ] ], "normalized": [] }, { "id": "283_T13", "type": "Metabolite", "text": [ "prolyl dipeptides" ], "offsets": [ [ 459, 476 ] ], "normalized": [] }, { "id": "283_T14", "type": "Metabolite", "text": [ "Pro" ], "offsets": [ [ 478, 481 ] ], "normalized": [] }, { "id": "283_T15", "type": "Metabolite", "text": [ "Hyp" ], "offsets": [ [ 486, 489 ] ], "normalized": [] }, { "id": "283_T16", "type": "Chemical", "text": [ "o-phthalaldehyde" ], "offsets": [ [ 557, 573 ] ], "normalized": [] }, { "id": "283_T17", "type": "Chemical", "text": [ "Pro-Hyp" ], "offsets": [ [ 668, 675 ] ], "normalized": [] }, { "id": "283_T18", "type": "Chemical", "text": [ "Pro-Gly" ], "offsets": [ [ 677, 684 ] ], "normalized": [] }, { "id": "283_T19", "type": "Chemical", "text": [ "Pro-Pro" ], "offsets": [ [ 689, 696 ] ], "normalized": [] }, { "id": "283_T20", "type": "Metabolite", "text": [ "Pro-Hyp" ], "offsets": [ [ 668, 675 ] ], "normalized": [] }, { "id": "283_T21", "type": "Metabolite", "text": [ "Pro-Gly" ], "offsets": [ [ 677, 684 ] ], "normalized": [] }, { "id": "283_T22", "type": "Metabolite", "text": [ "Pro-Pro" ], "offsets": [ [ 689, 696 ] ], "normalized": [] }, { "id": "283_T23", "type": "Metabolite", "text": [ "prolyl dipeptides" ], "offsets": [ [ 716, 733 ] ], "normalized": [] }, { "id": "283_T24", "type": "Chemical", "text": [ "prolyl dipeptides" ], "offsets": [ [ 716, 733 ] ], "normalized": [] }, { "id": "283_T25", "type": "Species", "text": [ "human" ], "offsets": [ [ 916, 921 ] ], "normalized": [] }, { "id": "283_T26", "type": "Metabolite", "text": [ "Pro-Hyp" ], "offsets": [ [ 867, 874 ] ], "normalized": [] }, { "id": "283_T27", "type": "Metabolite", "text": [ "Pro-Gly" ], "offsets": [ [ 876, 883 ] ], "normalized": [] }, { "id": "283_T28", "type": "Metabolite", "text": [ "Pro-Pro" ], "offsets": [ [ 885, 892 ] ], "normalized": [] }, { "id": "283_T29", "type": "Metabolite", "text": [ "Pro" ], "offsets": [ [ 894, 897 ] ], "normalized": [] }, { "id": "283_T30", "type": "Metabolite", "text": [ "Hyp" ], "offsets": [ [ 902, 905 ] ], "normalized": [] }, { "id": "283_T31", "type": "Chemical", "text": [ "Pro-Hyp" ], "offsets": [ [ 867, 874 ] ], "normalized": [] }, { "id": "283_T32", "type": "Chemical", "text": [ "Pro-Gly" ], "offsets": [ [ 876, 883 ] ], "normalized": [] }, { "id": "283_T33", "type": "Chemical", "text": [ "Pro-Pro" ], "offsets": [ [ 885, 892 ] ], "normalized": [] }, { "id": "283_T34", "type": "Chemical", "text": [ "Pro" ], "offsets": [ [ 894, 897 ] ], "normalized": [] }, { "id": "283_T35", "type": "Chemical", "text": [ "Hyp" ], "offsets": [ [ 902, 905 ] ], "normalized": [] }, { "id": "283_T36", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 1019, 1029 ] ], "normalized": [] } ]

[]

[]

[ { "id": "283_R1", "type": "Isolated_From", "arg1_id": "283_T26", "arg2_id": "283_T25", "normalized": [] }, { "id": "283_R2", "type": "Isolated_From", "arg1_id": "283_T27", "arg2_id": "283_T25", "normalized": [] }, { "id": "283_R3", "type": "Isolated_From", "arg1_id": "283_T28", "arg2_id": "283_T25", "normalized": [] }, { "id": "283_R4", "type": "Isolated_From", "arg1_id": "283_T29", "arg2_id": "283_T25", "normalized": [] }, { "id": "283_R5", "type": "Isolated_From", "arg1_id": "283_T30", "arg2_id": "283_T25", "normalized": [] } ]

[ { "id": "285", "type": "", "text": [ "1. The metabolism of loxtidine (1-methyl-5-[3-[3-[(1-piperidinyl) methyl] phenoxy] propyl] amino-1H-1,2,4-triazole-3-methanol) was studied in freshly isolated rat, dog and human hepatocytes. Metabolism in vitro was comparable with previously available in vivo data in all three species with the marked species differences observed in vivo being reproduced in the hepatocyte model. 2. The major route for the metabolism of loxtidine by rat hepatocytes was N-dealkylation to form the propionic acid and hydroxymethyl triazole metabolites. A minor metabolic route was the oxidation of loxtidine to a carboxylic acid metabolite. The major route of metabolism for loxtidine in dog hepatocytes was glucuronidation with oxidation to the carboxylic acid metabolite being of minor importance. Incubation of loxtidine with human hepatocytes resulted in the drug remaining largely unchanged but with the carboxylic acid metabolite being produced in minor amounts. 3. In vitro studies were undertaken with rat, dog and human hepatocytes to determine the Michaelis-Menten parameters Vmax and Km for the sum of all the metabolic pathways. These kinetic parameters were used to calculate the intrinsic clearance of loxtidine. Using appropriate scaling factors, the predicted in vivo hepatic clearance was then calculated. The predicted intrinsic clearances were 51.4 +/- 12.4, 8.0 +/- 0.8 and 1.0 +/- 0.6 ml/min/kg for rat, dog and human hepatocytes respectively. These data were then used to calculate hepatic clearances of 24.5, 3.1 and 0.2 ml/min/kg for rat, dog and man respectively. 4. In vivo hepatic and intrinsic clearances for loxtidine were determined in rat, dog and human volunteers. The hepatic clearances of loxtidine were 26.6, 6.6 and 0.4 ml/min/kg in rat, dog and man respectively and intrinsic clearances were 58.5, 18.6 and 2.0 ml/min/kg in rat, dog and man respectively. 5. The present studies demonstrate that the hepatocyte model may be a valuable in vitro tool for predicting both qualitative and quantitative aspects of the metabolism of a drug in animals and man at an early stage of the drug development process. \n" ], "offsets": [ [ 0, 2128 ] ] } ]

[ { "id": "285_T1", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 21, 30 ] ], "normalized": [] }, { "id": "285_T2", "type": "Chemical", "text": [ "1-methyl-5-[3-[3-[(1-piperidinyl) methyl] phenoxy] propyl] amino-1H-1,2,4-triazole-3-methanol" ], "offsets": [ [ 32, 125 ] ], "normalized": [] }, { "id": "285_T3", "type": "Species", "text": [ "rat" ], "offsets": [ [ 159, 162 ] ], "normalized": [] }, { "id": "285_T4", "type": "Species", "text": [ "dog" ], "offsets": [ [ 164, 167 ] ], "normalized": [] }, { "id": "285_T5", "type": "Species", "text": [ "human" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "285_T6", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 423, 432 ] ], "normalized": [] }, { "id": "285_T7", "type": "Species", "text": [ "rat" ], "offsets": [ [ 436, 439 ] ], "normalized": [] }, { "id": "285_T8", "type": "Chemical", "text": [ "propionic acid", "metabolite" ], "offsets": [ [ 483, 497 ], [ 525, 535 ] ], "normalized": [] }, { "id": "285_T9", "type": "Metabolite", "text": [ "propionic acid", "metabolite" ], "offsets": [ [ 483, 497 ], [ 525, 535 ] ], "normalized": [] }, { "id": "285_T10", "type": "Chemical", "text": [ "hydroxymethyl triazole metabolite" ], "offsets": [ [ 502, 535 ] ], "normalized": [] }, { "id": "285_T11", "type": "Metabolite", "text": [ "hydroxymethyl triazole metabolite" ], "offsets": [ [ 502, 535 ] ], "normalized": [] }, { "id": "285_T14", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 583, 592 ] ], "normalized": [] }, { "id": "285_T15", "type": "Metabolite", "text": [ "carboxylic acid metabolite" ], "offsets": [ [ 598, 624 ] ], "normalized": [] }, { "id": "285_T16", "type": "Chemical", "text": [ "carboxylic acid metabolite" ], "offsets": [ [ 598, 624 ] ], "normalized": [] }, { "id": "285_T17", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 660, 669 ] ], "normalized": [] }, { "id": "285_T18", "type": "Species", "text": [ "dog" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "285_T21", "type": "Chemical", "text": [ "carboxylic acid metabolite" ], "offsets": [ [ 731, 757 ] ], "normalized": [] }, { "id": "285_T22", "type": "Metabolite", "text": [ "carboxylic acid metabolite" ], "offsets": [ [ 731, 757 ] ], "normalized": [] }, { "id": "285_T23", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 799, 808 ] ], "normalized": [] }, { "id": "285_T24", "type": "Species", "text": [ "human" ], "offsets": [ [ 814, 819 ] ], "normalized": [] }, { "id": "285_T25", "type": "Chemical", "text": [ "drug" ], "offsets": [ [ 848, 852 ] ], "normalized": [] }, { "id": "285_T27", "type": "Metabolite", "text": [ "carboxylic acid metabolite" ], "offsets": [ [ 894, 920 ] ], "normalized": [] }, { "id": "285_T28", "type": "Chemical", "text": [ "carboxylic acid metabolite" ], "offsets": [ [ 894, 920 ] ], "normalized": [] }, { "id": "285_T29", "type": "Species", "text": [ "rat" ], "offsets": [ [ 995, 998 ] ], "normalized": [] }, { "id": "285_T30", "type": "Species", "text": [ "dog" ], "offsets": [ [ 1000, 1003 ] ], "normalized": [] }, { "id": "285_T31", "type": "Species", "text": [ "human" ], "offsets": [ [ 1009, 1014 ] ], "normalized": [] }, { "id": "285_T32", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 1202, 1211 ] ], "normalized": [] }, { "id": "285_T33", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1406, 1409 ] ], "normalized": [] }, { "id": "285_T34", "type": "Species", "text": [ "dog" ], "offsets": [ [ 1411, 1414 ] ], "normalized": [] }, { "id": "285_T35", "type": "Species", "text": [ "human" ], "offsets": [ [ 1419, 1424 ] ], "normalized": [] }, { "id": "285_T36", "type": "Species", "text": [ "dog" ], "offsets": [ [ 1549, 1554 ] ], "normalized": [] }, { "id": "285_T37", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1544, 1547 ] ], "normalized": [] }, { "id": "285_T38", "type": "Species", "text": [ "man" ], "offsets": [ [ 1558, 1561 ] ], "normalized": [] }, { "id": "285_T39", "type": "Chemical", "text": [ "loxtidine" ], "offsets": [ [ 1624, 1633 ] ], "normalized": [] }, { "id": "285_T40", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1653, 1656 ] ], "normalized": [] }, { "id": "285_T41", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1756, 1759 ] ], "normalized": [] }, { "id": "285_T42", "type": "Species", "text": [ "dog" ], "offsets": [ [ 1761, 1764 ] ], "normalized": [] }, { "id": "285_T43", "type": "Species", "text": [ "dog" ], "offsets": [ [ 1658, 1661 ] ], "normalized": [] }, { "id": "285_T44", "type": "Species", "text": [ "human" ], "offsets": [ [ 1666, 1671 ] ], "normalized": [] }, { "id": "285_T45", "type": "Species", "text": [ "man" ], "offsets": [ [ 1769, 1772 ] ], "normalized": [] }, { "id": "285_T46", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1848, 1851 ] ], "normalized": [] }, { "id": "285_T47", "type": "Species", "text": [ "dog" ], "offsets": [ [ 1853, 1856 ] ], "normalized": [] }, { "id": "285_T48", "type": "Species", "text": [ "man" ], "offsets": [ [ 1861, 1864 ] ], "normalized": [] }, { "id": "285_T49", "type": "Chemical", "text": [ "drug" ], "offsets": [ [ 2052, 2056 ] ], "normalized": [] }, { "id": "285_T50", "type": "Species", "text": [ "man" ], "offsets": [ [ 2072, 2075 ] ], "normalized": [] }, { "id": "285_T51", "type": "Chemical", "text": [ "drug" ], "offsets": [ [ 2101, 2105 ] ], "normalized": [] }, { "id": "285_T52", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 2036, 2046 ] ], "normalized": [] }, { "id": "285_T53", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 645, 655 ] ], "normalized": [] }, { "id": "285_T54", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 409, 419 ] ], "normalized": [] }, { "id": "285_T55", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 7, 17 ] ], "normalized": [] }, { "id": "285_T56", "type": "Biological_Activity", "text": [ "Metabolism" ], "offsets": [ [ 191, 201 ] ], "normalized": [] }, { "id": "285_T57", "type": "Species", "text": [ "volunteers" ], "offsets": [ [ 1672, 1682 ] ], "normalized": [] }, { "id": "285_T58", "type": "Species", "text": [ "animals" ], "offsets": [ [ 2060, 2067 ] ], "normalized": [] }, { "id": "285_T12", "type": "Biological_Activity", "text": [ "metabolic" ], "offsets": [ [ 1107, 1116 ] ], "normalized": [] } ]

[]

[]

[ { "id": "285_R1", "type": "Metabolite_Of", "arg1_id": "285_T9", "arg2_id": "285_T6", "normalized": [] }, { "id": "285_R2", "type": "Metabolite_Of", "arg1_id": "285_T11", "arg2_id": "285_T6", "normalized": [] }, { "id": "285_R3", "type": "Metabolite_Of", "arg1_id": "285_T15", "arg2_id": "285_T14", "normalized": [] }, { "id": "285_R4", "type": "Isolated_From", "arg1_id": "285_T9", "arg2_id": "285_T7", "normalized": [] }, { "id": "285_R5", "type": "Isolated_From", "arg1_id": "285_T11", "arg2_id": "285_T7", "normalized": [] }, { "id": "285_R6", "type": "Isolated_From", "arg1_id": "285_T15", "arg2_id": "285_T7", "normalized": [] }, { "id": "285_R7", "type": "Isolated_From", "arg1_id": "285_T22", "arg2_id": "285_T18", "normalized": [] }, { "id": "285_R8", "type": "Metabolite_Of", "arg1_id": "285_T22", "arg2_id": "285_T17", "normalized": [] }, { "id": "285_R10", "type": "Isolated_From", "arg1_id": "285_T27", "arg2_id": "285_T24", "normalized": [] }, { "id": "285_R11", "type": "Metabolite_Of", "arg1_id": "285_T27", "arg2_id": "285_T23", "normalized": [] } ]

[ { "id": "287", "type": "", "text": [ "Our development of vaccines to prevent shigellosis is based on the hypothesis that a critical (protective) level of serum IgG to the O-specific polysaccharide (O-SP) domain of Shigella lipopolysaccharide (LPS) confers immunity. The O-SP is a hapten and must be conjugated to a protein to induce serum antibodies. The O-SP of Shigella dysenteriae type 1 (approximately 27 tetrasaccharide repeat units), prepared by acid hydrolysis of the LPS, was bound to human serum albumin (HSA) by multiple point attachment (O-SP-HSA): The molar ratio of HSA to O-SP was 1.0. Synthetic saccharides, composed of one or multiples of the O-SP tetrasaccharide, equipped with a spacer at their reducing end, were bound to HSA by a single point attachment: The average molar ratios of the saccharides to HSA ranged from 4 to 24. Serum IgG anti-LPS, elicited in mice by O-SP-HSA or synthetic tetra-, octa-, dodeca-, and hexadecasaccharide fragments, was measured by ELISA. Outbred 6-week-old female mice were injected s.c. three times at biweekly intervals with 2.5 micrograms of saccharide as a conjugate and were bled 7 days after the second and third injections. Excepting the tetramer, conjugates of the octamer, dodecamer and hexadecamer elicited IgG LPS antibodies after the second injection, a statistically significant rise (booster) after the third injection, and higher levels than those vaccinated with O-SP-HSA (P = 0.0001). The highest geometric mean levels of IgG anti-LPS were elicited by the hexadecamer with 9 chains or 9 moles of saccharide/HSA (15.5 ELISA units) followed by the octamer with 20 chains (11.1 ELISA units) and the dodecamer with 10 chains (9.52 ELISA units). Clinical evaluation of these synthetic saccharides bound to a medically useful carrier is planned. \n" ], "offsets": [ [ 0, 1780 ] ] } ]

[ { "id": "287_T2", "type": "Protein", "text": [ "IgG" ], "offsets": [ [ 122, 125 ] ], "normalized": [] }, { "id": "287_T3", "type": "Chemical", "text": [ "O-specific polysaccharide" ], "offsets": [ [ 133, 158 ] ], "normalized": [] }, { "id": "287_T4", "type": "Species", "text": [ "Shigella" ], "offsets": [ [ 177, 185 ] ], "normalized": [] }, { "id": "287_T5", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 161, 165 ] ], "normalized": [] }, { "id": "287_T6", "type": "Chemical", "text": [ "lipopolysaccharide" ], "offsets": [ [ 186, 204 ] ], "normalized": [] }, { "id": "287_T7", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 206, 209 ] ], "normalized": [] }, { "id": "287_T8", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 233, 237 ] ], "normalized": [] }, { "id": "287_T9", "type": "Biological_Activity", "text": [ "hapten" ], "offsets": [ [ 244, 250 ] ], "normalized": [] }, { "id": "287_T10", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 279, 286 ] ], "normalized": [] }, { "id": "287_T11", "type": "Biological_Activity", "text": [ "induce" ], "offsets": [ [ 290, 296 ] ], "normalized": [] }, { "id": "287_T12", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 303, 313 ] ], "normalized": [] }, { "id": "287_T13", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 319, 323 ] ], "normalized": [] }, { "id": "287_T14", "type": "Species", "text": [ "Shigella dysenteriae type 1" ], "offsets": [ [ 327, 354 ] ], "normalized": [] }, { "id": "287_T15", "type": "Chemical", "text": [ "tetrasaccharide" ], "offsets": [ [ 373, 388 ] ], "normalized": [] }, { "id": "287_T16", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 416, 420 ] ], "normalized": [] }, { "id": "287_T17", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 439, 442 ] ], "normalized": [] }, { "id": "287_T18", "type": "Protein", "text": [ "human serum albumin" ], "offsets": [ [ 457, 476 ] ], "normalized": [] }, { "id": "287_T19", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 478, 481 ] ], "normalized": [] }, { "id": "287_T20", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 513, 517 ] ], "normalized": [] }, { "id": "287_T21", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 518, 521 ] ], "normalized": [] }, { "id": "287_T22", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 543, 546 ] ], "normalized": [] }, { "id": "287_T23", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 550, 554 ] ], "normalized": [] }, { "id": "287_T24", "type": "Chemical", "text": [ "saccharides" ], "offsets": [ [ 574, 585 ] ], "normalized": [] }, { "id": "287_T25", "type": "Chemical", "text": [ "O-SP tetrasaccharide" ], "offsets": [ [ 623, 643 ] ], "normalized": [] }, { "id": "287_T26", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 706, 709 ] ], "normalized": [] }, { "id": "287_T27", "type": "Chemical", "text": [ "saccharides" ], "offsets": [ [ 772, 783 ] ], "normalized": [] }, { "id": "287_T28", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "287_T29", "type": "Protein", "text": [ "IgG anti-LPS" ], "offsets": [ [ 818, 830 ] ], "normalized": [] }, { "id": "287_T30", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 827, 830 ] ], "normalized": [] }, { "id": "287_T31", "type": "Species", "text": [ "mice" ], "offsets": [ [ 844, 848 ] ], "normalized": [] }, { "id": "287_T32", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 852, 856 ] ], "normalized": [] }, { "id": "287_T33", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 857, 860 ] ], "normalized": [] }, { "id": "287_T34", "type": "Chemical", "text": [ "tetra", "saccharide" ], "offsets": [ [ 874, 879 ], [ 911, 921 ] ], "normalized": [] }, { "id": "287_T35", "type": "Chemical", "text": [ "octa", "saccharide" ], "offsets": [ [ 882, 886 ], [ 911, 921 ] ], "normalized": [] }, { "id": "287_T36", "type": "Chemical", "text": [ "dodeca", "saccharide" ], "offsets": [ [ 890, 896 ], [ 911, 921 ] ], "normalized": [] }, { "id": "287_T37", "type": "Chemical", "text": [ "hexadecasaccharide" ], "offsets": [ [ 903, 921 ] ], "normalized": [] }, { "id": "287_T38", "type": "Species", "text": [ "mice" ], "offsets": [ [ 982, 986 ] ], "normalized": [] }, { "id": "287_T39", "type": "Chemical", "text": [ "saccharide" ], "offsets": [ [ 1064, 1074 ] ], "normalized": [] }, { "id": "287_T40", "type": "Chemical", "text": [ "conjugate" ], "offsets": [ [ 1080, 1089 ] ], "normalized": [] }, { "id": "287_T41", "type": "Chemical", "text": [ "tetramer" ], "offsets": [ [ 1164, 1172 ] ], "normalized": [] }, { "id": "287_T42", "type": "Chemical", "text": [ "conjugates of the", "dodecamer" ], "offsets": [ [ 1174, 1191 ], [ 1201, 1210 ] ], "normalized": [] }, { "id": "287_T43", "type": "Chemical", "text": [ "conjugates of the octamer" ], "offsets": [ [ 1174, 1199 ] ], "normalized": [] }, { "id": "287_T44", "type": "Chemical", "text": [ "conjugates of the", "hexadecamer" ], "offsets": [ [ 1174, 1191 ], [ 1215, 1226 ] ], "normalized": [] }, { "id": "287_T45", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 1240, 1243 ] ], "normalized": [] }, { "id": "287_T46", "type": "Protein", "text": [ "IgG LPS antibodies" ], "offsets": [ [ 1236, 1254 ] ], "normalized": [] }, { "id": "287_T47", "type": "Chemical", "text": [ "O-SP" ], "offsets": [ [ 1399, 1403 ] ], "normalized": [] }, { "id": "287_T48", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 1404, 1407 ] ], "normalized": [] }, { "id": "287_T49", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 1468, 1471 ] ], "normalized": [] }, { "id": "287_T50", "type": "Protein", "text": [ "IgG anti-LPS" ], "offsets": [ [ 1459, 1471 ] ], "normalized": [] }, { "id": "287_T51", "type": "Chemical", "text": [ "hexadecamer" ], "offsets": [ [ 1493, 1504 ] ], "normalized": [] }, { "id": "287_T52", "type": "Chemical", "text": [ "saccharide" ], "offsets": [ [ 1533, 1543 ] ], "normalized": [] }, { "id": "287_T53", "type": "Protein", "text": [ "HSA" ], "offsets": [ [ 1544, 1547 ] ], "normalized": [] }, { "id": "287_T54", "type": "Chemical", "text": [ "octamer" ], "offsets": [ [ 1583, 1590 ] ], "normalized": [] }, { "id": "287_T55", "type": "Chemical", "text": [ "dodecamer" ], "offsets": [ [ 1633, 1642 ] ], "normalized": [] }, { "id": "287_T56", "type": "Chemical", "text": [ "saccharides" ], "offsets": [ [ 1718, 1729 ] ], "normalized": [] } ]

[]

[]

[ { "id": "287_R1", "type": "Associated_With", "arg1_id": "287_T8", "arg2_id": "287_T9", "normalized": [] } ]

[ { "id": "289", "type": "", "text": [ "An enzyme with lipase and esterase activity was purified from bovine pancreas. Furthermore, a non-radioactive lipase assay was developed which is 100 times more sensitive than the conventional methods and allowed the characterization of the lipase activity of the enzyme. The lipase activity increased 42 times in the presence of 10 mM sodium taurocholate, which for the first time provides direct evidence that a bile salt-activated lipase (bp-BAL) was isolated from bovine pancreas. This conclusion is further supported by the fact that the N-terminal amino acid sequence of this lipase/esterase is 88% homologous to human milk BAL and human pancreatic BAL. Staining with various lectins showed that bp-BAL is a glycoprotein which contains fucose residues. Previously from bovine pancreas a lysophospholipase has been purified and a gene was cloned and sequenced encoding an enzyme with cholesterol esterase/lysophospholipase activity. Comparison of the N-terminal amino acid sequence of bp-BAL with the deduced amino acid sequence of the latter revealed that they are identical. Furthermore, the molecular weight of the purified bp-BAL of 63,000, as estimated by SDS-PAGE, is very similar to that of the purified lysophospholipase (65,000) and to the theoretical molecular weight of 65,147 of the cholesterol esterase/lysophospholipase. These data suggest that these three enzymes are one and the same. \n" ], "offsets": [ [ 0, 1410 ] ] } ]

[ { "id": "289_T1", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 3, 9 ] ], "normalized": [] }, { "id": "289_T2", "type": "Protein", "text": [ "lipase" ], "offsets": [ [ 15, 21 ] ], "normalized": [] }, { "id": "289_T3", "type": "Biological_Activity", "text": [ "lipase" ], "offsets": [ [ 15, 21 ] ], "normalized": [] }, { "id": "289_T4", "type": "Protein", "text": [ "esterase" ], "offsets": [ [ 26, 34 ] ], "normalized": [] }, { "id": "289_T5", "type": "Biological_Activity", "text": [ "esterase" ], "offsets": [ [ 26, 34 ] ], "normalized": [] }, { "id": "289_T6", "type": "Species", "text": [ "bovine" ], "offsets": [ [ 62, 68 ] ], "normalized": [] }, { "id": "289_T8", "type": "Protein", "text": [ "lipase" ], "offsets": [ [ 110, 116 ] ], "normalized": [] }, { "id": "289_T9", "type": "Biological_Activity", "text": [ "lipase" ], "offsets": [ [ 241, 247 ] ], "normalized": [] }, { "id": "289_T10", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 264, 270 ] ], "normalized": [] }, { "id": "289_T11", "type": "Protein", "text": [ "lipase" ], "offsets": [ [ 241, 247 ] ], "normalized": [] }, { "id": "289_T12", "type": "Protein", "text": [ "lipase" ], "offsets": [ [ 276, 282 ] ], "normalized": [] }, { "id": "289_T13", "type": "Biological_Activity", "text": [ "lipase" ], "offsets": [ [ 276, 282 ] ], "normalized": [] }, { "id": "289_T14", "type": "Chemical", "text": [ "sodium taurocholate" ], "offsets": [ [ 336, 355 ] ], "normalized": [] }, { "id": "289_T15", "type": "Chemical", "text": [ "bile salt" ], "offsets": [ [ 414, 423 ] ], "normalized": [] }, { "id": "289_T16", "type": "Protein", "text": [ "bile salt-activated lipase" ], "offsets": [ [ 414, 440 ] ], "normalized": [] }, { "id": "289_T17", "type": "Protein", "text": [ "bp-BAL" ], "offsets": [ [ 442, 448 ] ], "normalized": [] }, { "id": "289_T18", "type": "Species", "text": [ "bovine" ], "offsets": [ [ 468, 474 ] ], "normalized": [] }, { "id": "289_T19", "type": "Chemical", "text": [ "N-terminal amino acid" ], "offsets": [ [ 543, 564 ] ], "normalized": [] }, { "id": "289_T20", "type": "Protein", "text": [ "lipase" ], "offsets": [ [ 582, 588 ] ], "normalized": [] }, { "id": "289_T21", "type": "Protein", "text": [ "esterase" ], "offsets": [ [ 589, 597 ] ], "normalized": [] }, { "id": "289_T22", "type": "Species", "text": [ "human" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "289_T23", "type": "Protein", "text": [ "milk BAL" ], "offsets": [ [ 625, 633 ] ], "normalized": [] }, { "id": "289_T24", "type": "Species", "text": [ "human" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "289_T25", "type": "Protein", "text": [ "pancreatic BAL" ], "offsets": [ [ 644, 658 ] ], "normalized": [] }, { "id": "289_T26", "type": "Protein", "text": [ "lectins" ], "offsets": [ [ 682, 689 ] ], "normalized": [] }, { "id": "289_T27", "type": "Protein", "text": [ "bp-BAL" ], "offsets": [ [ 702, 708 ] ], "normalized": [] }, { "id": "289_T28", "type": "Protein", "text": [ "glycoprotein" ], "offsets": [ [ 714, 726 ] ], "normalized": [] }, { "id": "289_T29", "type": "Chemical", "text": [ "fucose residues" ], "offsets": [ [ 742, 757 ] ], "normalized": [] }, { "id": "289_T30", "type": "Species", "text": [ "bovine" ], "offsets": [ [ 775, 781 ] ], "normalized": [] }, { "id": "289_T31", "type": "Protein", "text": [ "lysophospholipase" ], "offsets": [ [ 793, 810 ] ], "normalized": [] }, { "id": "289_T32", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 878, 884 ] ], "normalized": [] }, { "id": "289_T34", "type": "Biological_Activity", "text": [ "esterase" ], "offsets": [ [ 902, 910 ] ], "normalized": [] }, { "id": "289_T35", "type": "Protein", "text": [ "cholesterol esterase" ], "offsets": [ [ 890, 910 ] ], "normalized": [] }, { "id": "289_T36", "type": "Protein", "text": [ "lysophospholipase" ], "offsets": [ [ 911, 928 ] ], "normalized": [] }, { "id": "289_T37", "type": "Biological_Activity", "text": [ "lipase" ], "offsets": [ [ 922, 928 ] ], "normalized": [] }, { "id": "289_T39", "type": "Chemical", "text": [ "N-terminal amino acid" ], "offsets": [ [ 957, 978 ] ], "normalized": [] }, { "id": "289_T40", "type": "Protein", "text": [ "bp-BAL" ], "offsets": [ [ 991, 997 ] ], "normalized": [] }, { "id": "289_T41", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 1015, 1025 ] ], "normalized": [] }, { "id": "289_T42", "type": "Protein", "text": [ "bp-BAL" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "289_T43", "type": "Protein", "text": [ "lysophospholipase" ], "offsets": [ [ 1219, 1236 ] ], "normalized": [] }, { "id": "289_T45", "type": "Protein", "text": [ "cholesterol esterase" ], "offsets": [ [ 1303, 1323 ] ], "normalized": [] }, { "id": "289_T46", "type": "Protein", "text": [ "lysophospholipase" ], "offsets": [ [ 1324, 1341 ] ], "normalized": [] }, { "id": "289_T47", "type": "Protein", "text": [ "enzymes" ], "offsets": [ [ 1379, 1386 ] ], "normalized": [] } ]

[]

[]

[ { "id": "289_R1", "type": "Associated_With", "arg1_id": "289_T14", "arg2_id": "289_T13", "normalized": [] } ]

[ { "id": "291", "type": "", "text": [ "OBJECTIVE: To compare the pharmacokinetics and metabolism of R(+)- and S(-)- ketorolac in children. METHODS: Children from 3 to 18 years old received 0.6 mg/kg racemic ketorolac intravenously. Serial blood samples were obtained for 12 hours, and urine was collected for 12 to 24 hours. Racemic ketorolac was measured in plasma, and racemic ketorolac, para-hydroxyketorolac, and ketorolac glucuronide were measured in urine by HPLC. S(-)- and R(+)-ketorolac were measured in plasma; S(-)- and R(+)-ketorolac and ketorolac glucuronide were measured in urine by chiral HPLC separation. Plasma pharmacokinetic parameters for racemic drug and both enantiomers were determined for each patient. RESULTS: Clearance of racemic ketorolac in children was approximately 2 times the clearance reported in adults. Clearance of the S(-) enantiomer was 4 times that of the R(+) enantiomer. Terminal half-life of S(-)-ketorolac was 40% that of the R(+) enantiomer, and the apparent volume of distribution of the S(-) enantiomer was greater than that of the R(+) form. Recovery of S(-)-ketorolac glucuronide was 2.3 times that of the R(+) enantiomer. CONCLUSION: The higher clearance in children suggests that the weight-adjusted dose of ketorolac may have to be greater for children to achieve plasma concentrations comparable to those of adults. Because of the greater clearance and shorter half-life of S(-)-ketorolac, pharmacokinetic predictions based on racemic assays may overestimate the duration of pharmacologic effect. Enantiomeric pharmacokinetic differences are best explained by stereoselective plasma protein binding. Selective glucuronidation of the S(-) enantiomer suggests that stereoselective metabolism may also be a contributing factor. \n" ], "offsets": [ [ 0, 1744 ] ] } ]

[ { "id": "291_T1", "type": "Chemical", "text": [ "R(+)-", "ketorolac" ], "offsets": [ [ 61, 66 ], [ 77, 86 ] ], "normalized": [] }, { "id": "291_T2", "type": "Chemical", "text": [ "S(-)-", "ketorolac" ], "offsets": [ [ 71, 76 ], [ 77, 86 ] ], "normalized": [] }, { "id": "291_T3", "type": "Species", "text": [ "children" ], "offsets": [ [ 90, 98 ] ], "normalized": [] }, { "id": "291_T4", "type": "Species", "text": [ "Children" ], "offsets": [ [ 109, 117 ] ], "normalized": [] }, { "id": "291_T5", "type": "Chemical", "text": [ "racemic ketorolac" ], "offsets": [ [ 160, 177 ] ], "normalized": [] }, { "id": "291_T6", "type": "Chemical", "text": [ "ketorolac" ], "offsets": [ [ 168, 177 ] ], "normalized": [] }, { "id": "291_T7", "type": "Chemical", "text": [ "Racemic ketorolac" ], "offsets": [ [ 287, 304 ] ], "normalized": [] }, { "id": "291_T8", "type": "Chemical", "text": [ "ketorolac" ], "offsets": [ [ 295, 304 ] ], "normalized": [] }, { "id": "291_T10", "type": "Chemical", "text": [ "para-hydroxyketorolac" ], "offsets": [ [ 352, 373 ] ], "normalized": [] }, { "id": "291_T11", "type": "Metabolite", "text": [ "para-hydroxyketorolac" ], "offsets": [ [ 352, 373 ] ], "normalized": [] }, { "id": "291_T12", "type": "Chemical", "text": [ "ketorolac glucuronide" ], "offsets": [ [ 379, 400 ] ], "normalized": [] }, { "id": "291_T13", "type": "Metabolite", "text": [ "ketorolac glucuronide" ], "offsets": [ [ 379, 400 ] ], "normalized": [] }, { "id": "291_T14", "type": "Chemical", "text": [ "S(-)-", "ketorolac" ], "offsets": [ [ 433, 438 ], [ 448, 457 ] ], "normalized": [] }, { "id": "291_T15", "type": "Chemical", "text": [ "R(+)-ketorolac" ], "offsets": [ [ 443, 457 ] ], "normalized": [] }, { "id": "291_T16", "type": "Chemical", "text": [ "S(-)-", "ketorolac glucuronide" ], "offsets": [ [ 483, 488 ], [ 512, 533 ] ], "normalized": [] }, { "id": "291_T17", "type": "Chemical", "text": [ "S(-)-", "ketorolac" ], "offsets": [ [ 483, 488 ], [ 498, 507 ] ], "normalized": [] }, { "id": "291_T18", "type": "Chemical", "text": [ "R(+)-ketorolac" ], "offsets": [ [ 493, 507 ] ], "normalized": [] }, { "id": "291_T19", "type": "Chemical", "text": [ "R(+)-", "ketorolac glucuronide" ], "offsets": [ [ 493, 498 ], [ 512, 533 ] ], "normalized": [] }, { "id": "291_T20", "type": "Chemical", "text": [ "racemic ketorolac" ], "offsets": [ [ 713, 730 ] ], "normalized": [] }, { "id": "291_T21", "type": "Species", "text": [ "children" ], "offsets": [ [ 734, 742 ] ], "normalized": [] }, { "id": "291_T22", "type": "Species", "text": [ "adults" ], "offsets": [ [ 795, 801 ] ], "normalized": [] }, { "id": "291_T23", "type": "Chemical", "text": [ "S(-) enantiomer" ], "offsets": [ [ 820, 835 ] ], "normalized": [] }, { "id": "291_T24", "type": "Chemical", "text": [ "R(+) enantiomer" ], "offsets": [ [ 860, 875 ] ], "normalized": [] }, { "id": "291_T25", "type": "Chemical", "text": [ "S(-)-ketorolac" ], "offsets": [ [ 899, 913 ] ], "normalized": [] }, { "id": "291_T26", "type": "Chemical", "text": [ "R(+) enantiomer" ], "offsets": [ [ 935, 950 ] ], "normalized": [] }, { "id": "291_T27", "type": "Chemical", "text": [ "S(-) enantiomer" ], "offsets": [ [ 999, 1014 ] ], "normalized": [] }, { "id": "291_T28", "type": "Chemical", "text": [ "R(+) form" ], "offsets": [ [ 1044, 1053 ] ], "normalized": [] }, { "id": "291_T29", "type": "Chemical", "text": [ "S(-)-ketorolac glucuronide" ], "offsets": [ [ 1067, 1093 ] ], "normalized": [] }, { "id": "291_T30", "type": "Chemical", "text": [ "R(+) enantiomer" ], "offsets": [ [ 1120, 1135 ] ], "normalized": [] }, { "id": "291_T31", "type": "Chemical", "text": [ "ketorolac" ], "offsets": [ [ 1224, 1233 ] ], "normalized": [] }, { "id": "291_T32", "type": "Metabolite", "text": [ "S(-)-ketorolac glucuronide" ], "offsets": [ [ 1067, 1093 ] ], "normalized": [] }, { "id": "291_T33", "type": "Metabolite", "text": [ "R(+) enantiomer" ], "offsets": [ [ 1120, 1135 ] ], "normalized": [] }, { "id": "291_T34", "type": "Species", "text": [ "adults" ], "offsets": [ [ 1326, 1332 ] ], "normalized": [] }, { "id": "291_T35", "type": "Chemical", "text": [ "S(-)-ketorolac" ], "offsets": [ [ 1392, 1406 ] ], "normalized": [] }, { "id": "291_T36", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1601, 1608 ] ], "normalized": [] }, { "id": "291_T38", "type": "Chemical", "text": [ "S(-) enantiomer" ], "offsets": [ [ 1651, 1666 ] ], "normalized": [] }, { "id": "291_T39", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1697, 1707 ] ], "normalized": [] }, { "id": "291_T40", "type": "Chemical", "text": [ "racemic ketorolac" ], "offsets": [ [ 333, 350 ] ], "normalized": [] }, { "id": "291_T9", "type": "Chemical", "text": [ "ketorolac" ], "offsets": [ [ 341, 350 ] ], "normalized": [] }, { "id": "291_T41", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 47, 57 ] ], "normalized": [] }, { "id": "291_T42", "type": "Species", "text": [ "children" ], "offsets": [ [ 1173, 1181 ] ], "normalized": [] } ]

[]

[]

[ { "id": "291_R5", "type": "Metabolite_Of", "arg1_id": "291_T32", "arg2_id": "291_T20", "normalized": [] }, { "id": "291_R6", "type": "Isolated_From", "arg1_id": "291_T25", "arg2_id": "291_T21", "normalized": [] }, { "id": "291_R7", "type": "Metabolite_Of", "arg1_id": "291_T33", "arg2_id": "291_T20", "normalized": [] }, { "id": "291_R8", "type": "Isolated_From", "arg1_id": "291_T33", "arg2_id": "291_T21", "normalized": [] }, { "id": "291_R3", "type": "Isolated_From", "arg1_id": "291_T11", "arg2_id": "291_T4", "normalized": [] }, { "id": "291_R4", "type": "Isolated_From", "arg1_id": "291_T13", "arg2_id": "291_T4", "normalized": [] }, { "id": "291_R1", "type": "Metabolite_Of", "arg1_id": "291_T11", "arg2_id": "291_T9", "normalized": [] }, { "id": "291_R2", "type": "Metabolite_Of", "arg1_id": "291_T13", "arg2_id": "291_T9", "normalized": [] } ]

[ { "id": "293", "type": "", "text": [ "The antifungal activity of eberconazole, a new imidazole derivative, against 124 clinical isolates of Candida comprising eight different species and to 34 isolates of Cryptococcus neoformans was compared to those of clotrimazole and ketoconazole. MICs of eberconazole, determined by the National Committee for Clinical Laboratory Standards standardized microbroth method, were equal to or lower than those of other azoles, especially for Candida krusei and Candida glabrata, which are usually resistant to triazoles. \n" ], "offsets": [ [ 0, 519 ] ] } ]

[ { "id": "293_T1", "type": "Biological_Activity", "text": [ "antifungal" ], "offsets": [ [ 4, 14 ] ], "normalized": [] }, { "id": "293_T2", "type": "Chemical", "text": [ "eberconazole" ], "offsets": [ [ 27, 39 ] ], "normalized": [] }, { "id": "293_T3", "type": "Chemical", "text": [ "imidazole derivative" ], "offsets": [ [ 47, 67 ] ], "normalized": [] }, { "id": "293_T4", "type": "Species", "text": [ "Candida" ], "offsets": [ [ 103, 110 ] ], "normalized": [] }, { "id": "293_T5", "type": "Species", "text": [ "Cryptococcus neoformans" ], "offsets": [ [ 168, 191 ] ], "normalized": [] }, { "id": "293_T6", "type": "Chemical", "text": [ "clotrimazole" ], "offsets": [ [ 217, 229 ] ], "normalized": [] }, { "id": "293_T7", "type": "Chemical", "text": [ "ketoconazole" ], "offsets": [ [ 234, 246 ] ], "normalized": [] }, { "id": "293_T8", "type": "Chemical", "text": [ "eberconazole" ], "offsets": [ [ 256, 268 ] ], "normalized": [] }, { "id": "293_T9", "type": "Chemical", "text": [ "azoles" ], "offsets": [ [ 416, 422 ] ], "normalized": [] }, { "id": "293_T10", "type": "Species", "text": [ "Candida krusei" ], "offsets": [ [ 439, 453 ] ], "normalized": [] }, { "id": "293_T11", "type": "Species", "text": [ "Candida glabrata" ], "offsets": [ [ 458, 474 ] ], "normalized": [] }, { "id": "293_T12", "type": "Chemical", "text": [ "triazoles" ], "offsets": [ [ 507, 516 ] ], "normalized": [] } ]

[]

[]

[ { "id": "293_R1", "type": "Associated_With", "arg1_id": "293_T6", "arg2_id": "293_T1", "normalized": [] }, { "id": "293_R2", "type": "Associated_With", "arg1_id": "293_T7", "arg2_id": "293_T1", "normalized": [] }, { "id": "293_R3", "type": "Associated_With", "arg1_id": "293_T2", "arg2_id": "293_T1", "normalized": [] } ]

[ { "id": "295", "type": "", "text": [ "Long-chain fatty acyl-CoA synthetase (FACS) catalyzes esterification of long-chain fatty acids (LCFAs) with coenzyme A (CoA), the first step in fatty acid metabolism. FACS has been shown to play a role in LCFA import into bacteria and implicated to function in mammalian cell LCFA import. In the present study, we demonstrate that FACS overexpression in fibroblasts increases LCFA uptake, and overexpression of both FACS and the fatty acid transport protein (FATP) have synergistic effects on LCFA uptake. To explore how FACS contributes to LCFA import, we examined the subcellular location of this enzyme in 3T3-L1 adipocytes which natively express this protein and which efficiently take up LCFAs. We demonstrate for the first time that FACS is an integral membrane protein. Subcellular fractionation of adipocytes by differential density centrifugation reveals immunoreactive and enzymatically active FACS in several membrane fractions, including the plasma membrane. Immunofluorescence studies on adipocyte plasma membrane lawns confirm that FACS resides at the plasma membrane of adipocytes, where it co-distributes with FATP. Taken together, our data support a model in which imported LCFAs are immediately esterified at the plasma membrane upon uptake, and in which FATP and FACS function coordinately to facilitate LCFA movement across the plasma membrane of mammalian cells. \n" ], "offsets": [ [ 0, 1388 ] ] } ]

[ { "id": "295_T1", "type": "Protein", "text": [ "Long-chain fatty acyl-CoA synthetase" ], "offsets": [ [ 0, 36 ] ], "normalized": [] }, { "id": "295_T2", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 38, 42 ] ], "normalized": [] }, { "id": "295_T3", "type": "Chemical", "text": [ "long-chain fatty acids" ], "offsets": [ [ 72, 94 ] ], "normalized": [] }, { "id": "295_T4", "type": "Chemical", "text": [ "LCFAs" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "295_T5", "type": "Chemical", "text": [ "coenzyme A" ], "offsets": [ [ 108, 118 ] ], "normalized": [] }, { "id": "295_T6", "type": "Chemical", "text": [ "CoA" ], "offsets": [ [ 120, 123 ] ], "normalized": [] }, { "id": "295_T9", "type": "Chemical", "text": [ "fatty acid" ], "offsets": [ [ 144, 154 ] ], "normalized": [] }, { "id": "295_T10", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 167, 171 ] ], "normalized": [] }, { "id": "295_T12", "type": "Chemical", "text": [ "LCFA" ], "offsets": [ [ 205, 209 ] ], "normalized": [] }, { "id": "295_T15", "type": "Chemical", "text": [ "LCFA" ], "offsets": [ [ 277, 281 ] ], "normalized": [] }, { "id": "295_T16", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 332, 336 ] ], "normalized": [] }, { "id": "295_T18", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 417, 421 ] ], "normalized": [] }, { "id": "295_T19", "type": "Protein", "text": [ "fatty acid transport protein" ], "offsets": [ [ 430, 458 ] ], "normalized": [] }, { "id": "295_T20", "type": "Protein", "text": [ "FATP" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "295_T21", "type": "Chemical", "text": [ "LCFA" ], "offsets": [ [ 494, 498 ] ], "normalized": [] }, { "id": "295_T23", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 522, 526 ] ], "normalized": [] }, { "id": "295_T24", "type": "Chemical", "text": [ "LCFA" ], "offsets": [ [ 542, 546 ] ], "normalized": [] }, { "id": "295_T25", "type": "Chemical", "text": [ "LCFA" ], "offsets": [ [ 377, 381 ] ], "normalized": [] }, { "id": "295_T27", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 600, 606 ] ], "normalized": [] }, { "id": "295_T28", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 657, 664 ] ], "normalized": [] }, { "id": "295_T29", "type": "Chemical", "text": [ "LCFAs" ], "offsets": [ [ 695, 700 ] ], "normalized": [] }, { "id": "295_T30", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 741, 745 ] ], "normalized": [] }, { "id": "295_T31", "type": "Protein", "text": [ "membrane protein" ], "offsets": [ [ 761, 777 ] ], "normalized": [] }, { "id": "295_T32", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 906, 910 ] ], "normalized": [] }, { "id": "295_T33", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 1048, 1052 ] ], "normalized": [] }, { "id": "295_T34", "type": "Protein", "text": [ "FATP" ], "offsets": [ [ 1128, 1132 ] ], "normalized": [] }, { "id": "295_T35", "type": "Chemical", "text": [ "LCFAs" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "295_T37", "type": "Protein", "text": [ "FATP" ], "offsets": [ [ 1275, 1279 ] ], "normalized": [] }, { "id": "295_T38", "type": "Protein", "text": [ "FACS" ], "offsets": [ [ 1284, 1288 ] ], "normalized": [] }, { "id": "295_T39", "type": "Chemical", "text": [ "LCFA" ], "offsets": [ [ 1325, 1331 ] ], "normalized": [] }, { "id": "295_T41", "type": "Species", "text": [ "mammalian" ], "offsets": [ [ 1370, 1379 ] ], "normalized": [] }, { "id": "295_T7", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 155, 165 ] ], "normalized": [] }, { "id": "295_T11", "type": "Species", "text": [ "mammalian" ], "offsets": [ [ 262, 271 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "297", "type": "", "text": [ "The eight enzymes of the tricarboxylic acid (TCA) cycle are encoded by at least 15 different nuclear genes in Saccharomyces cerevisiae. We have constructed a set of yeast strains defective in these genes as part of a comprehensive analysis of the interactions among the TCA cycle proteins. The 15 major TCA cycle genes can be sorted into five phenotypic categories on the basis of their growth on nonfermentable carbon sources. We have previously reported a novel phenotype associated with mutants defective in the IDH2 gene encoding the Idh2p subunit of the NAD+-dependent isocitrate dehydrogenase (NAD-IDH). Null and nonsense idh2 mutants grow poorly on glycerol, but growth can be enhanced by extragenic mutations, termed glycerol suppressors, in the CIT1 gene encoding the TCA cycle citrate synthase and in other genes of oxidative metabolism. The TCA cycle mutant collection was utilized to search for other genes that can suppress idh2 mutants and to identify TCA cycle genes that display a similar suppressible growth phenotype on glycerol. Mutations in 7 TCA cycle genes were capable of functioning as suppressors for growth of idh2 mutants on glycerol. The only other TCA cycle gene to display the glycerol-suppressor-accumulation phenotype was IDH1, which encodes the companion Idh1p subunit of NAD-IDH. These results provide genetic evidence that NAD-IDH plays a unique role in TCA cycle function. \n" ], "offsets": [ [ 0, 1413 ] ] } ]

[ { "id": "297_T1", "type": "Protein", "text": [ "enzymes" ], "offsets": [ [ 10, 17 ] ], "normalized": [] }, { "id": "297_T4", "type": "Species", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 110, 134 ] ], "normalized": [] }, { "id": "297_T5", "type": "Chemical", "text": [ "tricarboxylic acid" ], "offsets": [ [ 25, 43 ] ], "normalized": [] }, { "id": "297_T6", "type": "Species", "text": [ "yeast" ], "offsets": [ [ 165, 170 ] ], "normalized": [] }, { "id": "297_T7", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 45, 48 ] ], "normalized": [] }, { "id": "297_T8", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 271, 274 ] ], "normalized": [] }, { "id": "297_T10", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 304, 307 ] ], "normalized": [] }, { "id": "297_T12", "type": "Chemical", "text": [ "carbon" ], "offsets": [ [ 413, 419 ] ], "normalized": [] }, { "id": "297_T13", "type": "Protein", "text": [ "NAD+-dependent isocitrate dehydrogenase" ], "offsets": [ [ 561, 600 ] ], "normalized": [] }, { "id": "297_T14", "type": "Protein", "text": [ "NAD-IDH" ], "offsets": [ [ 602, 609 ] ], "normalized": [] }, { "id": "297_T15", "type": "Chemical", "text": [ "glycerol" ], "offsets": [ [ 658, 666 ] ], "normalized": [] }, { "id": "297_T16", "type": "Protein", "text": [ "TCA cycle citrate synthase" ], "offsets": [ [ 779, 805 ] ], "normalized": [] }, { "id": "297_T17", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 838, 848 ] ], "normalized": [] }, { "id": "297_T19", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 854, 857 ] ], "normalized": [] }, { "id": "297_T21", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 969, 972 ] ], "normalized": [] }, { "id": "297_T22", "type": "Chemical", "text": [ "glycerol" ], "offsets": [ [ 1041, 1049 ] ], "normalized": [] }, { "id": "297_T23", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "297_T25", "type": "Chemical", "text": [ "glycerol" ], "offsets": [ [ 1155, 1163 ] ], "normalized": [] }, { "id": "297_T26", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 1180, 1183 ] ], "normalized": [] }, { "id": "297_T28", "type": "Chemical", "text": [ "glycerol" ], "offsets": [ [ 1210, 1218 ] ], "normalized": [] }, { "id": "297_T29", "type": "Protein", "text": [ "NAD-IDH" ], "offsets": [ [ 1361, 1368 ] ], "normalized": [] }, { "id": "297_T30", "type": "Chemical", "text": [ "TCA" ], "offsets": [ [ 1392, 1395 ] ], "normalized": [] }, { "id": "297_T32", "type": "Protein", "text": [ "TCA cycle proteins" ], "offsets": [ [ 271, 289 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "299", "type": "", "text": [ "On the 22nd day of gestation in rats, fetuses of acutely adrenalectomized mothers were injected subcutaneously with 0.43 muCi 4-14C-progesterone in 0.05 ml saline. Ten and 20 min after injection to fetuses, samples were taken to determine the 14C-progesterone metabolites in the plasma and adrenal glands. After extraction of the samples taken, the metabolites were separated by two-dimensional thin-layer chromatography and identified by autoradiography. 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, corticosterone and 11beta-hydroxyprogesterone were identified in the plasma of injected fetuses, and, in far smaller amounts, in the plasma of their mothers. The plasma of noninjected fetuses also contained very small amounts of these corticoids. The fetal adrenal glands contained far smaller amounts of radioactive steroids than the fetal plasma did. The results obtained show that steroids of fetal origin can cross the placenta in and out, constituting evidence that the fetal adrenal glands are the only source of the plasma corticoids of their adrenalectomized mothers. \n" ], "offsets": [ [ 0, 1092 ] ] } ]

[ { "id": "299_T1", "type": "Species", "text": [ "rats" ], "offsets": [ [ 32, 36 ] ], "normalized": [] }, { "id": "299_T2", "type": "Chemical", "text": [ "4-14C-progesterone" ], "offsets": [ [ 126, 144 ] ], "normalized": [] }, { "id": "299_T3", "type": "Chemical", "text": [ "progesterone" ], "offsets": [ [ 132, 144 ] ], "normalized": [] }, { "id": "299_T4", "type": "Chemical", "text": [ "saline" ], "offsets": [ [ 156, 162 ] ], "normalized": [] }, { "id": "299_T5", "type": "Metabolite", "text": [ "14C-progesterone metabolites" ], "offsets": [ [ 243, 271 ] ], "normalized": [] }, { "id": "299_T6", "type": "Chemical", "text": [ "14C-progesterone metabolites" ], "offsets": [ [ 243, 271 ] ], "normalized": [] }, { "id": "299_T7", "type": "Metabolite", "text": [ "metabolites" ], "offsets": [ [ 349, 360 ] ], "normalized": [] }, { "id": "299_T8", "type": "Chemical", "text": [ "metabolites" ], "offsets": [ [ 349, 360 ] ], "normalized": [] }, { "id": "299_T9", "type": "Chemical", "text": [ "11-deoxycorticosterone" ], "offsets": [ [ 456, 478 ] ], "normalized": [] }, { "id": "299_T10", "type": "Metabolite", "text": [ "11-deoxycorticosterone" ], "offsets": [ [ 456, 478 ] ], "normalized": [] }, { "id": "299_T11", "type": "Metabolite", "text": [ "18-hydroxy-11-deoxycorticosterone" ], "offsets": [ [ 480, 513 ] ], "normalized": [] }, { "id": "299_T12", "type": "Chemical", "text": [ "18-hydroxy-11-deoxycorticosterone" ], "offsets": [ [ 480, 513 ] ], "normalized": [] }, { "id": "299_T13", "type": "Chemical", "text": [ "corticosterone" ], "offsets": [ [ 515, 529 ] ], "normalized": [] }, { "id": "299_T14", "type": "Metabolite", "text": [ "corticosterone" ], "offsets": [ [ 515, 529 ] ], "normalized": [] }, { "id": "299_T15", "type": "Chemical", "text": [ "11beta-hydroxyprogesterone" ], "offsets": [ [ 534, 560 ] ], "normalized": [] }, { "id": "299_T16", "type": "Metabolite", "text": [ "11beta-hydroxyprogesterone" ], "offsets": [ [ 534, 560 ] ], "normalized": [] }, { "id": "299_T17", "type": "Chemical", "text": [ "corticoids" ], "offsets": [ [ 750, 760 ] ], "normalized": [] }, { "id": "299_T18", "type": "Chemical", "text": [ "steroids" ], "offsets": [ [ 832, 840 ] ], "normalized": [] }, { "id": "299_T19", "type": "Chemical", "text": [ "steroids" ], "offsets": [ [ 899, 907 ] ], "normalized": [] }, { "id": "299_T20", "type": "Chemical", "text": [ "corticoids" ], "offsets": [ [ 1045, 1055 ] ], "normalized": [] }, { "id": "299_T21", "type": "Metabolite", "text": [ "steroids" ], "offsets": [ [ 899, 907 ] ], "normalized": [] }, { "id": "299_T22", "type": "Metabolite", "text": [ "corticoids" ], "offsets": [ [ 1045, 1055 ] ], "normalized": [] }, { "id": "299_T23", "type": "Metabolite", "text": [ "steroids" ], "offsets": [ [ 832, 840 ] ], "normalized": [] }, { "id": "299_T24", "type": "Metabolite", "text": [ "corticoids" ], "offsets": [ [ 750, 760 ] ], "normalized": [] } ]

[]

[]

[ { "id": "299_R1", "type": "Isolated_From", "arg1_id": "299_T10", "arg2_id": "299_T1", "normalized": [] }, { "id": "299_R2", "type": "Isolated_From", "arg1_id": "299_T11", "arg2_id": "299_T1", "normalized": [] }, { "id": "299_R3", "type": "Isolated_From", "arg1_id": "299_T14", "arg2_id": "299_T1", "normalized": [] }, { "id": "299_R4", "type": "Isolated_From", "arg1_id": "299_T16", "arg2_id": "299_T1", "normalized": [] }, { "id": "299_R5", "type": "Metabolite_Of", "arg1_id": "299_T10", "arg2_id": "299_T3", "normalized": [] }, { "id": "299_R6", "type": "Metabolite_Of", "arg1_id": "299_T11", "arg2_id": "299_T3", "normalized": [] }, { "id": "299_R7", "type": "Metabolite_Of", "arg1_id": "299_T14", "arg2_id": "299_T3", "normalized": [] }, { "id": "299_R8", "type": "Metabolite_Of", "arg1_id": "299_T16", "arg2_id": "299_T3", "normalized": [] } ]

[ { "id": "301", "type": "", "text": [ "Ozone-oxygen mixture (ozone concentration 600 microg/l) was used in irrigations of the tympanic cavity in 52 patients with chronic purulent mesotympanitis (CPM). The course of the treatment consisted of 5-7 procedures. 18 CPM controls received standard treatment without the irrigations. The course of the ozone-oxygen irrigations produced good results: ear discharge and tympanic mucosa inflammation stopped in 81% of the irrigated patients, levels of myeloperoxidase which marks inflammation reduced significantly, bactericidal effects of the mixture were observed for all the detected pathogens, antibiotic sensitivity of the bacteria rose. Fast antiinflammatory result of ozone therapy was due not only to its bactericidal effect but also via its antihypoxic and immunomodulating mechanisms. \n" ], "offsets": [ [ 0, 797 ] ] } ]

[ { "id": "301_T1", "type": "Chemical", "text": [ "Ozone" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "301_T2", "type": "Chemical", "text": [ "oxygen" ], "offsets": [ [ 6, 12 ] ], "normalized": [] }, { "id": "301_T3", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 22, 27 ] ], "normalized": [] }, { "id": "301_T7", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 306, 311 ] ], "normalized": [] }, { "id": "301_T8", "type": "Chemical", "text": [ "oxygen" ], "offsets": [ [ 312, 318 ] ], "normalized": [] }, { "id": "301_T11", "type": "Chemical", "text": [ "Ozone-oxygen mixture" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "301_T12", "type": "Chemical", "text": [ "ozone-oxygen" ], "offsets": [ [ 306, 318 ] ], "normalized": [] }, { "id": "301_T13", "type": "Protein", "text": [ "myeloperoxidase" ], "offsets": [ [ 453, 468 ] ], "normalized": [] }, { "id": "301_T16", "type": "Biological_Activity", "text": [ "bactericidal" ], "offsets": [ [ 517, 529 ] ], "normalized": [] }, { "id": "301_T17", "type": "Biological_Activity", "text": [ "antiinflammatory" ], "offsets": [ [ 649, 665 ] ], "normalized": [] }, { "id": "301_T18", "type": "Chemical", "text": [ "ozone" ], "offsets": [ [ 676, 681 ] ], "normalized": [] }, { "id": "301_T19", "type": "Biological_Activity", "text": [ "bactericidal" ], "offsets": [ [ 714, 726 ] ], "normalized": [] }, { "id": "301_T20", "type": "Biological_Activity", "text": [ "antihypoxic" ], "offsets": [ [ 751, 762 ] ], "normalized": [] }, { "id": "301_T21", "type": "Biological_Activity", "text": [ "immunomodulating" ], "offsets": [ [ 767, 783 ] ], "normalized": [] }, { "id": "301_T22", "type": "Species", "text": [ "patients" ], "offsets": [ [ 433, 441 ] ], "normalized": [] }, { "id": "301_T23", "type": "Species", "text": [ "bacteria" ], "offsets": [ [ 629, 637 ] ], "normalized": [] }, { "id": "301_T24", "type": "Chemical", "text": [ "antibiotic" ], "offsets": [ [ 599, 609 ] ], "normalized": [] }, { "id": "301_T25", "type": "Biological_Activity", "text": [ "antibiotic" ], "offsets": [ [ 599, 609 ] ], "normalized": [] } ]

[]

[]

[ { "id": "301_R4", "type": "Associated_With", "arg1_id": "301_T12", "arg2_id": "301_T16", "normalized": [] }, { "id": "301_R5", "type": "Associated_With", "arg1_id": "301_T18", "arg2_id": "301_T17", "normalized": [] }, { "id": "301_R6", "type": "Associated_With", "arg1_id": "301_T18", "arg2_id": "301_T19", "normalized": [] }, { "id": "301_R7", "type": "Associated_With", "arg1_id": "301_T18", "arg2_id": "301_T20", "normalized": [] }, { "id": "301_R8", "type": "Associated_With", "arg1_id": "301_T18", "arg2_id": "301_T21", "normalized": [] } ]

[ { "id": "303", "type": "", "text": [ "A mixture of oligosaccharides produced by beta-galactosidase using lactose as a substrate was fractionated according to degree of polymerization using gel filtration, followed by high-pH anion-exchange chromatography. The fractions obtained were analyzed using monosaccharide analysis, methylation analysis, mass spectrometry, and NMR spectroscopy. Twelve novel non-reducing oligosaccharides were characterized, namely, [beta-D-Galp-(1-->4)]n-alpha-D-Glcp- (1<-->1)-beta-D-Galp[-(4<--1)-beta-D-Galp]m, with n, m = (1, 2, 3, or 4) and beta-D-Galp-(1-->2)-alpha-D-Glcp- (1<-->1)-beta-D-Galp. \n" ], "offsets": [ [ 0, 592 ] ] } ]

[ { "id": "303_T1", "type": "Chemical", "text": [ "oligosaccharides" ], "offsets": [ [ 13, 29 ] ], "normalized": [] }, { "id": "303_T2", "type": "Protein", "text": [ "beta-galactosidase" ], "offsets": [ [ 42, 60 ] ], "normalized": [] }, { "id": "303_T3", "type": "Chemical", "text": [ "lactose" ], "offsets": [ [ 67, 74 ] ], "normalized": [] }, { "id": "303_T5", "type": "Chemical", "text": [ "monosaccharide" ], "offsets": [ [ 261, 275 ] ], "normalized": [] }, { "id": "303_T6", "type": "Spectral_Data", "text": [ "mass spectrometry" ], "offsets": [ [ 308, 326 ] ], "normalized": [] }, { "id": "303_T7", "type": "Spectral_Data", "text": [ "NMR spectroscopy" ], "offsets": [ [ 332, 348 ] ], "normalized": [] }, { "id": "303_T8", "type": "Chemical", "text": [ "non-reducing oligosaccharides" ], "offsets": [ [ 363, 392 ] ], "normalized": [] }, { "id": "303_T9", "type": "Chemical", "text": [ "[beta-D-Galp-(1-->4)]n-alpha-D-Glcp- (1<-->1)-beta-D-Galp[-(4<--1)-beta-D-Galp]m, with n, m = (1, 2, 3, or 4)" ], "offsets": [ [ 421, 530 ] ], "normalized": [] }, { "id": "303_T10", "type": "Chemical", "text": [ "beta-D-Galp-(1-->2)-alpha-D-Glcp- (1<-->1)-beta-D-Galp" ], "offsets": [ [ 535, 589 ] ], "normalized": [] } ]

[]

[]

[ { "id": "303_R2", "type": "Associated_With", "arg1_id": "303_T9", "arg2_id": "303_T6", "normalized": [] }, { "id": "303_R3", "type": "Associated_With", "arg1_id": "303_T10", "arg2_id": "303_T6", "normalized": [] }, { "id": "303_R4", "type": "Associated_With", "arg1_id": "303_T9", "arg2_id": "303_T7", "normalized": [] }, { "id": "303_R5", "type": "Associated_With", "arg1_id": "303_T10", "arg2_id": "303_T7", "normalized": [] } ]

[ { "id": "305", "type": "", "text": [ "Activity-guided fractionation of the roots of Anthriscus sylvestris resulted in the isolation and characterization of five cytotoxic compounds, deoxypodophyllotoxin (1), falcarindiol (2), and angeloyl podophyllotoxin (5) from the hexane soluble fraction and morelensin (3), bursehernin (4) from the chloroform soluble fraction. It is the first report of the occurrence of compound 5 in nature. \n" ], "offsets": [ [ 0, 395 ] ] } ]

[ { "id": "305_T1", "type": "Species", "text": [ "Anthriscus sylvestris" ], "offsets": [ [ 46, 67 ] ], "normalized": [] }, { "id": "305_T2", "type": "Biological_Activity", "text": [ "cytotoxic" ], "offsets": [ [ 123, 132 ] ], "normalized": [] }, { "id": "305_T3", "type": "Metabolite", "text": [ "deoxypodophyllotoxin" ], "offsets": [ [ 144, 164 ] ], "normalized": [] }, { "id": "305_T4", "type": "Chemical", "text": [ "deoxypodophyllotoxin" ], "offsets": [ [ 144, 164 ] ], "normalized": [] }, { "id": "305_T5", "type": "Metabolite", "text": [ "falcarindiol" ], "offsets": [ [ 170, 182 ] ], "normalized": [] }, { "id": "305_T6", "type": "Chemical", "text": [ "falcarindiol" ], "offsets": [ [ 170, 182 ] ], "normalized": [] }, { "id": "305_T7", "type": "Chemical", "text": [ "angeloyl podophyllotoxin" ], "offsets": [ [ 192, 216 ] ], "normalized": [] }, { "id": "305_T8", "type": "Metabolite", "text": [ "angeloyl podophyllotoxin" ], "offsets": [ [ 192, 216 ] ], "normalized": [] }, { "id": "305_T9", "type": "Chemical", "text": [ "morelensin" ], "offsets": [ [ 258, 268 ] ], "normalized": [] }, { "id": "305_T10", "type": "Metabolite", "text": [ "morelensin" ], "offsets": [ [ 258, 268 ] ], "normalized": [] }, { "id": "305_T11", "type": "Chemical", "text": [ "bursehernin" ], "offsets": [ [ 274, 285 ] ], "normalized": [] }, { "id": "305_T12", "type": "Metabolite", "text": [ "bursehernin" ], "offsets": [ [ 274, 285 ] ], "normalized": [] }, { "id": "305_T13", "type": "Chemical", "text": [ "hexane" ], "offsets": [ [ 230, 236 ] ], "normalized": [] }, { "id": "305_T14", "type": "Chemical", "text": [ "chloroform" ], "offsets": [ [ 299, 309 ] ], "normalized": [] }, { "id": "305_T15", "type": "Chemical", "text": [ "compound 5" ], "offsets": [ [ 372, 382 ] ], "normalized": [] }, { "id": "305_T16", "type": "Metabolite", "text": [ "compound 5" ], "offsets": [ [ 372, 382 ] ], "normalized": [] } ]

[]

[]

[ { "id": "305_R1", "type": "Isolated_From", "arg1_id": "305_T3", "arg2_id": "305_T1", "normalized": [] }, { "id": "305_R2", "type": "Associated_With", "arg1_id": "305_T4", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R3", "type": "Associated_With", "arg1_id": "305_T3", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R4", "type": "Isolated_From", "arg1_id": "305_T5", "arg2_id": "305_T1", "normalized": [] }, { "id": "305_R5", "type": "Associated_With", "arg1_id": "305_T5", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R6", "type": "Associated_With", "arg1_id": "305_T6", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R7", "type": "Isolated_From", "arg1_id": "305_T8", "arg2_id": "305_T1", "normalized": [] }, { "id": "305_R8", "type": "Associated_With", "arg1_id": "305_T7", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R9", "type": "Associated_With", "arg1_id": "305_T8", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R10", "type": "Isolated_From", "arg1_id": "305_T10", "arg2_id": "305_T1", "normalized": [] }, { "id": "305_R11", "type": "Associated_With", "arg1_id": "305_T10", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R12", "type": "Associated_With", "arg1_id": "305_T9", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R13", "type": "Isolated_From", "arg1_id": "305_T12", "arg2_id": "305_T1", "normalized": [] }, { "id": "305_R14", "type": "Associated_With", "arg1_id": "305_T12", "arg2_id": "305_T2", "normalized": [] }, { "id": "305_R15", "type": "Associated_With", "arg1_id": "305_T11", "arg2_id": "305_T2", "normalized": [] } ]

[ { "id": "307", "type": "", "text": [ "The antioxidant activity of Eriobotrya japonica was determined by measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl) radical and lipid peroxidation produced when mouse liver homogenate was exposed to the air at 37 degrees C, using 2-thiobarbituric acid (TBA). The methanol extract and its fractions of Eriobotrya japonica leaves showed strong antioxidant activity. The antioxidant activity of EtOAc and n-BuOH soluble fractions were stronger than the others, and were further purified by repeated silica gel, MCl gel CHP-20P, and Sephadex LH-20 column chromatography. Antioxidant chlorogenic acid, quercetin-3-sambubioside from n-BuOH fraction, and methyl chlorogenate, kaempferol- and quercetin-3-rhamnosides, together with the inactive ursolic acid and 2 alpha-hydroxyursolic acid from EtOAc fraction were isolated. Antioxidant flavonoids and chlorogenic acid also showed prominent inhibitory activity against free radical generation in dichlorofluorescein (DCF) method. \n" ], "offsets": [ [ 0, 1004 ] ] } ]

[ { "id": "307_T1", "type": "Species", "text": [ "Eriobotrya japonica" ], "offsets": [ [ 28, 47 ] ], "normalized": [] }, { "id": "307_T2", "type": "Chemical", "text": [ "1,1-diphenyl-2-picrylhydrazyl", "radical" ], "offsets": [ [ 115, 144 ], [ 146, 153 ] ], "normalized": [] }, { "id": "307_T3", "type": "Chemical", "text": [ "DPPH", "radical" ], "offsets": [ [ 109, 113 ], [ 146, 153 ] ], "normalized": [] }, { "id": "307_T4", "type": "Biological_Activity", "text": [ "radical scavenging" ], "offsets": [ [ 80, 98 ] ], "normalized": [] }, { "id": "307_T6", "type": "Species", "text": [ "mouse" ], "offsets": [ [ 191, 196 ] ], "normalized": [] }, { "id": "307_T7", "type": "Chemical", "text": [ "2-thiobarbituric acid" ], "offsets": [ [ 260, 281 ] ], "normalized": [] }, { "id": "307_T8", "type": "Chemical", "text": [ "TBA" ], "offsets": [ [ 283, 286 ] ], "normalized": [] }, { "id": "307_T9", "type": "Chemical", "text": [ "air" ], "offsets": [ [ 233, 236 ] ], "normalized": [] }, { "id": "307_T10", "type": "Chemical", "text": [ "methanol" ], "offsets": [ [ 293, 301 ] ], "normalized": [] }, { "id": "307_T11", "type": "Species", "text": [ "Eriobotrya japonica" ], "offsets": [ [ 331, 350 ] ], "normalized": [] }, { "id": "307_T12", "type": "Biological_Activity", "text": [ "antioxidant" ], "offsets": [ [ 372, 383 ] ], "normalized": [] }, { "id": "307_T13", "type": "Biological_Activity", "text": [ "antioxidant" ], "offsets": [ [ 398, 409 ] ], "normalized": [] }, { "id": "307_T14", "type": "Chemical", "text": [ "EtOAc" ], "offsets": [ [ 422, 427 ] ], "normalized": [] }, { "id": "307_T15", "type": "Chemical", "text": [ "n-BuOH" ], "offsets": [ [ 432, 438 ] ], "normalized": [] }, { "id": "307_T16", "type": "Chemical", "text": [ "silica gel" ], "offsets": [ [ 526, 536 ] ], "normalized": [] }, { "id": "307_T17", "type": "Chemical", "text": [ "MCl gel CHP-20P" ], "offsets": [ [ 538, 553 ] ], "normalized": [] }, { "id": "307_T18", "type": "Chemical", "text": [ "Sephadex LH-20" ], "offsets": [ [ 559, 573 ] ], "normalized": [] }, { "id": "307_T19", "type": "Biological_Activity", "text": [ "Antioxidant" ], "offsets": [ [ 597, 608 ] ], "normalized": [] }, { "id": "307_T20", "type": "Chemical", "text": [ "chlorogenic acid" ], "offsets": [ [ 609, 625 ] ], "normalized": [] }, { "id": "307_T21", "type": "Chemical", "text": [ "quercetin-3-sambubioside" ], "offsets": [ [ 627, 651 ] ], "normalized": [] }, { "id": "307_T22", "type": "Chemical", "text": [ "n-BuOH" ], "offsets": [ [ 657, 663 ] ], "normalized": [] }, { "id": "307_T23", "type": "Chemical", "text": [ "methyl chlorogenate" ], "offsets": [ [ 678, 697 ] ], "normalized": [] }, { "id": "307_T24", "type": "Chemical", "text": [ "kaempferol", "-3-rhamnoside" ], "offsets": [ [ 699, 709 ], [ 724, 737 ] ], "normalized": [] }, { "id": "307_T25", "type": "Chemical", "text": [ "quercetin-3-rhamnoside" ], "offsets": [ [ 715, 737 ] ], "normalized": [] }, { "id": "307_T26", "type": "Chemical", "text": [ "ursolic acid" ], "offsets": [ [ 767, 779 ] ], "normalized": [] }, { "id": "307_T27", "type": "Chemical", "text": [ "2 alpha-hydroxyursolic acid" ], "offsets": [ [ 785, 812 ] ], "normalized": [] }, { "id": "307_T28", "type": "Chemical", "text": [ "EtOAc" ], "offsets": [ [ 818, 823 ] ], "normalized": [] }, { "id": "307_T29", "type": "Biological_Activity", "text": [ "Antioxidant" ], "offsets": [ [ 848, 859 ] ], "normalized": [] }, { "id": "307_T30", "type": "Chemical", "text": [ "flavonoids" ], "offsets": [ [ 860, 870 ] ], "normalized": [] }, { "id": "307_T31", "type": "Chemical", "text": [ "chlorogenic acid" ], "offsets": [ [ 875, 891 ] ], "normalized": [] }, { "id": "307_T33", "type": "Chemical", "text": [ "dichlorofluorescein" ], "offsets": [ [ 969, 988 ] ], "normalized": [] }, { "id": "307_T34", "type": "Chemical", "text": [ "DCF" ], "offsets": [ [ 990, 993 ] ], "normalized": [] }, { "id": "307_T35", "type": "Metabolite", "text": [ "chlorogenic acid" ], "offsets": [ [ 609, 625 ] ], "normalized": [] }, { "id": "307_T36", "type": "Metabolite", "text": [ "quercetin-3-sambubioside" ], "offsets": [ [ 627, 651 ] ], "normalized": [] }, { "id": "307_T37", "type": "Metabolite", "text": [ "methyl chlorogenate" ], "offsets": [ [ 678, 697 ] ], "normalized": [] }, { "id": "307_T38", "type": "Metabolite", "text": [ "kaempferol", "-3-rhamnoside" ], "offsets": [ [ 699, 709 ], [ 724, 737 ] ], "normalized": [] }, { "id": "307_T39", "type": "Metabolite", "text": [ "quercetin-3-rhamnoside" ], "offsets": [ [ 715, 737 ] ], "normalized": [] }, { "id": "307_T40", "type": "Metabolite", "text": [ "ursolic acid" ], "offsets": [ [ 767, 779 ] ], "normalized": [] }, { "id": "307_T41", "type": "Metabolite", "text": [ "2 alpha-hydroxyursolic acid" ], "offsets": [ [ 785, 812 ] ], "normalized": [] }, { "id": "307_T42", "type": "Metabolite", "text": [ "flavonoids" ], "offsets": [ [ 860, 870 ] ], "normalized": [] }, { "id": "307_T43", "type": "Metabolite", "text": [ "chlorogenic acid" ], "offsets": [ [ 875, 891 ] ], "normalized": [] }, { "id": "307_T44", "type": "Biological_Activity", "text": [ "antioxidant" ], "offsets": [ [ 4, 15 ] ], "normalized": [] }, { "id": "307_T5", "type": "Biological_Activity", "text": [ "inhibitory" ], "offsets": [ [ 914, 924 ] ], "normalized": [] } ]

[]

[]

[ { "id": "307_R1", "type": "Associated_With", "arg1_id": "307_T35", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R2", "type": "Associated_With", "arg1_id": "307_T20", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R3", "type": "Associated_With", "arg1_id": "307_T36", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R4", "type": "Associated_With", "arg1_id": "307_T21", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R5", "type": "Associated_With", "arg1_id": "307_T37", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R6", "type": "Associated_With", "arg1_id": "307_T23", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R7", "type": "Associated_With", "arg1_id": "307_T38", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R8", "type": "Associated_With", "arg1_id": "307_T24", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R9", "type": "Associated_With", "arg1_id": "307_T39", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R10", "type": "Associated_With", "arg1_id": "307_T25", "arg2_id": "307_T19", "normalized": [] }, { "id": "307_R11", "type": "Isolated_From", "arg1_id": "307_T35", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R12", "type": "Isolated_From", "arg1_id": "307_T36", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R13", "type": "Isolated_From", "arg1_id": "307_T37", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R14", "type": "Isolated_From", "arg1_id": "307_T38", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R15", "type": "Isolated_From", "arg1_id": "307_T39", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R16", "type": "Isolated_From", "arg1_id": "307_T40", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R17", "type": "Isolated_From", "arg1_id": "307_T41", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R18", "type": "Associated_With", "arg1_id": "307_T42", "arg2_id": "307_T29", "normalized": [] }, { "id": "307_R19", "type": "Associated_With", "arg1_id": "307_T30", "arg2_id": "307_T29", "normalized": [] }, { "id": "307_R20", "type": "Associated_With", "arg1_id": "307_T43", "arg2_id": "307_T29", "normalized": [] }, { "id": "307_R21", "type": "Associated_With", "arg1_id": "307_T31", "arg2_id": "307_T29", "normalized": [] }, { "id": "307_R26", "type": "Isolated_From", "arg1_id": "307_T42", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R27", "type": "Isolated_From", "arg1_id": "307_T43", "arg2_id": "307_T11", "normalized": [] }, { "id": "307_R22", "type": "Associated_With", "arg1_id": "307_T31", "arg2_id": "307_T5", "normalized": [] }, { "id": "307_R23", "type": "Associated_With", "arg1_id": "307_T43", "arg2_id": "307_T5", "normalized": [] }, { "id": "307_R24", "type": "Associated_With", "arg1_id": "307_T42", "arg2_id": "307_T5", "normalized": [] }, { "id": "307_R25", "type": "Associated_With", "arg1_id": "307_T30", "arg2_id": "307_T5", "normalized": [] } ]

[ { "id": "309", "type": "", "text": [ "The synthesis and the antimicrobial properties of a new series of cephalosporinic beta-lactam antibiotics is described. The data reported in the present paper show the potential of this type of substituted cephalosporins as new anti Gram-positive antibiotic drugs. In fact, all compounds tested showed a good in vitro antibacterial activity against the most relevant Gram-positive pathogens including resistant species that currently represent unmet medical need. On the contrary, the new synthesized compounds were found to be completely devoid of any activity on Gram-negative bacteria up to a concentration of the single agent of 128 microg/ml. \n" ], "offsets": [ [ 0, 649 ] ] } ]

[ { "id": "309_T1", "type": "Biological_Activity", "text": [ "antimicrobial" ], "offsets": [ [ 22, 35 ] ], "normalized": [] }, { "id": "309_T2", "type": "Chemical", "text": [ "cephalosporinic beta-lactam antibiotics" ], "offsets": [ [ 66, 105 ] ], "normalized": [] }, { "id": "309_T3", "type": "Biological_Activity", "text": [ "antibiotics" ], "offsets": [ [ 94, 105 ] ], "normalized": [] }, { "id": "309_T4", "type": "Chemical", "text": [ "substituted cephalosporins" ], "offsets": [ [ 194, 220 ] ], "normalized": [] }, { "id": "309_T6", "type": "Biological_Activity", "text": [ "antibiotic" ], "offsets": [ [ 247, 257 ] ], "normalized": [] }, { "id": "309_T7", "type": "Chemical", "text": [ "compounds" ], "offsets": [ [ 278, 287 ] ], "normalized": [] }, { "id": "309_T8", "type": "Biological_Activity", "text": [ "antibacterial" ], "offsets": [ [ 318, 331 ] ], "normalized": [] }, { "id": "309_T9", "type": "Chemical", "text": [ "compounds" ], "offsets": [ [ 501, 510 ] ], "normalized": [] }, { "id": "309_T5", "type": "Species", "text": [ "Gram-negative bacteria" ], "offsets": [ [ 565, 587 ] ], "normalized": [] }, { "id": "309_T11", "type": "Species", "text": [ "Gram-positive pathogens" ], "offsets": [ [ 367, 390 ] ], "normalized": [] }, { "id": "309_T12", "type": "Chemical", "text": [ "drugs" ], "offsets": [ [ 258, 263 ] ], "normalized": [] } ]

[]

[]

[ { "id": "309_R2", "type": "Associated_With", "arg1_id": "309_T4", "arg2_id": "309_T6", "normalized": [] }, { "id": "309_R3", "type": "Associated_With", "arg1_id": "309_T2", "arg2_id": "309_T3", "normalized": [] }, { "id": "309_R4", "type": "Associated_With", "arg1_id": "309_T2", "arg2_id": "309_T1", "normalized": [] } ]

[ { "id": "311", "type": "", "text": [ "BACKGROUND: Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. OBJECTIVE: We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. DESIGN: During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. RESULTS: Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. CONCLUSION: ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males. \n" ], "offsets": [ [ 0, 1690 ] ] } ]

[ { "id": "311_T1", "type": "Species", "text": [ "Vegetarians" ], "offsets": [ [ 12, 23 ] ], "normalized": [] }, { "id": "311_T2", "type": "Chemical", "text": [ "n-3 polyunsaturated fatty acids" ], "offsets": [ [ 73, 104 ] ], "normalized": [] }, { "id": "311_T3", "type": "Metabolite", "text": [ "n-3 polyunsaturated fatty acids" ], "offsets": [ [ 73, 104 ] ], "normalized": [] }, { "id": "311_T4", "type": "Chemical", "text": [ "PUFAs" ], "offsets": [ [ 106, 111 ] ], "normalized": [] }, { "id": "311_T5", "type": "Metabolite", "text": [ "PUFAs" ], "offsets": [ [ 106, 111 ] ], "normalized": [] }, { "id": "311_T6", "type": "Species", "text": [ "omnivores" ], "offsets": [ [ 121, 130 ] ], "normalized": [] }, { "id": "311_T7", "type": "Species", "text": [ "male vegetarians" ], "offsets": [ [ 156, 172 ] ], "normalized": [] }, { "id": "311_T8", "type": "Species", "text": [ "omnivores" ], "offsets": [ [ 216, 225 ] ], "normalized": [] }, { "id": "311_T9", "type": "Biological_Activity", "text": [ "platelet aggregability" ], "offsets": [ [ 185, 207 ] ], "normalized": [] }, { "id": "311_T10", "type": "Species", "text": [ "male vegetarians" ], "offsets": [ [ 262, 278 ] ], "normalized": [] }, { "id": "311_T11", "type": "Chemical", "text": [ "alpha-linolenic acid" ], "offsets": [ [ 332, 352 ] ], "normalized": [] }, { "id": "311_T12", "type": "Metabolite", "text": [ "alpha-linolenic acid" ], "offsets": [ [ 332, 352 ] ], "normalized": [] }, { "id": "311_T13", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 354, 357 ] ], "normalized": [] }, { "id": "311_T14", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 354, 357 ] ], "normalized": [] }, { "id": "311_T15", "type": "Chemical", "text": [ "PUFAs" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "311_T16", "type": "Metabolite", "text": [ "PUFAs" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "311_T17", "type": "Biological_Activity", "text": [ "platelet aggregability" ], "offsets": [ [ 447, 469 ] ], "normalized": [] }, { "id": "311_T18", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 723, 726 ] ], "normalized": [] }, { "id": "311_T19", "type": "Chemical", "text": [ "fat" ], "offsets": [ [ 612, 615 ] ], "normalized": [] }, { "id": "311_T20", "type": "Chemical", "text": [ "vegetable oils" ], "offsets": [ [ 634, 648 ] ], "normalized": [] }, { "id": "311_T21", "type": "Chemical", "text": [ "margarines" ], "offsets": [ [ 653, 663 ] ], "normalized": [] }, { "id": "311_T22", "type": "Chemical", "text": [ "safflower oil" ], "offsets": [ [ 744, 757 ] ], "normalized": [] }, { "id": "311_T23", "type": "Chemical", "text": [ "safflower oil-based margarine" ], "offsets": [ [ 762, 791 ] ], "normalized": [] }, { "id": "311_T24", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 840, 843 ] ], "normalized": [] }, { "id": "311_T25", "type": "Chemical", "text": [ "canola oil" ], "offsets": [ [ 861, 871 ] ], "normalized": [] }, { "id": "311_T26", "type": "Chemical", "text": [ "canola oil-based margarine" ], "offsets": [ [ 876, 902 ] ], "normalized": [] }, { "id": "311_T27", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 914, 917 ] ], "normalized": [] }, { "id": "311_T28", "type": "Chemical", "text": [ "linseed oil" ], "offsets": [ [ 935, 946 ] ], "normalized": [] }, { "id": "311_T29", "type": "Chemical", "text": [ "linseed oil-based margarine" ], "offsets": [ [ 951, 978 ] ], "normalized": [] }, { "id": "311_T30", "type": "Chemical", "text": [ "Eicosapentaenoic acid" ], "offsets": [ [ 1069, 1090 ] ], "normalized": [] }, { "id": "311_T31", "type": "Chemical", "text": [ "docosapentaenoic acid" ], "offsets": [ [ 1092, 1113 ] ], "normalized": [] }, { "id": "311_T32", "type": "Chemical", "text": [ "n-3 PUFAs" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "311_T33", "type": "Chemical", "text": [ "n-3", "PUFAs" ], "offsets": [ [ 1149, 1152 ], [ 1160, 1165 ] ], "normalized": [] }, { "id": "311_T34", "type": "Chemical", "text": [ "n-6 PUFAs" ], "offsets": [ [ 1156, 1165 ] ], "normalized": [] }, { "id": "311_T35", "type": "Chemical", "text": [ "arachidonic acid" ], "offsets": [ [ 1228, 1244 ] ], "normalized": [] }, { "id": "311_T36", "type": "Chemical", "text": [ "eicosapentaenoic acid" ], "offsets": [ [ 1248, 1269 ] ], "normalized": [] }, { "id": "311_T37", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 723, 726 ] ], "normalized": [] }, { "id": "311_T38", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 840, 843 ] ], "normalized": [] }, { "id": "311_T39", "type": "Metabolite", "text": [ "safflower oil" ], "offsets": [ [ 744, 757 ] ], "normalized": [] }, { "id": "311_T40", "type": "Metabolite", "text": [ "canola oil" ], "offsets": [ [ 861, 871 ] ], "normalized": [] }, { "id": "311_T41", "type": "Metabolite", "text": [ "linseed oil" ], "offsets": [ [ 935, 946 ] ], "normalized": [] }, { "id": "311_T42", "type": "Metabolite", "text": [ "Eicosapentaenoic acid" ], "offsets": [ [ 1069, 1090 ] ], "normalized": [] }, { "id": "311_T43", "type": "Metabolite", "text": [ "docosapentaenoic acid" ], "offsets": [ [ 1092, 1113 ] ], "normalized": [] }, { "id": "311_T44", "type": "Metabolite", "text": [ "n-3 PUFAs" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "311_T45", "type": "Metabolite", "text": [ "n-3", "PUFAs" ], "offsets": [ [ 1149, 1152 ], [ 1160, 1165 ] ], "normalized": [] }, { "id": "311_T46", "type": "Metabolite", "text": [ "n-6 PUFAs" ], "offsets": [ [ 1156, 1165 ] ], "normalized": [] }, { "id": "311_T47", "type": "Metabolite", "text": [ "arachidonic acid" ], "offsets": [ [ 1228, 1244 ] ], "normalized": [] }, { "id": "311_T48", "type": "Metabolite", "text": [ "eicosapentaenoic acid" ], "offsets": [ [ 1248, 1269 ] ], "normalized": [] }, { "id": "311_T49", "type": "Chemical", "text": [ "phospholipids" ], "offsets": [ [ 1308, 1321 ] ], "normalized": [] }, { "id": "311_T50", "type": "Chemical", "text": [ "phospholipids" ], "offsets": [ [ 1330, 1343 ] ], "normalized": [] }, { "id": "311_T51", "type": "Chemical", "text": [ "triacylglycerols" ], "offsets": [ [ 1349, 1365 ] ], "normalized": [] }, { "id": "311_T52", "type": "Metabolite", "text": [ "phospholipids" ], "offsets": [ [ 1308, 1321 ] ], "normalized": [] }, { "id": "311_T53", "type": "Metabolite", "text": [ "phospholipids" ], "offsets": [ [ 1330, 1343 ] ], "normalized": [] }, { "id": "311_T54", "type": "Metabolite", "text": [ "triacylglycerols" ], "offsets": [ [ 1349, 1365 ] ], "normalized": [] }, { "id": "311_T55", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 1392, 1395 ] ], "normalized": [] }, { "id": "311_T56", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 1392, 1395 ] ], "normalized": [] }, { "id": "311_T57", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 1404, 1407 ] ], "normalized": [] }, { "id": "311_T58", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 1404, 1407 ] ], "normalized": [] }, { "id": "311_T59", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 1435, 1438 ] ], "normalized": [] }, { "id": "311_T60", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 1435, 1438 ] ], "normalized": [] }, { "id": "311_T61", "type": "Metabolite", "text": [ "ALA" ], "offsets": [ [ 1527, 1530 ] ], "normalized": [] }, { "id": "311_T62", "type": "Chemical", "text": [ "ALA" ], "offsets": [ [ 1527, 1530 ] ], "normalized": [] }, { "id": "311_T63", "type": "Species", "text": [ "canola" ], "offsets": [ [ 1552, 1558 ] ], "normalized": [] }, { "id": "311_T64", "type": "Species", "text": [ "linseed" ], "offsets": [ [ 1563, 1570 ] ], "normalized": [] }, { "id": "311_T65", "type": "Species", "text": [ "safflower" ], "offsets": [ [ 744, 753 ] ], "normalized": [] }, { "id": "311_T66", "type": "Species", "text": [ "canola" ], "offsets": [ [ 861, 867 ] ], "normalized": [] }, { "id": "311_T67", "type": "Species", "text": [ "linseed" ], "offsets": [ [ 935, 942 ] ], "normalized": [] }, { "id": "311_T68", "type": "Chemical", "text": [ "n-3 PUFA" ], "offsets": [ [ 1599, 1607 ] ], "normalized": [] }, { "id": "311_T69", "type": "Chemical", "text": [ "phospholipids" ], "offsets": [ [ 1635, 1648 ] ], "normalized": [] }, { "id": "311_T70", "type": "Metabolite", "text": [ "phospholipids" ], "offsets": [ [ 1635, 1648 ] ], "normalized": [] }, { "id": "311_T71", "type": "Chemical", "text": [ "lipids" ], "offsets": [ [ 1661, 1667 ] ], "normalized": [] }, { "id": "311_T72", "type": "Metabolite", "text": [ "lipids" ], "offsets": [ [ 1661, 1667 ] ], "normalized": [] }, { "id": "311_T73", "type": "Species", "text": [ "vegetarian males" ], "offsets": [ [ 1671, 1687 ] ], "normalized": [] }, { "id": "311_T74", "type": "Chemical", "text": [ "thromboxane" ], "offsets": [ [ 419, 430 ] ], "normalized": [] }, { "id": "311_T75", "type": "Metabolite", "text": [ "thromboxane" ], "offsets": [ [ 419, 430 ] ], "normalized": [] }, { "id": "311_T76", "type": "Metabolite", "text": [ "n-3 PUFA" ], "offsets": [ [ 1599, 1607 ] ], "normalized": [] } ]

[]

[]

[ { "id": "311_R1", "type": "Isolated_From", "arg1_id": "311_T3", "arg2_id": "311_T1", "normalized": [] }, { "id": "311_R2", "type": "Isolated_From", "arg1_id": "311_T3", "arg2_id": "311_T6", "normalized": [] }, { "id": "311_R3", "type": "Isolated_From", "arg1_id": "311_T5", "arg2_id": "311_T6", "normalized": [] }, { "id": "311_R4", "type": "Isolated_From", "arg1_id": "311_T5", "arg2_id": "311_T1", "normalized": [] }, { "id": "311_R5", "type": "Isolated_From", "arg1_id": "311_T41", "arg2_id": "311_T67", "normalized": [] }, { "id": "311_R6", "type": "Isolated_From", "arg1_id": "311_T40", "arg2_id": "311_T66", "normalized": [] }, { "id": "311_R7", "type": "Isolated_From", "arg1_id": "311_T39", "arg2_id": "311_T65", "normalized": [] }, { "id": "311_R8", "type": "Isolated_From", "arg1_id": "311_T61", "arg2_id": "311_T63", "normalized": [] }, { "id": "311_R9", "type": "Isolated_From", "arg1_id": "311_T61", "arg2_id": "311_T64", "normalized": [] }, { "id": "311_R10", "type": "Isolated_From", "arg1_id": "311_T70", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R11", "type": "Isolated_From", "arg1_id": "311_T72", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R12", "type": "Isolated_From", "arg1_id": "311_T42", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R13", "type": "Isolated_From", "arg1_id": "311_T43", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R14", "type": "Isolated_From", "arg1_id": "311_T47", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R15", "type": "Isolated_From", "arg1_id": "311_T48", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R16", "type": "Isolated_From", "arg1_id": "311_T52", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R17", "type": "Isolated_From", "arg1_id": "311_T53", "arg2_id": "311_T73", "normalized": [] }, { "id": "311_R18", "type": "Isolated_From", "arg1_id": "311_T54", "arg2_id": "311_T73", "normalized": [] } ]

[ { "id": "313", "type": "", "text": [ "Organic nitrate esters, such as glyceryl trinitrate and isosorbide dinitrate, are a class of compounds used to treat a variety of vascular ailments. Their effectiveness relies on their ability to be bioactivated to nitric oxide (NO) which, in turn, relaxes vascular smooth muscle. Although there have been many biological studies that indicate that NO can be formed from organic nitrate esters in a biological environment, the chemical mechanism by which this occurs has yet to be established. Previous studies have implicated both flavins and thiols in organic nitrate ester bioactivation. Thus, we examined the chemical interactions of flavins and thiols with organic nitrate esters as a means of determining the role these species may play in NO production. Based on these studies we concluded that a reasonable chemical mechanism for organic nitrate ester bioactivation involves reduction to the organic nitrite ester followed by conversion to a nitrosothiol. The release of NO from nitrosothiols can occur via a variety of processes including reaction with dihydroflavins and NADH. \n" ], "offsets": [ [ 0, 1089 ] ] } ]

[ { "id": "313_T1", "type": "Chemical", "text": [ "Organic nitrate esters" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "313_T2", "type": "Chemical", "text": [ "glyceryl trinitrate" ], "offsets": [ [ 32, 51 ] ], "normalized": [] }, { "id": "313_T3", "type": "Chemical", "text": [ "isosorbide dinitrate" ], "offsets": [ [ 56, 76 ] ], "normalized": [] }, { "id": "313_T5", "type": "Chemical", "text": [ "nitric oxide" ], "offsets": [ [ 215, 227 ] ], "normalized": [] }, { "id": "313_T6", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 229, 231 ] ], "normalized": [] }, { "id": "313_T7", "type": "Metabolite", "text": [ "nitric oxide" ], "offsets": [ [ 215, 227 ] ], "normalized": [] }, { "id": "313_T8", "type": "Metabolite", "text": [ "NO" ], "offsets": [ [ 229, 231 ] ], "normalized": [] }, { "id": "313_T10", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 349, 351 ] ], "normalized": [] }, { "id": "313_T11", "type": "Metabolite", "text": [ "NO" ], "offsets": [ [ 349, 351 ] ], "normalized": [] }, { "id": "313_T12", "type": "Chemical", "text": [ "organic nitrate esters" ], "offsets": [ [ 371, 393 ] ], "normalized": [] }, { "id": "313_T13", "type": "Chemical", "text": [ "flavins" ], "offsets": [ [ 532, 539 ] ], "normalized": [] }, { "id": "313_T14", "type": "Chemical", "text": [ "thiols" ], "offsets": [ [ 544, 550 ] ], "normalized": [] }, { "id": "313_T15", "type": "Chemical", "text": [ "organic nitrate ester" ], "offsets": [ [ 554, 575 ] ], "normalized": [] }, { "id": "313_T16", "type": "Biological_Activity", "text": [ "bioactivation" ], "offsets": [ [ 576, 589 ] ], "normalized": [] }, { "id": "313_T17", "type": "Chemical", "text": [ "flavins" ], "offsets": [ [ 638, 645 ] ], "normalized": [] }, { "id": "313_T18", "type": "Chemical", "text": [ "thiols" ], "offsets": [ [ 650, 656 ] ], "normalized": [] }, { "id": "313_T19", "type": "Chemical", "text": [ "organic nitrate esters" ], "offsets": [ [ 662, 684 ] ], "normalized": [] }, { "id": "313_T20", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 746, 748 ] ], "normalized": [] }, { "id": "313_T22", "type": "Chemical", "text": [ "organic nitrate ester" ], "offsets": [ [ 838, 859 ] ], "normalized": [] }, { "id": "313_T23", "type": "Biological_Activity", "text": [ "bioactivation" ], "offsets": [ [ 860, 873 ] ], "normalized": [] }, { "id": "313_T24", "type": "Chemical", "text": [ "organic nitrite ester" ], "offsets": [ [ 900, 921 ] ], "normalized": [] }, { "id": "313_T25", "type": "Metabolite", "text": [ "organic nitrite ester" ], "offsets": [ [ 900, 921 ] ], "normalized": [] }, { "id": "313_T26", "type": "Chemical", "text": [ "nitrosothiol" ], "offsets": [ [ 950, 962 ] ], "normalized": [] }, { "id": "313_T27", "type": "Metabolite", "text": [ "nitrosothiol" ], "offsets": [ [ 950, 962 ] ], "normalized": [] }, { "id": "313_T28", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 979, 981 ] ], "normalized": [] }, { "id": "313_T29", "type": "Metabolite", "text": [ "NO" ], "offsets": [ [ 979, 981 ] ], "normalized": [] }, { "id": "313_T30", "type": "Chemical", "text": [ "nitrosothiols" ], "offsets": [ [ 987, 1000 ] ], "normalized": [] }, { "id": "313_T31", "type": "Metabolite", "text": [ "nitrosothiols" ], "offsets": [ [ 987, 1000 ] ], "normalized": [] }, { "id": "313_T32", "type": "Chemical", "text": [ "dihydroflavins" ], "offsets": [ [ 1063, 1077 ] ], "normalized": [] }, { "id": "313_T33", "type": "Chemical", "text": [ "NADH" ], "offsets": [ [ 1082, 1086 ] ], "normalized": [] } ]

[]

[]

[ { "id": "313_R4", "type": "Metabolite_Of", "arg1_id": "313_T7", "arg2_id": "313_T2", "normalized": [] }, { "id": "313_R5", "type": "Metabolite_Of", "arg1_id": "313_T7", "arg2_id": "313_T3", "normalized": [] }, { "id": "313_R6", "type": "Metabolite_Of", "arg1_id": "313_T8", "arg2_id": "313_T3", "normalized": [] }, { "id": "313_R7", "type": "Metabolite_Of", "arg1_id": "313_T8", "arg2_id": "313_T2", "normalized": [] }, { "id": "313_R12", "type": "Metabolite_Of", "arg1_id": "313_T11", "arg2_id": "313_T12", "normalized": [] }, { "id": "313_R13", "type": "Associated_With", "arg1_id": "313_T13", "arg2_id": "313_T16", "normalized": [] }, { "id": "313_R14", "type": "Associated_With", "arg1_id": "313_T14", "arg2_id": "313_T16", "normalized": [] }, { "id": "313_R15", "type": "Metabolite_Of", "arg1_id": "313_T25", "arg2_id": "313_T22", "normalized": [] }, { "id": "313_R16", "type": "Metabolite_Of", "arg1_id": "313_T27", "arg2_id": "313_T24", "normalized": [] }, { "id": "313_R17", "type": "Metabolite_Of", "arg1_id": "313_T29", "arg2_id": "313_T30", "normalized": [] } ]

[ { "id": "315", "type": "", "text": [ "Plant cell suspension cultures of Rauwolfia produce within 1 week approximately 250 nkat/l of raucaffricine-O-beta-D-glucosidase. A five step procedure using anion exchange chromatography, chromatography on hydroxylapatite, gel filtration and FPLC-chromatography on Mono Q and Mono P delivered in a yield of 0.9% approximately 1200-fold enriched glucosidase. A short protocol employing DEAE sepharose, TSK 55 S gel chromatography and purification on Mono Q gave a 5% recovery of glucosidase which was 340-fold enriched. SDS-PAGE showed a Mr for the enzyme of 61 kDa. The enzyme is not glycosylated. Structural investigation of the enzyme product, vomilenine, demonstrated that the alkaloid exists in aqueous solutions in an equilibrium of 21(R)- and 21(S)-vomilenine in a ratio of 3.4:1. Proteolysis of the pure enzyme with endoproteinase Lys C revealed six peptide fragments with 6-24 amino acids which were sequenced. The two largest fragments showed sequences, of which the motif Val-Thr-Glu-Asn-Gly is typical for beta-glucosidases. Sequence alignment of these fragments demonstrated high homologies to linamarase from Manihot esculenta (81% identity) or to beta-glucosidase from Prunus avium (79% identity). Raucaffricine-O-beta-D-glucosidase seems to be a new member of the family 1 of glycosyl hydrolases. \n" ], "offsets": [ [ 0, 1315 ] ] } ]

[ { "id": "315_T1", "type": "Species", "text": [ "Rauwolfia" ], "offsets": [ [ 34, 43 ] ], "normalized": [] }, { "id": "315_T2", "type": "Protein", "text": [ "raucaffricine-O-beta-D-glucosidase" ], "offsets": [ [ 94, 128 ] ], "normalized": [] }, { "id": "315_T3", "type": "Chemical", "text": [ "anion" ], "offsets": [ [ 158, 163 ] ], "normalized": [] }, { "id": "315_T4", "type": "Chemical", "text": [ "hydroxylapatite" ], "offsets": [ [ 207, 222 ] ], "normalized": [] }, { "id": "315_T5", "type": "Protein", "text": [ "glucosidase" ], "offsets": [ [ 347, 358 ] ], "normalized": [] }, { "id": "315_T6", "type": "Chemical", "text": [ "DEAE sepharose" ], "offsets": [ [ 387, 401 ] ], "normalized": [] }, { "id": "315_T7", "type": "Chemical", "text": [ "TSK 55 S gel" ], "offsets": [ [ 403, 415 ] ], "normalized": [] }, { "id": "315_T8", "type": "Chemical", "text": [ "Mono Q" ], "offsets": [ [ 451, 457 ] ], "normalized": [] }, { "id": "315_T9", "type": "Protein", "text": [ "glucosidase" ], "offsets": [ [ 480, 491 ] ], "normalized": [] }, { "id": "315_T10", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 550, 556 ] ], "normalized": [] }, { "id": "315_T11", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 572, 578 ] ], "normalized": [] }, { "id": "315_T12", "type": "Chemical", "text": [ "glycosylated" ], "offsets": [ [ 586, 598 ] ], "normalized": [] }, { "id": "315_T13", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 632, 638 ] ], "normalized": [] }, { "id": "315_T15", "type": "Chemical", "text": [ "vomilenine" ], "offsets": [ [ 648, 658 ] ], "normalized": [] }, { "id": "315_T16", "type": "Chemical", "text": [ "alkaloid" ], "offsets": [ [ 682, 690 ] ], "normalized": [] }, { "id": "315_T17", "type": "Chemical", "text": [ "21(R)-", "vomilenine" ], "offsets": [ [ 740, 746 ], [ 757, 767 ] ], "normalized": [] }, { "id": "315_T18", "type": "Chemical", "text": [ "21(S)-vomilenine" ], "offsets": [ [ 751, 767 ] ], "normalized": [] }, { "id": "315_T19", "type": "Metabolite", "text": [ "vomilenine" ], "offsets": [ [ 648, 658 ] ], "normalized": [] }, { "id": "315_T20", "type": "Metabolite", "text": [ "21(R)-", "vomilenine" ], "offsets": [ [ 740, 746 ], [ 757, 767 ] ], "normalized": [] }, { "id": "315_T21", "type": "Metabolite", "text": [ "21(S)-vomilenine" ], "offsets": [ [ 751, 767 ] ], "normalized": [] }, { "id": "315_T22", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 813, 819 ] ], "normalized": [] }, { "id": "315_T23", "type": "Protein", "text": [ "endoproteinase Lys C" ], "offsets": [ [ 825, 845 ] ], "normalized": [] }, { "id": "315_T25", "type": "Chemical", "text": [ "peptide fragments" ], "offsets": [ [ 859, 876 ] ], "normalized": [] }, { "id": "315_T26", "type": "Chemical", "text": [ "amino acids" ], "offsets": [ [ 887, 898 ] ], "normalized": [] }, { "id": "315_T27", "type": "Chemical", "text": [ "Val-Thr-Glu-Asn-Gly" ], "offsets": [ [ 984, 1003 ] ], "normalized": [] }, { "id": "315_T28", "type": "Protein", "text": [ "beta-glucosidases" ], "offsets": [ [ 1019, 1036 ] ], "normalized": [] }, { "id": "315_T29", "type": "Protein", "text": [ "linamarase" ], "offsets": [ [ 1108, 1118 ] ], "normalized": [] }, { "id": "315_T30", "type": "Species", "text": [ "Manihot esculenta" ], "offsets": [ [ 1124, 1141 ] ], "normalized": [] }, { "id": "315_T31", "type": "Protein", "text": [ "beta-glucosidase" ], "offsets": [ [ 1163, 1179 ] ], "normalized": [] }, { "id": "315_T32", "type": "Species", "text": [ "Prunus avium" ], "offsets": [ [ 1185, 1197 ] ], "normalized": [] }, { "id": "315_T33", "type": "Protein", "text": [ "Raucaffricine-O-beta-D-glucosidase" ], "offsets": [ [ 1214, 1248 ] ], "normalized": [] }, { "id": "315_T34", "type": "Protein", "text": [ "glycosyl hydrolases" ], "offsets": [ [ 1293, 1312 ] ], "normalized": [] }, { "id": "315_T35", "type": "Chemical", "text": [ "Mono Q" ], "offsets": [ [ 267, 273 ] ], "normalized": [] }, { "id": "315_T36", "type": "Chemical", "text": [ "Mono P" ], "offsets": [ [ 278, 284 ] ], "normalized": [] } ]

[]

[]

[ { "id": "315_R2", "type": "Isolated_From", "arg1_id": "315_T19", "arg2_id": "315_T1", "normalized": [] }, { "id": "315_R3", "type": "Isolated_From", "arg1_id": "315_T20", "arg2_id": "315_T1", "normalized": [] }, { "id": "315_R4", "type": "Isolated_From", "arg1_id": "315_T21", "arg2_id": "315_T1", "normalized": [] } ]

[ { "id": "317", "type": "", "text": [ "The hydroxylation at C-2 of testosterone and 5alpha-dihydrotestosterone is measured by isolation of HTO after incubating \"metabolically labile\" tritium labeled steroids with the enzymes. After hydroxylation of testosterone in rat liver 2alpha-hydroxytestosterone was isolated and identified by gaschromatography and mass spectra. \n" ], "offsets": [ [ 0, 331 ] ] } ]

[ { "id": "317_T1", "type": "Chemical", "text": [ "testosterone" ], "offsets": [ [ 28, 40 ] ], "normalized": [] }, { "id": "317_T2", "type": "Chemical", "text": [ "5alpha-dihydrotestosterone" ], "offsets": [ [ 45, 71 ] ], "normalized": [] }, { "id": "317_T3", "type": "Chemical", "text": [ "HTO" ], "offsets": [ [ 100, 103 ] ], "normalized": [] }, { "id": "317_T4", "type": "Chemical", "text": [ "tritium" ], "offsets": [ [ 144, 151 ] ], "normalized": [] }, { "id": "317_T5", "type": "Chemical", "text": [ "tritium labeled steroids" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "317_T6", "type": "Species", "text": [ "rat" ], "offsets": [ [ 226, 229 ] ], "normalized": [] }, { "id": "317_T7", "type": "Protein", "text": [ "enzymes" ], "offsets": [ [ 178, 185 ] ], "normalized": [] }, { "id": "317_T8", "type": "Chemical", "text": [ "testosterone" ], "offsets": [ [ 210, 222 ] ], "normalized": [] }, { "id": "317_T9", "type": "Chemical", "text": [ "2alpha-hydroxytestosterone" ], "offsets": [ [ 236, 262 ] ], "normalized": [] }, { "id": "317_T10", "type": "Metabolite", "text": [ "2alpha-hydroxytestosterone" ], "offsets": [ [ 236, 262 ] ], "normalized": [] }, { "id": "317_T11", "type": "Spectral_Data", "text": [ "gaschromatography and mass spectra" ], "offsets": [ [ 294, 328 ] ], "normalized": [] } ]

[]

[]

[ { "id": "317_R1", "type": "Metabolite_Of", "arg1_id": "317_T10", "arg2_id": "317_T8", "normalized": [] }, { "id": "317_R2", "type": "Isolated_From", "arg1_id": "317_T10", "arg2_id": "317_T6", "normalized": [] }, { "id": "317_R3", "type": "Associated_With", "arg1_id": "317_T10", "arg2_id": "317_T11", "normalized": [] }, { "id": "317_R4", "type": "Associated_With", "arg1_id": "317_T9", "arg2_id": "317_T11", "normalized": [] } ]

[ { "id": "319", "type": "", "text": [ "Concentration of L-cystathionine was distinctly increased in rabbit brain within the period of maximal action of drugs, stimulating the central nervous system (phenamine, strychnine corasole). A distinct decrease in content of L-cystathionine was observed within one hour after the administration of strychnine and corasole. \n" ], "offsets": [ [ 0, 327 ] ] } ]

[ { "id": "319_T1", "type": "Chemical", "text": [ "L-cystathionine" ], "offsets": [ [ 17, 32 ] ], "normalized": [] }, { "id": "319_T2", "type": "Metabolite", "text": [ "L-cystathionine" ], "offsets": [ [ 17, 32 ] ], "normalized": [] }, { "id": "319_T3", "type": "Species", "text": [ "rabbit" ], "offsets": [ [ 61, 67 ] ], "normalized": [] }, { "id": "319_T5", "type": "Chemical", "text": [ "phenamine" ], "offsets": [ [ 161, 170 ] ], "normalized": [] }, { "id": "319_T7", "type": "Chemical", "text": [ "strychnine" ], "offsets": [ [ 172, 182 ] ], "normalized": [] }, { "id": "319_T8", "type": "Chemical", "text": [ "corasole" ], "offsets": [ [ 183, 191 ] ], "normalized": [] }, { "id": "319_T10", "type": "Chemical", "text": [ "strychnine" ], "offsets": [ [ 301, 311 ] ], "normalized": [] }, { "id": "319_T11", "type": "Chemical", "text": [ "corasole" ], "offsets": [ [ 316, 324 ] ], "normalized": [] }, { "id": "319_T6", "type": "Chemical", "text": [ "L-cystathionine" ], "offsets": [ [ 228, 243 ] ], "normalized": [] }, { "id": "319_T12", "type": "Metabolite", "text": [ "L-cystathionine" ], "offsets": [ [ 228, 243 ] ], "normalized": [] }, { "id": "319_T9", "type": "Chemical", "text": [ "drugs" ], "offsets": [ [ 114, 119 ] ], "normalized": [] }, { "id": "319_T4", "type": "Biological_Activity", "text": [ "stimulating" ], "offsets": [ [ 121, 132 ] ], "normalized": [] } ]

[]

[]

[ { "id": "319_R7", "type": "Isolated_From", "arg1_id": "319_T2", "arg2_id": "319_T3", "normalized": [] }, { "id": "319_R1", "type": "Associated_With", "arg1_id": "319_T5", "arg2_id": "319_T4", "normalized": [] }, { "id": "319_R2", "type": "Associated_With", "arg1_id": "319_T8", "arg2_id": "319_T4", "normalized": [] }, { "id": "319_R3", "type": "Associated_With", "arg1_id": "319_T7", "arg2_id": "319_T4", "normalized": [] } ]

[ { "id": "321", "type": "", "text": [ "It is shown that 6-ketoderivatives of natural sapogenins, viz. agigenin, diosgenin and alliogenin, display the anabolic activity and do not manifest any androgenic properties. The compoud IV/(25 R)-5alpha-spirostan-2alpha, 3beta, 5alpha-triol-6-OH/produces an accelerated gain of weight in rats, and also an increase in the weight of the liver, heart, kidneys, musculus tibiliasis anterior and augments the total amount of protein therein. All of the above-mentioned changes become more pronounced with the study substance introduced to young animals. Castration of sexually immature rats greatly mitigates the anabolic effect of the compound IV. \n" ], "offsets": [ [ 0, 648 ] ] } ]

[ { "id": "321_T1", "type": "Chemical", "text": [ "6-ketoderivatives of natural sapogenins" ], "offsets": [ [ 17, 56 ] ], "normalized": [] }, { "id": "321_T2", "type": "Chemical", "text": [ "6-ketoderivatives of", "agigenin" ], "offsets": [ [ 17, 37 ], [ 63, 71 ] ], "normalized": [] }, { "id": "321_T3", "type": "Metabolite", "text": [ "agigenin" ], "offsets": [ [ 63, 71 ] ], "normalized": [] }, { "id": "321_T4", "type": "Chemical", "text": [ "6-ketoderivatives of", "diosgenin" ], "offsets": [ [ 17, 37 ], [ 73, 82 ] ], "normalized": [] }, { "id": "321_T5", "type": "Chemical", "text": [ "diosgenin" ], "offsets": [ [ 73, 82 ] ], "normalized": [] }, { "id": "321_T6", "type": "Metabolite", "text": [ "diosgenin" ], "offsets": [ [ 73, 82 ] ], "normalized": [] }, { "id": "321_T7", "type": "Chemical", "text": [ "agigenin" ], "offsets": [ [ 63, 71 ] ], "normalized": [] }, { "id": "321_T8", "type": "Chemical", "text": [ "6-ketoderivatives of", "alliogenin" ], "offsets": [ [ 17, 37 ], [ 87, 97 ] ], "normalized": [] }, { "id": "321_T9", "type": "Chemical", "text": [ "alliogenin" ], "offsets": [ [ 87, 97 ] ], "normalized": [] }, { "id": "321_T10", "type": "Metabolite", "text": [ "alliogenin" ], "offsets": [ [ 87, 97 ] ], "normalized": [] }, { "id": "321_T11", "type": "Biological_Activity", "text": [ "anabolic" ], "offsets": [ [ 111, 119 ] ], "normalized": [] }, { "id": "321_T12", "type": "Chemical", "text": [ "(25 R)-5alpha-spirostan-2alpha, 3beta, 5alpha-triol-6-OH" ], "offsets": [ [ 191, 247 ] ], "normalized": [] }, { "id": "321_T13", "type": "Chemical", "text": [ "compoud IV" ], "offsets": [ [ 180, 190 ] ], "normalized": [] }, { "id": "321_T14", "type": "Biological_Activity", "text": [ "androgenic" ], "offsets": [ [ 153, 163 ] ], "normalized": [] }, { "id": "321_T15", "type": "Species", "text": [ "rats" ], "offsets": [ [ 290, 294 ] ], "normalized": [] }, { "id": "321_T16", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 423, 430 ] ], "normalized": [] }, { "id": "321_T17", "type": "Species", "text": [ "rats" ], "offsets": [ [ 584, 588 ] ], "normalized": [] }, { "id": "321_T18", "type": "Biological_Activity", "text": [ "anabolic" ], "offsets": [ [ 611, 619 ] ], "normalized": [] }, { "id": "321_T20", "type": "Chemical", "text": [ "compound IV" ], "offsets": [ [ 634, 645 ] ], "normalized": [] } ]

[]

[]

[ { "id": "321_R1", "type": "Associated_With", "arg1_id": "321_T8", "arg2_id": "321_T11", "normalized": [] }, { "id": "321_R2", "type": "Associated_With", "arg1_id": "321_T4", "arg2_id": "321_T11", "normalized": [] }, { "id": "321_R3", "type": "Associated_With", "arg1_id": "321_T2", "arg2_id": "321_T11", "normalized": [] }, { "id": "321_R4", "type": "Associated_With", "arg1_id": "321_T13", "arg2_id": "321_T14", "normalized": [] }, { "id": "321_R5", "type": "Associated_With", "arg1_id": "321_T12", "arg2_id": "321_T14", "normalized": [] }, { "id": "321_R6", "type": "Associated_With", "arg1_id": "321_T13", "arg2_id": "321_T18", "normalized": [] }, { "id": "321_R7", "type": "Associated_With", "arg1_id": "321_T12", "arg2_id": "321_T18", "normalized": [] }, { "id": "321_R10", "type": "Associated_With", "arg1_id": "321_T20", "arg2_id": "321_T18", "normalized": [] } ]

[ { "id": "323", "type": "", "text": [ "\n" ], "offsets": [ [ 0, 1 ] ] } ]

[]

[]

[]

[]

[ { "id": "325", "type": "", "text": [ "Three triterpenoid saponins were isolated from the methanol extract of the stem bark of Kalopanax pictum Nakai var. magnificum (Araliaceae). The structures of these saponins were identified as hederagenin 3-O-alpha-L-arabinopyranoside, hederagenin-3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinop yranoside and 3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester. \n" ], "offsets": [ [ 0, 482 ] ] } ]

[ { "id": "325_T1", "type": "Chemical", "text": [ "triterpenoid saponins" ], "offsets": [ [ 6, 27 ] ], "normalized": [] }, { "id": "325_T2", "type": "Chemical", "text": [ "methanol" ], "offsets": [ [ 51, 59 ] ], "normalized": [] }, { "id": "325_T3", "type": "Species", "text": [ "Kalopanax pictum Nakai var. magnificum" ], "offsets": [ [ 88, 126 ] ], "normalized": [] }, { "id": "325_T4", "type": "Chemical", "text": [ "saponins" ], "offsets": [ [ 165, 173 ] ], "normalized": [] }, { "id": "325_T5", "type": "Chemical", "text": [ "hederagenin 3-O-alpha-L-arabinopyranoside" ], "offsets": [ [ 193, 234 ] ], "normalized": [] }, { "id": "325_T6", "type": "Metabolite", "text": [ "hederagenin 3-O-alpha-L-arabinopyranoside" ], "offsets": [ [ 193, 234 ] ], "normalized": [] }, { "id": "325_T7", "type": "Chemical", "text": [ "hederagenin-3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinop yranoside" ], "offsets": [ [ 236, 309 ] ], "normalized": [] }, { "id": "325_T8", "type": "Metabolite", "text": [ "hederagenin-3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinop yranoside" ], "offsets": [ [ 236, 309 ] ], "normalized": [] }, { "id": "325_T9", "type": "Chemical", "text": [ "3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester" ], "offsets": [ [ 314, 479 ] ], "normalized": [] }, { "id": "325_T10", "type": "Metabolite", "text": [ "3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester" ], "offsets": [ [ 314, 479 ] ], "normalized": [] }, { "id": "325_T11", "type": "Species", "text": [ "Araliaceae" ], "offsets": [ [ 128, 138 ] ], "normalized": [] } ]

[]

[]

[ { "id": "325_R1", "type": "Isolated_From", "arg1_id": "325_T6", "arg2_id": "325_T3", "normalized": [] }, { "id": "325_R2", "type": "Isolated_From", "arg1_id": "325_T8", "arg2_id": "325_T3", "normalized": [] }, { "id": "325_R3", "type": "Isolated_From", "arg1_id": "325_T10", "arg2_id": "325_T3", "normalized": [] } ]

[ { "id": "327", "type": "", "text": [ "A key step in fungal biosynthesis of lysine, enzymatic reduction of alpha-aminoadipate at C6 to the semialdehyde, requires two gene products in Saccharomyces cerevisiae, Lys2 and Lys5. Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis. Lys2 was subcloned from S. cerevisiae and expressed in and purified from Escherichia coli as a full-length 155-kDa enzyme, as a 105-kDa adenylation/peptidyl carrier protein (A/PCP) fragment (residues 1-924), and as a 14-kDa PCP fragment (residues 809-924). The apo-PCP fragment was covalently modified to phosphopantetheinylated holo-PCP by pure Lys5 and CoASH with a Km of 1 microM and kcat of 3 min-1 for both the PCP and CoASH substrates. The adenylation domain of the A/PCP fragment activated S-carboxymethyl-L-cysteine (kcat/Km = 840 mM-1 min-1) at 16% the efficiency of L-alpha-aminoadipate in [32P]PPi/ATP exchange assays. The holo form of the A/PCP 105-kDa fragment of Lys2 covalently aminoacylated itself with [35S]S-carboxymethyl-L-cysteine. Addition of NADPH discharged the covalent acyl-S-PCP Lys2, consistent with a reductive cleavage of the acyl-S-enzyme intermediate. These results identify the Lys5/Lys2 pair as a two-component system in which Lys5 covalently primes Lys2, allowing alpha-aminoadipate reductase activity by holo-Lys2 with catalytic cycles of autoaminoacylation and reductive cleavage. This is a novel mechanism for a fungal enzyme essential for amino acid metabolism. \n" ], "offsets": [ [ 0, 1607 ] ] } ]

[ { "id": "327_T1", "type": "Species", "text": [ "fungal" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "327_T2", "type": "Chemical", "text": [ "lysine" ], "offsets": [ [ 37, 43 ] ], "normalized": [] }, { "id": "327_T3", "type": "Metabolite", "text": [ "lysine" ], "offsets": [ [ 37, 43 ] ], "normalized": [] }, { "id": "327_T5", "type": "Chemical", "text": [ "alpha-aminoadipate" ], "offsets": [ [ 68, 86 ] ], "normalized": [] }, { "id": "327_T6", "type": "Metabolite", "text": [ "alpha-aminoadipate" ], "offsets": [ [ 68, 86 ] ], "normalized": [] }, { "id": "327_T7", "type": "Chemical", "text": [ "semialdehyde", "alpha-aminoadipate" ], "offsets": [ [ 100, 112 ], [ 68, 86 ] ], "normalized": [] }, { "id": "327_T8", "type": "Metabolite", "text": [ "semialdehyde", "alpha-aminoadipate" ], "offsets": [ [ 100, 112 ], [ 68, 86 ] ], "normalized": [] }, { "id": "327_T9", "type": "Species", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 144, 168 ] ], "normalized": [] }, { "id": "327_T10", "type": "Protein", "text": [ "Lys2" ], "offsets": [ [ 170, 174 ] ], "normalized": [] }, { "id": "327_T11", "type": "Protein", "text": [ "Lys5" ], "offsets": [ [ 179, 183 ] ], "normalized": [] }, { "id": "327_T13", "type": "Protein", "text": [ "Lys5" ], "offsets": [ [ 215, 219 ] ], "normalized": [] }, { "id": "327_T14", "type": "Chemical", "text": [ "coenzyme A" ], "offsets": [ [ 282, 292 ] ], "normalized": [] }, { "id": "327_T15", "type": "Chemical", "text": [ "CoASH" ], "offsets": [ [ 294, 299 ] ], "normalized": [] }, { "id": "327_T16", "type": "Chemical", "text": [ "phosphopantetheinylate" ], "offsets": [ [ 321, 343 ] ], "normalized": [] }, { "id": "327_T17", "type": "Protein", "text": [ "Lys2" ], "offsets": [ [ 366, 370 ] ], "normalized": [] }, { "id": "327_T18", "type": "Protein", "text": [ "Lys2" ], "offsets": [ [ 403, 407 ] ], "normalized": [] }, { "id": "327_T19", "type": "Species", "text": [ "S. cerevisiae" ], "offsets": [ [ 427, 440 ] ], "normalized": [] }, { "id": "327_T20", "type": "Species", "text": [ "Escherichia coli" ], "offsets": [ [ 476, 492 ] ], "normalized": [] }, { "id": "327_T21", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 518, 524 ] ], "normalized": [] }, { "id": "327_T22", "type": "Protein", "text": [ "adenylation/peptidyl carrier protein" ], "offsets": [ [ 539, 575 ] ], "normalized": [] }, { "id": "327_T23", "type": "Protein", "text": [ "A/PCP" ], "offsets": [ [ 577, 582 ] ], "normalized": [] }, { "id": "327_T24", "type": "Protein", "text": [ "PCP" ], "offsets": [ [ 628, 631 ] ], "normalized": [] }, { "id": "327_T25", "type": "Protein", "text": [ "apo-PCP" ], "offsets": [ [ 665, 672 ] ], "normalized": [] }, { "id": "327_T26", "type": "Protein", "text": [ "phosphopantetheinylated holo-PCP" ], "offsets": [ [ 709, 741 ] ], "normalized": [] }, { "id": "327_T27", "type": "Protein", "text": [ "Lys5" ], "offsets": [ [ 750, 754 ] ], "normalized": [] }, { "id": "327_T28", "type": "Chemical", "text": [ "CoASH" ], "offsets": [ [ 759, 764 ] ], "normalized": [] }, { "id": "327_T29", "type": "Protein", "text": [ "PCP" ], "offsets": [ [ 821, 824 ] ], "normalized": [] }, { "id": "327_T30", "type": "Chemical", "text": [ "CoASH" ], "offsets": [ [ 829, 834 ] ], "normalized": [] }, { "id": "327_T31", "type": "Protein", "text": [ "A/PCP" ], "offsets": [ [ 877, 882 ] ], "normalized": [] }, { "id": "327_T32", "type": "Chemical", "text": [ "S-carboxymethyl-L-cysteine" ], "offsets": [ [ 902, 928 ] ], "normalized": [] }, { "id": "327_T33", "type": "Chemical", "text": [ "L-alpha-aminoadipate" ], "offsets": [ [ 981, 1001 ] ], "normalized": [] }, { "id": "327_T34", "type": "Chemical", "text": [ "[32P]PPi" ], "offsets": [ [ 1005, 1013 ] ], "normalized": [] }, { "id": "327_T35", "type": "Chemical", "text": [ "ATP" ], "offsets": [ [ 1014, 1017 ] ], "normalized": [] }, { "id": "327_T36", "type": "Protein", "text": [ "A/PCP" ], "offsets": [ [ 1056, 1061 ] ], "normalized": [] }, { "id": "327_T37", "type": "Protein", "text": [ "Lys2" ], "offsets": [ [ 1082, 1086 ] ], "normalized": [] }, { "id": "327_T38", "type": "Chemical", "text": [ "[35S]S-carboxymethyl-L-cysteine" ], "offsets": [ [ 1124, 1155 ] ], "normalized": [] }, { "id": "327_T39", "type": "Chemical", "text": [ "S-carboxymethyl-L-cysteine" ], "offsets": [ [ 1129, 1155 ] ], "normalized": [] }, { "id": "327_T40", "type": "Chemical", "text": [ "NADPH" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "327_T41", "type": "Protein", "text": [ "acyl-S-enzyme" ], "offsets": [ [ 1260, 1273 ] ], "normalized": [] }, { "id": "327_T42", "type": "Protein", "text": [ "acyl-S-PCP Lys2" ], "offsets": [ [ 1199, 1214 ] ], "normalized": [] }, { "id": "327_T43", "type": "Protein", "text": [ "Lys5" ], "offsets": [ [ 1315, 1319 ] ], "normalized": [] }, { "id": "327_T44", "type": "Protein", "text": [ "Lys2" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "327_T45", "type": "Protein", "text": [ "Lys5" ], "offsets": [ [ 1366, 1370 ] ], "normalized": [] }, { "id": "327_T46", "type": "Protein", "text": [ "Lys2" ], "offsets": [ [ 1389, 1393 ] ], "normalized": [] }, { "id": "327_T47", "type": "Protein", "text": [ "alpha-aminoadipate reductase" ], "offsets": [ [ 1404, 1432 ] ], "normalized": [] }, { "id": "327_T48", "type": "Chemical", "text": [ "alpha-aminoadipate" ], "offsets": [ [ 1404, 1422 ] ], "normalized": [] }, { "id": "327_T50", "type": "Protein", "text": [ "holo-Lys2" ], "offsets": [ [ 1445, 1454 ] ], "normalized": [] }, { "id": "327_T54", "type": "Species", "text": [ "fungal" ], "offsets": [ [ 1555, 1561 ] ], "normalized": [] }, { "id": "327_T55", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1562, 1568 ] ], "normalized": [] }, { "id": "327_T56", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 1583, 1593 ] ], "normalized": [] }, { "id": "327_T57", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1594, 1604 ] ], "normalized": [] }, { "id": "327_T4", "type": "Biological_Activity", "text": [ "reductase" ], "offsets": [ [ 1423, 1432 ] ], "normalized": [] }, { "id": "327_T12", "type": "Biological_Activity", "text": [ "reduction" ], "offsets": [ [ 55, 64 ] ], "normalized": [] }, { "id": "327_T49", "type": "Biological_Activity", "text": [ "reductive" ], "offsets": [ [ 1234, 1243 ] ], "normalized": [] }, { "id": "327_T51", "type": "Biological_Activity", "text": [ "reductive" ], "offsets": [ [ 1503, 1512 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "329", "type": "", "text": [ "Rat liver 60-kDa lysophospholipase-transacylase catalyzes not only the hydrolysis of 1-acyl-sn-glycero-3-phosphocholine, but also the transfer of its acyl chain to a second molecule of 1-acyl-sn-glycero-3-phosphocholine to form phosphatidylcholine (H. Sugimoto, S. Yamashita, J. Biol. Chem. 269 (1994) 6252-6258). Here we report the detailed characterization of the transacylase activity of the enzyme. The enzyme mediated three types of acyl transfer between donor and acceptor lipids, transferring acyl residues from: (1) the sn-1 to -1(3); (2) sn-1 to -2; and (3) sn-2 to -1 positions. In the sn-1 to -1(3) transfer, the sn-1 acyl residue of 1-acyl-sn-glycero-3-phosphocholine was transferred to the sn-1(3) positions of glycerol and 2-acyl-sn-glycerol, producing 1(3)-acyl-sn-glycerol and 1,2-diacyl-sn-glycerol, respectively. In the sn-1 to -2 transfer, the sn-1 acyl residue of 1-acyl-sn-glycero-3-phosphocholine was transferred to not only the sn-2 positions of 1-acyl-sn-glycero-3-phosphocholine, but also 1-acyl-sn-glycero-3-phosphoethanolamine, producing phosphatidylcholine and phosphatidylethanolamine, respectively. 1-Acyl-sn-glycero-3-phospho-myo-inositol and 1-acyl-sn-glycero-3-phosphoserine were much less effectively transacylated by the enzyme. In the sn-2 to -1 transfer, the sn-2 acyl residue of 2-acyl-sn-glycero-3-phosphocholine was transferred to the sn-1 position of 2-acyl-sn-glycero-3-phosphocholine and 2-acyl-sn-glycero-3-phosphoethanolamine, producing phosphatidylcholine and phosphatidylethanolamine, respectively. Consistently, the enzyme hydrolyzed the sn-2 acyl residue from 2-acyl-sn-glycero-3-phosphocholine. By the sn-2 to -1 transfer activity, arachidonic acid was transferred from the sn-2 position of donor lipids to the sn-1 position of acceptor lipids, thus producing 1-arachidonoyl phosphatidylcholine. When 2-arachidonoyl-sn-glycero-3-phosphocholine was used as the sole substrate, diarachidonoyl phosphatidylcholine was synthesized at a rate of 0.23 micromol/min/mg protein. Thus, 60-kDa lysophospholipase-transacylase may play a role in the synthesis of 1-arachidonoyl phosphatidylcholine needed for important cell functions, such as anandamide synthesis. \n" ], "offsets": [ [ 0, 2210 ] ] } ]

[ { "id": "329_T1", "type": "Species", "text": [ "Rat" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "329_T2", "type": "Protein", "text": [ "lysophospholipase-transacylase" ], "offsets": [ [ 17, 47 ] ], "normalized": [] }, { "id": "329_T3", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 85, 119 ] ], "normalized": [] }, { "id": "329_T4", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 185, 219 ] ], "normalized": [] }, { "id": "329_T5", "type": "Chemical", "text": [ "phosphatidylcholine" ], "offsets": [ [ 228, 247 ] ], "normalized": [] }, { "id": "329_T7", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 395, 401 ] ], "normalized": [] }, { "id": "329_T9", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 407, 413 ] ], "normalized": [] }, { "id": "329_T11", "type": "Chemical", "text": [ "lipids" ], "offsets": [ [ 480, 486 ] ], "normalized": [] }, { "id": "329_T12", "type": "Chemical", "text": [ "acyl residues" ], "offsets": [ [ 501, 514 ] ], "normalized": [] }, { "id": "329_T13", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 646, 680 ] ], "normalized": [] }, { "id": "329_T14", "type": "Chemical", "text": [ "glycerol" ], "offsets": [ [ 725, 733 ] ], "normalized": [] }, { "id": "329_T15", "type": "Chemical", "text": [ "2-acyl-sn-glycerol" ], "offsets": [ [ 738, 756 ] ], "normalized": [] }, { "id": "329_T16", "type": "Chemical", "text": [ "1(3)-acyl-sn-glycerol" ], "offsets": [ [ 768, 789 ] ], "normalized": [] }, { "id": "329_T17", "type": "Chemical", "text": [ "1,2-diacyl-sn-glycerol" ], "offsets": [ [ 794, 816 ] ], "normalized": [] }, { "id": "329_T18", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 886, 920 ] ], "normalized": [] }, { "id": "329_T19", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 972, 1006 ] ], "normalized": [] }, { "id": "329_T20", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphoethanolamine" ], "offsets": [ [ 1017, 1056 ] ], "normalized": [] }, { "id": "329_T21", "type": "Chemical", "text": [ "phosphatidylcholine" ], "offsets": [ [ 1068, 1087 ] ], "normalized": [] }, { "id": "329_T22", "type": "Chemical", "text": [ "phosphatidylethanolamine" ], "offsets": [ [ 1092, 1116 ] ], "normalized": [] }, { "id": "329_T23", "type": "Chemical", "text": [ "1-Acyl-sn-glycero-3-phospho-myo-inositol" ], "offsets": [ [ 1132, 1172 ] ], "normalized": [] }, { "id": "329_T24", "type": "Chemical", "text": [ "1-acyl-sn-glycero-3-phosphoserine" ], "offsets": [ [ 1178, 1211 ] ], "normalized": [] }, { "id": "329_T26", "type": "Chemical", "text": [ "2-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 1321, 1355 ] ], "normalized": [] }, { "id": "329_T27", "type": "Chemical", "text": [ "2-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 1396, 1430 ] ], "normalized": [] }, { "id": "329_T28", "type": "Chemical", "text": [ "2-acyl-sn-glycero-3-phosphoethanolamine" ], "offsets": [ [ 1435, 1474 ] ], "normalized": [] }, { "id": "329_T29", "type": "Chemical", "text": [ "phosphatidylcholine" ], "offsets": [ [ 1486, 1505 ] ], "normalized": [] }, { "id": "329_T30", "type": "Chemical", "text": [ "phosphatidylethanolamine" ], "offsets": [ [ 1510, 1534 ] ], "normalized": [] }, { "id": "329_T31", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1568, 1574 ] ], "normalized": [] }, { "id": "329_T33", "type": "Chemical", "text": [ "2-acyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 1613, 1647 ] ], "normalized": [] }, { "id": "329_T34", "type": "Chemical", "text": [ "arachidonic acid" ], "offsets": [ [ 1686, 1702 ] ], "normalized": [] }, { "id": "329_T35", "type": "Chemical", "text": [ "lipids" ], "offsets": [ [ 1751, 1757 ] ], "normalized": [] }, { "id": "329_T36", "type": "Chemical", "text": [ "lipids" ], "offsets": [ [ 1791, 1797 ] ], "normalized": [] }, { "id": "329_T37", "type": "Chemical", "text": [ "1-arachidonoyl phosphatidylcholine" ], "offsets": [ [ 1814, 1848 ] ], "normalized": [] }, { "id": "329_T38", "type": "Chemical", "text": [ "2-arachidonoyl-sn-glycero-3-phosphocholine" ], "offsets": [ [ 1855, 1897 ] ], "normalized": [] }, { "id": "329_T39", "type": "Chemical", "text": [ "diarachidonoyl phosphatidylcholine" ], "offsets": [ [ 1931, 1965 ] ], "normalized": [] }, { "id": "329_T40", "type": "Protein", "text": [ "lysophospholipase-transacylase" ], "offsets": [ [ 2039, 2069 ] ], "normalized": [] }, { "id": "329_T41", "type": "Chemical", "text": [ "1-arachidonoyl phosphatidylcholine" ], "offsets": [ [ 2107, 2141 ] ], "normalized": [] }, { "id": "329_T42", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 2187, 2197 ] ], "normalized": [] }, { "id": "329_T8", "type": "Protein", "text": [ "transacylase" ], "offsets": [ [ 366, 378 ] ], "normalized": [] }, { "id": "329_T47", "type": "Chemical", "text": [ "acyl residue" ], "offsets": [ [ 630, 642 ] ], "normalized": [] }, { "id": "329_T48", "type": "Chemical", "text": [ "acyl residue" ], "offsets": [ [ 870, 882 ] ], "normalized": [] }, { "id": "329_T49", "type": "Chemical", "text": [ "acyl residue" ], "offsets": [ [ 1305, 1317 ] ], "normalized": [] }, { "id": "329_T50", "type": "Chemical", "text": [ "acyl residue" ], "offsets": [ [ 1595, 1607 ] ], "normalized": [] }, { "id": "329_T51", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1260, 1266 ] ], "normalized": [] }, { "id": "329_T6", "type": "Biological_Activity", "text": [ "transacylase" ], "offsets": [ [ 366, 378 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "331", "type": "", "text": [ "Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose from UDP-Gal to glucosylceramide, and thus participates in the biosynthesis of most glycolipids in mammals. We have isolated and sequenced the cDNA clone encoding human lactosylceramide synthase. The deduced amino acid sequence of the human lactosylceramide synthase showed 94.2% identity with rat lactosylceramide synthase. Northern blotting analysis revealed that lactosylceramide synthase mRNA was expressed in various tissues, with the highest level in brain and adrenal gland. \n" ], "offsets": [ [ 0, 564 ] ] } ]

[ { "id": "331_T1", "type": "Protein", "text": [ "Lactosylceramide synthase" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "331_T2", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 32, 38 ] ], "normalized": [] }, { "id": "331_T3", "type": "Chemical", "text": [ "galactose" ], "offsets": [ [ 70, 79 ] ], "normalized": [] }, { "id": "331_T4", "type": "Chemical", "text": [ "UDP-Gal" ], "offsets": [ [ 85, 92 ] ], "normalized": [] }, { "id": "331_T5", "type": "Chemical", "text": [ "glucosylceramide" ], "offsets": [ [ 96, 112 ] ], "normalized": [] }, { "id": "331_T7", "type": "Species", "text": [ "mammals" ], "offsets": [ [ 179, 186 ] ], "normalized": [] }, { "id": "331_T8", "type": "Species", "text": [ "human" ], "offsets": [ [ 243, 248 ] ], "normalized": [] }, { "id": "331_T9", "type": "Protein", "text": [ "lactosylceramide synthase" ], "offsets": [ [ 249, 274 ] ], "normalized": [] }, { "id": "331_T10", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "331_T11", "type": "Species", "text": [ "human" ], "offsets": [ [ 316, 321 ] ], "normalized": [] }, { "id": "331_T12", "type": "Protein", "text": [ "lactosylceramide synthase" ], "offsets": [ [ 322, 347 ] ], "normalized": [] }, { "id": "331_T13", "type": "Species", "text": [ "rat" ], "offsets": [ [ 375, 378 ] ], "normalized": [] }, { "id": "331_T14", "type": "Protein", "text": [ "lactosylceramide synthase" ], "offsets": [ [ 379, 404 ] ], "normalized": [] }, { "id": "331_T15", "type": "Protein", "text": [ "lactosylceramide synthase" ], "offsets": [ [ 447, 472 ] ], "normalized": [] }, { "id": "331_T17", "type": "Metabolite", "text": [ "glycolipids" ], "offsets": [ [ 164, 175 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "333", "type": "", "text": [ "A highly sensitive and specific fluorimetric method was developed for the determination of oxamniquine in biological fluids (urine and plasma). The proposed method is based on the reduction of oxamniquine using zinc/calcium chloride to obtain its nitroso derivative. The latter is then allowed to react with 2-cyanoacetamide to get a highly fluorescent product. The different experimental parameters affecting the intensity of the fluorescence were carefully studied and incorporated into the procedure. Under the described conditions, the method is applicable over the concentration range of 0.08-0.88 microgram/ml with a minimum detectability (S/N = 2) of 8 ng/ml. The percentage recoveries from spiked urine and plasma were 99.75 +/- 1.58 and 97.46 +/- 0.44%, respectively. \n" ], "offsets": [ [ 0, 779 ] ] } ]

[ { "id": "333_T1", "type": "Chemical", "text": [ "oxamniquine" ], "offsets": [ [ 91, 102 ] ], "normalized": [] }, { "id": "333_T2", "type": "Chemical", "text": [ "oxamniquine" ], "offsets": [ [ 193, 204 ] ], "normalized": [] }, { "id": "333_T3", "type": "Chemical", "text": [ "zinc" ], "offsets": [ [ 211, 215 ] ], "normalized": [] }, { "id": "333_T4", "type": "Chemical", "text": [ "calcium chloride" ], "offsets": [ [ 216, 232 ] ], "normalized": [] }, { "id": "333_T5", "type": "Chemical", "text": [ "nitroso derivative" ], "offsets": [ [ 247, 265 ] ], "normalized": [] }, { "id": "333_T6", "type": "Chemical", "text": [ "2-cyanoacetamide" ], "offsets": [ [ 308, 324 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "335", "type": "", "text": [ "Up to now, different methods in guinea pig sensitization were used, to assess contact sensitization potential of low molecular weight chemicals. In order to compare the efficiency of the epicutaneous, intradermal and combined sensitization methods, two stronger sensitizers, the water soluble chlormethylimidazoline hydrochloride (CMI) and the lipid soluble 1,3-dinitrochlorobenzene (DNCB) were used for the experiments. Eleven modified sensitization methods were performed. In a first trial each substance was tested on 10 animals. In a further study those techniques which had produced the best results, that is the highest degree of sensitization, were applied to 25 to 30 animals. For comparison of the results of the various methods, a mean sensitization index was calculated. The best results were achieved with the Maximization Test of Magnusson & Kligman (1969) and the Split Adjuvant Technique of Maguire & Chase (1967). \n" ], "offsets": [ [ 0, 933 ] ] } ]

[ { "id": "335_T1", "type": "Species", "text": [ "guinea pig" ], "offsets": [ [ 32, 42 ] ], "normalized": [] }, { "id": "335_T4", "type": "Chemical", "text": [ "water" ], "offsets": [ [ 279, 284 ] ], "normalized": [] }, { "id": "335_T5", "type": "Chemical", "text": [ "chlormethylimidazoline hydrochloride" ], "offsets": [ [ 293, 329 ] ], "normalized": [] }, { "id": "335_T6", "type": "Chemical", "text": [ "CMI" ], "offsets": [ [ 331, 334 ] ], "normalized": [] }, { "id": "335_T7", "type": "Chemical", "text": [ "lipid" ], "offsets": [ [ 344, 349 ] ], "normalized": [] }, { "id": "335_T8", "type": "Chemical", "text": [ "1,3-dinitrochlorobenzene" ], "offsets": [ [ 358, 382 ] ], "normalized": [] }, { "id": "335_T9", "type": "Chemical", "text": [ "DNCB" ], "offsets": [ [ 384, 388 ] ], "normalized": [] }, { "id": "335_T10", "type": "Biological_Activity", "text": [ "sensitizers" ], "offsets": [ [ 262, 273 ] ], "normalized": [] }, { "id": "335_T14", "type": "Chemical", "text": [ "low molecular weight chemicals" ], "offsets": [ [ 113, 143 ] ], "normalized": [] } ]

[]

[]

[ { "id": "335_R1", "type": "Associated_With", "arg1_id": "335_T5", "arg2_id": "335_T10", "normalized": [] }, { "id": "335_R2", "type": "Associated_With", "arg1_id": "335_T6", "arg2_id": "335_T10", "normalized": [] }, { "id": "335_R3", "type": "Associated_With", "arg1_id": "335_T8", "arg2_id": "335_T10", "normalized": [] }, { "id": "335_R4", "type": "Associated_With", "arg1_id": "335_T9", "arg2_id": "335_T10", "normalized": [] } ]

[ { "id": "337", "type": "", "text": [ "The relationship between taurine and aging of brain neural cells was studied by using primary human fetal brain neural cells cultured in serum-free medium. The results indicated that the activity of superoxide dismutase (SOD) was significantly higher in taurine added group than the control group cultured for 6, 9 and 15 days (P < 0.05). With different taurine levels, the SOD activities of 50 mg/L and 200 mg/L taurine groups were significantly higher than the control group cultured for 6 days (P < 0.05). After 3-day culture, the activity of glutathione peroxidase (GSH-Px) in the taurine added group was significantly higher than the control group (P < 0.05). The membrane lipid fluidity of neural cells decreased with time in control group, but was stable in the group treated with taurine. The fluidity was more stable in the groups treated with 50, 200 and 400 mg/L groups cultured for 6 days, compared with the control group (P < 0.05 or 0.01). The present study showed that taurine is necessary for maintaining membrane lipid fluidity of neural cells in proper levels, and plays an important role in postponing the aging process of brain neural cells. \n" ], "offsets": [ [ 0, 1164 ] ] } ]

[ { "id": "337_T1", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 25, 32 ] ], "normalized": [] }, { "id": "337_T3", "type": "Species", "text": [ "human" ], "offsets": [ [ 94, 99 ] ], "normalized": [] }, { "id": "337_T4", "type": "Protein", "text": [ "superoxide dismutase" ], "offsets": [ [ 199, 219 ] ], "normalized": [] }, { "id": "337_T5", "type": "Protein", "text": [ "SOD" ], "offsets": [ [ 221, 224 ] ], "normalized": [] }, { "id": "337_T7", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 254, 261 ] ], "normalized": [] }, { "id": "337_T8", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 354, 361 ] ], "normalized": [] }, { "id": "337_T9", "type": "Protein", "text": [ "SOD" ], "offsets": [ [ 374, 377 ] ], "normalized": [] }, { "id": "337_T11", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 413, 420 ] ], "normalized": [] }, { "id": "337_T12", "type": "Protein", "text": [ "glutathione peroxidase" ], "offsets": [ [ 546, 568 ] ], "normalized": [] }, { "id": "337_T13", "type": "Protein", "text": [ "GSH-Px" ], "offsets": [ [ 570, 576 ] ], "normalized": [] }, { "id": "337_T15", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 585, 592 ] ], "normalized": [] }, { "id": "337_T16", "type": "Chemical", "text": [ "lipid" ], "offsets": [ [ 678, 683 ] ], "normalized": [] }, { "id": "337_T18", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 788, 795 ] ], "normalized": [] }, { "id": "337_T20", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 984, 991 ] ], "normalized": [] }, { "id": "337_T2", "type": "Biological_Activity", "text": [ "dismutase" ], "offsets": [ [ 210, 219 ] ], "normalized": [] }, { "id": "337_T6", "type": "Biological_Activity", "text": [ "peroxidase" ], "offsets": [ [ 558, 568 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "339", "type": "", "text": [ "Microsomal cytochrome P450-dependent lauric acid hydroxylase activities were characterized in liver, kidney, and intestinal mucosa of the sea bass (Dicentrarchus labrax). Microsomes from these organs generated (omega-1)-hydroxylauric acid and a mixture of positional isomers including (omega)-, (omega-2)-, (omega-3)- and (omega-4)-hydroxylauric acids, which were identified by RP-HPLC and GC-MS analysis. Peroxisome proliferators, such as clofibrate and especially di(2-ethylhexyl) phthalate, increased kidney microsomal lauric acid hydroxylase activities. The synthesis of 11-hydroxylauric acid was enhanced 5.3-fold in kidney microsomes. Liver microsomal lauric acid hydroxylase activities were weakly affected and no significant induction was found in small intestine microsomes from clofibrate or di(2-ethylhexyl) phthalate-treated fish. The differences in lauric acid metabolisation and the tissue-specific induction by peroxisome proliferators suggest the involvement of several P450s in this reaction. Incubations of liver and kidney microsomes with lauric acid analogues (11- or 10-dodecynoic acids) resulted in a time- and concentration-dependent loss of lauric acid hydroxylase activities. The induction of these activities in fish by phthalates, which are widely-distributed environmental pollutants, may be taken into consideration for the development of new biomarkers. \n" ], "offsets": [ [ 0, 1388 ] ] } ]

[ { "id": "339_T1", "type": "Protein", "text": [ "cytochrome P450" ], "offsets": [ [ 11, 26 ] ], "normalized": [] }, { "id": "339_T2", "type": "Protein", "text": [ "lauric acid hydroxylase" ], "offsets": [ [ 37, 60 ] ], "normalized": [] }, { "id": "339_T3", "type": "Species", "text": [ "sea bass" ], "offsets": [ [ 138, 146 ] ], "normalized": [] }, { "id": "339_T4", "type": "Species", "text": [ "Dicentrarchus labrax" ], "offsets": [ [ 148, 168 ] ], "normalized": [] }, { "id": "339_T5", "type": "Chemical", "text": [ "(omega-1)-hydroxylauric acid" ], "offsets": [ [ 210, 238 ] ], "normalized": [] }, { "id": "339_T6", "type": "Metabolite", "text": [ "(omega-1)-hydroxylauric acid" ], "offsets": [ [ 210, 238 ] ], "normalized": [] }, { "id": "339_T7", "type": "Chemical", "text": [ "(omega)-", "hydroxylauric acid" ], "offsets": [ [ 285, 293 ], [ 332, 350 ] ], "normalized": [] }, { "id": "339_T8", "type": "Metabolite", "text": [ "(omega)-", "hydroxylauric acid" ], "offsets": [ [ 285, 293 ], [ 332, 350 ] ], "normalized": [] }, { "id": "339_T9", "type": "Chemical", "text": [ "(omega-2)-", "hydroxylauric acid" ], "offsets": [ [ 295, 305 ], [ 332, 350 ] ], "normalized": [] }, { "id": "339_T10", "type": "Metabolite", "text": [ "(omega-2)-", "hydroxylauric acid" ], "offsets": [ [ 295, 305 ], [ 332, 350 ] ], "normalized": [] }, { "id": "339_T11", "type": "Chemical", "text": [ "(omega-3)-" ], "offsets": [ [ 307, 317 ] ], "normalized": [] }, { "id": "339_T12", "type": "Metabolite", "text": [ "(omega-3)-" ], "offsets": [ [ 307, 317 ] ], "normalized": [] }, { "id": "339_T13", "type": "Chemical", "text": [ "(omega-4)-hydroxylauric acid" ], "offsets": [ [ 322, 350 ] ], "normalized": [] }, { "id": "339_T14", "type": "Metabolite", "text": [ "(omega-4)-hydroxylauric acid" ], "offsets": [ [ 322, 350 ] ], "normalized": [] }, { "id": "339_T15", "type": "Spectral_Data", "text": [ "GC-MS analysis" ], "offsets": [ [ 390, 404 ] ], "normalized": [] }, { "id": "339_T16", "type": "Biological_Activity", "text": [ "Peroxisome proliferator" ], "offsets": [ [ 406, 429 ] ], "normalized": [] }, { "id": "339_T17", "type": "Chemical", "text": [ "clofibrate" ], "offsets": [ [ 440, 450 ] ], "normalized": [] }, { "id": "339_T18", "type": "Chemical", "text": [ "di(2-ethylhexyl) phthalate" ], "offsets": [ [ 466, 492 ] ], "normalized": [] }, { "id": "339_T19", "type": "Protein", "text": [ "lauric acid hydroxylase" ], "offsets": [ [ 522, 545 ] ], "normalized": [] }, { "id": "339_T21", "type": "Chemical", "text": [ "11-hydroxylauric acid" ], "offsets": [ [ 575, 596 ] ], "normalized": [] }, { "id": "339_T23", "type": "Chemical", "text": [ "lauric acid" ], "offsets": [ [ 37, 48 ] ], "normalized": [] }, { "id": "339_T24", "type": "Protein", "text": [ "lauric acid hydroxylase" ], "offsets": [ [ 658, 681 ] ], "normalized": [] }, { "id": "339_T26", "type": "Chemical", "text": [ "clofibrate" ], "offsets": [ [ 789, 799 ] ], "normalized": [] }, { "id": "339_T27", "type": "Chemical", "text": [ "di(2-ethylhexyl) phthalate" ], "offsets": [ [ 803, 829 ] ], "normalized": [] }, { "id": "339_T28", "type": "Species", "text": [ "fish" ], "offsets": [ [ 838, 842 ] ], "normalized": [] }, { "id": "339_T29", "type": "Chemical", "text": [ "lauric acid" ], "offsets": [ [ 864, 875 ] ], "normalized": [] }, { "id": "339_T31", "type": "Biological_Activity", "text": [ "peroxisome proliferator" ], "offsets": [ [ 928, 951 ] ], "normalized": [] }, { "id": "339_T32", "type": "Protein", "text": [ "P450s" ], "offsets": [ [ 988, 993 ] ], "normalized": [] }, { "id": "339_T33", "type": "Chemical", "text": [ "lauric acid" ], "offsets": [ [ 1060, 1071 ] ], "normalized": [] }, { "id": "339_T34", "type": "Chemical", "text": [ "lauric acid analogues" ], "offsets": [ [ 1060, 1081 ] ], "normalized": [] }, { "id": "339_T35", "type": "Chemical", "text": [ "11-", "dodecynoic acid" ], "offsets": [ [ 1083, 1086 ], [ 1093, 1108 ] ], "normalized": [] }, { "id": "339_T36", "type": "Chemical", "text": [ "10-dodecynoic acid" ], "offsets": [ [ 1090, 1108 ] ], "normalized": [] }, { "id": "339_T37", "type": "Protein", "text": [ "lauric acid hydroxylase" ], "offsets": [ [ 1167, 1190 ] ], "normalized": [] }, { "id": "339_T39", "type": "Species", "text": [ "fish" ], "offsets": [ [ 1240, 1246 ] ], "normalized": [] }, { "id": "339_T40", "type": "Chemical", "text": [ "phthalates" ], "offsets": [ [ 1249, 1259 ] ], "normalized": [] }, { "id": "339_T42", "type": "Biological_Activity", "text": [ "biomarkers" ], "offsets": [ [ 1375, 1385 ] ], "normalized": [] }, { "id": "339_T20", "type": "Biological_Activity", "text": [ "metabolisation" ], "offsets": [ [ 876, 890 ] ], "normalized": [] } ]

[]

[]

[ { "id": "339_R1", "type": "Associated_With", "arg1_id": "339_T6", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R2", "type": "Associated_With", "arg1_id": "339_T5", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R3", "type": "Associated_With", "arg1_id": "339_T8", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R4", "type": "Associated_With", "arg1_id": "339_T7", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R5", "type": "Associated_With", "arg1_id": "339_T10", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R6", "type": "Associated_With", "arg1_id": "339_T9", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R7", "type": "Associated_With", "arg1_id": "339_T12", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R8", "type": "Associated_With", "arg1_id": "339_T11", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R9", "type": "Associated_With", "arg1_id": "339_T14", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R10", "type": "Associated_With", "arg1_id": "339_T13", "arg2_id": "339_T15", "normalized": [] }, { "id": "339_R11", "type": "Associated_With", "arg1_id": "339_T17", "arg2_id": "339_T16", "normalized": [] }, { "id": "339_R12", "type": "Associated_With", "arg1_id": "339_T18", "arg2_id": "339_T16", "normalized": [] }, { "id": "339_R15", "type": "Isolated_From", "arg1_id": "339_T8", "arg2_id": "339_T3", "normalized": [] }, { "id": "339_R19", "type": "Isolated_From", "arg1_id": "339_T8", "arg2_id": "339_T4", "normalized": [] }, { "id": "339_R20", "type": "Isolated_From", "arg1_id": "339_T14", "arg2_id": "339_T3", "normalized": [] }, { "id": "339_R21", "type": "Isolated_From", "arg1_id": "339_T14", "arg2_id": "339_T4", "normalized": [] }, { "id": "339_R22", "type": "Isolated_From", "arg1_id": "339_T10", "arg2_id": "339_T3", "normalized": [] }, { "id": "339_R23", "type": "Isolated_From", "arg1_id": "339_T10", "arg2_id": "339_T4", "normalized": [] }, { "id": "339_R24", "type": "Isolated_From", "arg1_id": "339_T12", "arg2_id": "339_T3", "normalized": [] }, { "id": "339_R25", "type": "Isolated_From", "arg1_id": "339_T12", "arg2_id": "339_T4", "normalized": [] }, { "id": "339_R26", "type": "Isolated_From", "arg1_id": "339_T6", "arg2_id": "339_T3", "normalized": [] }, { "id": "339_R27", "type": "Isolated_From", "arg1_id": "339_T6", "arg2_id": "339_T4", "normalized": [] }, { "id": "339_R13", "type": "Binds_With", "arg1_id": "339_T17", "arg2_id": "339_T19", "normalized": [] }, { "id": "339_R14", "type": "Binds_With", "arg1_id": "339_T18", "arg2_id": "339_T19", "normalized": [] }, { "id": "339_R28", "type": "Binds_With", "arg1_id": "339_T35", "arg2_id": "339_T37", "normalized": [] }, { "id": "339_R29", "type": "Binds_With", "arg1_id": "339_T36", "arg2_id": "339_T37", "normalized": [] } ]

[ { "id": "341", "type": "", "text": [ "6-Chloro-7-arylamino-5,8-isoquinolinediones were newly synthesized and evaluated for in vitro cytotoxic activities against five human solid tumor cell lines. Among them, 5b, 5c and 5d exhibited potent activities against the cell lines HCT-15 and SK-MEL-2. \n" ], "offsets": [ [ 0, 258 ] ] } ]

[ { "id": "341_T1", "type": "Chemical", "text": [ "6-Chloro-7-arylamino-5,8-isoquinolinediones" ], "offsets": [ [ 0, 43 ] ], "normalized": [] }, { "id": "341_T2", "type": "Biological_Activity", "text": [ "cytotoxic" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "341_T3", "type": "Species", "text": [ "human" ], "offsets": [ [ 129, 134 ] ], "normalized": [] }, { "id": "341_T5", "type": "Chemical", "text": [ "5b" ], "offsets": [ [ 171, 173 ] ], "normalized": [] }, { "id": "341_T6", "type": "Chemical", "text": [ "5c" ], "offsets": [ [ 175, 177 ] ], "normalized": [] }, { "id": "341_T7", "type": "Chemical", "text": [ "5d" ], "offsets": [ [ 182, 184 ] ], "normalized": [] } ]

[]

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[ { "id": "341_R4", "type": "Associated_With", "arg1_id": "341_T5", "arg2_id": "341_T2", "normalized": [] }, { "id": "341_R5", "type": "Associated_With", "arg1_id": "341_T6", "arg2_id": "341_T2", "normalized": [] }, { "id": "341_R6", "type": "Associated_With", "arg1_id": "341_T7", "arg2_id": "341_T2", "normalized": [] } ]

[ { "id": "343", "type": "", "text": [ "We developed a novel fluorometric assay method for the measurement of glycosyltransferase activities using mono- and di-saccharides aminated and tagged with 7-hydroxycoumarin-3-carboxylic acid (coumarin) as substrates, N-acetylglucosamine (GlcNAc)-coumarin for beta1,4-galactosyltransferase from bovine milk and Gal beta1-4GlcNAc-coumarin for alpha2,3- and alpha2,6-sialyltransferases from rat liver. Using Gal beta1-3GlcNAc and Gal beta1-4Glc-NAc-coumarin, alpha1,3/4- and alpha1,3-fucosyltransferase activities were also determined, respectively. These enzymatic products liberated by the reactions of glycosyltransferases in the presence of sugar nucleotides, were separated by a normal phase or an ion-pair reversed phase HPLC with an isocratic elution and fluorescence detection. We applied this assay method to determine the glycosyltransferase activities in 8 kinds of human tumor cell lines, including the cell lines derived from hepatocytes (HuH-7, HepG2), colonic cells (Colo205, HT-29), myelocytes (HL-60, U-937), B-lymphocytes (Daudi) and T-lymphocytes (Jurkat). This assay method is accurate and easy compared with other isotopic and non-isotopic assay methods, and is sensitive enough to measure glycosyltransferase activities in cell homogenates. \n" ], "offsets": [ [ 0, 1264 ] ] } ]

[ { "id": "343_T1", "type": "Protein", "text": [ "glycosyltransferase" ], "offsets": [ [ 70, 89 ] ], "normalized": [] }, { "id": "343_T3", "type": "Chemical", "text": [ "mono-", "saccharides" ], "offsets": [ [ 107, 112 ], [ 120, 131 ] ], "normalized": [] }, { "id": "343_T4", "type": "Chemical", "text": [ "di-saccharides" ], "offsets": [ [ 117, 131 ] ], "normalized": [] }, { "id": "343_T5", "type": "Chemical", "text": [ "7-hydroxycoumarin-3-carboxylic acid" ], "offsets": [ [ 157, 192 ] ], "normalized": [] }, { "id": "343_T6", "type": "Chemical", "text": [ "coumarin" ], "offsets": [ [ 194, 202 ] ], "normalized": [] }, { "id": "343_T7", "type": "Chemical", "text": [ "N-acetylglucosamine", "coumarin" ], "offsets": [ [ 219, 238 ], [ 248, 256 ] ], "normalized": [] }, { "id": "343_T8", "type": "Chemical", "text": [ "GlcNAc", "coumarin" ], "offsets": [ [ 240, 246 ], [ 248, 256 ] ], "normalized": [] }, { "id": "343_T9", "type": "Protein", "text": [ "beta1,4-galactosyltransferase" ], "offsets": [ [ 261, 290 ] ], "normalized": [] }, { "id": "343_T10", "type": "Species", "text": [ "bovine" ], "offsets": [ [ 296, 302 ] ], "normalized": [] }, { "id": "343_T11", "type": "Chemical", "text": [ "Gal beta1-4GlcNAc-coumarin" ], "offsets": [ [ 312, 338 ] ], "normalized": [] }, { "id": "343_T12", "type": "Protein", "text": [ "alpha2,3-", "sialyltransferase" ], "offsets": [ [ 343, 352 ], [ 366, 383 ] ], "normalized": [] }, { "id": "343_T13", "type": "Protein", "text": [ "alpha2,6-sialyltransferase" ], "offsets": [ [ 357, 383 ] ], "normalized": [] }, { "id": "343_T14", "type": "Species", "text": [ "rat" ], "offsets": [ [ 390, 393 ] ], "normalized": [] }, { "id": "343_T18", "type": "Chemical", "text": [ "Gal beta1-3GlcNAc" ], "offsets": [ [ 407, 424 ] ], "normalized": [] }, { "id": "343_T19", "type": "Chemical", "text": [ "Gal beta1-4Glc-NAc-coumarin" ], "offsets": [ [ 429, 456 ] ], "normalized": [] }, { "id": "343_T22", "type": "Protein", "text": [ "glycosyltransferases" ], "offsets": [ [ 604, 624 ] ], "normalized": [] }, { "id": "343_T23", "type": "Chemical", "text": [ "sugar nucleotides" ], "offsets": [ [ 644, 661 ] ], "normalized": [] }, { "id": "343_T25", "type": "Protein", "text": [ "glycosyltransferase" ], "offsets": [ [ 832, 851 ] ], "normalized": [] }, { "id": "343_T26", "type": "Species", "text": [ "human" ], "offsets": [ [ 877, 882 ] ], "normalized": [] }, { "id": "343_T28", "type": "Protein", "text": [ "glycosyltransferase" ], "offsets": [ [ 1211, 1230 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "345", "type": "", "text": [ "Anandamide (N-arachidonoylethanolamine) and six fatty acid ethanolamides were synthesized and their pharmacological effects in mice were assessed using catalepsy, hypothermia and pentobarbital-induced sleep prolongation as indices. The effects of phenylmethylsulfonyl fluoride (PMSF) pretreatment on anandamide effects were also evaluated and discussed in relation to inhibition of anandamide amidohydrolase in mouse brain and liver. The cataleptogenic effect of anandamide (ED50=6.0 mg/kg, i.v.) was 4 to 6 times more active than those of N-oleoyl- (ED50=26.5 mg/kg, i.v.) and N-linoleoylethanolamine (ED50=37.5 mg/kg, i.v.), although the peak time in the effect was observed within 1 min after i.v. administration. None of the saturated fatty acid ethanolamides (N-myristoyl-, N-palmitoyl-, N-stearoyl- and N-arachidoylethanolamine) showed a positive response in the cataleptogenic effect even at a dose up to 40 mg/kg i.v. Anandamide, N-linoleoyl-, N-oleoyl- and N-myristoylethanolamine (10 mg/kg, i.v.) produced a significant hypothermia (0.19 to 0.59 degrees C) at 5 to 15 min after administration. The duration of the effects of these ethanolamides was also relatively short. Anandamide, N-linoleoyl-, N-oleoyl- and N-palmitoylethanolamine (5 or 10 mg/kg, i.v.) significantly prolonged pentobarbital-induced sleeping time by 148-207% of control sleeping time. The cataleptogenic effect of anandamide was markedly potentiated by pretreatment of mice with PMSF (100 mg/kg, i.p.). The ED50 (mg/kg, i.v.) of anandamide was 0.48 (0.24-0.96) in PMSF-pretreated mice. The pretreatment of mice with PMSF significantly decreased the metabolic clearance rate of anandamide in microsomal fractions of liver and brain. Thus, the Vmax/Km values of brain and hepatic microsomes were 26 and 10%, respectively, as compared with those of control mice. The present study demonstrated that anandamide and N-acylethanolamines of unsaturated fatty acids exhibited cannabinoid-like effects in mice, and that anandamide amidohydrolase has an important role in the pharmacological effects of anandamide in vivo. \n" ], "offsets": [ [ 0, 2098 ] ] } ]

[ { "id": "345_T1", "type": "Chemical", "text": [ "Anandamide" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "345_T2", "type": "Chemical", "text": [ "N-arachidonoylethanolamine" ], "offsets": [ [ 12, 38 ] ], "normalized": [] }, { "id": "345_T3", "type": "Chemical", "text": [ "fatty acid ethanolamides" ], "offsets": [ [ 48, 72 ] ], "normalized": [] }, { "id": "345_T5", "type": "Species", "text": [ "mice" ], "offsets": [ [ 127, 131 ] ], "normalized": [] }, { "id": "345_T8", "type": "Chemical", "text": [ "pentobarbital" ], "offsets": [ [ 179, 192 ] ], "normalized": [] }, { "id": "345_T10", "type": "Chemical", "text": [ "phenylmethylsulfonyl fluoride" ], "offsets": [ [ 247, 276 ] ], "normalized": [] }, { "id": "345_T11", "type": "Chemical", "text": [ "PMSF" ], "offsets": [ [ 278, 282 ] ], "normalized": [] }, { "id": "345_T12", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 300, 310 ] ], "normalized": [] }, { "id": "345_T13", "type": "Protein", "text": [ "anandamide amidohydrolase" ], "offsets": [ [ 382, 407 ] ], "normalized": [] }, { "id": "345_T15", "type": "Species", "text": [ "mouse" ], "offsets": [ [ 411, 416 ] ], "normalized": [] }, { "id": "345_T16", "type": "Biological_Activity", "text": [ "cataleptogenic" ], "offsets": [ [ 438, 452 ] ], "normalized": [] }, { "id": "345_T17", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 463, 475 ] ], "normalized": [] }, { "id": "345_T18", "type": "Chemical", "text": [ "N-oleoyl-", "ethanolamine" ], "offsets": [ [ 541, 550 ], [ 590, 602 ] ], "normalized": [] }, { "id": "345_T19", "type": "Chemical", "text": [ "N-linoleoylethanolamine" ], "offsets": [ [ 579, 602 ] ], "normalized": [] }, { "id": "345_T20", "type": "Chemical", "text": [ "saturated fatty acid ethanolamides" ], "offsets": [ [ 730, 764 ] ], "normalized": [] }, { "id": "345_T21", "type": "Chemical", "text": [ "N-myristoyl-", "ethanolamine" ], "offsets": [ [ 766, 778 ], [ 822, 834 ] ], "normalized": [] }, { "id": "345_T22", "type": "Chemical", "text": [ "N-palmitoyl-", "ethanolamine" ], "offsets": [ [ 780, 792 ], [ 822, 834 ] ], "normalized": [] }, { "id": "345_T23", "type": "Chemical", "text": [ "N-stearoyl-", "ethanolamine" ], "offsets": [ [ 794, 805 ], [ 822, 834 ] ], "normalized": [] }, { "id": "345_T24", "type": "Chemical", "text": [ "N-arachidoylethanolamine" ], "offsets": [ [ 810, 834 ] ], "normalized": [] }, { "id": "345_T25", "type": "Biological_Activity", "text": [ "cataleptogenic" ], "offsets": [ [ 870, 884 ] ], "normalized": [] }, { "id": "345_T27", "type": "Chemical", "text": [ "Anandamide" ], "offsets": [ [ 927, 937 ] ], "normalized": [] }, { "id": "345_T28", "type": "Chemical", "text": [ "N-linoleoyl-", "ethanolamine" ], "offsets": [ [ 939, 951 ], [ 978, 990 ] ], "normalized": [] }, { "id": "345_T29", "type": "Chemical", "text": [ "N-oleoyl-", "ethanolamine" ], "offsets": [ [ 953, 962 ], [ 978, 990 ] ], "normalized": [] }, { "id": "345_T30", "type": "Chemical", "text": [ "N-myristoylethanolamine" ], "offsets": [ [ 967, 990 ] ], "normalized": [] }, { "id": "345_T31", "type": "Chemical", "text": [ "ethanolamides" ], "offsets": [ [ 1144, 1157 ] ], "normalized": [] }, { "id": "345_T33", "type": "Chemical", "text": [ "Anandamide" ], "offsets": [ [ 1185, 1195 ] ], "normalized": [] }, { "id": "345_T34", "type": "Chemical", "text": [ "N-linoleoyl-", "ethanolamine" ], "offsets": [ [ 1197, 1209 ], [ 1236, 1248 ] ], "normalized": [] }, { "id": "345_T35", "type": "Chemical", "text": [ "N-oleoyl-", "ethanolamine" ], "offsets": [ [ 1211, 1220 ], [ 1236, 1248 ] ], "normalized": [] }, { "id": "345_T36", "type": "Chemical", "text": [ "N-palmitoylethanolamine" ], "offsets": [ [ 1225, 1248 ] ], "normalized": [] }, { "id": "345_T37", "type": "Biological_Activity", "text": [ "cataleptogenic" ], "offsets": [ [ 1373, 1387 ] ], "normalized": [] }, { "id": "345_T38", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 1398, 1408 ] ], "normalized": [] }, { "id": "345_T39", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1453, 1457 ] ], "normalized": [] }, { "id": "345_T40", "type": "Chemical", "text": [ "PMSF" ], "offsets": [ [ 1463, 1467 ] ], "normalized": [] }, { "id": "345_T41", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 1513, 1523 ] ], "normalized": [] }, { "id": "345_T42", "type": "Chemical", "text": [ "PMSF" ], "offsets": [ [ 1548, 1552 ] ], "normalized": [] }, { "id": "345_T43", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1564, 1568 ] ], "normalized": [] }, { "id": "345_T44", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1590, 1594 ] ], "normalized": [] }, { "id": "345_T45", "type": "Chemical", "text": [ "PMSF" ], "offsets": [ [ 1600, 1604 ] ], "normalized": [] }, { "id": "345_T46", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 1661, 1671 ] ], "normalized": [] }, { "id": "345_T48", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1838, 1842 ] ], "normalized": [] }, { "id": "345_T49", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 1880, 1890 ] ], "normalized": [] }, { "id": "345_T50", "type": "Chemical", "text": [ "N-acylethanolamines of unsaturated fatty acids" ], "offsets": [ [ 1895, 1941 ] ], "normalized": [] }, { "id": "345_T51", "type": "Chemical", "text": [ "cannabinoid" ], "offsets": [ [ 1952, 1963 ] ], "normalized": [] }, { "id": "345_T53", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1980, 1984 ] ], "normalized": [] }, { "id": "345_T54", "type": "Protein", "text": [ "anandamide amidohydrolase" ], "offsets": [ [ 1995, 2020 ] ], "normalized": [] }, { "id": "345_T55", "type": "Chemical", "text": [ "anandamide" ], "offsets": [ [ 2077, 2087 ] ], "normalized": [] }, { "id": "345_T56", "type": "Chemical", "text": [ "pentobarbital" ], "offsets": [ [ 1295, 1308 ] ], "normalized": [] } ]

[]

[]

[ { "id": "345_R1", "type": "Associated_With", "arg1_id": "345_T17", "arg2_id": "345_T16", "normalized": [] }, { "id": "345_R2", "type": "Associated_With", "arg1_id": "345_T18", "arg2_id": "345_T16", "normalized": [] }, { "id": "345_R3", "type": "Associated_With", "arg1_id": "345_T19", "arg2_id": "345_T16", "normalized": [] }, { "id": "345_R12", "type": "Associated_With", "arg1_id": "345_T38", "arg2_id": "345_T37", "normalized": [] } ]

[ { "id": "347", "type": "", "text": [ "Localized 1H NMR homonuclear J editing spectroscopy was used to measure the concentration of 2-pyrrolidinone (PRDN) in the human occipital lobe of five normal and six epileptic subjects taking vigabatrin. PRDN is a lactam cyclization product of gamma-aminobutyric acid (GABA). From a localized volume of 13.5 cm3 in the occipital cortex, the concentration of PRDN ranged from 0.2 to 0.3 micromol/g in normal subjects, whereas in epileptic subjects on vigabatrin PRDN was elevated to 0.6 +/- 0.1 micromol/g. The elevated PRDN in patients on vigabatrin was in accord with raised GABA levels compared with normals. 1H NMR measurements of PRDN will be important in assessment of the role of this metabolite for improved seizure control. \n" ], "offsets": [ [ 0, 734 ] ] } ]

[ { "id": "347_T1", "type": "Spectral_Data", "text": [ "1H NMR homonuclear J editing spectroscopy" ], "offsets": [ [ 10, 51 ] ], "normalized": [] }, { "id": "347_T2", "type": "Chemical", "text": [ "2-pyrrolidinone" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "347_T3", "type": "Chemical", "text": [ "PRDN" ], "offsets": [ [ 110, 114 ] ], "normalized": [] }, { "id": "347_T4", "type": "Metabolite", "text": [ "2-pyrrolidinone" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "347_T5", "type": "Metabolite", "text": [ "PRDN" ], "offsets": [ [ 110, 114 ] ], "normalized": [] }, { "id": "347_T6", "type": "Species", "text": [ "human" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "347_T7", "type": "Chemical", "text": [ "vigabatrin" ], "offsets": [ [ 193, 203 ] ], "normalized": [] }, { "id": "347_T9", "type": "Species", "text": [ "subjects" ], "offsets": [ [ 177, 185 ] ], "normalized": [] }, { "id": "347_T10", "type": "Chemical", "text": [ "PRDN" ], "offsets": [ [ 205, 209 ] ], "normalized": [] }, { "id": "347_T11", "type": "Chemical", "text": [ "lactam" ], "offsets": [ [ 215, 221 ] ], "normalized": [] }, { "id": "347_T12", "type": "Chemical", "text": [ "gamma-aminobutyric acid" ], "offsets": [ [ 245, 268 ] ], "normalized": [] }, { "id": "347_T13", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 270, 274 ] ], "normalized": [] }, { "id": "347_T14", "type": "Metabolite", "text": [ "PRDN" ], "offsets": [ [ 205, 209 ] ], "normalized": [] }, { "id": "347_T15", "type": "Metabolite", "text": [ "PRDN" ], "offsets": [ [ 359, 363 ] ], "normalized": [] }, { "id": "347_T16", "type": "Chemical", "text": [ "PRDN" ], "offsets": [ [ 359, 363 ] ], "normalized": [] }, { "id": "347_T17", "type": "Species", "text": [ "subjects" ], "offsets": [ [ 408, 416 ] ], "normalized": [] }, { "id": "347_T19", "type": "Species", "text": [ "subjects" ], "offsets": [ [ 439, 447 ] ], "normalized": [] }, { "id": "347_T20", "type": "Chemical", "text": [ "vigabatrin" ], "offsets": [ [ 451, 461 ] ], "normalized": [] }, { "id": "347_T21", "type": "Chemical", "text": [ "PRDN" ], "offsets": [ [ 462, 466 ] ], "normalized": [] }, { "id": "347_T22", "type": "Metabolite", "text": [ "PRDN" ], "offsets": [ [ 520, 524 ] ], "normalized": [] }, { "id": "347_T23", "type": "Species", "text": [ "patients" ], "offsets": [ [ 528, 536 ] ], "normalized": [] }, { "id": "347_T24", "type": "Chemical", "text": [ "vigabatrin" ], "offsets": [ [ 540, 550 ] ], "normalized": [] }, { "id": "347_T25", "type": "Metabolite", "text": [ "GABA" ], "offsets": [ [ 577, 581 ] ], "normalized": [] }, { "id": "347_T26", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 577, 581 ] ], "normalized": [] }, { "id": "347_T27", "type": "Spectral_Data", "text": [ "1H NMR" ], "offsets": [ [ 612, 618 ] ], "normalized": [] }, { "id": "347_T28", "type": "Metabolite", "text": [ "PRDN" ], "offsets": [ [ 635, 639 ] ], "normalized": [] }, { "id": "347_T29", "type": "Chemical", "text": [ "PRDN" ], "offsets": [ [ 635, 639 ] ], "normalized": [] }, { "id": "347_T30", "type": "Chemical", "text": [ "PRDN" ], "offsets": [ [ 520, 524 ] ], "normalized": [] } ]

[]

[]

[ { "id": "347_R1", "type": "Metabolite_Of", "arg1_id": "347_T14", "arg2_id": "347_T12", "normalized": [] }, { "id": "347_R2", "type": "Metabolite_Of", "arg1_id": "347_T14", "arg2_id": "347_T13", "normalized": [] }, { "id": "347_R3", "type": "Metabolite_Of", "arg1_id": "347_T4", "arg2_id": "347_T12", "normalized": [] }, { "id": "347_R4", "type": "Associated_With", "arg1_id": "347_T4", "arg2_id": "347_T1", "normalized": [] }, { "id": "347_R5", "type": "Associated_With", "arg1_id": "347_T2", "arg2_id": "347_T1", "normalized": [] }, { "id": "347_R6", "type": "Associated_With", "arg1_id": "347_T28", "arg2_id": "347_T27", "normalized": [] }, { "id": "347_R7", "type": "Associated_With", "arg1_id": "347_T29", "arg2_id": "347_T27", "normalized": [] }, { "id": "347_R8", "type": "Associated_With", "arg1_id": "347_T5", "arg2_id": "347_T1", "normalized": [] }, { "id": "347_R9", "type": "Associated_With", "arg1_id": "347_T3", "arg2_id": "347_T1", "normalized": [] } ]

[ { "id": "349", "type": "", "text": [ "A novel type of NADPH-dependent sepiapterin reductase, which catalysed uniquely the reduction of sepiapterin to l-threo-dihydrobiopterin, was purified 533-fold from the cytosolic fraction of Chlorobium tepidum, with an overall yield of 3%. The native enzyme had a molecular mass of 55 kDa and SDS/PAGE revealed that the enzyme consists of two subunits with a molecular mass of 26 kDa. The enzyme was optimally active at pH8.8 and 50 degrees C. Apparent Km values for sepiapterin and NADPH were 21 and 6.2 microM, respectively, and the kcat value was 5.0 s-1. Diacetyl could also serve as a substrate, with a Km of 4.0 mM. The inhibitory effects of N-acetylserotonin, N-acetyldopamine and melatonin were very weak. The Ki value of N-acetyldopamine was measured as 400 microM. The N-terminal amino acid sequence was revealed as Met-Lys-His-Ile-Leu-Leu-Ile-Thr-Gly-Ala-Xaa-Lys - Lys - Ile - Xaa - Arg - Ala - Ile - Ala - Leu - Glu - Xaa - Ala - Arg - Xaa-Xaa-Xaa-His-His-His-, which shared relatively high sequence similarity with other sepiapterin reductases. \n" ], "offsets": [ [ 0, 1060 ] ] } ]

[ { "id": "349_T1", "type": "Chemical", "text": [ "NADPH" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "349_T2", "type": "Chemical", "text": [ "sepiapterin" ], "offsets": [ [ 32, 43 ] ], "normalized": [] }, { "id": "349_T3", "type": "Protein", "text": [ "NADPH-dependent sepiapterin reductase" ], "offsets": [ [ 16, 53 ] ], "normalized": [] }, { "id": "349_T4", "type": "Chemical", "text": [ "sepiapterin" ], "offsets": [ [ 97, 108 ] ], "normalized": [] }, { "id": "349_T5", "type": "Chemical", "text": [ "l-threo-dihydrobiopterin" ], "offsets": [ [ 112, 136 ] ], "normalized": [] }, { "id": "349_T6", "type": "Species", "text": [ "Chlorobium tepidum" ], "offsets": [ [ 191, 209 ] ], "normalized": [] }, { "id": "349_T8", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 251, 257 ] ], "normalized": [] }, { "id": "349_T9", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 320, 326 ] ], "normalized": [] }, { "id": "349_T10", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 389, 395 ] ], "normalized": [] }, { "id": "349_T11", "type": "Chemical", "text": [ "sepiapterin" ], "offsets": [ [ 467, 478 ] ], "normalized": [] }, { "id": "349_T12", "type": "Chemical", "text": [ "NADPH" ], "offsets": [ [ 483, 488 ] ], "normalized": [] }, { "id": "349_T13", "type": "Chemical", "text": [ "Diacetyl" ], "offsets": [ [ 559, 567 ] ], "normalized": [] }, { "id": "349_T14", "type": "Chemical", "text": [ "N-acetylserotonin" ], "offsets": [ [ 648, 665 ] ], "normalized": [] }, { "id": "349_T15", "type": "Chemical", "text": [ "N-acetyldopamine" ], "offsets": [ [ 667, 683 ] ], "normalized": [] }, { "id": "349_T16", "type": "Chemical", "text": [ "melatonin" ], "offsets": [ [ 688, 697 ] ], "normalized": [] }, { "id": "349_T17", "type": "Biological_Activity", "text": [ "inhibitory" ], "offsets": [ [ 626, 636 ] ], "normalized": [] }, { "id": "349_T18", "type": "Chemical", "text": [ "N-acetyldopamine" ], "offsets": [ [ 731, 747 ] ], "normalized": [] }, { "id": "349_T19", "type": "Chemical", "text": [ "N-terminal amino acid" ], "offsets": [ [ 780, 801 ] ], "normalized": [] }, { "id": "349_T20", "type": "Protein", "text": [ "sepiapterin reductases" ], "offsets": [ [ 1035, 1057 ] ], "normalized": [] }, { "id": "349_T21", "type": "Chemical", "text": [ "Met-Lys-His-Ile-Leu-Leu-Ile-Thr-Gly-Ala-Xaa-Lys - Lys - Ile - Xaa - Arg - Ala - Ile - Ala - Leu - Glu - Xaa - Ala - Arg - Xaa-Xaa-Xaa-His-His-His-" ], "offsets": [ [ 827, 973 ] ], "normalized": [] }, { "id": "349_T7", "type": "Biological_Activity", "text": [ "reduction" ], "offsets": [ [ 84, 93 ] ], "normalized": [] } ]

[]

[]

[ { "id": "349_R3", "type": "Associated_With", "arg1_id": "349_T14", "arg2_id": "349_T17", "normalized": [] }, { "id": "349_R4", "type": "Associated_With", "arg1_id": "349_T15", "arg2_id": "349_T17", "normalized": [] }, { "id": "349_R5", "type": "Associated_With", "arg1_id": "349_T16", "arg2_id": "349_T17", "normalized": [] } ]

[ { "id": "351", "type": "", "text": [ "Stachyose synthase (STS) (EC 2.4.1.67) was purified 313-fold from mature seeds of lentil. The final preparation had a specific activity of 9.09 nkat stachyose formed per milligram of protein. The enzyme was a monomeric protein with a molecular mass of 88.6 kDa (SDS-PAGE) and an isoelectric point of 4.8 (chromatofocusing). Western analysis revealed cross-reactivity of polyclonal antibodies raised against STS from adzuki bean with the lentil enzyme. The purified enzyme catalyzed a range of different galactosyl transfer reactions. In addition to the genuine STS reaction (raffinose + galactinol --> stachyose + myo-inositol), the enzyme catalyzed the reversible galactosyl transfer from galactinol to d-pinitol (1d-3-O-methyl-chiro-inositol), yielding galactopinitol A (O-alpha-d-galactopyranosyl-(1 --> 2)-4-O-methyl-d-chiro-inositol) and myo-inositol. Galactopinitol A could be further galactosylated by STS to give ciceritol (O-alpha-d-galactopyranosyl-(1 --> 6)-O-alpha-d-galactopyranosyl-(1 --> 2)-4-O-methyl-d-chiro-inositol). Enzymatic synthesis of galactopinitol A and ciceritol is a new observation. However, STS was not only able to utilize galactopinitol A as galactosyl acceptor, but also as galactosyl donor to form stachyose from raffinose. The role of STS in the metabolism of galactosyl cyclitols and oligosaccharides in plant seeds is discussed. \n" ], "offsets": [ [ 0, 1368 ] ] } ]

[ { "id": "351_T1", "type": "Protein", "text": [ "Stachyose synthase" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "351_T2", "type": "Protein", "text": [ "STS" ], "offsets": [ [ 20, 23 ] ], "normalized": [] }, { "id": "351_T3", "type": "Protein", "text": [ "EC 2.4.1.67" ], "offsets": [ [ 26, 37 ] ], "normalized": [] }, { "id": "351_T4", "type": "Species", "text": [ "lentil" ], "offsets": [ [ 82, 88 ] ], "normalized": [] }, { "id": "351_T5", "type": "Chemical", "text": [ "stachyose" ], "offsets": [ [ 149, 158 ] ], "normalized": [] }, { "id": "351_T6", "type": "Metabolite", "text": [ "stachyose" ], "offsets": [ [ 149, 158 ] ], "normalized": [] }, { "id": "351_T7", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 183, 190 ] ], "normalized": [] }, { "id": "351_T8", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 196, 202 ] ], "normalized": [] }, { "id": "351_T9", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 219, 226 ] ], "normalized": [] }, { "id": "351_T10", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 381, 391 ] ], "normalized": [] }, { "id": "351_T11", "type": "Protein", "text": [ "STS" ], "offsets": [ [ 407, 410 ] ], "normalized": [] }, { "id": "351_T12", "type": "Species", "text": [ "adzuki bean" ], "offsets": [ [ 416, 427 ] ], "normalized": [] }, { "id": "351_T13", "type": "Species", "text": [ "lentil" ], "offsets": [ [ 437, 443 ] ], "normalized": [] }, { "id": "351_T14", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 444, 450 ] ], "normalized": [] }, { "id": "351_T15", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 465, 471 ] ], "normalized": [] }, { "id": "351_T17", "type": "Protein", "text": [ "STS" ], "offsets": [ [ 562, 565 ] ], "normalized": [] }, { "id": "351_T18", "type": "Chemical", "text": [ "raffinose" ], "offsets": [ [ 576, 585 ] ], "normalized": [] }, { "id": "351_T19", "type": "Chemical", "text": [ "galactinol" ], "offsets": [ [ 588, 598 ] ], "normalized": [] }, { "id": "351_T20", "type": "Metabolite", "text": [ "stachyose" ], "offsets": [ [ 603, 612 ] ], "normalized": [] }, { "id": "351_T21", "type": "Metabolite", "text": [ "myo-inositol" ], "offsets": [ [ 615, 627 ] ], "normalized": [] }, { "id": "351_T22", "type": "Metabolite", "text": [ "raffinose" ], "offsets": [ [ 576, 585 ] ], "normalized": [] }, { "id": "351_T23", "type": "Metabolite", "text": [ "galactinol" ], "offsets": [ [ 588, 598 ] ], "normalized": [] }, { "id": "351_T24", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 634, 640 ] ], "normalized": [] }, { "id": "351_T25", "type": "Chemical", "text": [ "galactosyl" ], "offsets": [ [ 666, 676 ] ], "normalized": [] }, { "id": "351_T26", "type": "Chemical", "text": [ "galactinol" ], "offsets": [ [ 691, 701 ] ], "normalized": [] }, { "id": "351_T27", "type": "Chemical", "text": [ "d-pinitol" ], "offsets": [ [ 705, 714 ] ], "normalized": [] }, { "id": "351_T28", "type": "Chemical", "text": [ "1d-3-O-methyl-chiro-inositol" ], "offsets": [ [ 716, 744 ] ], "normalized": [] }, { "id": "351_T29", "type": "Chemical", "text": [ "galactopinitol A" ], "offsets": [ [ 756, 772 ] ], "normalized": [] }, { "id": "351_T30", "type": "Chemical", "text": [ "O-alpha-d-galactopyranosyl-(1 --> 2)-4-O-methyl-d-chiro-inositol" ], "offsets": [ [ 774, 838 ] ], "normalized": [] }, { "id": "351_T31", "type": "Chemical", "text": [ "myo-inositol" ], "offsets": [ [ 844, 856 ] ], "normalized": [] }, { "id": "351_T32", "type": "Chemical", "text": [ "Galactopinitol A" ], "offsets": [ [ 858, 874 ] ], "normalized": [] }, { "id": "351_T35", "type": "Protein", "text": [ "STS" ], "offsets": [ [ 910, 913 ] ], "normalized": [] }, { "id": "351_T36", "type": "Chemical", "text": [ "ciceritol" ], "offsets": [ [ 922, 931 ] ], "normalized": [] }, { "id": "351_T37", "type": "Chemical", "text": [ "O-alpha-d-galactopyranosyl-(1 --> 6)-O-alpha-d-galactopyranosyl-(1 --> 2)-4-O-methyl-d-chiro-inositol" ], "offsets": [ [ 933, 1034 ] ], "normalized": [] }, { "id": "351_T38", "type": "Chemical", "text": [ "galactopinitol A" ], "offsets": [ [ 1060, 1076 ] ], "normalized": [] }, { "id": "351_T39", "type": "Chemical", "text": [ "ciceritol" ], "offsets": [ [ 1081, 1090 ] ], "normalized": [] }, { "id": "351_T41", "type": "Protein", "text": [ "STS" ], "offsets": [ [ 1271, 1274 ] ], "normalized": [] }, { "id": "351_T40", "type": "Protein", "text": [ "STS" ], "offsets": [ [ 1122, 1125 ] ], "normalized": [] }, { "id": "351_T42", "type": "Chemical", "text": [ "galactosyl cyclitols" ], "offsets": [ [ 1296, 1316 ] ], "normalized": [] }, { "id": "351_T43", "type": "Chemical", "text": [ "oligosaccharides" ], "offsets": [ [ 1321, 1337 ] ], "normalized": [] }, { "id": "351_T44", "type": "Species", "text": [ "plant" ], "offsets": [ [ 1341, 1346 ] ], "normalized": [] }, { "id": "351_T46", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1282, 1292 ] ], "normalized": [] }, { "id": "351_T47", "type": "Chemical", "text": [ "galactopinitol A" ], "offsets": [ [ 1155, 1171 ] ], "normalized": [] }, { "id": "351_T48", "type": "Biological_Activity", "text": [ "acceptor" ], "offsets": [ [ 1186, 1194 ] ], "normalized": [] }, { "id": "351_T49", "type": "Biological_Activity", "text": [ "donor" ], "offsets": [ [ 1219, 1224 ] ], "normalized": [] }, { "id": "351_T50", "type": "Chemical", "text": [ "stachyose" ], "offsets": [ [ 1233, 1242 ] ], "normalized": [] }, { "id": "351_T51", "type": "Chemical", "text": [ "raffinose" ], "offsets": [ [ 1248, 1257 ] ], "normalized": [] }, { "id": "351_T52", "type": "Chemical", "text": [ "stachyose" ], "offsets": [ [ 603, 612 ] ], "normalized": [] }, { "id": "351_T53", "type": "Chemical", "text": [ "myo-inositol" ], "offsets": [ [ 615, 627 ] ], "normalized": [] }, { "id": "351_T16", "type": "Chemical", "text": [ "galactosyl" ], "offsets": [ [ 503, 513 ] ], "normalized": [] } ]

[]

[]

[ { "id": "351_R1", "type": "Isolated_From", "arg1_id": "351_T6", "arg2_id": "351_T4", "normalized": [] }, { "id": "351_R2", "type": "Associated_With", "arg1_id": "351_T47", "arg2_id": "351_T48", "normalized": [] }, { "id": "351_R3", "type": "Associated_With", "arg1_id": "351_T47", "arg2_id": "351_T49", "normalized": [] } ]

[ { "id": "353", "type": "", "text": [ "We have identified a series of novel inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase by randomly screening natural product extracts using an in vitro biochemical assay designed to identify inhibitors of integrase-catalysed strand transfer. Equisetin recovered from the fungus Fusarium heterosporum and a novel enantiomeric homologue of equisetin from Phoma sp. were isolated as inhibitors of HIV-1 integrase in vitro. Two additional analogues, a novel decalin derivative, integric acid, and oteromycin were also discovered to be inhibitors of integrase. Equisetin and related compounds inhibit 3' end-processing and strand transfer as well as disintegration catalysed by either the full-length enzyme or the truncated integrase core domain (amino acids 50-212). These compounds also inhibit strand transfer reactions catalysed by stable complexes assembled in vitro and integration reactions catalysed by pre-integration complexes isolated from HIV-1-infected cells. The compounds described in this report are structurally novel and mechanistically distinct from many previously described inhibitors of HIV-1 integrase. These results demonstrate the utility of using an appropriately configured assay to identify compounds that are effective post-assembly and the potential of isolating novel integrase inhibitors from complex natural product extracts. \n" ], "offsets": [ [ 0, 1377 ] ] } ]

[ { "id": "353_T1", "type": "Protein", "text": [ "human immunodeficiency virus type 1", "integrase" ], "offsets": [ [ 51, 86 ], [ 95, 104 ] ], "normalized": [] }, { "id": "353_T2", "type": "Protein", "text": [ "HIV-1", "integrase" ], "offsets": [ [ 88, 93 ], [ 95, 104 ] ], "normalized": [] }, { "id": "353_T4", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 37, 46 ] ], "normalized": [] }, { "id": "353_T6", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 210, 219 ] ], "normalized": [] }, { "id": "353_T7", "type": "Metabolite", "text": [ "Equisetin" ], "offsets": [ [ 261, 270 ] ], "normalized": [] }, { "id": "353_T8", "type": "Chemical", "text": [ "Equisetin" ], "offsets": [ [ 261, 270 ] ], "normalized": [] }, { "id": "353_T9", "type": "Species", "text": [ "Fusarium heterosporum" ], "offsets": [ [ 297, 318 ] ], "normalized": [] }, { "id": "353_T10", "type": "Chemical", "text": [ "enantiomeric homologue of equisetin" ], "offsets": [ [ 332, 367 ] ], "normalized": [] }, { "id": "353_T11", "type": "Metabolite", "text": [ "enantiomeric homologue of equisetin" ], "offsets": [ [ 332, 367 ] ], "normalized": [] }, { "id": "353_T12", "type": "Species", "text": [ "Phoma sp." ], "offsets": [ [ 373, 382 ] ], "normalized": [] }, { "id": "353_T13", "type": "Protein", "text": [ "HIV-1 integrase" ], "offsets": [ [ 414, 429 ] ], "normalized": [] }, { "id": "353_T14", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 400, 409 ] ], "normalized": [] }, { "id": "353_T15", "type": "Chemical", "text": [ "decalin derivative" ], "offsets": [ [ 474, 492 ] ], "normalized": [] }, { "id": "353_T16", "type": "Chemical", "text": [ "integric acid" ], "offsets": [ [ 494, 507 ] ], "normalized": [] }, { "id": "353_T17", "type": "Chemical", "text": [ "oteromycin" ], "offsets": [ [ 513, 523 ] ], "normalized": [] }, { "id": "353_T18", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 551, 560 ] ], "normalized": [] }, { "id": "353_T19", "type": "Protein", "text": [ "integrase" ], "offsets": [ [ 565, 574 ] ], "normalized": [] }, { "id": "353_T21", "type": "Chemical", "text": [ "Equisetin" ], "offsets": [ [ 576, 585 ] ], "normalized": [] }, { "id": "353_T22", "type": "Metabolite", "text": [ "Equisetin" ], "offsets": [ [ 576, 585 ] ], "normalized": [] }, { "id": "353_T23", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 608, 615 ] ], "normalized": [] }, { "id": "353_T25", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 716, 722 ] ], "normalized": [] }, { "id": "353_T26", "type": "Chemical", "text": [ "amino acids" ], "offsets": [ [ 763, 774 ] ], "normalized": [] }, { "id": "353_T27", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 805, 812 ] ], "normalized": [] }, { "id": "353_T29", "type": "Biological_Activity", "text": [ "inhibitors" ], "offsets": [ [ 1111, 1121 ] ], "normalized": [] }, { "id": "353_T30", "type": "Protein", "text": [ "HIV-1 integrase" ], "offsets": [ [ 1125, 1140 ] ], "normalized": [] }, { "id": "353_T31", "type": "Protein", "text": [ "integrase" ], "offsets": [ [ 1316, 1325 ] ], "normalized": [] }, { "id": "353_T32", "type": "Biological_Activity", "text": [ "inhibitors" ], "offsets": [ [ 1326, 1336 ] ], "normalized": [] }, { "id": "353_T33", "type": "Chemical", "text": [ "compounds" ], "offsets": [ [ 1235, 1244 ] ], "normalized": [] } ]

[]

[]

[ { "id": "353_R1", "type": "Isolated_From", "arg1_id": "353_T7", "arg2_id": "353_T9", "normalized": [] }, { "id": "353_R2", "type": "Isolated_From", "arg1_id": "353_T11", "arg2_id": "353_T12", "normalized": [] }, { "id": "353_R3", "type": "Associated_With", "arg1_id": "353_T7", "arg2_id": "353_T14", "normalized": [] }, { "id": "353_R4", "type": "Associated_With", "arg1_id": "353_T8", "arg2_id": "353_T14", "normalized": [] }, { "id": "353_R5", "type": "Associated_With", "arg1_id": "353_T11", "arg2_id": "353_T14", "normalized": [] }, { "id": "353_R6", "type": "Associated_With", "arg1_id": "353_T10", "arg2_id": "353_T14", "normalized": [] }, { "id": "353_R11", "type": "Associated_With", "arg1_id": "353_T16", "arg2_id": "353_T18", "normalized": [] }, { "id": "353_R12", "type": "Associated_With", "arg1_id": "353_T17", "arg2_id": "353_T18", "normalized": [] }, { "id": "353_R15", "type": "Associated_With", "arg1_id": "353_T21", "arg2_id": "353_T23", "normalized": [] }, { "id": "353_R16", "type": "Associated_With", "arg1_id": "353_T22", "arg2_id": "353_T23", "normalized": [] }, { "id": "353_R17", "type": "Associated_With", "arg1_id": "353_T16", "arg2_id": "353_T23", "normalized": [] }, { "id": "353_R18", "type": "Associated_With", "arg1_id": "353_T17", "arg2_id": "353_T23", "normalized": [] }, { "id": "353_R25", "type": "Associated_With", "arg1_id": "353_T22", "arg2_id": "353_T27", "normalized": [] }, { "id": "353_R26", "type": "Associated_With", "arg1_id": "353_T21", "arg2_id": "353_T27", "normalized": [] }, { "id": "353_R29", "type": "Associated_With", "arg1_id": "353_T16", "arg2_id": "353_T27", "normalized": [] }, { "id": "353_R30", "type": "Associated_With", "arg1_id": "353_T17", "arg2_id": "353_T27", "normalized": [] }, { "id": "353_R31", "type": "Binds_With", "arg1_id": "353_T8", "arg2_id": "353_T13", "normalized": [] }, { "id": "353_R32", "type": "Binds_With", "arg1_id": "353_T7", "arg2_id": "353_T13", "normalized": [] }, { "id": "353_R33", "type": "Binds_With", "arg1_id": "353_T10", "arg2_id": "353_T13", "normalized": [] }, { "id": "353_R34", "type": "Binds_With", "arg1_id": "353_T11", "arg2_id": "353_T13", "normalized": [] }, { "id": "353_R7", "type": "Binds_With", "arg1_id": "353_T16", "arg2_id": "353_T19", "normalized": [] }, { "id": "353_R8", "type": "Binds_With", "arg1_id": "353_T17", "arg2_id": "353_T19", "normalized": [] }, { "id": "353_R9", "type": "Binds_With", "arg1_id": "353_T16", "arg2_id": "353_T13", "normalized": [] }, { "id": "353_R10", "type": "Binds_With", "arg1_id": "353_T17", "arg2_id": "353_T13", "normalized": [] } ]

[ { "id": "355", "type": "", "text": [ "AIMS: The present study was conducted to evaluate metabolism of the enantiomers of verapamil and norverapamil using a broad range of cytochrome P450 isoforms and measure the kinetic parameters of these processes. METHODS: Cytochrome P450 cDNA-expressed cells and microsomes from a P450-expressed lymphoblastoid cell line were incubated with 40 microm concentrations of R- or S-verapamil and R- or S-norverapamil and metabolite formation measured by h.p.l.c. as an initial screening. Those isoforms exhibiting substantial activity were then studied over a range of substrate concentrations (2.5-450 microm ) to estimate the kinetic parameters for metabolite formation. RESULTS: P450s 3A4, 3A5, 2C8 and to a minor extent 2E1 were involved in the metabolism of the enantiomers of verapamil. Estimated Km values for the production of D-617 and norverapamil by P450 s 3A4 and 3A5 were similar (range=60-127 microm ) regardless of the enantiomer of verapamil studied while the Vmax estimates were also similar (range=4-8 pmol min-1 pmol-1 P450). Only nominal production of D-620 by these isoforms was noted. Interestingly, P450 2C8 readily metabolized both S- and R-verapamil to D-617, norverapamil and PR-22 with only slightly higher Km values than noted for P450s 3A4 and 3A5. However, the Vmax estimates for P450 2C8 metabolism of S- and R-verapamil were in general greater (range=8-15 pmol min-1 pmol-1 P450) than those noted for P450 s 3A4 and 3A5 with preference noted for metabolism of the S-enantiomer. Similarly, P450 s 3A4, 3A5 and 2C8 also mediated the metabolism of the enantiomers of norverapamil with minor contributions by P450 s 2D6 and 2E1. P450s 3A4 and 3A5 readily formed the D-620 metabolite with generally a lower Km and higher Vmax for S-norverapamil than for the R-enantiomer. In contrast, P450 2C8 produced both the D-620 and PR-22 metabolites from the enantiomers of norverapamil, again with stereoselective preference seen for the S-enantiomer. CONCLUSIONS: These results confirm that P450s 3A4, 3A5 and 2C8 play a major role in verapamil metabolism and demonstrate that norverapamil can also be further metabolized by the P450s. \n" ], "offsets": [ [ 0, 2156 ] ] } ]

[ { "id": "355_T1", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 83, 92 ] ], "normalized": [] }, { "id": "355_T2", "type": "Chemical", "text": [ "norverapamil" ], "offsets": [ [ 97, 109 ] ], "normalized": [] }, { "id": "355_T3", "type": "Chemical", "text": [ "enantiomers of verapamil" ], "offsets": [ [ 68, 92 ] ], "normalized": [] }, { "id": "355_T4", "type": "Chemical", "text": [ "enantiomers of", "norverapamil" ], "offsets": [ [ 68, 82 ], [ 97, 109 ] ], "normalized": [] }, { "id": "355_T5", "type": "Protein", "text": [ "cytochrome P450" ], "offsets": [ [ 133, 148 ] ], "normalized": [] }, { "id": "355_T6", "type": "Protein", "text": [ "Cytochrome P450 cDNA" ], "offsets": [ [ 222, 242 ] ], "normalized": [] }, { "id": "355_T7", "type": "Chemical", "text": [ "R-", "verapamil" ], "offsets": [ [ 369, 371 ], [ 377, 386 ] ], "normalized": [] }, { "id": "355_T8", "type": "Chemical", "text": [ "S-verapamil" ], "offsets": [ [ 375, 386 ] ], "normalized": [] }, { "id": "355_T9", "type": "Chemical", "text": [ "R-", "norverapamil" ], "offsets": [ [ 391, 393 ], [ 400, 412 ] ], "normalized": [] }, { "id": "355_T10", "type": "Chemical", "text": [ "S-norverapamil" ], "offsets": [ [ 398, 412 ] ], "normalized": [] }, { "id": "355_T13", "type": "Protein", "text": [ "P450", "3A5" ], "offsets": [ [ 679, 683 ], [ 690, 693 ] ], "normalized": [] }, { "id": "355_T14", "type": "Protein", "text": [ "P450", "2C8" ], "offsets": [ [ 679, 683 ], [ 695, 698 ] ], "normalized": [] }, { "id": "355_T15", "type": "Protein", "text": [ "P450", "3A4" ], "offsets": [ [ 679, 683 ], [ 685, 688 ] ], "normalized": [] }, { "id": "355_T16", "type": "Protein", "text": [ "P450", "2E1" ], "offsets": [ [ 679, 683 ], [ 722, 725 ] ], "normalized": [] }, { "id": "355_T17", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 780, 789 ] ], "normalized": [] }, { "id": "355_T18", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 747, 757 ] ], "normalized": [] }, { "id": "355_T19", "type": "Chemical", "text": [ "D-617" ], "offsets": [ [ 833, 838 ] ], "normalized": [] }, { "id": "355_T20", "type": "Metabolite", "text": [ "D-617" ], "offsets": [ [ 833, 838 ] ], "normalized": [] }, { "id": "355_T21", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 946, 955 ] ], "normalized": [] }, { "id": "355_T22", "type": "Chemical", "text": [ "norverapamil" ], "offsets": [ [ 843, 855 ] ], "normalized": [] }, { "id": "355_T23", "type": "Metabolite", "text": [ "norverapamil" ], "offsets": [ [ 843, 855 ] ], "normalized": [] }, { "id": "355_T24", "type": "Protein", "text": [ "P450", "3A5" ], "offsets": [ [ 859, 863 ], [ 874, 877 ] ], "normalized": [] }, { "id": "355_T25", "type": "Protein", "text": [ "P450", "3A4" ], "offsets": [ [ 859, 863 ], [ 866, 869 ] ], "normalized": [] }, { "id": "355_T26", "type": "Chemical", "text": [ "D-620" ], "offsets": [ [ 1070, 1075 ] ], "normalized": [] }, { "id": "355_T27", "type": "Metabolite", "text": [ "D-620" ], "offsets": [ [ 1070, 1075 ] ], "normalized": [] }, { "id": "355_T28", "type": "Protein", "text": [ "P450 2C8" ], "offsets": [ [ 1120, 1128 ] ], "normalized": [] }, { "id": "355_T29", "type": "Chemical", "text": [ "S-", "verapamil" ], "offsets": [ [ 1154, 1156 ], [ 1163, 1172 ] ], "normalized": [] }, { "id": "355_T30", "type": "Chemical", "text": [ "R-verapamil" ], "offsets": [ [ 1161, 1172 ] ], "normalized": [] }, { "id": "355_T31", "type": "Chemical", "text": [ "D-617" ], "offsets": [ [ 1176, 1181 ] ], "normalized": [] }, { "id": "355_T32", "type": "Chemical", "text": [ "norverapamil" ], "offsets": [ [ 1183, 1195 ] ], "normalized": [] }, { "id": "355_T33", "type": "Chemical", "text": [ "PR-22" ], "offsets": [ [ 1200, 1205 ] ], "normalized": [] }, { "id": "355_T34", "type": "Protein", "text": [ "P450", "3A5" ], "offsets": [ [ 1257, 1261 ], [ 1271, 1274 ] ], "normalized": [] }, { "id": "355_T35", "type": "Protein", "text": [ "P450", "3A4" ], "offsets": [ [ 1257, 1261 ], [ 1263, 1266 ] ], "normalized": [] }, { "id": "355_T36", "type": "Metabolite", "text": [ "D-617" ], "offsets": [ [ 1176, 1181 ] ], "normalized": [] }, { "id": "355_T37", "type": "Metabolite", "text": [ "norverapamil" ], "offsets": [ [ 1183, 1195 ] ], "normalized": [] }, { "id": "355_T38", "type": "Metabolite", "text": [ "PR-22" ], "offsets": [ [ 1200, 1205 ] ], "normalized": [] }, { "id": "355_T39", "type": "Protein", "text": [ "P450 2C8" ], "offsets": [ [ 1308, 1316 ] ], "normalized": [] }, { "id": "355_T42", "type": "Protein", "text": [ "P450" ], "offsets": [ [ 1404, 1408 ] ], "normalized": [] }, { "id": "355_T43", "type": "Protein", "text": [ "P450", "3A5" ], "offsets": [ [ 1431, 1435 ], [ 1446, 1449 ] ], "normalized": [] }, { "id": "355_T44", "type": "Protein", "text": [ "P450", "3A4" ], "offsets": [ [ 1431, 1435 ], [ 1438, 1441 ] ], "normalized": [] }, { "id": "355_T45", "type": "Protein", "text": [ "P450", "2C8" ], "offsets": [ [ 1519, 1523 ], [ 1539, 1542 ] ], "normalized": [] }, { "id": "355_T46", "type": "Protein", "text": [ "P450", "3A5" ], "offsets": [ [ 1519, 1523 ], [ 1531, 1534 ] ], "normalized": [] }, { "id": "355_T47", "type": "Protein", "text": [ "P450", "3A4" ], "offsets": [ [ 1519, 1523 ], [ 1526, 1529 ] ], "normalized": [] }, { "id": "355_T49", "type": "Protein", "text": [ "P450", "2E1" ], "offsets": [ [ 1636, 1640 ], [ 1651, 1654 ] ], "normalized": [] }, { "id": "355_T50", "type": "Protein", "text": [ "P450", "2D6" ], "offsets": [ [ 1636, 1640 ], [ 1643, 1646 ] ], "normalized": [] }, { "id": "355_T51", "type": "Protein", "text": [ "P450s", "3A5" ], "offsets": [ [ 1656, 1661 ], [ 1670, 1673 ] ], "normalized": [] }, { "id": "355_T52", "type": "Protein", "text": [ "P450s", "3A4" ], "offsets": [ [ 1656, 1661 ], [ 1662, 1665 ] ], "normalized": [] }, { "id": "355_T53", "type": "Metabolite", "text": [ "D-620" ], "offsets": [ [ 1693, 1698 ] ], "normalized": [] }, { "id": "355_T54", "type": "Chemical", "text": [ "D-620" ], "offsets": [ [ 1693, 1698 ] ], "normalized": [] }, { "id": "355_T55", "type": "Chemical", "text": [ "S-norverapamil" ], "offsets": [ [ 1756, 1770 ] ], "normalized": [] }, { "id": "355_T56", "type": "Protein", "text": [ "P450 2C8" ], "offsets": [ [ 1811, 1819 ] ], "normalized": [] }, { "id": "355_T57", "type": "Chemical", "text": [ "D-620" ], "offsets": [ [ 1838, 1843 ] ], "normalized": [] }, { "id": "355_T58", "type": "Metabolite", "text": [ "D-620" ], "offsets": [ [ 1838, 1843 ] ], "normalized": [] }, { "id": "355_T59", "type": "Metabolite", "text": [ "PR-22" ], "offsets": [ [ 1848, 1853 ] ], "normalized": [] }, { "id": "355_T60", "type": "Chemical", "text": [ "PR-22" ], "offsets": [ [ 1848, 1853 ] ], "normalized": [] }, { "id": "355_T61", "type": "Chemical", "text": [ "norverapamil" ], "offsets": [ [ 1890, 1902 ] ], "normalized": [] }, { "id": "355_T62", "type": "Protein", "text": [ "P450", "3A5" ], "offsets": [ [ 2009, 2013 ], [ 2020, 2023 ] ], "normalized": [] }, { "id": "355_T63", "type": "Protein", "text": [ "P450", "2C8" ], "offsets": [ [ 2009, 2013 ], [ 2028, 2031 ] ], "normalized": [] }, { "id": "355_T64", "type": "Protein", "text": [ "P450", "3A4" ], "offsets": [ [ 2009, 2013 ], [ 2015, 2018 ] ], "normalized": [] }, { "id": "355_T65", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 2054, 2063 ] ], "normalized": [] }, { "id": "355_T67", "type": "Chemical", "text": [ "norverapamil" ], "offsets": [ [ 2096, 2108 ] ], "normalized": [] }, { "id": "355_T68", "type": "Protein", "text": [ "P450s" ], "offsets": [ [ 2148, 2153 ] ], "normalized": [] }, { "id": "355_T70", "type": "Chemical", "text": [ "S-", "verapamil" ], "offsets": [ [ 1331, 1333 ], [ 1340, 1349 ] ], "normalized": [] }, { "id": "355_T71", "type": "Chemical", "text": [ "R-verapamil" ], "offsets": [ [ 1338, 1349 ] ], "normalized": [] }, { "id": "355_T73", "type": "Chemical", "text": [ "S-enantiomer" ], "offsets": [ [ 1494, 1506 ] ], "normalized": [] }, { "id": "355_T74", "type": "Chemical", "text": [ "R-enantiomer" ], "offsets": [ [ 1784, 1796 ] ], "normalized": [] }, { "id": "355_T76", "type": "Metabolite", "text": [ "norverapamil" ], "offsets": [ [ 2096, 2108 ] ], "normalized": [] }, { "id": "355_T41", "type": "Chemical", "text": [ "norverapamil" ], "offsets": [ [ 1595, 1607 ] ], "normalized": [] }, { "id": "355_T69", "type": "Chemical", "text": [ "S-enantiomer" ], "offsets": [ [ 1955, 1967 ] ], "normalized": [] }, { "id": "355_T11", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1317, 1327 ] ], "normalized": [] }, { "id": "355_T12", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1476, 1486 ] ], "normalized": [] }, { "id": "355_T40", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 50, 60 ] ], "normalized": [] }, { "id": "355_T48", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1561, 1571 ] ], "normalized": [] }, { "id": "355_T66", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 2064, 2074 ] ], "normalized": [] }, { "id": "355_T72", "type": "Biological_Activity", "text": [ "metabolized" ], "offsets": [ [ 1137, 1148 ] ], "normalized": [] }, { "id": "355_T75", "type": "Biological_Activity", "text": [ "metabolized" ], "offsets": [ [ 2129, 2140 ] ], "normalized": [] }, { "id": "355_T77", "type": "Biological_Activity", "text": [ "metabolite formation" ], "offsets": [ [ 648, 668 ] ], "normalized": [] }, { "id": "355_T78", "type": "Biological_Activity", "text": [ "metabolite formation" ], "offsets": [ [ 417, 437 ] ], "normalized": [] } ]

[]

[]

[ { "id": "355_R1", "type": "Metabolite_Of", "arg1_id": "355_T20", "arg2_id": "355_T21", "normalized": [] }, { "id": "355_R2", "type": "Metabolite_Of", "arg1_id": "355_T23", "arg2_id": "355_T21", "normalized": [] }, { "id": "355_R3", "type": "Metabolite_Of", "arg1_id": "355_T27", "arg2_id": "355_T21", "normalized": [] }, { "id": "355_R4", "type": "Metabolite_Of", "arg1_id": "355_T36", "arg2_id": "355_T29", "normalized": [] }, { "id": "355_R5", "type": "Metabolite_Of", "arg1_id": "355_T37", "arg2_id": "355_T29", "normalized": [] }, { "id": "355_R6", "type": "Metabolite_Of", "arg1_id": "355_T38", "arg2_id": "355_T29", "normalized": [] }, { "id": "355_R7", "type": "Metabolite_Of", "arg1_id": "355_T36", "arg2_id": "355_T30", "normalized": [] }, { "id": "355_R8", "type": "Metabolite_Of", "arg1_id": "355_T37", "arg2_id": "355_T30", "normalized": [] }, { "id": "355_R9", "type": "Metabolite_Of", "arg1_id": "355_T38", "arg2_id": "355_T30", "normalized": [] }, { "id": "355_R10", "type": "Metabolite_Of", "arg1_id": "355_T53", "arg2_id": "355_T55", "normalized": [] }, { "id": "355_R11", "type": "Metabolite_Of", "arg1_id": "355_T58", "arg2_id": "355_T61", "normalized": [] }, { "id": "355_R12", "type": "Metabolite_Of", "arg1_id": "355_T59", "arg2_id": "355_T61", "normalized": [] }, { "id": "355_R13", "type": "Metabolite_Of", "arg1_id": "355_T53", "arg2_id": "355_T74", "normalized": [] }, { "id": "355_R14", "type": "Metabolite_Of", "arg1_id": "355_T76", "arg2_id": "355_T65", "normalized": [] } ]

[ { "id": "357", "type": "", "text": [ "Phenylacetic acids are common intermediates in the microbial metabolism of various aromatic substrates including phenylalanine. In the denitrifying bacterium Thauera aromatica phenylacetate is oxidized, under anoxic conditions, to the common intermediate benzoyl-CoA via the intermediates phenylacetyl-CoA and phenylglyoxylate (benzoylformate). The enzyme that catalyzes the four-electron oxidation of phenylacetyl-CoA has been purified from this bacterium and studied. The enzyme preparation catalyzes the reaction phenylacetyl-CoA + 2 quinone + 2 H2O --> phenylglyoxylate + 2 quinone H2 + CoASH. Phenylacetyl-CoA:acceptor oxidoreductase is a membrane-bound molybdenum-iron-sulfur protein. The purest preparations contained three subunits of 93, 27, and 26 kDa. Ubiquinone is most likely to act as the electron acceptor, and the oxygen atom introduced into the product is derived from water. The protein preparations contained 0.66 mol Mo, 30 mol Fe, and 25 mol acid-labile sulfur per mol of native enzyme, assuming a native molecular mass of 280 kDa. Phenylglyoxylyl-CoA, but not mandelyl-CoA, was observed as a free intermediate. All enzyme preparations also catalyzed the subsequent hydrolytic release of coenzyme A from phenylglyoxylyl-CoA but not from phenylacetyl-CoA. The enzyme is reversibly inactivated by a low concentration of cyanide, but is remarkably stable with respect to oxygen. This new member of the molybdoproteins represents the first example of an enzyme which catalyzes the alpha-oxidation of a CoA-activated carboxylic acid without utilizing molecular oxygen. \n" ], "offsets": [ [ 0, 1589 ] ] } ]

[ { "id": "357_T1", "type": "Chemical", "text": [ "Phenylacetic acids" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "357_T2", "type": "Chemical", "text": [ "phenylalanine" ], "offsets": [ [ 113, 126 ] ], "normalized": [] }, { "id": "357_T4", "type": "Species", "text": [ "Thauera aromatica" ], "offsets": [ [ 158, 175 ] ], "normalized": [] }, { "id": "357_T5", "type": "Chemical", "text": [ "phenylacetate" ], "offsets": [ [ 176, 189 ] ], "normalized": [] }, { "id": "357_T7", "type": "Chemical", "text": [ "benzoyl-CoA" ], "offsets": [ [ 255, 266 ] ], "normalized": [] }, { "id": "357_T8", "type": "Metabolite", "text": [ "benzoyl-CoA" ], "offsets": [ [ 255, 266 ] ], "normalized": [] }, { "id": "357_T9", "type": "Chemical", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 289, 305 ] ], "normalized": [] }, { "id": "357_T10", "type": "Metabolite", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 289, 305 ] ], "normalized": [] }, { "id": "357_T11", "type": "Chemical", "text": [ "phenylglyoxylate" ], "offsets": [ [ 310, 326 ] ], "normalized": [] }, { "id": "357_T12", "type": "Metabolite", "text": [ "phenylglyoxylate" ], "offsets": [ [ 310, 326 ] ], "normalized": [] }, { "id": "357_T13", "type": "Metabolite", "text": [ "benzoylformate" ], "offsets": [ [ 328, 342 ] ], "normalized": [] }, { "id": "357_T14", "type": "Chemical", "text": [ "benzoylformate" ], "offsets": [ [ 328, 342 ] ], "normalized": [] }, { "id": "357_T15", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 349, 355 ] ], "normalized": [] }, { "id": "357_T16", "type": "Chemical", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 402, 418 ] ], "normalized": [] }, { "id": "357_T17", "type": "Metabolite", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 402, 418 ] ], "normalized": [] }, { "id": "357_T19", "type": "Species", "text": [ "bacterium" ], "offsets": [ [ 447, 456 ] ], "normalized": [] }, { "id": "357_T20", "type": "Chemical", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 517, 533 ] ], "normalized": [] }, { "id": "357_T21", "type": "Chemical", "text": [ "quinone" ], "offsets": [ [ 538, 545 ] ], "normalized": [] }, { "id": "357_T22", "type": "Chemical", "text": [ "H2O" ], "offsets": [ [ 550, 553 ] ], "normalized": [] }, { "id": "357_T23", "type": "Chemical", "text": [ "phenylglyoxylate" ], "offsets": [ [ 558, 574 ] ], "normalized": [] }, { "id": "357_T24", "type": "Chemical", "text": [ "quinone H2" ], "offsets": [ [ 579, 589 ] ], "normalized": [] }, { "id": "357_T25", "type": "Chemical", "text": [ "CoASH" ], "offsets": [ [ 592, 597 ] ], "normalized": [] }, { "id": "357_T26", "type": "Protein", "text": [ "Phenylacetyl-CoA:acceptor oxidoreductase" ], "offsets": [ [ 599, 639 ] ], "normalized": [] }, { "id": "357_T27", "type": "Chemical", "text": [ "molybdenum" ], "offsets": [ [ 660, 670 ] ], "normalized": [] }, { "id": "357_T28", "type": "Chemical", "text": [ "iron" ], "offsets": [ [ 671, 675 ] ], "normalized": [] }, { "id": "357_T29", "type": "Chemical", "text": [ "sulfur" ], "offsets": [ [ 676, 682 ] ], "normalized": [] }, { "id": "357_T30", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 683, 690 ] ], "normalized": [] }, { "id": "357_T31", "type": "Chemical", "text": [ "Ubiquinone" ], "offsets": [ [ 764, 774 ] ], "normalized": [] }, { "id": "357_T32", "type": "Biological_Activity", "text": [ "electron acceptor" ], "offsets": [ [ 804, 821 ] ], "normalized": [] }, { "id": "357_T33", "type": "Chemical", "text": [ "oxygen atom" ], "offsets": [ [ 831, 842 ] ], "normalized": [] }, { "id": "357_T34", "type": "Chemical", "text": [ "water" ], "offsets": [ [ 887, 892 ] ], "normalized": [] }, { "id": "357_T35", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 898, 905 ] ], "normalized": [] }, { "id": "357_T36", "type": "Chemical", "text": [ "Mo" ], "offsets": [ [ 938, 940 ] ], "normalized": [] }, { "id": "357_T37", "type": "Chemical", "text": [ "Fe" ], "offsets": [ [ 949, 951 ] ], "normalized": [] }, { "id": "357_T39", "type": "Chemical", "text": [ "sulfur" ], "offsets": [ [ 976, 982 ] ], "normalized": [] }, { "id": "357_T38", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1001, 1007 ] ], "normalized": [] }, { "id": "357_T40", "type": "Chemical", "text": [ "Phenylglyoxylyl-CoA" ], "offsets": [ [ 1054, 1073 ] ], "normalized": [] }, { "id": "357_T41", "type": "Chemical", "text": [ "mandelyl-CoA" ], "offsets": [ [ 1083, 1095 ] ], "normalized": [] }, { "id": "357_T42", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1138, 1144 ] ], "normalized": [] }, { "id": "357_T44", "type": "Chemical", "text": [ "coenzyme A" ], "offsets": [ [ 1210, 1220 ] ], "normalized": [] }, { "id": "357_T45", "type": "Chemical", "text": [ "phenylglyoxylyl-CoA" ], "offsets": [ [ 1226, 1245 ] ], "normalized": [] }, { "id": "357_T46", "type": "Chemical", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 1259, 1275 ] ], "normalized": [] }, { "id": "357_T47", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1281, 1287 ] ], "normalized": [] }, { "id": "357_T48", "type": "Chemical", "text": [ "cyanide" ], "offsets": [ [ 1341, 1348 ] ], "normalized": [] }, { "id": "357_T49", "type": "Chemical", "text": [ "oxygen" ], "offsets": [ [ 1391, 1397 ] ], "normalized": [] }, { "id": "357_T50", "type": "Protein", "text": [ "molybdoproteins" ], "offsets": [ [ 1423, 1438 ] ], "normalized": [] }, { "id": "357_T51", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 1474, 1480 ] ], "normalized": [] }, { "id": "357_T53", "type": "Chemical", "text": [ "molecular oxygen" ], "offsets": [ [ 1570, 1586 ] ], "normalized": [] }, { "id": "357_T55", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 61, 71 ] ], "normalized": [] }, { "id": "357_T56", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "357_T57", "type": "Metabolite", "text": [ "phenylacetyl-CoA" ], "offsets": [ [ 517, 533 ] ], "normalized": [] }, { "id": "357_T58", "type": "Metabolite", "text": [ "quinone" ], "offsets": [ [ 538, 545 ] ], "normalized": [] }, { "id": "357_T59", "type": "Metabolite", "text": [ "phenylglyoxylate" ], "offsets": [ [ 558, 574 ] ], "normalized": [] }, { "id": "357_T60", "type": "Metabolite", "text": [ "quinone H2" ], "offsets": [ [ 579, 589 ] ], "normalized": [] }, { "id": "357_T61", "type": "Metabolite", "text": [ "CoASH" ], "offsets": [ [ 592, 597 ] ], "normalized": [] }, { "id": "357_T62", "type": "Metabolite", "text": [ "Ubiquinone" ], "offsets": [ [ 764, 774 ] ], "normalized": [] }, { "id": "357_T63", "type": "Metabolite", "text": [ "Phenylglyoxylyl-CoA" ], "offsets": [ [ 1054, 1073 ] ], "normalized": [] }, { "id": "357_T64", "type": "Metabolite", "text": [ "phenylglyoxylyl-CoA" ], "offsets": [ [ 1226, 1245 ] ], "normalized": [] }, { "id": "357_T3", "type": "Chemical", "text": [ "CoA-activated carboxylic acid" ], "offsets": [ [ 1522, 1551 ] ], "normalized": [] } ]

[]

[]

[ { "id": "357_R2", "type": "Metabolite_Of", "arg1_id": "357_T8", "arg2_id": "357_T11", "normalized": [] }, { "id": "357_R3", "type": "Metabolite_Of", "arg1_id": "357_T8", "arg2_id": "357_T14", "normalized": [] }, { "id": "357_R4", "type": "Metabolite_Of", "arg1_id": "357_T10", "arg2_id": "357_T5", "normalized": [] }, { "id": "357_R5", "type": "Metabolite_Of", "arg1_id": "357_T12", "arg2_id": "357_T5", "normalized": [] }, { "id": "357_R6", "type": "Metabolite_Of", "arg1_id": "357_T13", "arg2_id": "357_T5", "normalized": [] }, { "id": "357_R7", "type": "Metabolite_Of", "arg1_id": "357_T12", "arg2_id": "357_T9", "normalized": [] }, { "id": "357_R8", "type": "Metabolite_Of", "arg1_id": "357_T13", "arg2_id": "357_T9", "normalized": [] }, { "id": "357_R1", "type": "Associated_With", "arg1_id": "357_T31", "arg2_id": "357_T32", "normalized": [] }, { "id": "357_R9", "type": "Metabolite_Of", "arg1_id": "357_T63", "arg2_id": "357_T20", "normalized": [] }, { "id": "357_R10", "type": "Metabolite_Of", "arg1_id": "357_T59", "arg2_id": "357_T40", "normalized": [] } ]

[ { "id": "359", "type": "", "text": [ "Phlorisovalerophenone synthase (VPS), a novel aromatic polyketide synthase, was purified to homogeneity from 4.2 mg protein extract obtained from hop (Humulus lupulus L.) cone glandular hairs. The enzyme uses isovaleryl-CoA or isobutyryl-CoA and three molecules of malonyl-CoA to form phlorisovalerophenone or phlorisobutyrophenone, intermediates in the biosynthesis of the hop bitter acids (alpha- and beta-acids). VPS is an homodimeric enzyme, with subunits of 45 kDa. The pI of the enzyme was 6.1. Km values of 4 microm for isovaleryl-CoA, 10 microm for isobutyryl-CoA and 33 microm for malonyl-CoA, were found. The amino-acid sequences of two peptides, obtained by digestion of VPS, showed that the enzyme is highly homologous to plant chalcone synthases. The functional and structural relationship between VPS and other aromatic polyketide synthases is discussed. \n" ], "offsets": [ [ 0, 871 ] ] } ]

[ { "id": "359_T1", "type": "Protein", "text": [ "Phlorisovalerophenone synthase" ], "offsets": [ [ 0, 30 ] ], "normalized": [] }, { "id": "359_T2", "type": "Protein", "text": [ "VPS" ], "offsets": [ [ 32, 35 ] ], "normalized": [] }, { "id": "359_T3", "type": "Protein", "text": [ "aromatic polyketide synthase" ], "offsets": [ [ 46, 74 ] ], "normalized": [] }, { "id": "359_T4", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 116, 123 ] ], "normalized": [] }, { "id": "359_T5", "type": "Species", "text": [ "hop" ], "offsets": [ [ 146, 149 ] ], "normalized": [] }, { "id": "359_T6", "type": "Species", "text": [ "Humulus lupulus" ], "offsets": [ [ 151, 166 ] ], "normalized": [] }, { "id": "359_T7", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 197, 203 ] ], "normalized": [] }, { "id": "359_T8", "type": "Chemical", "text": [ "isovaleryl-CoA" ], "offsets": [ [ 209, 223 ] ], "normalized": [] }, { "id": "359_T9", "type": "Chemical", "text": [ "isobutyryl-CoA" ], "offsets": [ [ 227, 241 ] ], "normalized": [] }, { "id": "359_T10", "type": "Chemical", "text": [ "malonyl-CoA" ], "offsets": [ [ 265, 276 ] ], "normalized": [] }, { "id": "359_T11", "type": "Chemical", "text": [ "phlorisovalerophenone" ], "offsets": [ [ 285, 306 ] ], "normalized": [] }, { "id": "359_T12", "type": "Chemical", "text": [ "phlorisobutyrophenone" ], "offsets": [ [ 310, 331 ] ], "normalized": [] }, { "id": "359_T13", "type": "Species", "text": [ "hop" ], "offsets": [ [ 374, 377 ] ], "normalized": [] }, { "id": "359_T14", "type": "Chemical", "text": [ "bitter acids" ], "offsets": [ [ 378, 390 ] ], "normalized": [] }, { "id": "359_T15", "type": "Chemical", "text": [ "alpha-", "acids" ], "offsets": [ [ 392, 398 ], [ 408, 413 ] ], "normalized": [] }, { "id": "359_T16", "type": "Chemical", "text": [ "beta-acids" ], "offsets": [ [ 403, 413 ] ], "normalized": [] }, { "id": "359_T18", "type": "Protein", "text": [ "VPS" ], "offsets": [ [ 416, 419 ] ], "normalized": [] }, { "id": "359_T19", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 438, 444 ] ], "normalized": [] }, { "id": "359_T20", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 486, 492 ] ], "normalized": [] }, { "id": "359_T21", "type": "Chemical", "text": [ "isovaleryl-CoA" ], "offsets": [ [ 528, 542 ] ], "normalized": [] }, { "id": "359_T22", "type": "Chemical", "text": [ "isobutyryl-CoA" ], "offsets": [ [ 558, 572 ] ], "normalized": [] }, { "id": "359_T23", "type": "Chemical", "text": [ "malonyl-CoA" ], "offsets": [ [ 591, 602 ] ], "normalized": [] }, { "id": "359_T24", "type": "Chemical", "text": [ "amino-acid" ], "offsets": [ [ 620, 630 ] ], "normalized": [] }, { "id": "359_T25", "type": "Chemical", "text": [ "peptides" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "359_T26", "type": "Protein", "text": [ "VPS" ], "offsets": [ [ 683, 686 ] ], "normalized": [] }, { "id": "359_T27", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 704, 710 ] ], "normalized": [] }, { "id": "359_T28", "type": "Protein", "text": [ "plant chalcone synthases" ], "offsets": [ [ 735, 759 ] ], "normalized": [] }, { "id": "359_T29", "type": "Protein", "text": [ "VPS" ], "offsets": [ [ 812, 815 ] ], "normalized": [] }, { "id": "359_T30", "type": "Protein", "text": [ "aromatic polyketide synthases" ], "offsets": [ [ 826, 855 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "361", "type": "", "text": [ "Supplementation of vegetable proteins with various essential amino acids is an effective means of improving proteins quality. Unfortunately, simple amino acid additions to foods which must be heat processed and cooked is not without consequences. Under these conditions, methionine interacts with reducing sugars yielding methional through the Strecker degradation reaction. This generation of methional during heat treatment imparts undesirable sulfur odors and flavors to the food rendering it organoleptically unacceptable. Similarly, threonine and lysine are also susceptible to interaction with reducing sugars rendering them nutritionally unavailable. Acetylated derivatives of methionine, threonine and lysine have been studied to determine their utility in overcoming the inherent problems associated with each amino acid. To this end, N-acetyl-L-methionine and N-acetyl-L-threonine were found to be fully available to promote growth of rats. To the contrary, neither the alpha nor the epsilon, monoacetylated derivative of L-Lysine nor the alpha, epsilon diacetyl derivative of L-Lysine were effective in significantly promoting the growth of rats. Utilization of N-acetyl-L-methionine by humans has also been studied and shown to be as effective as methionine in improving the quality of vegetable proteins deficient in sulfur amino acids. \n" ], "offsets": [ [ 0, 1356 ] ] } ]

[ { "id": "361_T1", "type": "Protein", "text": [ "vegetable proteins" ], "offsets": [ [ 19, 37 ] ], "normalized": [] }, { "id": "361_T2", "type": "Chemical", "text": [ "essential amino acids" ], "offsets": [ [ 51, 72 ] ], "normalized": [] }, { "id": "361_T3", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 148, 158 ] ], "normalized": [] }, { "id": "361_T4", "type": "Chemical", "text": [ "methionine" ], "offsets": [ [ 271, 281 ] ], "normalized": [] }, { "id": "361_T5", "type": "Chemical", "text": [ "reducing sugars" ], "offsets": [ [ 297, 312 ] ], "normalized": [] }, { "id": "361_T6", "type": "Chemical", "text": [ "methional" ], "offsets": [ [ 322, 331 ] ], "normalized": [] }, { "id": "361_T7", "type": "Chemical", "text": [ "methional" ], "offsets": [ [ 395, 404 ] ], "normalized": [] }, { "id": "361_T8", "type": "Chemical", "text": [ "sulfur" ], "offsets": [ [ 447, 453 ] ], "normalized": [] }, { "id": "361_T9", "type": "Chemical", "text": [ "threonine" ], "offsets": [ [ 539, 548 ] ], "normalized": [] }, { "id": "361_T10", "type": "Chemical", "text": [ "lysine" ], "offsets": [ [ 553, 559 ] ], "normalized": [] }, { "id": "361_T11", "type": "Chemical", "text": [ "reducing sugars" ], "offsets": [ [ 601, 616 ] ], "normalized": [] }, { "id": "361_T12", "type": "Chemical", "text": [ "Acetylated derivatives of", "threonine" ], "offsets": [ [ 659, 684 ], [ 697, 706 ] ], "normalized": [] }, { "id": "361_T13", "type": "Chemical", "text": [ "Acetylated derivatives of" ], "offsets": [ [ 659, 684 ] ], "normalized": [] }, { "id": "361_T14", "type": "Chemical", "text": [ "Acetylated derivatives of methionine", "lysine" ], "offsets": [ [ 659, 695 ], [ 711, 717 ] ], "normalized": [] }, { "id": "361_T15", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 820, 830 ] ], "normalized": [] }, { "id": "361_T16", "type": "Chemical", "text": [ "N-acetyl-L-methionine" ], "offsets": [ [ 845, 866 ] ], "normalized": [] }, { "id": "361_T17", "type": "Chemical", "text": [ "N-acetyl-L-threonine" ], "offsets": [ [ 872, 892 ] ], "normalized": [] }, { "id": "361_T19", "type": "Species", "text": [ "rats" ], "offsets": [ [ 947, 951 ] ], "normalized": [] }, { "id": "361_T20", "type": "Chemical", "text": [ "monoacetylated derivative of L-Lysine", "alpha" ], "offsets": [ [ 1006, 1044 ], [ 983, 988 ] ], "normalized": [] }, { "id": "361_T21", "type": "Chemical", "text": [ "epsilon, monoacetylated derivative of L-Lysine" ], "offsets": [ [ 997, 1044 ] ], "normalized": [] }, { "id": "361_T22", "type": "Chemical", "text": [ "alpha, epsilon diacetyl derivative of L-Lysine" ], "offsets": [ [ 1053, 1099 ] ], "normalized": [] }, { "id": "361_T24", "type": "Chemical", "text": [ "N-acetyl-L-methionine" ], "offsets": [ [ 1177, 1198 ] ], "normalized": [] }, { "id": "361_T25", "type": "Species", "text": [ "humans" ], "offsets": [ [ 1203, 1209 ] ], "normalized": [] }, { "id": "361_T26", "type": "Chemical", "text": [ "methionine" ], "offsets": [ [ 1264, 1274 ] ], "normalized": [] }, { "id": "361_T29", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 108, 116 ] ], "normalized": [] }, { "id": "361_T27", "type": "Protein", "text": [ "vegetable proteins" ], "offsets": [ [ 1303, 1321 ] ], "normalized": [] }, { "id": "361_T28", "type": "Chemical", "text": [ "sulfur amino acids" ], "offsets": [ [ 1335, 1353 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "363", "type": "", "text": [ "Nigericin is an ionophore commonly used at the end of experiments to calibrate intracellularly trapped pH-sensitive dyes. In the present study, we explore the possibility that residual nigericin from dye calibration in one experiment might interfere with intracellular pH (pHi) changes in the next. Using the pH-sensitive fluorescent dye 2', 7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF), we measured pHi in cultured rat renal mesangial cells. Nigericin contamination caused: (i) an increase in acid loading during the pHi decrease elicited by removing extracellular Na+, (ii) an increase in acid extrusion during the pHi increase caused by elevating extracellular [K+], and (iii) an acid shift in the pHi dependence of the background intracellular acid loading unmasked by inhibiting Na-H exchange with ethylisopropylamiloride (EIPA). However, contamination had no effect on the pHi dependence of Na-H exchange, computed by adding the pHi dependencies of total acid extrusion and background acid loading. Nigericin contamination can be conveniently minimized by using a separate line to deliver nigericin to the cells, and by briefly washing the tubing with ethanol and water after each experiment. \n" ], "offsets": [ [ 0, 1209 ] ] } ]

[ { "id": "363_T1", "type": "Chemical", "text": [ "Nigericin" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "363_T2", "type": "Biological_Activity", "text": [ "ionophore" ], "offsets": [ [ 16, 25 ] ], "normalized": [] }, { "id": "363_T4", "type": "Chemical", "text": [ "nigericin" ], "offsets": [ [ 185, 194 ] ], "normalized": [] }, { "id": "363_T6", "type": "Chemical", "text": [ "2', 7'-bis(carboxyethyl)-5,6-carboxyfluorescein" ], "offsets": [ [ 339, 386 ] ], "normalized": [] }, { "id": "363_T7", "type": "Chemical", "text": [ "BCECF" ], "offsets": [ [ 388, 393 ] ], "normalized": [] }, { "id": "363_T8", "type": "Species", "text": [ "rat" ], "offsets": [ [ 424, 427 ] ], "normalized": [] }, { "id": "363_T9", "type": "Chemical", "text": [ "Nigericin" ], "offsets": [ [ 451, 460 ] ], "normalized": [] }, { "id": "363_T10", "type": "Chemical", "text": [ "Na+" ], "offsets": [ [ 574, 577 ] ], "normalized": [] }, { "id": "363_T11", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 502, 506 ] ], "normalized": [] }, { "id": "363_T12", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "363_T13", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 691, 695 ] ], "normalized": [] }, { "id": "363_T14", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 756, 760 ] ], "normalized": [] }, { "id": "363_T15", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 792, 794 ] ], "normalized": [] }, { "id": "363_T16", "type": "Chemical", "text": [ "H" ], "offsets": [ [ 795, 796 ] ], "normalized": [] }, { "id": "363_T17", "type": "Chemical", "text": [ "ethylisopropylamiloride" ], "offsets": [ [ 811, 834 ] ], "normalized": [] }, { "id": "363_T18", "type": "Chemical", "text": [ "EIPA" ], "offsets": [ [ 836, 840 ] ], "normalized": [] }, { "id": "363_T19", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 905, 907 ] ], "normalized": [] }, { "id": "363_T20", "type": "Chemical", "text": [ "H" ], "offsets": [ [ 908, 909 ] ], "normalized": [] }, { "id": "363_T21", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 969, 973 ] ], "normalized": [] }, { "id": "363_T22", "type": "Chemical", "text": [ "acid" ], "offsets": [ [ 999, 1003 ] ], "normalized": [] }, { "id": "363_T23", "type": "Chemical", "text": [ "Nigericin" ], "offsets": [ [ 1014, 1023 ] ], "normalized": [] }, { "id": "363_T24", "type": "Chemical", "text": [ "nigericin" ], "offsets": [ [ 1104, 1113 ] ], "normalized": [] }, { "id": "363_T25", "type": "Chemical", "text": [ "ethanol" ], "offsets": [ [ 1167, 1174 ] ], "normalized": [] }, { "id": "363_T26", "type": "Chemical", "text": [ "water" ], "offsets": [ [ 1179, 1184 ] ], "normalized": [] }, { "id": "363_T27", "type": "Chemical", "text": [ "K+" ], "offsets": [ [ 673, 675 ] ], "normalized": [] } ]

[]

[]

[ { "id": "363_R1", "type": "Associated_With", "arg1_id": "363_T1", "arg2_id": "363_T2", "normalized": [] } ]

[ { "id": "365", "type": "", "text": [ "The fatty acid composition of caprine milk fat was studied using capillary gas chromatography. Milk was obtained from five goat herds belonging to different breeders in the Murcia region (Spain) and collected monthly (from November to May). The results showed significant differences among herds mainly in long-chain fatty acids (C16:0, C18:0, and C18:2). There were five branched-chain fatty acids (iso- and anteiso-C15:0, iso- and anteiso-C17:0, and iso-C16:0) with > 0.1% of the total fatty acid methyl esters and another 31 (the most monomethylated) with < 0.1%, including 4-ethyloctanoate, which is implicated in goat-like flavors. To study the content of trans unsaturated fatty acids, the fatty acid methyl esters were previously fractionated by AgNO3-thin layer chromatography. The mean contents of trans-C16:1 and trans-C18:1 were 0.16 and 2.12%, respectively. The distribution profile of trans-C18:1 was also studied. \n" ], "offsets": [ [ 0, 932 ] ] } ]

[ { "id": "365_T1", "type": "Chemical", "text": [ "fatty acid" ], "offsets": [ [ 4, 14 ] ], "normalized": [] }, { "id": "365_T2", "type": "Species", "text": [ "caprine" ], "offsets": [ [ 30, 37 ] ], "normalized": [] }, { "id": "365_T3", "type": "Species", "text": [ "goat" ], "offsets": [ [ 123, 127 ] ], "normalized": [] }, { "id": "365_T4", "type": "Chemical", "text": [ "long-chain fatty acids" ], "offsets": [ [ 306, 328 ] ], "normalized": [] }, { "id": "365_T5", "type": "Chemical", "text": [ "C16:0" ], "offsets": [ [ 330, 335 ] ], "normalized": [] }, { "id": "365_T6", "type": "Chemical", "text": [ "C18:0" ], "offsets": [ [ 337, 342 ] ], "normalized": [] }, { "id": "365_T7", "type": "Chemical", "text": [ "C18:2" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "365_T8", "type": "Chemical", "text": [ "branched-chain fatty acids" ], "offsets": [ [ 372, 398 ] ], "normalized": [] }, { "id": "365_T9", "type": "Metabolite", "text": [ "C16:0" ], "offsets": [ [ 330, 335 ] ], "normalized": [] }, { "id": "365_T10", "type": "Metabolite", "text": [ "C18:0" ], "offsets": [ [ 337, 342 ] ], "normalized": [] }, { "id": "365_T11", "type": "Metabolite", "text": [ "C18:2" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "365_T12", "type": "Chemical", "text": [ "iso-", "C15:0" ], "offsets": [ [ 400, 404 ], [ 417, 422 ] ], "normalized": [] }, { "id": "365_T13", "type": "Metabolite", "text": [ "iso", "-C15:0" ], "offsets": [ [ 400, 403 ], [ 416, 422 ] ], "normalized": [] }, { "id": "365_T14", "type": "Chemical", "text": [ "anteiso-C15:0" ], "offsets": [ [ 409, 422 ] ], "normalized": [] }, { "id": "365_T15", "type": "Metabolite", "text": [ "anteiso-C15:0" ], "offsets": [ [ 409, 422 ] ], "normalized": [] }, { "id": "365_T16", "type": "Chemical", "text": [ "iso-", "C17:0" ], "offsets": [ [ 424, 428 ], [ 441, 446 ] ], "normalized": [] }, { "id": "365_T17", "type": "Metabolite", "text": [ "iso-", "C17:0" ], "offsets": [ [ 424, 428 ], [ 441, 446 ] ], "normalized": [] }, { "id": "365_T18", "type": "Chemical", "text": [ "anteiso-C17:0" ], "offsets": [ [ 433, 446 ] ], "normalized": [] }, { "id": "365_T19", "type": "Metabolite", "text": [ "anteiso-C17:0" ], "offsets": [ [ 433, 446 ] ], "normalized": [] }, { "id": "365_T20", "type": "Chemical", "text": [ "iso-C16:0" ], "offsets": [ [ 452, 461 ] ], "normalized": [] }, { "id": "365_T21", "type": "Metabolite", "text": [ "iso-C16:0" ], "offsets": [ [ 452, 461 ] ], "normalized": [] }, { "id": "365_T22", "type": "Chemical", "text": [ "fatty acid methyl esters" ], "offsets": [ [ 488, 512 ] ], "normalized": [] }, { "id": "365_T23", "type": "Chemical", "text": [ "4-ethyloctanoate" ], "offsets": [ [ 578, 594 ] ], "normalized": [] }, { "id": "365_T24", "type": "Metabolite", "text": [ "4-ethyloctanoate" ], "offsets": [ [ 578, 594 ] ], "normalized": [] }, { "id": "365_T25", "type": "Species", "text": [ "goat" ], "offsets": [ [ 619, 623 ] ], "normalized": [] }, { "id": "365_T26", "type": "Chemical", "text": [ "trans unsaturated fatty acids" ], "offsets": [ [ 663, 692 ] ], "normalized": [] }, { "id": "365_T27", "type": "Chemical", "text": [ "fatty acid methyl esters" ], "offsets": [ [ 698, 722 ] ], "normalized": [] }, { "id": "365_T28", "type": "Chemical", "text": [ "AgNO3" ], "offsets": [ [ 756, 761 ] ], "normalized": [] }, { "id": "365_T29", "type": "Chemical", "text": [ "trans-C16:1" ], "offsets": [ [ 810, 821 ] ], "normalized": [] }, { "id": "365_T30", "type": "Metabolite", "text": [ "trans-C16:1" ], "offsets": [ [ 810, 821 ] ], "normalized": [] }, { "id": "365_T31", "type": "Chemical", "text": [ "trans-C18:1" ], "offsets": [ [ 826, 837 ] ], "normalized": [] }, { "id": "365_T32", "type": "Metabolite", "text": [ "trans-C18:1" ], "offsets": [ [ 826, 837 ] ], "normalized": [] }, { "id": "365_T33", "type": "Chemical", "text": [ "trans-C18:1" ], "offsets": [ [ 901, 912 ] ], "normalized": [] }, { "id": "365_T34", "type": "Metabolite", "text": [ "trans-C18:1" ], "offsets": [ [ 901, 912 ] ], "normalized": [] } ]

[]

[]

[ { "id": "365_R1", "type": "Isolated_From", "arg1_id": "365_T9", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R2", "type": "Isolated_From", "arg1_id": "365_T10", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R3", "type": "Isolated_From", "arg1_id": "365_T11", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R4", "type": "Isolated_From", "arg1_id": "365_T13", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R5", "type": "Isolated_From", "arg1_id": "365_T15", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R6", "type": "Isolated_From", "arg1_id": "365_T17", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R7", "type": "Isolated_From", "arg1_id": "365_T19", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R8", "type": "Isolated_From", "arg1_id": "365_T21", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R9", "type": "Isolated_From", "arg1_id": "365_T24", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R10", "type": "Isolated_From", "arg1_id": "365_T30", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R11", "type": "Isolated_From", "arg1_id": "365_T32", "arg2_id": "365_T3", "normalized": [] }, { "id": "365_R12", "type": "Isolated_From", "arg1_id": "365_T34", "arg2_id": "365_T3", "normalized": [] } ]

[ { "id": "367", "type": "", "text": [ "Phosphatoquinones A and B were isolated from the cultured broth of Streptomyces sp. TA-0363 and their structures were elucidated by spectroscopic analyses. Phosphatoquinones A and B inhibited the protein tyrosine phosphatase activity prepared from human Ball-1 cells with IC50 of 28 microM and 2.9 microM, respectively. \n" ], "offsets": [ [ 0, 321 ] ] } ]

[ { "id": "367_T1", "type": "Chemical", "text": [ "Phosphatoquinone", "A" ], "offsets": [ [ 0, 16 ], [ 18, 19 ] ], "normalized": [] }, { "id": "367_T2", "type": "Chemical", "text": [ "Phosphatoquinone", "B" ], "offsets": [ [ 0, 16 ], [ 24, 25 ] ], "normalized": [] }, { "id": "367_T3", "type": "Species", "text": [ "Streptomyces sp. TA-0363" ], "offsets": [ [ 67, 91 ] ], "normalized": [] }, { "id": "367_T4", "type": "Metabolite", "text": [ "Phosphatoquinone", "A" ], "offsets": [ [ 0, 16 ], [ 18, 19 ] ], "normalized": [] }, { "id": "367_T5", "type": "Metabolite", "text": [ "Phosphatoquinone", "B" ], "offsets": [ [ 0, 16 ], [ 24, 25 ] ], "normalized": [] }, { "id": "367_T6", "type": "Spectral_Data", "text": [ "spectroscopic analyses" ], "offsets": [ [ 132, 154 ] ], "normalized": [] }, { "id": "367_T7", "type": "Chemical", "text": [ "Phosphatoquinone", "A" ], "offsets": [ [ 156, 172 ], [ 174, 175 ] ], "normalized": [] }, { "id": "367_T8", "type": "Metabolite", "text": [ "Phosphatoquinone", "B" ], "offsets": [ [ 156, 172 ], [ 180, 181 ] ], "normalized": [] }, { "id": "367_T9", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 182, 191 ] ], "normalized": [] }, { "id": "367_T10", "type": "Protein", "text": [ "protein tyrosine phosphatase" ], "offsets": [ [ 196, 224 ] ], "normalized": [] }, { "id": "367_T11", "type": "Chemical", "text": [ "Phosphatoquinone", "B" ], "offsets": [ [ 156, 172 ], [ 180, 181 ] ], "normalized": [] }, { "id": "367_T12", "type": "Metabolite", "text": [ "Phosphatoquinone", "A" ], "offsets": [ [ 156, 172 ], [ 174, 175 ] ], "normalized": [] }, { "id": "367_T13", "type": "Species", "text": [ "human" ], "offsets": [ [ 248, 253 ] ], "normalized": [] }, { "id": "367_T14", "type": "Biological_Activity", "text": [ "phosphatase" ], "offsets": [ [ 213, 224 ] ], "normalized": [] } ]

[]

[]

[ { "id": "367_R1", "type": "Isolated_From", "arg1_id": "367_T4", "arg2_id": "367_T3", "normalized": [] }, { "id": "367_R2", "type": "Isolated_From", "arg1_id": "367_T5", "arg2_id": "367_T3", "normalized": [] }, { "id": "367_R3", "type": "Associated_With", "arg1_id": "367_T1", "arg2_id": "367_T6", "normalized": [] }, { "id": "367_R4", "type": "Associated_With", "arg1_id": "367_T2", "arg2_id": "367_T6", "normalized": [] }, { "id": "367_R5", "type": "Associated_With", "arg1_id": "367_T5", "arg2_id": "367_T6", "normalized": [] }, { "id": "367_R6", "type": "Associated_With", "arg1_id": "367_T5", "arg2_id": "367_T6", "normalized": [] }, { "id": "367_R7", "type": "Associated_With", "arg1_id": "367_T7", "arg2_id": "367_T9", "normalized": [] }, { "id": "367_R8", "type": "Associated_With", "arg1_id": "367_T8", "arg2_id": "367_T9", "normalized": [] }, { "id": "367_R9", "type": "Associated_With", "arg1_id": "367_T12", "arg2_id": "367_T9", "normalized": [] }, { "id": "367_R10", "type": "Associated_With", "arg1_id": "367_T11", "arg2_id": "367_T9", "normalized": [] } ]

[ { "id": "369", "type": "", "text": [ "The biosynthesis of polyketomycin was investigated by feeding 13C-labeled acetate and propionate to the growing cultures of Streptomyces diastatochromogenes Tu 6028. 13C NMR spectral analysis demonstrated the polyketide origin of the aglycone and the dimethylsalicyloyl moieties. The O-methyl group and 6-CH3 of the aglycone as well as 3B-CH3 of L-axenose and 3C-CH3 of the salicyloyl residue were labeled by feeding L-[methyl-13C]methionine. Both deoxysugars emerged from D-glucose. The biosynthesis of the aglycone and the assembly of the glycoside are discussed. The polyketomycin producing strain may be a candidate for further exploration in combinatorial biosynthesis. \n" ], "offsets": [ [ 0, 676 ] ] } ]

[ { "id": "369_T1", "type": "Chemical", "text": [ "polyketomycin" ], "offsets": [ [ 20, 33 ] ], "normalized": [] }, { "id": "369_T2", "type": "Chemical", "text": [ "13C-labeled acetate" ], "offsets": [ [ 62, 81 ] ], "normalized": [] }, { "id": "369_T3", "type": "Chemical", "text": [ "13C-labeled", "propionate" ], "offsets": [ [ 62, 73 ], [ 86, 96 ] ], "normalized": [] }, { "id": "369_T4", "type": "Chemical", "text": [ "acetate" ], "offsets": [ [ 74, 81 ] ], "normalized": [] }, { "id": "369_T5", "type": "Chemical", "text": [ "propionate" ], "offsets": [ [ 86, 96 ] ], "normalized": [] }, { "id": "369_T6", "type": "Species", "text": [ "Streptomyces diastatochromogenes Tu 6028" ], "offsets": [ [ 124, 164 ] ], "normalized": [] }, { "id": "369_T7", "type": "Spectral_Data", "text": [ "13C NMR spectral analysis" ], "offsets": [ [ 166, 191 ] ], "normalized": [] }, { "id": "369_T8", "type": "Chemical", "text": [ "polyketide" ], "offsets": [ [ 209, 219 ] ], "normalized": [] }, { "id": "369_T9", "type": "Chemical", "text": [ "aglycone", "moieties" ], "offsets": [ [ 234, 242 ], [ 270, 278 ] ], "normalized": [] }, { "id": "369_T10", "type": "Chemical", "text": [ "dimethylsalicyloyl moieties" ], "offsets": [ [ 251, 278 ] ], "normalized": [] }, { "id": "369_T11", "type": "Chemical", "text": [ "O-methyl group" ], "offsets": [ [ 284, 298 ] ], "normalized": [] }, { "id": "369_T12", "type": "Chemical", "text": [ "6-CH3" ], "offsets": [ [ 303, 308 ] ], "normalized": [] }, { "id": "369_T13", "type": "Chemical", "text": [ "aglycone" ], "offsets": [ [ 316, 324 ] ], "normalized": [] }, { "id": "369_T14", "type": "Chemical", "text": [ "3B-CH3" ], "offsets": [ [ 336, 342 ] ], "normalized": [] }, { "id": "369_T15", "type": "Chemical", "text": [ "L-axenose" ], "offsets": [ [ 346, 355 ] ], "normalized": [] }, { "id": "369_T16", "type": "Metabolite", "text": [ "polyketomycin" ], "offsets": [ [ 20, 33 ] ], "normalized": [] }, { "id": "369_T17", "type": "Chemical", "text": [ "3C-CH3" ], "offsets": [ [ 360, 366 ] ], "normalized": [] }, { "id": "369_T18", "type": "Chemical", "text": [ "salicyloyl residue" ], "offsets": [ [ 374, 392 ] ], "normalized": [] }, { "id": "369_T19", "type": "Chemical", "text": [ "L-[methyl-13C]methionine" ], "offsets": [ [ 417, 441 ] ], "normalized": [] }, { "id": "369_T20", "type": "Chemical", "text": [ "deoxysugars" ], "offsets": [ [ 448, 459 ] ], "normalized": [] }, { "id": "369_T21", "type": "Chemical", "text": [ "D-glucose" ], "offsets": [ [ 473, 482 ] ], "normalized": [] }, { "id": "369_T22", "type": "Chemical", "text": [ "aglycone" ], "offsets": [ [ 508, 516 ] ], "normalized": [] }, { "id": "369_T23", "type": "Chemical", "text": [ "glycoside" ], "offsets": [ [ 541, 550 ] ], "normalized": [] }, { "id": "369_T24", "type": "Chemical", "text": [ "polyketomycin" ], "offsets": [ [ 570, 583 ] ], "normalized": [] }, { "id": "369_T25", "type": "Metabolite", "text": [ "polyketomycin" ], "offsets": [ [ 570, 583 ] ], "normalized": [] } ]

[]

[]

[ { "id": "369_R1", "type": "Isolated_From", "arg1_id": "369_T16", "arg2_id": "369_T6", "normalized": [] }, { "id": "369_R2", "type": "Metabolite_Of", "arg1_id": "369_T16", "arg2_id": "369_T4", "normalized": [] }, { "id": "369_R3", "type": "Metabolite_Of", "arg1_id": "369_T16", "arg2_id": "369_T5", "normalized": [] }, { "id": "369_R4", "type": "Associated_With", "arg1_id": "369_T8", "arg2_id": "369_T7", "normalized": [] }, { "id": "369_R5", "type": "Associated_With", "arg1_id": "369_T9", "arg2_id": "369_T7", "normalized": [] }, { "id": "369_R6", "type": "Associated_With", "arg1_id": "369_T10", "arg2_id": "369_T7", "normalized": [] } ]

[ { "id": "371", "type": "", "text": [ "The effect of thirteen different fungal azaphilones, which have a common 6-iso-chromane-like ring, was tested on cholesteryl ester transfer protein (CETP) activity in vitro. Chaetoviridin B showed the most potent inhibitory activity with an IC50 value of < 6.2 microM, followed by sclerotiorin with an IC50 value of 19.4 microM. Rotiorin, chaetoviridin A and rubrorotiorin had moderate inhibitory activity (IC50 ; 30 approximately 40 microM), but others showed very weak or no inhibitory activity. The relationship between the structures and their inhibitory activity indicated that the presence of an electrophilic ketone(s) and/or enone(s) at both C-6 and C-8 positions in the isochromane-like ring is essential for eliciting CETP inhibitory activity. The transfer activity of both CE and TG was inhibited by sclerotiorin to approximately the same extent (IC50: 14.4 and 10.3 microM, respectively). A model of the reaction suggested that sclerotiorin reacts with a primary amine of amino acids such as lysine in the protein to form a covalent bond. \n" ], "offsets": [ [ 0, 1052 ] ] } ]

[ { "id": "371_T1", "type": "Species", "text": [ "fungal" ], "offsets": [ [ 33, 39 ] ], "normalized": [] }, { "id": "371_T2", "type": "Chemical", "text": [ "azaphilones" ], "offsets": [ [ 40, 51 ] ], "normalized": [] }, { "id": "371_T3", "type": "Metabolite", "text": [ "azaphilones" ], "offsets": [ [ 40, 51 ] ], "normalized": [] }, { "id": "371_T4", "type": "Chemical", "text": [ "6-iso-chromane" ], "offsets": [ [ 73, 87 ] ], "normalized": [] }, { "id": "371_T5", "type": "Protein", "text": [ "cholesteryl ester transfer protein" ], "offsets": [ [ 113, 147 ] ], "normalized": [] }, { "id": "371_T6", "type": "Protein", "text": [ "CETP" ], "offsets": [ [ 149, 153 ] ], "normalized": [] }, { "id": "371_T9", "type": "Chemical", "text": [ "Chaetoviridin B" ], "offsets": [ [ 174, 189 ] ], "normalized": [] }, { "id": "371_T12", "type": "Biological_Activity", "text": [ "transfer" ], "offsets": [ [ 131, 139 ] ], "normalized": [] }, { "id": "371_T13", "type": "Chemical", "text": [ "sclerotiorin" ], "offsets": [ [ 281, 293 ] ], "normalized": [] }, { "id": "371_T14", "type": "Chemical", "text": [ "Rotiorin" ], "offsets": [ [ 329, 337 ] ], "normalized": [] }, { "id": "371_T15", "type": "Chemical", "text": [ "chaetoviridin A" ], "offsets": [ [ 339, 354 ] ], "normalized": [] }, { "id": "371_T16", "type": "Chemical", "text": [ "rubrorotiorin" ], "offsets": [ [ 359, 372 ] ], "normalized": [] }, { "id": "371_T19", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 477, 486 ] ], "normalized": [] }, { "id": "371_T20", "type": "Biological_Activity", "text": [ "inhibitory" ], "offsets": [ [ 548, 558 ] ], "normalized": [] }, { "id": "371_T21", "type": "Chemical", "text": [ "ketone" ], "offsets": [ [ 616, 622 ] ], "normalized": [] }, { "id": "371_T22", "type": "Chemical", "text": [ "enone" ], "offsets": [ [ 633, 638 ] ], "normalized": [] }, { "id": "371_T23", "type": "Chemical", "text": [ "isochromane-like ring" ], "offsets": [ [ 679, 700 ] ], "normalized": [] }, { "id": "371_T24", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 386, 395 ] ], "normalized": [] }, { "id": "371_T25", "type": "Chemical", "text": [ "CE" ], "offsets": [ [ 784, 786 ] ], "normalized": [] }, { "id": "371_T26", "type": "Chemical", "text": [ "TG" ], "offsets": [ [ 791, 793 ] ], "normalized": [] }, { "id": "371_T27", "type": "Chemical", "text": [ "sclerotiorin" ], "offsets": [ [ 811, 823 ] ], "normalized": [] }, { "id": "371_T28", "type": "Chemical", "text": [ "sclerotiorin" ], "offsets": [ [ 940, 952 ] ], "normalized": [] }, { "id": "371_T29", "type": "Chemical", "text": [ "primary amine" ], "offsets": [ [ 967, 980 ] ], "normalized": [] }, { "id": "371_T30", "type": "Chemical", "text": [ "amino acids" ], "offsets": [ [ 984, 995 ] ], "normalized": [] }, { "id": "371_T31", "type": "Chemical", "text": [ "lysine" ], "offsets": [ [ 1004, 1010 ] ], "normalized": [] }, { "id": "371_T32", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1018, 1025 ] ], "normalized": [] }, { "id": "371_T33", "type": "Metabolite", "text": [ "Chaetoviridin B" ], "offsets": [ [ 174, 189 ] ], "normalized": [] }, { "id": "371_T34", "type": "Metabolite", "text": [ "sclerotiorin" ], "offsets": [ [ 281, 293 ] ], "normalized": [] }, { "id": "371_T35", "type": "Metabolite", "text": [ "Rotiorin" ], "offsets": [ [ 329, 337 ] ], "normalized": [] }, { "id": "371_T36", "type": "Metabolite", "text": [ "chaetoviridin A" ], "offsets": [ [ 339, 354 ] ], "normalized": [] }, { "id": "371_T37", "type": "Metabolite", "text": [ "rubrorotiorin" ], "offsets": [ [ 359, 372 ] ], "normalized": [] }, { "id": "371_T10", "type": "Biological_Activity", "text": [ "inhibitory" ], "offsets": [ [ 733, 743 ] ], "normalized": [] }, { "id": "371_T11", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 798, 807 ] ], "normalized": [] } ]

[]

[]

[ { "id": "371_R5", "type": "Associated_With", "arg1_id": "371_T9", "arg2_id": "371_T12", "normalized": [] }, { "id": "371_R6", "type": "Associated_With", "arg1_id": "371_T13", "arg2_id": "371_T12", "normalized": [] }, { "id": "371_R12", "type": "Associated_With", "arg1_id": "371_T14", "arg2_id": "371_T24", "normalized": [] }, { "id": "371_R16", "type": "Associated_With", "arg1_id": "371_T15", "arg2_id": "371_T24", "normalized": [] }, { "id": "371_R17", "type": "Associated_With", "arg1_id": "371_T16", "arg2_id": "371_T24", "normalized": [] }, { "id": "371_R19", "type": "Associated_With", "arg1_id": "371_T33", "arg2_id": "371_T12", "normalized": [] }, { "id": "371_R20", "type": "Associated_With", "arg1_id": "371_T34", "arg2_id": "371_T12", "normalized": [] }, { "id": "371_R21", "type": "Associated_With", "arg1_id": "371_T35", "arg2_id": "371_T24", "normalized": [] }, { "id": "371_R24", "type": "Associated_With", "arg1_id": "371_T36", "arg2_id": "371_T24", "normalized": [] }, { "id": "371_R31", "type": "Associated_With", "arg1_id": "371_T37", "arg2_id": "371_T24", "normalized": [] }, { "id": "371_R1", "type": "Binds_With", "arg1_id": "371_T33", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R2", "type": "Binds_With", "arg1_id": "371_T33", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R36", "type": "Binds_With", "arg1_id": "371_T9", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R37", "type": "Binds_With", "arg1_id": "371_T9", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R3", "type": "Binds_With", "arg1_id": "371_T34", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R4", "type": "Binds_With", "arg1_id": "371_T34", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R34", "type": "Binds_With", "arg1_id": "371_T13", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R35", "type": "Binds_With", "arg1_id": "371_T13", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R7", "type": "Binds_With", "arg1_id": "371_T35", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R8", "type": "Binds_With", "arg1_id": "371_T14", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R9", "type": "Binds_With", "arg1_id": "371_T35", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R10", "type": "Binds_With", "arg1_id": "371_T14", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R11", "type": "Binds_With", "arg1_id": "371_T36", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R25", "type": "Binds_With", "arg1_id": "371_T15", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R26", "type": "Binds_With", "arg1_id": "371_T36", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R28", "type": "Binds_With", "arg1_id": "371_T15", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R29", "type": "Binds_With", "arg1_id": "371_T37", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R30", "type": "Binds_With", "arg1_id": "371_T16", "arg2_id": "371_T5", "normalized": [] }, { "id": "371_R32", "type": "Binds_With", "arg1_id": "371_T16", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R33", "type": "Binds_With", "arg1_id": "371_T16", "arg2_id": "371_T6", "normalized": [] }, { "id": "371_R13", "type": "Associated_With", "arg1_id": "371_T27", "arg2_id": "371_T11", "normalized": [] } ]

[ { "id": "373", "type": "", "text": [ "\n" ], "offsets": [ [ 0, 1 ] ] } ]

[]

[]

[]

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[ { "id": "375", "type": "", "text": [ "Six new (1-6) and three known (7-9) sesquiterpene esters were isolated from the roots of Celastrus orbiculatus. The structures of the new compounds were elucidated as 1beta-acetoxy-6alpha-furoyloxy-9alpha-benzoyl oxydihydro-beta-agarofur an (1), 1beta-acetoxy-6alpha-benzoyloxy-9alpha-furoyloxydih ydro-beta-agarofur an (2), 1beta-acetoxy-6alpha, 9alpha-difuroyloxydihydro-beta-agarofuran (3), 1beta, 2beta-diacetoxy-6alpha-furoyloxy-9alpha-benzo yloxydihydro-beta-agarof uran (4), 1beta-acetoxy-2beta, 6alpha-difuroyloxy-9alpha-benzoyloxydihydro-beta -agarofuran (5), and 1beta-acetoxy-2beta,6alpha, 9alpha-tribenzoyloxydihydro-beta-agarofuran (6). Compounds 4, 5, and 7-9 were shown to be more active than verapamil in reversing vinblastine resistance in multidrug-resistant KB-V1 cells. \n" ], "offsets": [ [ 0, 793 ] ] } ]

[ { "id": "375_T1", "type": "Chemical", "text": [ "sesquiterpene esters" ], "offsets": [ [ 36, 56 ] ], "normalized": [] }, { "id": "375_T2", "type": "Species", "text": [ "Celastrus orbiculatus" ], "offsets": [ [ 89, 110 ] ], "normalized": [] }, { "id": "375_T3", "type": "Chemical", "text": [ "1beta-acetoxy-6alpha-furoyloxy-9alpha-benzoyl oxydihydro-beta-agarofur an" ], "offsets": [ [ 167, 240 ] ], "normalized": [] }, { "id": "375_T4", "type": "Metabolite", "text": [ "1beta-acetoxy-6alpha-furoyloxy-9alpha-benzoyl oxydihydro-beta-agarofur an" ], "offsets": [ [ 167, 240 ] ], "normalized": [] }, { "id": "375_T5", "type": "Chemical", "text": [ "1beta-acetoxy-6alpha-benzoyloxy-9alpha-furoyloxydih ydro-beta-agarofur an" ], "offsets": [ [ 246, 319 ] ], "normalized": [] }, { "id": "375_T6", "type": "Metabolite", "text": [ "1beta-acetoxy-6alpha-benzoyloxy-9alpha-furoyloxydih ydro-beta-agarofur an" ], "offsets": [ [ 246, 319 ] ], "normalized": [] }, { "id": "375_T7", "type": "Chemical", "text": [ "1beta-acetoxy-6alpha, 9alpha-difuroyloxydihydro-beta-agarofuran" ], "offsets": [ [ 325, 388 ] ], "normalized": [] }, { "id": "375_T8", "type": "Metabolite", "text": [ "1beta-acetoxy-6alpha, 9alpha-difuroyloxydihydro-beta-agarofuran" ], "offsets": [ [ 325, 388 ] ], "normalized": [] }, { "id": "375_T9", "type": "Chemical", "text": [ "1beta, 2beta-diacetoxy-6alpha-furoyloxy-9alpha-benzo yloxydihydro-beta-agarof uran" ], "offsets": [ [ 394, 476 ] ], "normalized": [] }, { "id": "375_T10", "type": "Metabolite", "text": [ "1beta, 2beta-diacetoxy-6alpha-furoyloxy-9alpha-benzo yloxydihydro-beta-agarof uran" ], "offsets": [ [ 394, 476 ] ], "normalized": [] }, { "id": "375_T11", "type": "Chemical", "text": [ "1beta-acetoxy-2beta, 6alpha-difuroyloxy-9alpha-benzoyloxydihydro-beta -agarofuran" ], "offsets": [ [ 483, 564 ] ], "normalized": [] }, { "id": "375_T12", "type": "Metabolite", "text": [ "1beta-acetoxy-2beta, 6alpha-difuroyloxy-9alpha-benzoyloxydihydro-beta -agarofuran" ], "offsets": [ [ 483, 564 ] ], "normalized": [] }, { "id": "375_T13", "type": "Chemical", "text": [ "1beta-acetoxy-2beta,6alpha, 9alpha-tribenzoyloxydihydro-beta-agarofuran" ], "offsets": [ [ 574, 645 ] ], "normalized": [] }, { "id": "375_T14", "type": "Metabolite", "text": [ "1beta-acetoxy-2beta,6alpha, 9alpha-tribenzoyloxydihydro-beta-agarofuran" ], "offsets": [ [ 574, 645 ] ], "normalized": [] }, { "id": "375_T16", "type": "Chemical", "text": [ "vinblastine" ], "offsets": [ [ 733, 744 ] ], "normalized": [] }, { "id": "375_T17", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 710, 719 ] ], "normalized": [] }, { "id": "375_T18", "type": "Chemical", "text": [ "1-6" ], "offsets": [ [ 9, 12 ] ], "normalized": [] }, { "id": "375_T19", "type": "Chemical", "text": [ "7-9" ], "offsets": [ [ 31, 34 ] ], "normalized": [] }, { "id": "375_T20", "type": "Chemical", "text": [ "7-9" ], "offsets": [ [ 672, 675 ] ], "normalized": [] }, { "id": "375_T21", "type": "Metabolite", "text": [ "7-9" ], "offsets": [ [ 672, 675 ] ], "normalized": [] }, { "id": "375_T22", "type": "Metabolite", "text": [ "7-9" ], "offsets": [ [ 31, 34 ] ], "normalized": [] }, { "id": "375_T23", "type": "Metabolite", "text": [ "1-6" ], "offsets": [ [ 9, 12 ] ], "normalized": [] }, { "id": "375_T15", "type": "Biological_Activity", "text": [ "reversing" ], "offsets": [ [ 723, 732 ] ], "normalized": [] } ]

[]

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[ { "id": "375_R1", "type": "Isolated_From", "arg1_id": "375_T4", "arg2_id": "375_T2", "normalized": [] }, { "id": "375_R2", "type": "Isolated_From", "arg1_id": "375_T6", "arg2_id": "375_T2", "normalized": [] }, { "id": "375_R3", "type": "Isolated_From", "arg1_id": "375_T8", "arg2_id": "375_T2", "normalized": [] }, { "id": "375_R4", "type": "Isolated_From", "arg1_id": "375_T10", "arg2_id": "375_T2", "normalized": [] }, { "id": "375_R5", "type": "Isolated_From", "arg1_id": "375_T12", "arg2_id": "375_T2", "normalized": [] }, { "id": "375_R6", "type": "Isolated_From", "arg1_id": "375_T14", "arg2_id": "375_T2", "normalized": [] } ]

[ { "id": "377", "type": "", "text": [ "The nor mutant of Aspergillus flavus has a defective norsolorinic acid reductase, and thus the aflatoxin biosynthetic pathway is blocked, resulting in the accumulation of norsolorinic acid, a bright red-orange pigment. We developed a visual agar plate assay to monitor yeast strains for their ability to inhibit aflatoxin production by visually scoring the accumulation of this pigment of the nor mutant. We identified yeast strains that reduced the red-orange pigment accumulation in the nor mutant. These yeasts also reduced aflatoxin accumulation by a toxigenic strain of A. flavus. These yeasts may be useful for reducing aflatoxin contamination of food commodities. \n" ], "offsets": [ [ 0, 674 ] ] } ]

[ { "id": "377_T1", "type": "Species", "text": [ "Aspergillus flavus" ], "offsets": [ [ 18, 36 ] ], "normalized": [] }, { "id": "377_T2", "type": "Protein", "text": [ "norsolorinic acid reductase" ], "offsets": [ [ 53, 80 ] ], "normalized": [] }, { "id": "377_T3", "type": "Chemical", "text": [ "aflatoxin" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "377_T4", "type": "Metabolite", "text": [ "aflatoxin" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "377_T5", "type": "Chemical", "text": [ "norsolorinic acid" ], "offsets": [ [ 171, 188 ] ], "normalized": [] }, { "id": "377_T6", "type": "Metabolite", "text": [ "norsolorinic acid" ], "offsets": [ [ 171, 188 ] ], "normalized": [] }, { "id": "377_T7", "type": "Species", "text": [ "nor mutant of Aspergillus flavus" ], "offsets": [ [ 4, 36 ] ], "normalized": [] }, { "id": "377_T9", "type": "Chemical", "text": [ "agar" ], "offsets": [ [ 241, 245 ] ], "normalized": [] }, { "id": "377_T10", "type": "Species", "text": [ "yeast" ], "offsets": [ [ 269, 274 ] ], "normalized": [] }, { "id": "377_T11", "type": "Chemical", "text": [ "aflatoxin" ], "offsets": [ [ 312, 321 ] ], "normalized": [] }, { "id": "377_T12", "type": "Metabolite", "text": [ "aflatoxin" ], "offsets": [ [ 312, 321 ] ], "normalized": [] }, { "id": "377_T13", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 304, 311 ] ], "normalized": [] }, { "id": "377_T14", "type": "Species", "text": [ "yeast" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "377_T17", "type": "Species", "text": [ "yeasts" ], "offsets": [ [ 508, 514 ] ], "normalized": [] }, { "id": "377_T18", "type": "Species", "text": [ "yeasts" ], "offsets": [ [ 594, 600 ] ], "normalized": [] }, { "id": "377_T19", "type": "Chemical", "text": [ "aflatoxin" ], "offsets": [ [ 528, 537 ] ], "normalized": [] }, { "id": "377_T20", "type": "Metabolite", "text": [ "aflatoxin" ], "offsets": [ [ 528, 537 ] ], "normalized": [] }, { "id": "377_T22", "type": "Species", "text": [ "A. flavus" ], "offsets": [ [ 577, 586 ] ], "normalized": [] }, { "id": "377_T23", "type": "Biological_Activity", "text": [ "toxigenic" ], "offsets": [ [ 557, 566 ] ], "normalized": [] }, { "id": "377_T24", "type": "Chemical", "text": [ "aflatoxin" ], "offsets": [ [ 628, 637 ] ], "normalized": [] }, { "id": "377_T25", "type": "Metabolite", "text": [ "aflatoxin" ], "offsets": [ [ 628, 637 ] ], "normalized": [] }, { "id": "377_T27", "type": "Species", "text": [ "nor mutant" ], "offsets": [ [ 490, 500 ] ], "normalized": [] } ]

[]

[]

[ { "id": "377_R3", "type": "Isolated_From", "arg1_id": "377_T6", "arg2_id": "377_T7", "normalized": [] }, { "id": "377_R4", "type": "Isolated_From", "arg1_id": "377_T6", "arg2_id": "377_T1", "normalized": [] } ]

[ { "id": "379", "type": "", "text": [ "During the course of our screening program for low molecular natural products with their ability to potentiate and/or mimic neurotrophic effect of NGF, a novel fungal metabolite, phenylacetic acid hydrazide derivative NG-061 was isolated from the fermentation broth of Penicillium minioluteum F-4627. NG-061 enhanced and mimicked neurotrophic effect of NGF on neurite outgrowth in a rat pheochromocytoma cell line PC12. \n" ], "offsets": [ [ 0, 421 ] ] } ]

[ { "id": "379_T1", "type": "Metabolite", "text": [ "natural products" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "379_T2", "type": "Chemical", "text": [ "natural products" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "379_T5", "type": "Protein", "text": [ "NGF" ], "offsets": [ [ 147, 150 ] ], "normalized": [] }, { "id": "379_T6", "type": "Species", "text": [ "fungal" ], "offsets": [ [ 160, 166 ] ], "normalized": [] }, { "id": "379_T7", "type": "Chemical", "text": [ "metabolite" ], "offsets": [ [ 167, 177 ] ], "normalized": [] }, { "id": "379_T8", "type": "Metabolite", "text": [ "metabolite" ], "offsets": [ [ 167, 177 ] ], "normalized": [] }, { "id": "379_T9", "type": "Chemical", "text": [ "phenylacetic acid hydrazide derivative" ], "offsets": [ [ 179, 217 ] ], "normalized": [] }, { "id": "379_T10", "type": "Chemical", "text": [ "NG-061" ], "offsets": [ [ 218, 224 ] ], "normalized": [] }, { "id": "379_T11", "type": "Metabolite", "text": [ "NG-061" ], "offsets": [ [ 218, 224 ] ], "normalized": [] }, { "id": "379_T12", "type": "Species", "text": [ "Penicillium minioluteum F-4627" ], "offsets": [ [ 269, 299 ] ], "normalized": [] }, { "id": "379_T13", "type": "Chemical", "text": [ "NG-061" ], "offsets": [ [ 301, 307 ] ], "normalized": [] }, { "id": "379_T14", "type": "Metabolite", "text": [ "NG-061" ], "offsets": [ [ 301, 307 ] ], "normalized": [] }, { "id": "379_T16", "type": "Biological_Activity", "text": [ "neurotrophic" ], "offsets": [ [ 330, 342 ] ], "normalized": [] }, { "id": "379_T17", "type": "Species", "text": [ "rat" ], "offsets": [ [ 383, 386 ] ], "normalized": [] }, { "id": "379_T3", "type": "Protein", "text": [ "NGF" ], "offsets": [ [ 353, 356 ] ], "normalized": [] }, { "id": "379_T4", "type": "Biological_Activity", "text": [ "neurotrophic" ], "offsets": [ [ 124, 136 ] ], "normalized": [] } ]

[]

[]

[ { "id": "379_R1", "type": "Isolated_From", "arg1_id": "379_T11", "arg2_id": "379_T12", "normalized": [] }, { "id": "379_R2", "type": "Associated_With", "arg1_id": "379_T14", "arg2_id": "379_T16", "normalized": [] }, { "id": "379_R4", "type": "Associated_With", "arg1_id": "379_T13", "arg2_id": "379_T16", "normalized": [] } ]

[ { "id": "381", "type": "", "text": [ "The structure of NG-061, a new potentiator of nerve growth factor (NGF) isolated from Penicillium minioluteum F-4627, was determined by spectroscopic analysis and X-ray diffraction method to be phenylacetic acid 2-(2-methoxy-4-oxocyclohexa-2,4-dienylidene)-hydrazide. \n" ], "offsets": [ [ 0, 270 ] ] } ]

[ { "id": "381_T1", "type": "Chemical", "text": [ "NG-061" ], "offsets": [ [ 17, 23 ] ], "normalized": [] }, { "id": "381_T2", "type": "Metabolite", "text": [ "NG-061" ], "offsets": [ [ 17, 23 ] ], "normalized": [] }, { "id": "381_T3", "type": "Biological_Activity", "text": [ "potentiator" ], "offsets": [ [ 31, 42 ] ], "normalized": [] }, { "id": "381_T4", "type": "Species", "text": [ "Penicillium minioluteum F-4627" ], "offsets": [ [ 87, 117 ] ], "normalized": [] }, { "id": "381_T5", "type": "Spectral_Data", "text": [ "spectroscopic analysis" ], "offsets": [ [ 137, 159 ] ], "normalized": [] }, { "id": "381_T6", "type": "Spectral_Data", "text": [ "X-ray diffraction" ], "offsets": [ [ 164, 181 ] ], "normalized": [] }, { "id": "381_T7", "type": "Chemical", "text": [ "phenylacetic acid 2-(2-methoxy-4-oxocyclohexa-2,4-dienylidene)-hydrazide" ], "offsets": [ [ 195, 267 ] ], "normalized": [] }, { "id": "381_T8", "type": "Metabolite", "text": [ "phenylacetic acid 2-(2-methoxy-4-oxocyclohexa-2,4-dienylidene)-hydrazide" ], "offsets": [ [ 195, 267 ] ], "normalized": [] }, { "id": "381_T9", "type": "Protein", "text": [ "nerve growth factor" ], "offsets": [ [ 46, 65 ] ], "normalized": [] }, { "id": "381_T10", "type": "Protein", "text": [ "NGF" ], "offsets": [ [ 67, 70 ] ], "normalized": [] } ]

[]

[]

[ { "id": "381_R1", "type": "Associated_With", "arg1_id": "381_T1", "arg2_id": "381_T3", "normalized": [] }, { "id": "381_R2", "type": "Associated_With", "arg1_id": "381_T2", "arg2_id": "381_T3", "normalized": [] }, { "id": "381_R3", "type": "Isolated_From", "arg1_id": "381_T2", "arg2_id": "381_T4", "normalized": [] }, { "id": "381_R4", "type": "Isolated_From", "arg1_id": "381_T8", "arg2_id": "381_T4", "normalized": [] }, { "id": "381_R5", "type": "Associated_With", "arg1_id": "381_T7", "arg2_id": "381_T3", "normalized": [] }, { "id": "381_R6", "type": "Associated_With", "arg1_id": "381_T8", "arg2_id": "381_T3", "normalized": [] }, { "id": "381_R7", "type": "Associated_With", "arg1_id": "381_T7", "arg2_id": "381_T5", "normalized": [] }, { "id": "381_R8", "type": "Associated_With", "arg1_id": "381_T7", "arg2_id": "381_T6", "normalized": [] }, { "id": "381_R9", "type": "Associated_With", "arg1_id": "381_T8", "arg2_id": "381_T5", "normalized": [] }, { "id": "381_R10", "type": "Associated_With", "arg1_id": "381_T8", "arg2_id": "381_T6", "normalized": [] }, { "id": "381_R11", "type": "Associated_With", "arg1_id": "381_T2", "arg2_id": "381_T5", "normalized": [] }, { "id": "381_R12", "type": "Associated_With", "arg1_id": "381_T2", "arg2_id": "381_T6", "normalized": [] }, { "id": "381_R13", "type": "Associated_With", "arg1_id": "381_T1", "arg2_id": "381_T5", "normalized": [] }, { "id": "381_R14", "type": "Associated_With", "arg1_id": "381_T1", "arg2_id": "381_T6", "normalized": [] } ]

[ { "id": "383", "type": "", "text": [ "A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo. \n" ], "offsets": [ [ 0, 274 ] ] } ]

[ { "id": "383_T1", "type": "Biological_Activity", "text": [ "antibiotic" ], "offsets": [ [ 16, 26 ] ], "normalized": [] }, { "id": "383_T2", "type": "Chemical", "text": [ "gilvusmycin" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "383_T3", "type": "Metabolite", "text": [ "gilvusmycin" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "383_T4", "type": "Species", "text": [ "Streptomyces sp. QM16" ], "offsets": [ [ 78, 99 ] ], "normalized": [] }, { "id": "383_T5", "type": "Chemical", "text": [ "gilvusmycin" ], "offsets": [ [ 118, 129 ] ], "normalized": [] }, { "id": "383_T6", "type": "Metabolite", "text": [ "gilvusmycin" ], "offsets": [ [ 118, 129 ] ], "normalized": [] }, { "id": "383_T7", "type": "Chemical", "text": [ "CC-1065" ], "offsets": [ [ 145, 152 ] ], "normalized": [] }, { "id": "383_T8", "type": "Spectral_Data", "text": [ "NMR spectral analysis" ], "offsets": [ [ 171, 192 ] ], "normalized": [] }, { "id": "383_T9", "type": "Metabolite", "text": [ "Gilvusmycin" ], "offsets": [ [ 194, 205 ] ], "normalized": [] }, { "id": "383_T10", "type": "Chemical", "text": [ "Gilvusmycin" ], "offsets": [ [ 194, 205 ] ], "normalized": [] }, { "id": "383_T11", "type": "Biological_Activity", "text": [ "antitumor" ], "offsets": [ [ 216, 225 ] ], "normalized": [] }, { "id": "383_T13", "type": "Species", "text": [ "murine" ], "offsets": [ [ 243, 249 ] ], "normalized": [] }, { "id": "383_T14", "type": "Biological_Activity", "text": [ "antitumor" ], "offsets": [ [ 6, 15 ] ], "normalized": [] }, { "id": "383_T15", "type": "Chemical", "text": [ "antibiotic" ], "offsets": [ [ 16, 26 ] ], "normalized": [] } ]

[]

[]

[ { "id": "383_R1", "type": "Isolated_From", "arg1_id": "383_T3", "arg2_id": "383_T4", "normalized": [] }, { "id": "383_R2", "type": "Associated_With", "arg1_id": "383_T6", "arg2_id": "383_T8", "normalized": [] }, { "id": "383_R3", "type": "Associated_With", "arg1_id": "383_T5", "arg2_id": "383_T8", "normalized": [] }, { "id": "383_R4", "type": "Associated_With", "arg1_id": "383_T9", "arg2_id": "383_T11", "normalized": [] }, { "id": "383_R5", "type": "Associated_With", "arg1_id": "383_T10", "arg2_id": "383_T11", "normalized": [] }, { "id": "383_R6", "type": "Associated_With", "arg1_id": "383_T3", "arg2_id": "383_T1", "normalized": [] }, { "id": "383_R7", "type": "Associated_With", "arg1_id": "383_T2", "arg2_id": "383_T1", "normalized": [] }, { "id": "383_R8", "type": "Associated_With", "arg1_id": "383_T3", "arg2_id": "383_T14", "normalized": [] }, { "id": "383_R9", "type": "Associated_With", "arg1_id": "383_T2", "arg2_id": "383_T14", "normalized": [] } ]

[ { "id": "385", "type": "", "text": [ "A combination of atovaquone and proguanil has been found to be quite effective in treating malaria, with little evidence of the emergence of resistance when atovaquone was used as a single agent. We have examined possible mechanisms for the synergy between these two drugs. While proguanil by itself had no effect on electron transport or mitochondrial membrane potential (DeltaPsim), it significantly enhanced the ability of atovaquone to collapse DeltaPsim when used in combination. This enhancement was observed at pharmacologically achievable doses. Proguanil acted as a biguanide rather than as its metabolite cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the atovaquone effect; another DHFR inhibitor, pyrimethamine, also had no enhancing effect. Proguanil-mediated enhancement was specific for atovaquone, since the effects of other mitochondrial electron transport inhibitors, such as myxothiazole and antimycin, were not altered by inclusion of proguanil. Surprisingly, proguanil did not enhance the ability of atovaquone to inhibit mitochondrial electron transport in malaria parasites. These results suggest that proguanil in its prodrug form acts in synergy with atovaquone by lowering the effective concentration at which atovaquone collapses DeltaPsim in malaria parasites. This could explain the paradoxical success of the atovaquone-proguanil combination even in regions where proguanil alone is ineffective due to resistance. The results also suggest that the atovaquone-proguanil combination may act as a site-specific uncoupler of parasite mitochondria in a selective manner. \n" ], "offsets": [ [ 0, 1630 ] ] } ]

[ { "id": "385_T1", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 17, 27 ] ], "normalized": [] }, { "id": "385_T2", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 32, 41 ] ], "normalized": [] }, { "id": "385_T4", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 157, 167 ] ], "normalized": [] }, { "id": "385_T5", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 280, 289 ] ], "normalized": [] }, { "id": "385_T6", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 426, 436 ] ], "normalized": [] }, { "id": "385_T11", "type": "Chemical", "text": [ "Proguanil" ], "offsets": [ [ 555, 564 ] ], "normalized": [] }, { "id": "385_T12", "type": "Chemical", "text": [ "biguanide" ], "offsets": [ [ 576, 585 ] ], "normalized": [] }, { "id": "385_T13", "type": "Chemical", "text": [ "cycloguanil" ], "offsets": [ [ 616, 627 ] ], "normalized": [] }, { "id": "385_T14", "type": "Metabolite", "text": [ "cycloguanil" ], "offsets": [ [ 616, 627 ] ], "normalized": [] }, { "id": "385_T15", "type": "Protein", "text": [ "dihydrofolate reductase" ], "offsets": [ [ 640, 663 ] ], "normalized": [] }, { "id": "385_T16", "type": "Protein", "text": [ "DHFR" ], "offsets": [ [ 665, 669 ] ], "normalized": [] }, { "id": "385_T17", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 671, 680 ] ], "normalized": [] }, { "id": "385_T22", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 697, 707 ] ], "normalized": [] }, { "id": "385_T23", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 729, 738 ] ], "normalized": [] }, { "id": "385_T24", "type": "Protein", "text": [ "DHFR" ], "offsets": [ [ 724, 728 ] ], "normalized": [] }, { "id": "385_T26", "type": "Chemical", "text": [ "pyrimethamine" ], "offsets": [ [ 740, 753 ] ], "normalized": [] }, { "id": "385_T27", "type": "Chemical", "text": [ "Proguanil" ], "offsets": [ [ 785, 794 ] ], "normalized": [] }, { "id": "385_T28", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 833, 843 ] ], "normalized": [] }, { "id": "385_T29", "type": "Biological_Activity", "text": [ "inhibitor" ], "offsets": [ [ 906, 915 ] ], "normalized": [] }, { "id": "385_T30", "type": "Chemical", "text": [ "myxothiazole" ], "offsets": [ [ 926, 938 ] ], "normalized": [] }, { "id": "385_T31", "type": "Chemical", "text": [ "antimycin" ], "offsets": [ [ 943, 952 ] ], "normalized": [] }, { "id": "385_T32", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 987, 996 ] ], "normalized": [] }, { "id": "385_T33", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 1012, 1021 ] ], "normalized": [] }, { "id": "385_T34", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 1053, 1063 ] ], "normalized": [] }, { "id": "385_T35", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 1067, 1074 ] ], "normalized": [] }, { "id": "385_T36", "type": "Species", "text": [ "malaria parasites" ], "offsets": [ [ 1111, 1128 ] ], "normalized": [] }, { "id": "385_T37", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 1157, 1166 ] ], "normalized": [] }, { "id": "385_T38", "type": "Biological_Activity", "text": [ "prodrug" ], "offsets": [ [ 1174, 1181 ] ], "normalized": [] }, { "id": "385_T39", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 1208, 1218 ] ], "normalized": [] }, { "id": "385_T41", "type": "Species", "text": [ "malaria parasites" ], "offsets": [ [ 1302, 1319 ] ], "normalized": [] }, { "id": "385_T42", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 1268, 1278 ] ], "normalized": [] }, { "id": "385_T43", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 1372, 1382 ] ], "normalized": [] }, { "id": "385_T44", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 1383, 1392 ] ], "normalized": [] }, { "id": "385_T45", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 1427, 1436 ] ], "normalized": [] }, { "id": "385_T46", "type": "Chemical", "text": [ "atovaquone" ], "offsets": [ [ 1511, 1521 ] ], "normalized": [] }, { "id": "385_T47", "type": "Chemical", "text": [ "proguanil" ], "offsets": [ [ 1522, 1531 ] ], "normalized": [] }, { "id": "385_T49", "type": "Chemical", "text": [ "atovaquone-proguanil combination" ], "offsets": [ [ 1511, 1543 ] ], "normalized": [] } ]

[]

[]

[ { "id": "385_R5", "type": "Metabolite_Of", "arg1_id": "385_T14", "arg2_id": "385_T11", "normalized": [] }, { "id": "385_R6", "type": "Associated_With", "arg1_id": "385_T14", "arg2_id": "385_T17", "normalized": [] }, { "id": "385_R7", "type": "Associated_With", "arg1_id": "385_T13", "arg2_id": "385_T17", "normalized": [] }, { "id": "385_R15", "type": "Associated_With", "arg1_id": "385_T26", "arg2_id": "385_T23", "normalized": [] }, { "id": "385_R17", "type": "Associated_With", "arg1_id": "385_T30", "arg2_id": "385_T29", "normalized": [] }, { "id": "385_R18", "type": "Associated_With", "arg1_id": "385_T31", "arg2_id": "385_T29", "normalized": [] }, { "id": "385_R19", "type": "Associated_With", "arg1_id": "385_T28", "arg2_id": "385_T29", "normalized": [] }, { "id": "385_R20", "type": "Associated_With", "arg1_id": "385_T34", "arg2_id": "385_T35", "normalized": [] }, { "id": "385_R1", "type": "Binds_With", "arg1_id": "385_T13", "arg2_id": "385_T15", "normalized": [] }, { "id": "385_R2", "type": "Binds_With", "arg1_id": "385_T14", "arg2_id": "385_T15", "normalized": [] }, { "id": "385_R3", "type": "Binds_With", "arg1_id": "385_T14", "arg2_id": "385_T16", "normalized": [] }, { "id": "385_R4", "type": "Binds_With", "arg1_id": "385_T13", "arg2_id": "385_T16", "normalized": [] }, { "id": "385_R8", "type": "Binds_With", "arg1_id": "385_T26", "arg2_id": "385_T24", "normalized": [] } ]

[ { "id": "387", "type": "", "text": [ "Ethylene glycol is a serious toxin that children frequently ingest. Diagnosis and treatment of this poisoning are challenging and frequently involve the use of novel therapies. In the past year, fomepizole (4-methylpyrazole) has been approved for use as an antidote in the treatment of ethylene glycol poisoning in adults, and the first article reporting the use of fomepizole in a pediatric ethylene glycol exposure was published. As a result, the therapy of ethylene glycol poisoning in children is likely to change from the traditional approach of ethanol administration coupled with hemodialysis to the administration of fomepizole with or without hemodialysis. \n" ], "offsets": [ [ 0, 668 ] ] } ]

[ { "id": "387_T1", "type": "Chemical", "text": [ "Ethylene glycol" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "387_T2", "type": "Biological_Activity", "text": [ "toxin" ], "offsets": [ [ 29, 34 ] ], "normalized": [] }, { "id": "387_T3", "type": "Species", "text": [ "children" ], "offsets": [ [ 40, 48 ] ], "normalized": [] }, { "id": "387_T6", "type": "Chemical", "text": [ "fomepizole" ], "offsets": [ [ 195, 205 ] ], "normalized": [] }, { "id": "387_T7", "type": "Chemical", "text": [ "4-methylpyrazole" ], "offsets": [ [ 207, 223 ] ], "normalized": [] }, { "id": "387_T8", "type": "Biological_Activity", "text": [ "antidote" ], "offsets": [ [ 257, 265 ] ], "normalized": [] }, { "id": "387_T10", "type": "Chemical", "text": [ "ethylene glycol" ], "offsets": [ [ 286, 301 ] ], "normalized": [] }, { "id": "387_T11", "type": "Species", "text": [ "adults" ], "offsets": [ [ 316, 322 ] ], "normalized": [] }, { "id": "387_T12", "type": "Chemical", "text": [ "fomepizole" ], "offsets": [ [ 367, 377 ] ], "normalized": [] }, { "id": "387_T13", "type": "Species", "text": [ "pediatric" ], "offsets": [ [ 383, 392 ] ], "normalized": [] }, { "id": "387_T14", "type": "Chemical", "text": [ "ethylene glycol" ], "offsets": [ [ 393, 408 ] ], "normalized": [] }, { "id": "387_T15", "type": "Chemical", "text": [ "ethylene glycol" ], "offsets": [ [ 461, 476 ] ], "normalized": [] }, { "id": "387_T16", "type": "Biological_Activity", "text": [ "poisoning" ], "offsets": [ [ 477, 486 ] ], "normalized": [] }, { "id": "387_T17", "type": "Species", "text": [ "children" ], "offsets": [ [ 490, 498 ] ], "normalized": [] }, { "id": "387_T18", "type": "Chemical", "text": [ "ethanol" ], "offsets": [ [ 552, 559 ] ], "normalized": [] }, { "id": "387_T20", "type": "Chemical", "text": [ "fomepizole" ], "offsets": [ [ 626, 636 ] ], "normalized": [] }, { "id": "387_T4", "type": "Biological_Activity", "text": [ "poisoning" ], "offsets": [ [ 302, 311 ] ], "normalized": [] } ]

[]

[]

[ { "id": "387_R1", "type": "Associated_With", "arg1_id": "387_T1", "arg2_id": "387_T2", "normalized": [] }, { "id": "387_R2", "type": "Associated_With", "arg1_id": "387_T6", "arg2_id": "387_T8", "normalized": [] }, { "id": "387_R5", "type": "Associated_With", "arg1_id": "387_T7", "arg2_id": "387_T8", "normalized": [] }, { "id": "387_R3", "type": "Associated_With", "arg1_id": "387_T10", "arg2_id": "387_T4", "normalized": [] } ]

[ { "id": "389", "type": "", "text": [ "It was studied the amino acids pattern in serum and cerebrospinal fluid of 12 and 8 patients, respectively, suffering from optic epidemic neuropathy diagnosed between 1995 and 1997 (endemic period). The cerebrospinal fluid of 16 patients diagnosed during the epidemic (1992) was also studied. The analysis of amino acids in serum and cerebrospinal fluid was made by high resolution liquid chromatography with fluorescent detection, previous derivation with orthofthallic aldehyde. As in the previous study, no important deficiencies of the essential amino acids were observed in the serum of the studied patients. Lower concentrations of threonine, aspartic acid and taurine were found in the serum of patients with epidemic optic neuropathy diagnosed in the endemic period. Taurine plays an important role in the structure and function of photoreceptors of the retina. It is synthesized in the necessary amounts in man, so it must be supplied in the diet. As it is only present in food of animal origin, it is considered that the deficiency of taurine may contribute to the development of optic epidemic neuritis in our patients. Samples of cerebrospinal fluid were analyzed during the epidemic and endemic periods and it was observed an increase of the glutamic and aspartic acid in the epidemic period and of glutamic acid during the endemic. The excess of excitotoxic amino acids in the cerebrospinal fluid supports the previous neurocognitive studies that suggested the affection of the central nervous system in these patients. \n" ], "offsets": [ [ 0, 1537 ] ] } ]

[ { "id": "389_T1", "type": "Chemical", "text": [ "amino acids" ], "offsets": [ [ 19, 30 ] ], "normalized": [] }, { "id": "389_T2", "type": "Species", "text": [ "patients" ], "offsets": [ [ 84, 92 ] ], "normalized": [] }, { "id": "389_T4", "type": "Species", "text": [ "patients" ], "offsets": [ [ 229, 237 ] ], "normalized": [] }, { "id": "389_T5", "type": "Chemical", "text": [ "amino acids" ], "offsets": [ [ 309, 320 ] ], "normalized": [] }, { "id": "389_T6", "type": "Chemical", "text": [ "orthofthallic aldehyde" ], "offsets": [ [ 457, 479 ] ], "normalized": [] }, { "id": "389_T7", "type": "Chemical", "text": [ "essential amino acids" ], "offsets": [ [ 540, 561 ] ], "normalized": [] }, { "id": "389_T8", "type": "Species", "text": [ "patients" ], "offsets": [ [ 604, 612 ] ], "normalized": [] }, { "id": "389_T9", "type": "Chemical", "text": [ "threonine" ], "offsets": [ [ 638, 647 ] ], "normalized": [] }, { "id": "389_T10", "type": "Chemical", "text": [ "aspartic acid" ], "offsets": [ [ 649, 662 ] ], "normalized": [] }, { "id": "389_T11", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 667, 674 ] ], "normalized": [] }, { "id": "389_T12", "type": "Species", "text": [ "patients" ], "offsets": [ [ 702, 710 ] ], "normalized": [] }, { "id": "389_T14", "type": "Chemical", "text": [ "Taurine" ], "offsets": [ [ 775, 784 ] ], "normalized": [] }, { "id": "389_T15", "type": "Metabolite", "text": [ "threonine" ], "offsets": [ [ 638, 647 ] ], "normalized": [] }, { "id": "389_T16", "type": "Metabolite", "text": [ "aspartic acid" ], "offsets": [ [ 649, 662 ] ], "normalized": [] }, { "id": "389_T17", "type": "Metabolite", "text": [ "taurine" ], "offsets": [ [ 667, 674 ] ], "normalized": [] }, { "id": "389_T18", "type": "Metabolite", "text": [ "Taurine" ], "offsets": [ [ 775, 784 ] ], "normalized": [] }, { "id": "389_T20", "type": "Species", "text": [ "man" ], "offsets": [ [ 917, 920 ] ], "normalized": [] }, { "id": "389_T21", "type": "Chemical", "text": [ "taurine" ], "offsets": [ [ 1046, 1053 ] ], "normalized": [] }, { "id": "389_T22", "type": "Metabolite", "text": [ "taurine" ], "offsets": [ [ 1046, 1053 ] ], "normalized": [] }, { "id": "389_T24", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1122, 1130 ] ], "normalized": [] }, { "id": "389_T25", "type": "Chemical", "text": [ "glutamic", "acid" ], "offsets": [ [ 1256, 1264 ], [ 1278, 1282 ] ], "normalized": [] }, { "id": "389_T26", "type": "Chemical", "text": [ "aspartic acid" ], "offsets": [ [ 1269, 1282 ] ], "normalized": [] }, { "id": "389_T27", "type": "Chemical", "text": [ "glutamic acid" ], "offsets": [ [ 1313, 1326 ] ], "normalized": [] }, { "id": "389_T28", "type": "Biological_Activity", "text": [ "excitotoxic" ], "offsets": [ [ 1361, 1372 ] ], "normalized": [] }, { "id": "389_T29", "type": "Chemical", "text": [ "amino acids" ], "offsets": [ [ 1373, 1384 ] ], "normalized": [] }, { "id": "389_T30", "type": "Species", "text": [ "patients" ], "offsets": [ [ 1526, 1534 ] ], "normalized": [] }, { "id": "389_T31", "type": "Metabolite", "text": [ "glutamic", "acid" ], "offsets": [ [ 1256, 1264 ], [ 1278, 1282 ] ], "normalized": [] }, { "id": "389_T32", "type": "Metabolite", "text": [ "aspartic acid" ], "offsets": [ [ 1269, 1282 ] ], "normalized": [] }, { "id": "389_T33", "type": "Metabolite", "text": [ "glutamic acid" ], "offsets": [ [ 1313, 1326 ] ], "normalized": [] } ]

[]

[]

[ { "id": "389_R3", "type": "Isolated_From", "arg1_id": "389_T15", "arg2_id": "389_T12", "normalized": [] }, { "id": "389_R4", "type": "Isolated_From", "arg1_id": "389_T16", "arg2_id": "389_T12", "normalized": [] }, { "id": "389_R5", "type": "Isolated_From", "arg1_id": "389_T17", "arg2_id": "389_T12", "normalized": [] } ]

[ { "id": "391", "type": "", "text": [ "The kinetic properties of bacterial and rat liver glutathione S-transferases (GST) active with dichloromethane (DCM) were compared. The theta class glutathione S-transferase (rGSTTI-1) from rat liver had an affinity for dihalomethanes lower by three orders of magnitude (K(app) > 50 mM) than the bacterial DCM dehalogenase/GST from Methylophilus sp. DM11. Unlike the bacterial DCM dehalogenase, the rat enzyme was unable to support growth of the dehalogenase minus Methylobacterium sp. DM4-2cr mutant with DCM. Moreover, the presence of DCM inhibited growth with methanol of the DM4-2cr transconjugant expressing the rat liver GSTT1-1. In Salmonella typhimurium TA1535, expression of rat and bacterial DCM-active GST from a plasmid in the presence of DCM yielded up to 5.3 times more reversions to histidine prototrophy in the transconjugant expressing the rat enzyme. Under the same conditions, however, GST-mediated conversion of DCM to formaldehyde was lower in cell-free extracts of the transconjugant expressing the rat GSTT1 than in the corresponding strain expressing the bacterial DCM dehalogenase. This provided new evidence that formaldehyde was not the main toxicant associated with GST-mediated DCM conversion, and indicated that an intermediate in the transformation of DCM by GST, presumably S-chloromethylglutathione, was responsible for the observed effects. The marked differences in substrate affinity of rat and bacterial DCM-active GST, as well as in the toxicity and genotoxicity associated with expression of these enzymes in bacteria, suggest that bacterial DCM dehalogenases/GST have evolved to minimise the toxic effects associated with glutathione-mediated catalysis of DCM conversion. \n" ], "offsets": [ [ 0, 1715 ] ] } ]

[ { "id": "391_T1", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 26, 35 ] ], "normalized": [] }, { "id": "391_T2", "type": "Species", "text": [ "rat" ], "offsets": [ [ 40, 43 ] ], "normalized": [] }, { "id": "391_T3", "type": "Protein", "text": [ "glutathione S-transferases" ], "offsets": [ [ 50, 76 ] ], "normalized": [] }, { "id": "391_T4", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 78, 81 ] ], "normalized": [] }, { "id": "391_T5", "type": "Chemical", "text": [ "dichloromethane" ], "offsets": [ [ 95, 110 ] ], "normalized": [] }, { "id": "391_T6", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 112, 115 ] ], "normalized": [] }, { "id": "391_T7", "type": "Protein", "text": [ "theta class glutathione S-transferase" ], "offsets": [ [ 136, 173 ] ], "normalized": [] }, { "id": "391_T8", "type": "Protein", "text": [ "rGSTTI-1" ], "offsets": [ [ 175, 183 ] ], "normalized": [] }, { "id": "391_T9", "type": "Species", "text": [ "rat" ], "offsets": [ [ 190, 193 ] ], "normalized": [] }, { "id": "391_T11", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 296, 305 ] ], "normalized": [] }, { "id": "391_T12", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 306, 309 ] ], "normalized": [] }, { "id": "391_T13", "type": "Protein", "text": [ "DCM dehalogenase" ], "offsets": [ [ 306, 322 ] ], "normalized": [] }, { "id": "391_T14", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 323, 326 ] ], "normalized": [] }, { "id": "391_T15", "type": "Species", "text": [ "Methylophilus sp. DM11" ], "offsets": [ [ 332, 354 ] ], "normalized": [] }, { "id": "391_T16", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 367, 378 ] ], "normalized": [] }, { "id": "391_T17", "type": "Protein", "text": [ "DCM dehalogenase" ], "offsets": [ [ 378, 394 ] ], "normalized": [] }, { "id": "391_T18", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 378, 381 ] ], "normalized": [] }, { "id": "391_T19", "type": "Species", "text": [ "rat" ], "offsets": [ [ 400, 403 ] ], "normalized": [] }, { "id": "391_T20", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 404, 410 ] ], "normalized": [] }, { "id": "391_T21", "type": "Protein", "text": [ "dehalogenase" ], "offsets": [ [ 447, 459 ] ], "normalized": [] }, { "id": "391_T22", "type": "Species", "text": [ "Methylobacterium sp. DM4-2cr" ], "offsets": [ [ 466, 494 ] ], "normalized": [] }, { "id": "391_T23", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 507, 510 ] ], "normalized": [] }, { "id": "391_T24", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 538, 541 ] ], "normalized": [] }, { "id": "391_T25", "type": "Chemical", "text": [ "methanol" ], "offsets": [ [ 564, 572 ] ], "normalized": [] }, { "id": "391_T26", "type": "Species", "text": [ "DM4-2cr" ], "offsets": [ [ 580, 587 ] ], "normalized": [] }, { "id": "391_T27", "type": "Species", "text": [ "rat" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "391_T28", "type": "Protein", "text": [ "GSTT1-1" ], "offsets": [ [ 628, 635 ] ], "normalized": [] }, { "id": "391_T29", "type": "Species", "text": [ "Salmonella typhimurium TA1535" ], "offsets": [ [ 640, 669 ] ], "normalized": [] }, { "id": "391_T30", "type": "Species", "text": [ "rat" ], "offsets": [ [ 685, 688 ] ], "normalized": [] }, { "id": "391_T31", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 693, 704 ] ], "normalized": [] }, { "id": "391_T32", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 704, 707 ] ], "normalized": [] }, { "id": "391_T33", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "391_T34", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 753, 756 ] ], "normalized": [] }, { "id": "391_T36", "type": "Chemical", "text": [ "histidine" ], "offsets": [ [ 800, 809 ] ], "normalized": [] }, { "id": "391_T37", "type": "Species", "text": [ "rat" ], "offsets": [ [ 859, 862 ] ], "normalized": [] }, { "id": "391_T38", "type": "Protein", "text": [ "enzyme" ], "offsets": [ [ 863, 869 ] ], "normalized": [] }, { "id": "391_T39", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 907, 910 ] ], "normalized": [] }, { "id": "391_T41", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 934, 937 ] ], "normalized": [] }, { "id": "391_T42", "type": "Chemical", "text": [ "formaldehyde" ], "offsets": [ [ 941, 953 ] ], "normalized": [] }, { "id": "391_T43", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1023, 1026 ] ], "normalized": [] }, { "id": "391_T44", "type": "Protein", "text": [ "GSTT1" ], "offsets": [ [ 1027, 1032 ] ], "normalized": [] }, { "id": "391_T45", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 1081, 1090 ] ], "normalized": [] }, { "id": "391_T46", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 1091, 1094 ] ], "normalized": [] }, { "id": "391_T47", "type": "Protein", "text": [ "DCM dehalogenase" ], "offsets": [ [ 1091, 1107 ] ], "normalized": [] }, { "id": "391_T48", "type": "Chemical", "text": [ "formaldehyde" ], "offsets": [ [ 1141, 1153 ] ], "normalized": [] }, { "id": "391_T49", "type": "Biological_Activity", "text": [ "toxicant" ], "offsets": [ [ 1171, 1179 ] ], "normalized": [] }, { "id": "391_T50", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 1196, 1199 ] ], "normalized": [] }, { "id": "391_T51", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 1209, 1212 ] ], "normalized": [] }, { "id": "391_T52", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 1285, 1288 ] ], "normalized": [] }, { "id": "391_T53", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 1292, 1295 ] ], "normalized": [] }, { "id": "391_T54", "type": "Chemical", "text": [ "S-chloromethylglutathione" ], "offsets": [ [ 1308, 1333 ] ], "normalized": [] }, { "id": "391_T55", "type": "Species", "text": [ "rat" ], "offsets": [ [ 1425, 1428 ] ], "normalized": [] }, { "id": "391_T56", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 1433, 1442 ] ], "normalized": [] }, { "id": "391_T57", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 1443, 1446 ] ], "normalized": [] }, { "id": "391_T58", "type": "Protein", "text": [ "DCM-active GST" ], "offsets": [ [ 1443, 1457 ] ], "normalized": [] }, { "id": "391_T59", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 1454, 1457 ] ], "normalized": [] }, { "id": "391_T60", "type": "Biological_Activity", "text": [ "toxicity" ], "offsets": [ [ 1477, 1485 ] ], "normalized": [] }, { "id": "391_T61", "type": "Biological_Activity", "text": [ "genotoxicity" ], "offsets": [ [ 1490, 1502 ] ], "normalized": [] }, { "id": "391_T62", "type": "Protein", "text": [ "enzymes" ], "offsets": [ [ 1539, 1546 ] ], "normalized": [] }, { "id": "391_T63", "type": "Species", "text": [ "bacteria" ], "offsets": [ [ 1550, 1558 ] ], "normalized": [] }, { "id": "391_T64", "type": "Species", "text": [ "bacterial" ], "offsets": [ [ 1573, 1582 ] ], "normalized": [] }, { "id": "391_T65", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 1583, 1586 ] ], "normalized": [] }, { "id": "391_T66", "type": "Protein", "text": [ "DCM dehalogenases" ], "offsets": [ [ 1583, 1600 ] ], "normalized": [] }, { "id": "391_T67", "type": "Protein", "text": [ "GST" ], "offsets": [ [ 1601, 1604 ] ], "normalized": [] }, { "id": "391_T69", "type": "Chemical", "text": [ "glutathione" ], "offsets": [ [ 1664, 1675 ] ], "normalized": [] }, { "id": "391_T70", "type": "Chemical", "text": [ "DCM" ], "offsets": [ [ 1698, 1701 ] ], "normalized": [] }, { "id": "391_T73", "type": "Chemical", "text": [ "dihalomethanes" ], "offsets": [ [ 220, 234 ] ], "normalized": [] }, { "id": "391_T74", "type": "Biological_Activity", "text": [ "inhibited" ], "offsets": [ [ 542, 551 ] ], "normalized": [] }, { "id": "391_T10", "type": "Biological_Activity", "text": [ "toxic" ], "offsets": [ [ 1634, 1639 ] ], "normalized": [] } ]

[]

[]

[ { "id": "391_R3", "type": "Binds_With", "arg1_id": "391_T5", "arg2_id": "391_T3", "normalized": [] }, { "id": "391_R4", "type": "Binds_With", "arg1_id": "391_T6", "arg2_id": "391_T3", "normalized": [] } ]

[ { "id": "393", "type": "", "text": [ "Late-onset drinking is a common problem in elderly people related to stress induced by social isolation. Experiments were performed in order to evaluate the effects of alprazolam, a benzodiazepine agonist anxiolytic, on the free-choice ethanol consumption in aged rats subjected to isolation stress. The animals we offered a two-bottle choice consumption (one of 0.2% saccharin and the other with 10% ethanol/0.2% saccharin) and then exposed to 4 days of isolation stress on an irregular, unpredictable schedule. Stress resulted in significant increase in ethanol consumption. Treatment with alprazolam (1 mg/Kg) partially reversed this adverse effect of stress. \n" ], "offsets": [ [ 0, 667 ] ] } ]

[ { "id": "393_T1", "type": "Species", "text": [ "people" ], "offsets": [ [ 51, 57 ] ], "normalized": [] }, { "id": "393_T2", "type": "Chemical", "text": [ "alprazolam" ], "offsets": [ [ 169, 179 ] ], "normalized": [] }, { "id": "393_T3", "type": "Chemical", "text": [ "benzodiazepine" ], "offsets": [ [ 183, 197 ] ], "normalized": [] }, { "id": "393_T4", "type": "Biological_Activity", "text": [ "agonist" ], "offsets": [ [ 198, 205 ] ], "normalized": [] }, { "id": "393_T5", "type": "Chemical", "text": [ "ethanol" ], "offsets": [ [ 237, 244 ] ], "normalized": [] }, { "id": "393_T7", "type": "Species", "text": [ "rats" ], "offsets": [ [ 265, 269 ] ], "normalized": [] }, { "id": "393_T9", "type": "Species", "text": [ "animals" ], "offsets": [ [ 305, 312 ] ], "normalized": [] }, { "id": "393_T10", "type": "Chemical", "text": [ "saccharin" ], "offsets": [ [ 369, 378 ] ], "normalized": [] }, { "id": "393_T11", "type": "Chemical", "text": [ "ethanol" ], "offsets": [ [ 402, 409 ] ], "normalized": [] }, { "id": "393_T12", "type": "Chemical", "text": [ "saccharin" ], "offsets": [ [ 415, 424 ] ], "normalized": [] }, { "id": "393_T15", "type": "Chemical", "text": [ "ethanol" ], "offsets": [ [ 558, 565 ] ], "normalized": [] }, { "id": "393_T16", "type": "Chemical", "text": [ "alprazolam" ], "offsets": [ [ 594, 604 ] ], "normalized": [] }, { "id": "393_T18", "type": "Biological_Activity", "text": [ "anxiolytic" ], "offsets": [ [ 206, 216 ] ], "normalized": [] } ]

[]

[]

[ { "id": "393_R1", "type": "Associated_With", "arg1_id": "393_T2", "arg2_id": "393_T4", "normalized": [] }, { "id": "393_R2", "type": "Associated_With", "arg1_id": "393_T2", "arg2_id": "393_T18", "normalized": [] } ]

[ { "id": "395", "type": "", "text": [ "We investigated the effect of tetrahydroswertianolin (THS), a hepatoprotective agent from Swertia japonica, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (D-GalN) (700 mg/kg, i.p.) and lipopolysaccharide (LPS) (10 microg/kg, i.p.) in mice. Apoptotic symptoms were observed at the initial stage of liver damage. By 5 hr after intoxication, hepatic DNA fragmentation had risen to 2123%, with the value in untreated mice set at 100%, without a significant elevation of serum alanine transaminase (ALT) activity. There was a parallel increase in hepatocytes undergoing chromatin condensation and apoptotic body formation. By 8 hr after intoxication, serum ALT activity had risen to 3707 U/L. Pretreatment with THS (50 mg/kg, p.o.) at 18 and 2 hr before intoxication significantly reduced DNA fragmentation to 821% of that in untreated mice and prevented the emergence of chromatin condensation and apoptotic body formation. A significant and dose-dependent reduction in serum ALT activity at 8 hr also was observed with THS pretreatment. These effects of THS were different from those observed from pretreatment with glycyrrhizin (GCR), which is a clinically used hepatoprotective agent with membrane-stabilizing activity. GCR pretreatment (100 mg/kg, p.o.) did not inhibit hepatic DNA fragmentation (1588% of untreated mice), although this compound significantly protected against serum ALT elevation (1463 U/L). These data suggest that an inhibitory effect on the progression of hepatic apoptosis prior to liver injury may be involved in the hepatoprotective mechanisms of THS, whereas it appears that GCR affects the processes after apoptosis. In a separate experiment, we found that the concentration of serum TNF-alpha rose to 2016 pg/mL at 1 hr after intoxication of mice with D-GalN and LPS, but this increase was suppressed by THS pretreatment (10, 50, or 200 mg/kg, p.o.) to 716, 454, or 406 pg/mL, respectively. Further study with a reverse transcriptase-polymerase chain reaction method showed that THS blocked TNF-alpha production at the transcriptional level. Because TNF-alpha is a critical mediator to elicit apoptosis in this model, the property of suppressing TNF-alpha production may be of prime importance for THS inhibition of hepatic apoptosis. \n" ], "offsets": [ [ 0, 2321 ] ] } ]

[ { "id": "395_T1", "type": "Chemical", "text": [ "tetrahydroswertianolin" ], "offsets": [ [ 30, 52 ] ], "normalized": [] }, { "id": "395_T2", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 54, 57 ] ], "normalized": [] }, { "id": "395_T3", "type": "Biological_Activity", "text": [ "hepatoprotective" ], "offsets": [ [ 62, 78 ] ], "normalized": [] }, { "id": "395_T4", "type": "Species", "text": [ "Swertia japonica" ], "offsets": [ [ 90, 106 ] ], "normalized": [] }, { "id": "395_T5", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 111, 138 ] ], "normalized": [] }, { "id": "395_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 140, 149 ] ], "normalized": [] }, { "id": "395_T7", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 169, 178 ] ], "normalized": [] }, { "id": "395_T9", "type": "Chemical", "text": [ "D-galactosamine" ], "offsets": [ [ 190, 205 ] ], "normalized": [] }, { "id": "395_T10", "type": "Chemical", "text": [ "D-GalN" ], "offsets": [ [ 207, 213 ] ], "normalized": [] }, { "id": "395_T11", "type": "Chemical", "text": [ "lipopolysaccharide" ], "offsets": [ [ 237, 255 ] ], "normalized": [] }, { "id": "395_T12", "type": "Species", "text": [ "mice" ], "offsets": [ [ 286, 290 ] ], "normalized": [] }, { "id": "395_T13", "type": "Biological_Activity", "text": [ "Apoptotic" ], "offsets": [ [ 292, 301 ] ], "normalized": [] }, { "id": "395_T16", "type": "Species", "text": [ "mice" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "395_T17", "type": "Protein", "text": [ "alanine transaminase" ], "offsets": [ [ 524, 544 ] ], "normalized": [] }, { "id": "395_T18", "type": "Protein", "text": [ "ALT" ], "offsets": [ [ 546, 549 ] ], "normalized": [] }, { "id": "395_T21", "type": "Protein", "text": [ "ALT" ], "offsets": [ [ 705, 710 ] ], "normalized": [] }, { "id": "395_T23", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 760, 763 ] ], "normalized": [] }, { "id": "395_T25", "type": "Species", "text": [ "mice" ], "offsets": [ [ 887, 891 ] ], "normalized": [] }, { "id": "395_T28", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 1072, 1075 ] ], "normalized": [] }, { "id": "395_T29", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 1107, 1110 ] ], "normalized": [] }, { "id": "395_T30", "type": "Chemical", "text": [ "glycyrrhizin" ], "offsets": [ [ 1169, 1181 ] ], "normalized": [] }, { "id": "395_T31", "type": "Chemical", "text": [ "GCR" ], "offsets": [ [ 1183, 1186 ] ], "normalized": [] }, { "id": "395_T32", "type": "Biological_Activity", "text": [ "hepatoprotective" ], "offsets": [ [ 1216, 1232 ] ], "normalized": [] }, { "id": "395_T34", "type": "Chemical", "text": [ "GCR" ], "offsets": [ [ 1275, 1278 ] ], "normalized": [] }, { "id": "395_T37", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 1541, 1550 ] ], "normalized": [] }, { "id": "395_T38", "type": "Biological_Activity", "text": [ "hepatoprotective" ], "offsets": [ [ 1596, 1612 ] ], "normalized": [] }, { "id": "395_T39", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 1627, 1630 ] ], "normalized": [] }, { "id": "395_T40", "type": "Chemical", "text": [ "GCR" ], "offsets": [ [ 1656, 1659 ] ], "normalized": [] }, { "id": "395_T41", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 1688, 1697 ] ], "normalized": [] }, { "id": "395_T42", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1766, 1775 ] ], "normalized": [] }, { "id": "395_T43", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1826, 1830 ] ], "normalized": [] }, { "id": "395_T44", "type": "Chemical", "text": [ "D-GalN" ], "offsets": [ [ 1836, 1842 ] ], "normalized": [] }, { "id": "395_T45", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 1847, 1850 ] ], "normalized": [] }, { "id": "395_T46", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 1888, 1891 ] ], "normalized": [] }, { "id": "395_T47", "type": "Protein", "text": [ "reverse transcriptase-polymerase" ], "offsets": [ [ 1996, 2028 ] ], "normalized": [] }, { "id": "395_T48", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 2063, 2066 ] ], "normalized": [] }, { "id": "395_T49", "type": "Biological_Activity", "text": [ "blocked" ], "offsets": [ [ 2067, 2074 ] ], "normalized": [] }, { "id": "395_T50", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2075, 2084 ] ], "normalized": [] }, { "id": "395_T51", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2134, 2143 ] ], "normalized": [] }, { "id": "395_T52", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 2177, 2186 ] ], "normalized": [] }, { "id": "395_T53", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2230, 2239 ] ], "normalized": [] }, { "id": "395_T54", "type": "Biological_Activity", "text": [ "suppressing" ], "offsets": [ [ 2218, 2229 ] ], "normalized": [] }, { "id": "395_T55", "type": "Chemical", "text": [ "THS" ], "offsets": [ [ 2283, 2286 ] ], "normalized": [] }, { "id": "395_T56", "type": "Biological_Activity", "text": [ "inhibition" ], "offsets": [ [ 2287, 2297 ] ], "normalized": [] }, { "id": "395_T60", "type": "Protein", "text": [ "ALT" ], "offsets": [ [ 1028, 1031 ] ], "normalized": [] }, { "id": "395_T61", "type": "Species", "text": [ "mice" ], "offsets": [ [ 1372, 1376 ] ], "normalized": [] }, { "id": "395_T62", "type": "Protein", "text": [ "ALT" ], "offsets": [ [ 1440, 1443 ] ], "normalized": [] }, { "id": "395_T8", "type": "Biological_Activity", "text": [ "inhibitory" ], "offsets": [ [ 1493, 1503 ] ], "normalized": [] }, { "id": "395_T14", "type": "Biological_Activity", "text": [ "apoptosis" ], "offsets": [ [ 2309, 2318 ] ], "normalized": [] }, { "id": "395_T15", "type": "Biological_Activity", "text": [ "transaminase" ], "offsets": [ [ 532, 544 ] ], "normalized": [] }, { "id": "395_T19", "type": "Metabolite", "text": [ "tetrahydroswertianolin" ], "offsets": [ [ 30, 52 ] ], "normalized": [] }, { "id": "395_T20", "type": "Metabolite", "text": [ "THS" ], "offsets": [ [ 54, 57 ] ], "normalized": [] }, { "id": "395_T22", "type": "Chemical", "text": [ "LPS" ], "offsets": [ [ 257, 260 ] ], "normalized": [] }, { "id": "395_T24", "type": "Biological_Activity", "text": [ "inhibit" ], "offsets": [ [ 1318, 1325 ] ], "normalized": [] }, { "id": "395_T26", "type": "Biological_Activity", "text": [ "protected" ], "offsets": [ [ 1416, 1425 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "397", "type": "", "text": [ "Daphnia are an important and widely studied model species in ecological and toxicological studies throughout the world and an official (OECD) recommended test organism. Their small size, wide distribution and easy growth conditions make this organism ideal for functional genomics based studies, including metabolic profiling and transcriptomics. In this study we used an integrated systems approach in which transcriptomic, metabolomic and energetic responses of juvenile (4days old) daphnids were evaluated in response to exposure to two poly aromatic hydrocarbons (pyrene and fluoranthene) and binary mixtures thereof. In addition, these responses were linked to responses measured during chronic experiments (21days) assessing survival, growth and reproductive traits. Custom Daphnia magna microarrays were used to assess transcriptomic changes. Hierarchical cluster analysis did not result in a clear distinction between the single compounds suggesting similar molecular modes of action. Cluster analysis with both the single compounds and the binary mixture treatments resulted in a separation of treatments based on differences in toxic ratios rather than component differences. Changes in the metabolic profiles of the organisms were investigated using Nuclear Magnetic Resonance Spectroscopy and Gas and Liquid Chromatography Mass Spectrometry. These multivariate metabolomic datasets were analyzed with Principal Components Analysis and Partial Least Squares Discriminant Analysis. The major metabolite changes responsible for the differences observed indicated a disturbance in aminosugar metabolism in all cases. The study demonstrates the potential of 'omics' to provide screening tools for monitoring of the freshwater environment--in invertebrate species--which is reasonably rapid, cost-effective and has the potential to greatly increase the amount of information obtained from aquatic toxicology testing. \n" ], "offsets": [ [ 0, 1926 ] ] } ]

[ { "id": "397_T1", "type": "Species", "text": [ "Daphnia" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "397_T2", "type": "Species", "text": [ "daphnids" ], "offsets": [ [ 486, 494 ] ], "normalized": [] }, { "id": "397_T3", "type": "Chemical", "text": [ "poly aromatic hydrocarbons" ], "offsets": [ [ 541, 568 ] ], "normalized": [] }, { "id": "397_T4", "type": "Chemical", "text": [ "pyrene" ], "offsets": [ [ 570, 576 ] ], "normalized": [] }, { "id": "397_T5", "type": "Chemical", "text": [ "fluoranthene" ], "offsets": [ [ 581, 593 ] ], "normalized": [] }, { "id": "397_T6", "type": "Species", "text": [ "Daphnia magna" ], "offsets": [ [ 782, 795 ] ], "normalized": [] }, { "id": "397_T7", "type": "Spectral_Data", "text": [ "Nuclear Magnetic Resonance Spectroscopy" ], "offsets": [ [ 1263, 1302 ] ], "normalized": [] }, { "id": "397_T10", "type": "Biological_Activity", "text": [ "metabolism" ], "offsets": [ [ 1602, 1612 ] ], "normalized": [] }, { "id": "397_T11", "type": "Spectral_Data", "text": [ "Gas", "Chromatography Mass Spectrometry" ], "offsets": [ [ 1307, 1310 ], [ 1322, 1354 ] ], "normalized": [] }, { "id": "397_T12", "type": "Spectral_Data", "text": [ "Liquid Chromatography Mass Spectrometry" ], "offsets": [ [ 1315, 1354 ] ], "normalized": [] }, { "id": "397_T8", "type": "Species", "text": [ "invertebrate" ], "offsets": [ [ 1751, 1763 ] ], "normalized": [] }, { "id": "397_T9", "type": "Chemical", "text": [ "aminosugar" ], "offsets": [ [ 1591, 1601 ] ], "normalized": [] } ]

[]

[]

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