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0 | 10026165 | [
{
"id": "1",
"type": "",
"text": [
"3,4-Dihydroxyphenylalanine (Dopa) decarboxylase is a stereospecific pyridoxal 5'-phosphate (PLP)-dependent alpha-decarboxylase that converts L-aromatic amino acids into their corresponding amines. We now report that reaction of the enzyme with D-5-hydroxytryptophan or D-Dopa results in a time-dependent inactivation and conversion of the PLP coenzyme to pyridoxamine 5'-phosphate and PLP-D-amino acid Pictet-Spengler adducts, which have been identified by high performance liquid chromatography. We also show that the reaction specificity of Dopa decarboxylase toward aromatic amines depends on the experimental conditions. Whereas oxidative deamination occurs under aerobic conditions (Bertoldi, M., Moore, P. S., Maras, B., Dominici, P., and Borri Voltattorni, C. (1996) J. Biol. Chem. 271, 23954-23959; Bertoldi, M., Dominici, P., Moore, P. S., Maras, B., and Borri Voltattorni, C. (1998) Biochemistry 37, 6552-6561), half-transamination and Pictet-Spengler reactions take place under anaerobic conditions. Moreover, we examined the reaction specificity of nicked Dopa decarboxylase, obtained by selective tryptic cleavage of the native enzyme between Lys334 and His335. Although this enzymatic species does not exhibit either decarboxylase or oxidative deamination activities, it retains a large percentage of the native transaminase activity toward D-aromatic amino acids and displays a slow transaminase activity toward aromatic amines. These transamination reactions occur concomitantly with the formation of cyclic coenzyme-substrate adducts. Together with additional data, we thus suggest that native Dopa decarboxylase can exist as an equilibrium among \"open,\" \"half-open,\" and \"closed\" forms. \n"
],
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{
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0,
47
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"text": [
"3,4-Dihydroxyphenylalanine (Dopa) decarboxylase"
],
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{
"id": "1_T7",
"type": "Protein",
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107,
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"text": [
"alpha-decarboxylase"
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{
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141,
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],
"text": [
"L-aromatic amino acids"
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{
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189,
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"text": [
"amines"
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{
"id": "1_T10",
"type": "Chemical",
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[
245,
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],
"text": [
"D-5-hydroxytryptophan"
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232,
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"text": [
"enzyme"
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{
"id": "1_T13",
"type": "Chemical",
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270,
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],
"text": [
"D-Dopa"
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{
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"type": "Chemical",
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340,
343
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],
"text": [
"PLP"
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344,
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],
"text": [
"coenzyme"
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{
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"type": "Chemical",
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[
356,
381
]
],
"text": [
"pyridoxamine 5'-phosphate"
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},
{
"id": "1_T17",
"type": "Chemical",
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[
386,
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],
"text": [
"PLP-D-amino acid Pictet-Spengler adducts"
],
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},
{
"id": "1_T18",
"type": "Chemical",
"offsets": [
[
386,
402
]
],
"text": [
"PLP-D-amino acid"
],
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},
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"type": "Protein",
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[
545,
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]
],
"text": [
"Dopa decarboxylase"
],
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},
{
"id": "1_T21",
"type": "Chemical",
"offsets": [
[
572,
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]
],
"text": [
"aromatic amines"
],
"normalized": []
},
{
"id": "1_T22",
"type": "Protein",
"offsets": [
[
1072,
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]
],
"text": [
"Dopa decarboxylase"
],
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},
{
"id": "1_T24",
"type": "Biological_Activity",
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1235,
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"text": [
"decarboxylase"
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},
{
"id": "1_T25",
"type": "Biological_Activity",
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[
1252,
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]
],
"text": [
"oxidative deamination"
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},
{
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1330,
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],
"text": [
"transaminase"
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},
{
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],
"text": [
"D-aromatic amino acids"
],
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},
{
"id": "1_T28",
"type": "Biological_Activity",
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[
1402,
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]
],
"text": [
"transaminase"
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{
"id": "1_T29",
"type": "Chemical",
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1431,
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]
],
"text": [
"aromatic amines."
],
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},
{
"id": "1_T30",
"type": "Chemical",
"offsets": [
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1528,
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],
"text": [
"coenzyme-substrate adduct"
],
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},
{
"id": "1_T31",
"type": "Protein",
"offsets": [
[
1615,
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]
],
"text": [
"Dopa decarboxylase"
],
"normalized": []
},
{
"id": "1_T33",
"type": "Protein",
"offsets": [
[
68,
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]
],
"text": [
"pyridoxal 5'-phosphate (PLP)-dependent alpha-decarboxylase"
],
"normalized": []
},
{
"id": "1_T1",
"type": "Chemical",
"offsets": [
[
68,
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]
],
"text": [
"pyridoxal 5'-phosphate"
],
"normalized": []
},
{
"id": "1_T2",
"type": "Chemical",
"offsets": [
[
92,
95
]
],
"text": [
"PLP"
],
"normalized": []
}
] | [] | [] | [
{
"id": "1_R4",
"type": "Associated_With",
"arg1_id": "1_T14",
"arg2_id": "1_T15",
"normalized": []
}
] |
2 | 10027587 | [
{
"id": "3",
"type": "",
"text": [
"Extracts of the creosote bush (Larrea tridentata, family Zygophyllaceae) have long been used as a folk remedy for Type II (non-insulin-dependent) diabetes by native Americans in southwestern North America. In this study we have evaluated the metabolic effects of masoprocol, a pure compound isolated from the creosote bush, in a rat model of Type II diabetes. Animals were fed a 20% fat (by weight) diet for 2 weeks prior to intravenous injection with streptozotocin (STZ, 0.19 mmol/kg). Diabetic animals (glucose 16-33 mmol/l) were treated with vehicle, metformin (0.83 mmol/kg body weight) or masoprocol (0.83 mmol/kg body weight) twice a day for 4 days. Masoprocol treatment lowered glucose concentrations an average of 35% compared with vehicle (14.2+/-1.1 vs 21.7+/-1.0 mmol/l, p < 0.001), a reduction similar to metformin treatment (12.8+/-0.9 mmol/l), without any change in insulin concentration. Masoprocol treatment also lowered triglyceride concentrations 80% compared with vehicle (1.0+/-0.1 vs 4.8+/-0.3 mmol/l, p < 0.001), a reduction far greater than following metformin treatment (3.6+/-0.3 mmol/l). Non-esterified fatty acid and glycerol concentration were decreased by approximately 65% by masoprocol compared with vehicle, a reduction approximately twice as great as seen with metformin (p < 0.001). The effect of masoprocol on in vivo insulin-mediated glucose disposal was evaluated by infusing fat-fed/STZ rats with glucose (0.22 mmol kg x min(-1)) and insulin (30 pmol x kg x min(-1)) for 5 h. In response to the infusion, steady-state plasma glucose concentrations were reduced 30% in masoprocol-treated animals compared with vehicle controls (p < 0.05) with no change noted in rats treated with metformin. The effect of masoprocol treatment was also tested in primary adipocytes isolated from normal animals. Adipocytes treated with masoprocol (30 micromol/l) had higher basal and insulin-stimulated glucose clearance than did adipocytes treated with vehicle (p <0.05). These data show that masoprocol decreases both plasma glucose and triglyceride concentrations in fat-fed/STZ rats, presumably as a result of its ability to both increase glucose disposal and decrease lipolysis. \n"
],
"offsets": [
[
0,
2208
]
]
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] | [
{
"id": "3_T1",
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[
16,
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"text": [
"creosote bush"
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},
{
"id": "3_T2",
"type": "Species",
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[
31,
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]
],
"text": [
"Larrea tridentata"
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},
{
"id": "3_T4",
"type": "Metabolite",
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263,
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]
],
"text": [
"masoprocol"
],
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{
"id": "3_T5",
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263,
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],
"text": [
"masoprocol"
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"creosote bush"
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{
"id": "3_T7",
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[
329,
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]
],
"text": [
"rat"
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},
{
"id": "3_T8",
"type": "Chemical",
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[
453,
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]
],
"text": [
"streptozotocin"
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},
{
"id": "3_T9",
"type": "Chemical",
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[
556,
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]
],
"text": [
"metformin"
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"normalized": []
},
{
"id": "3_T10",
"type": "Chemical",
"offsets": [
[
596,
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]
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"text": [
"masoprocol"
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},
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"id": "3_T11",
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[
658,
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]
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"text": [
"Masoprocol"
],
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},
{
"id": "3_T12",
"type": "Chemical",
"offsets": [
[
687,
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]
],
"text": [
"glucose"
],
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},
{
"id": "3_T14",
"type": "Chemical",
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[
819,
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]
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"text": [
"metformin"
],
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},
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"id": "3_T15",
"type": "Protein",
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[
882,
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]
],
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"insulin"
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},
{
"id": "3_T16",
"type": "Chemical",
"offsets": [
[
905,
915
]
],
"text": [
"Masoprocol"
],
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},
{
"id": "3_T17",
"type": "Chemical",
"offsets": [
[
939,
951
]
],
"text": [
"triglyceride"
],
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},
{
"id": "3_T18",
"type": "Chemical",
"offsets": [
[
1076,
1085
]
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"text": [
"metformin"
],
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},
{
"id": "3_T19",
"type": "Chemical",
"offsets": [
[
1116,
1141
]
],
"text": [
"Non-esterified fatty acid"
],
"normalized": []
},
{
"id": "3_T20",
"type": "Chemical",
"offsets": [
[
1146,
1154
]
],
"text": [
"glycerol"
],
"normalized": []
},
{
"id": "3_T21",
"type": "Chemical",
"offsets": [
[
1208,
1218
]
],
"text": [
"masoprocol"
],
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},
{
"id": "3_T22",
"type": "Chemical",
"offsets": [
[
1296,
1305
]
],
"text": [
"metformin"
],
"normalized": []
},
{
"id": "3_T23",
"type": "Metabolite",
"offsets": [
[
1333,
1343
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T24",
"type": "Protein",
"offsets": [
[
1355,
1362
]
],
"text": [
"insulin"
],
"normalized": []
},
{
"id": "3_T25",
"type": "Chemical",
"offsets": [
[
1372,
1379
]
],
"text": [
"glucose"
],
"normalized": []
},
{
"id": "3_T26",
"type": "Chemical",
"offsets": [
[
1423,
1426
]
],
"text": [
"STZ"
],
"normalized": []
},
{
"id": "3_T27",
"type": "Chemical",
"offsets": [
[
469,
472
]
],
"text": [
"STZ"
],
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},
{
"id": "3_T28",
"type": "Chemical",
"offsets": [
[
1437,
1444
]
],
"text": [
"glucose"
],
"normalized": []
},
{
"id": "3_T29",
"type": "Protein",
"offsets": [
[
1474,
1481
]
],
"text": [
"insulin"
],
"normalized": []
},
{
"id": "3_T30",
"type": "Chemical",
"offsets": [
[
1566,
1573
]
],
"text": [
"glucose"
],
"normalized": []
},
{
"id": "3_T31",
"type": "Metabolite",
"offsets": [
[
1609,
1619
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T32",
"type": "Species",
"offsets": [
[
1427,
1431
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "3_T33",
"type": "Species",
"offsets": [
[
1702,
1706
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "3_T34",
"type": "Chemical",
"offsets": [
[
1720,
1729
]
],
"text": [
"metformin"
],
"normalized": []
},
{
"id": "3_T35",
"type": "Chemical",
"offsets": [
[
1746,
1756
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T36",
"type": "Chemical",
"offsets": [
[
1859,
1869
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T37",
"type": "Protein",
"offsets": [
[
1907,
1914
]
],
"text": [
"insulin"
],
"normalized": []
},
{
"id": "3_T38",
"type": "Chemical",
"offsets": [
[
1926,
1933
]
],
"text": [
"glucose"
],
"normalized": []
},
{
"id": "3_T39",
"type": "Protein",
"offsets": [
[
127,
134
]
],
"text": [
"insulin"
],
"normalized": []
},
{
"id": "3_T40",
"type": "Chemical",
"offsets": [
[
2050,
2057
]
],
"text": [
"glucose"
],
"normalized": []
},
{
"id": "3_T41",
"type": "Chemical",
"offsets": [
[
2062,
2074
]
],
"text": [
"triglyceride"
],
"normalized": []
},
{
"id": "3_T42",
"type": "Chemical",
"offsets": [
[
2101,
2104
]
],
"text": [
"STZ"
],
"normalized": []
},
{
"id": "3_T43",
"type": "Species",
"offsets": [
[
2105,
2109
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "3_T44",
"type": "Chemical",
"offsets": [
[
2166,
2173
]
],
"text": [
"glucose"
],
"normalized": []
},
{
"id": "3_T46",
"type": "Species",
"offsets": [
[
158,
174
]
],
"text": [
"native Americans"
],
"normalized": []
},
{
"id": "3_T47",
"type": "Metabolite",
"offsets": [
[
596,
606
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T48",
"type": "Metabolite",
"offsets": [
[
658,
668
]
],
"text": [
"Masoprocol"
],
"normalized": []
},
{
"id": "3_T50",
"type": "Metabolite",
"offsets": [
[
905,
915
]
],
"text": [
"Masoprocol"
],
"normalized": []
},
{
"id": "3_T52",
"type": "Metabolite",
"offsets": [
[
1746,
1756
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T53",
"type": "Chemical",
"offsets": [
[
1609,
1619
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T54",
"type": "Metabolite",
"offsets": [
[
1859,
1869
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T55",
"type": "Chemical",
"offsets": [
[
2017,
2027
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T56",
"type": "Metabolite",
"offsets": [
[
2017,
2027
]
],
"text": [
"masoprocol"
],
"normalized": []
},
{
"id": "3_T57",
"type": "Metabolite",
"offsets": [
[
939,
951
]
],
"text": [
"triglyceride"
],
"normalized": []
},
{
"id": "3_T61",
"type": "Chemical",
"offsets": [
[
1333,
1343
]
],
"text": [
"masoprocol"
],
"normalized": []
}
] | [] | [] | [
{
"id": "3_R1",
"type": "Isolated_From",
"arg1_id": "3_T4",
"arg2_id": "3_T2",
"normalized": []
},
{
"id": "3_R2",
"type": "Isolated_From",
"arg1_id": "3_T4",
"arg2_id": "3_T1",
"normalized": []
},
{
"id": "3_R3",
"type": "Isolated_From",
"arg1_id": "3_T4",
"arg2_id": "3_T6",
"normalized": []
},
{
"id": "3_R4",
"type": "Isolated_From",
"arg1_id": "3_T47",
"arg2_id": "3_T6",
"normalized": []
}
] |
4 | 10027798 | [
{
"id": "5",
"type": "",
"text": [
"Recently, it was shown that diclofenac was metabolized in rats to reactive benzoquinone imines via cytochrome P450-catalyzed oxidation. These metabolites also were detected in human hepatocyte cultures in the form of glutathione (GSH) adducts. This report describes the results of further studies aimed at characterizing the human hepatic P450-mediated bioactivation of diclofenac. The reactive metabolites formed in vitro were trapped by GSH and analyzed by LC/MS/MS. Thus, three GSH adducts, namely, 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified in incubations of diclofenac with human liver microsomes in the presence of NADPH and GSH. The formation of the adducts was taken to reflect the intermediacy of the corresponding putative benzoquinone imines. While M2 was the dominant metabolite over a substrate concentration range of 10-50 microM, M1 and M3 became equally important products at >/=100 microM diclofenac. The formation of M2 was inhibited by sulfaphenazole or an anti-P450 2C9 antibody (5-10% of control values). The formation of M1 and M3 was inhibited by troleandomycin, ketoconazole, or an anti-P450 3A4 antibody (30-50% of control values). In studies in which recombinant P450 isoforms were used, M2 was generated only by P450 2C9-catalyzed reaction, while M1 and M3 were produced by P450 3A4-catalyzed reaction. Good correlations were established between the extent of formation of M2 and P450 2C9 activities (r = 0.93, n = 10) and between the extent of formation of M1 and M3 and P450 3A4 activities (r = 0.98, n = 10) in human liver microsomal incubations. Taken together, the data suggest that the biotransformation of diclofenac to M2 is P450 2C9-dependent, whereas metabolism of the drug to M1 and M3 involves mainly P450 3A4. Although P450s 2C9 and 3A4 both catalyze the bioactivation of diclofenac, P450 2C9 is capable of producing the benzoquinone imine intermediate at lower drug concentrations which may be more clinically relevant. \n"
],
"offsets": [
[
0,
2084
]
]
}
] | [
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"id": "5_T1",
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28,
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]
],
"text": [
"diclofenac"
],
"normalized": []
},
{
"id": "5_T2",
"type": "Species",
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[
58,
62
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "5_T3",
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[
75,
94
]
],
"text": [
"benzoquinone imines"
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},
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"Recently, it was shown that diclofenac was metabolized in rats to reactive benzoquinone imines via cytochrome P450-catalyzed oxidation. These metabolites also were detected in human hepatocyte cultures in the form of glutathione (GSH) adducts. This report describes the results of further studies aimed at characterizing the human hepatic P450-mediated bioactivation of diclofenac. The reactive metabolites formed in vitro were trapped by GSH and analyzed by LC/MS/MS. Thus, three GSH adducts, namely, 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified in incubations of diclofenac with human liver microsomes in the presence of NADPH and GSH. The formation of the adducts was taken to reflect the intermediacy of the corresponding putative benzoquinone imines. While M2 was the dominant metabolite over a substrate concentration range of 10-50 microM, M1 and M3 became equally important products at >/=100 microM diclofenac. The formation of M2 was inhibited by sulfaphenazole or an anti-P450 2C9 antibody (5-10% of control values). The formation of M1 and M3 was inhibited by troleandomycin, ketoconazole, or an anti-P450 3A4 antibody (30-50% of control values). In studies in which recombinant P450 isoforms were used, M2 was generated only by P450 2C9-catalyzed reaction, while M1 and M3 were produced by P450 3A4-catalyzed reaction. Good correlations were established between the extent of formation of M2 and P450 2C9 activities (r = 0.93, n = 10) and between the extent of formation of M1 and M3 and P450 3A4 activities (r = 0.98, n = 10) in human liver microsomal incubations. Taken together, the data suggest that the biotransformation of diclofenac to M2 is P450 2C9-dependent, whereas metabolism of the drug to M1 and M3 involves mainly P450 3A4. Although P450s 2C9 and 3A4 both catalyze the bioactivation of diclofenac, P450 2C9 is capable of producing the benzoqu"
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"id": "5_R17",
"type": "Associated_With",
"arg1_id": "5_T22",
"arg2_id": "5_T87",
"normalized": []
},
{
"id": "5_R18",
"type": "Associated_With",
"arg1_id": "5_T25",
"arg2_id": "5_T87",
"normalized": []
}
] |
6 | 10027801 | [
{
"id": "7",
"type": "",
"text": [
"Cytochrome P450 2C11 in rats was recently found to metabolize diclofenac into a highly reactive product that covalently bound to this enzyme before it could diffuse away and react with other proteins. To determine whether cytochromes P450 in human liver could catalyze a similar reaction, we have studied the covalent binding of diclofenac in vitro to liver microsomes of 16 individuals. Only three of 16 samples were found by immunoblot analysis to activate diclofenac appreciably to form protein adducts in a NADPH-dependent pathway. Cytochrome P450 2C9, which catalyzes the major route of oxidative metabolism of diclofenac to produce 4'-hydroxydiclofenac, did not appear to be responsible for the formation of the protein adducts, because sulfaphenazole, an inhibitor of this enzyme, did not affect protein adduct formation. In contrast, troleandomycin, an inhibitor of P450 3A4, inhibited both protein adduct formation and 5-hydroxylation of diclofenac. These findings were confirmed with the use of baculovirus-expressed human P450 2C9 and P450 3A4. One possible reactive intermediate that would be expected to bind covalently to liver proteins was the p-benzoquinone imine derivative of 5-hydroxydiclofenac. This product was formed by an apparent metal-catalyzed oxidation of 5-hydroxydiclofenac that was inhibited by EDTA, glutathione, and NADPH. The p-benzoquinone imine decomposition product bound covalently to human liver microsomes in vitro in a reaction that was inhibited by GSH. In contrast, GSH did not prevent the covalent binding of diclofenac to human liver microsomes. These results suggest that for appreciable P450-mediated bioactivation of diclofenac to occur in vivo, an individual may have to have both high activities of P450 3A4 and perhaps low activities of other enzymes that catalyze competing pathways of metabolism of diclofenac. Moreover, the p-benzoquinone imine derivative of 5-hydroxydiclofenac probably has a role in covalent binding in the liver only under the conditions where levels of NADPH, GSH, and other reducing agents would be expected to be low. \n"
],
"offsets": [
[
0,
2098
]
]
}
] | [
{
"id": "7_T1",
"type": "Protein",
"offsets": [
[
0,
20
]
],
"text": [
"Cytochrome P450 2C11"
],
"normalized": []
},
{
"id": "7_T2",
"type": "Species",
"offsets": [
[
24,
28
]
],
"text": [
"rats"
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},
{
"id": "7_T3",
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62,
72
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},
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"id": "7_T4",
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222,
238
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],
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"cytochromes P450"
],
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},
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"id": "7_T5",
"type": "Species",
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242,
247
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],
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"human"
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"id": "7_T6",
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329,
339
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],
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"diclofenac"
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},
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"id": "7_T7",
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[
460,
470
]
],
"text": [
"diclofenac"
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},
{
"id": "7_T8",
"type": "Chemical",
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[
512,
517
]
],
"text": [
"NADPH"
],
"normalized": []
},
{
"id": "7_T9",
"type": "Protein",
"offsets": [
[
537,
556
]
],
"text": [
"Cytochrome P450 2C9"
],
"normalized": []
},
{
"id": "7_T10",
"type": "Chemical",
"offsets": [
[
617,
627
]
],
"text": [
"diclofenac"
],
"normalized": []
},
{
"id": "7_T11",
"type": "Biological_Activity",
"offsets": [
[
603,
613
]
],
"text": [
"metabolism"
],
"normalized": []
},
{
"id": "7_T12",
"type": "Metabolite",
"offsets": [
[
639,
659
]
],
"text": [
"4'-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T13",
"type": "Chemical",
"offsets": [
[
639,
659
]
],
"text": [
"4'-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T14",
"type": "Chemical",
"offsets": [
[
745,
759
]
],
"text": [
"sulfaphenazole"
],
"normalized": []
},
{
"id": "7_T16",
"type": "Chemical",
"offsets": [
[
845,
859
]
],
"text": [
"troleandomycin"
],
"normalized": []
},
{
"id": "7_T17",
"type": "Biological_Activity",
"offsets": [
[
864,
873
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "7_T18",
"type": "Chemical",
"offsets": [
[
931,
949
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[
950,
960
]
],
"text": [
"5-hydroxylation of",
"diclofenac"
],
"normalized": []
},
{
"id": "7_T19",
"type": "Species",
"offsets": [
[
1030,
1035
]
],
"text": [
"human"
],
"normalized": []
},
{
"id": "7_T20",
"type": "Protein",
"offsets": [
[
1036,
1044
]
],
"text": [
"P450 2C9"
],
"normalized": []
},
{
"id": "7_T21",
"type": "Protein",
"offsets": [
[
1049,
1057
]
],
"text": [
"P450 3A4"
],
"normalized": []
},
{
"id": "7_T23",
"type": "Chemical",
"offsets": [
[
1162,
1216
]
],
"text": [
"p-benzoquinone imine derivative of 5-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T22",
"type": "Chemical",
"offsets": [
[
1286,
1305
]
],
"text": [
"5-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T24",
"type": "Metabolite",
"offsets": [
[
1286,
1305
]
],
"text": [
"5-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T25",
"type": "Chemical",
"offsets": [
[
1328,
1332
]
],
"text": [
"EDTA"
],
"normalized": []
},
{
"id": "7_T26",
"type": "Chemical",
"offsets": [
[
1334,
1345
]
],
"text": [
"glutathione"
],
"normalized": []
},
{
"id": "7_T27",
"type": "Chemical",
"offsets": [
[
1351,
1356
]
],
"text": [
"NADPH"
],
"normalized": []
},
{
"id": "7_T28",
"type": "Chemical",
"offsets": [
[
1257,
1262
]
],
"text": [
"metal"
],
"normalized": []
},
{
"id": "7_T29",
"type": "Chemical",
"offsets": [
[
1362,
1382
]
],
"text": [
"p-benzoquinone imine"
],
"normalized": []
},
{
"id": "7_T30",
"type": "Chemical",
"offsets": [
[
1493,
1496
]
],
"text": [
"GSH"
],
"normalized": []
},
{
"id": "7_T32",
"type": "Chemical",
"offsets": [
[
1511,
1514
]
],
"text": [
"GSH"
],
"normalized": []
},
{
"id": "7_T33",
"type": "Chemical",
"offsets": [
[
1555,
1565
]
],
"text": [
"diclofenac"
],
"normalized": []
},
{
"id": "7_T34",
"type": "Species",
"offsets": [
[
1569,
1574
]
],
"text": [
"human"
],
"normalized": []
},
{
"id": "7_T35",
"type": "Species",
"offsets": [
[
1425,
1430
]
],
"text": [
"human"
],
"normalized": []
},
{
"id": "7_T36",
"type": "Protein",
"offsets": [
[
1636,
1640
]
],
"text": [
"P450"
],
"normalized": []
},
{
"id": "7_T37",
"type": "Chemical",
"offsets": [
[
1667,
1677
]
],
"text": [
"diclofenac"
],
"normalized": []
},
{
"id": "7_T38",
"type": "Protein",
"offsets": [
[
1751,
1759
]
],
"text": [
"P450 3A4"
],
"normalized": []
},
{
"id": "7_T39",
"type": "Chemical",
"offsets": [
[
1854,
1864
]
],
"text": [
"diclofenac"
],
"normalized": []
},
{
"id": "7_T40",
"type": "Chemical",
"offsets": [
[
1880,
1900
],
[
1915,
1934
]
],
"text": [
"p-benzoquinone imine",
"5-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T41",
"type": "Chemical",
"offsets": [
[
1915,
1934
]
],
"text": [
"5-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T42",
"type": "Chemical",
"offsets": [
[
2030,
2035
]
],
"text": [
"NADPH"
],
"normalized": []
},
{
"id": "7_T43",
"type": "Chemical",
"offsets": [
[
2037,
2040
]
],
"text": [
"GSH"
],
"normalized": []
},
{
"id": "7_T44",
"type": "Chemical",
"offsets": [
[
2052,
2067
]
],
"text": [
"reducing agents"
],
"normalized": []
},
{
"id": "7_T45",
"type": "Protein",
"offsets": [
[
134,
140
]
],
"text": [
"enzyme"
],
"normalized": []
},
{
"id": "7_T46",
"type": "Protein",
"offsets": [
[
491,
506
]
],
"text": [
"protein adducts"
],
"normalized": []
},
{
"id": "7_T47",
"type": "Protein",
"offsets": [
[
720,
735
]
],
"text": [
"protein adducts"
],
"normalized": []
},
{
"id": "7_T48",
"type": "Protein",
"offsets": [
[
806,
820
]
],
"text": [
"protein adduct"
],
"normalized": []
},
{
"id": "7_T49",
"type": "Protein",
"offsets": [
[
902,
915
]
],
"text": [
"protein adduc"
],
"normalized": []
},
{
"id": "7_T50",
"type": "Protein",
"offsets": [
[
1145,
1153
]
],
"text": [
"proteins"
],
"normalized": []
},
{
"id": "7_T51",
"type": "Chemical",
"offsets": [
[
1197,
1216
]
],
"text": [
"5-hydroxydiclofenac"
],
"normalized": []
},
{
"id": "7_T52",
"type": "Biological_Activity",
"offsets": [
[
764,
773
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "7_T54",
"type": "Protein",
"offsets": [
[
877,
885
]
],
"text": [
"P450 3A4"
],
"normalized": []
},
{
"id": "7_T31",
"type": "Protein",
"offsets": [
[
1796,
1803
]
],
"text": [
"enzymes"
],
"normalized": []
},
{
"id": "7_T15",
"type": "Biological_Activity",
"offsets": [
[
1315,
1324
]
],
"text": [
"inhibited"
],
"normalized": []
},
{
"id": "7_T53",
"type": "Biological_Activity",
"offsets": [
[
1480,
1489
]
],
"text": [
"inhibited"
],
"normalized": []
},
{
"id": "7_T55",
"type": "Biological_Activity",
"offsets": [
[
318,
325
]
],
"text": [
"binding"
],
"normalized": []
},
{
"id": "7_T56",
"type": "Biological_Activity",
"offsets": [
[
1544,
1551
]
],
"text": [
"binding"
],
"normalized": []
},
{
"id": "7_T57",
"type": "Biological_Activity",
"offsets": [
[
1840,
1850
]
],
"text": [
"metabolism"
],
"normalized": []
},
{
"id": "7_T58",
"type": "Biological_Activity",
"offsets": [
[
1967,
1974
]
],
"text": [
"binding"
],
"normalized": []
}
] | [] | [] | [
{
"id": "7_R1",
"type": "Metabolite_Of",
"arg1_id": "7_T12",
"arg2_id": "7_T10",
"normalized": []
},
{
"id": "7_R2",
"type": "Associated_With",
"arg1_id": "7_T14",
"arg2_id": "7_T52",
"normalized": []
},
{
"id": "7_R5",
"type": "Binds_With",
"arg1_id": "7_T14",
"arg2_id": "7_T9",
"normalized": []
},
{
"id": "7_R3",
"type": "Associated_With",
"arg1_id": "7_T16",
"arg2_id": "7_T17",
"normalized": []
},
{
"id": "7_R6",
"type": "Binds_With",
"arg1_id": "7_T16",
"arg2_id": "7_T54",
"normalized": []
},
{
"id": "7_R4",
"type": "Associated_With",
"arg1_id": "7_T25",
"arg2_id": "7_T15",
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},
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"id": "7_R7",
"type": "Associated_With",
"arg1_id": "7_T26",
"arg2_id": "7_T15",
"normalized": []
},
{
"id": "7_R8",
"type": "Associated_With",
"arg1_id": "7_T27",
"arg2_id": "7_T15",
"normalized": []
},
{
"id": "7_R9",
"type": "Associated_With",
"arg1_id": "7_T30",
"arg2_id": "7_T53",
"normalized": []
},
{
"id": "7_R10",
"type": "Associated_With",
"arg1_id": "7_T6",
"arg2_id": "7_T55",
"normalized": []
},
{
"id": "7_R11",
"type": "Associated_With",
"arg1_id": "7_T33",
"arg2_id": "7_T56",
"normalized": []
},
{
"id": "7_R12",
"type": "Associated_With",
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},
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"type": "Associated_With",
"arg1_id": "7_T39",
"arg2_id": "7_T57",
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},
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"type": "Associated_With",
"arg1_id": "7_T40",
"arg2_id": "7_T58",
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}
] |
8 | 10027870 | [
{
"id": "9",
"type": "",
"text": [
"The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo. \n"
],
"offsets": [
[
0,
1750
]
]
}
] | [
{
"id": "9_T1",
"type": "Biological_Activity",
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11,
20
]
],
"text": [
"analgesic"
],
"normalized": []
},
{
"id": "9_T2",
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33,
42
]
],
"text": [
"ketorolac"
],
"normalized": []
},
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"id": "9_T3",
"type": "Species",
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46,
52
]
],
"text": [
"humans"
],
"normalized": []
},
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"id": "9_T4",
"type": "Chemical",
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[
72,
108
]
],
"text": [
"nonsteroidal anti-inflammatory drugs"
],
"normalized": []
},
{
"id": "9_T5",
"type": "Biological_Activity",
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[
85,
102
]
],
"text": [
"anti-inflammatory"
],
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},
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"id": "9_T6",
"type": "Chemical",
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110,
116
]
],
"text": [
"NSAIDs"
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},
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209,
218
]
],
"text": [
"analgesic"
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},
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"id": "9_T8",
"type": "Chemical",
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172,
177
]
],
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"NSAID"
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},
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"id": "9_T9",
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275,
290
]
],
"text": [
"(R,S)-ketorolac"
],
"normalized": []
},
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"id": "9_T11",
"type": "Protein",
"offsets": [
[
364,
378
]
],
"text": [
"cyclooxygenase"
],
"normalized": []
},
{
"id": "9_T13",
"type": "Protein",
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[
380,
383
]
],
"text": [
"COX"
],
"normalized": []
},
{
"id": "9_T14",
"type": "Biological_Activity",
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[
385,
394
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "9_T15",
"type": "Chemical",
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[
397,
409
]
],
"text": [
"indomethacin"
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"normalized": []
},
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"id": "9_T16",
"type": "Chemical",
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[
411,
415
]
],
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"INDO"
],
"normalized": []
},
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"id": "9_T17",
"type": "Chemical",
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[
421,
438
]
],
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"diclofenac sodium"
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},
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"id": "9_T18",
"type": "Chemical",
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440,
442
]
],
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"DS"
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},
{
"id": "9_T19",
"type": "Biological_Activity",
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[
476,
485
]
],
"text": [
"inhibitor"
],
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},
{
"id": "9_T20",
"type": "Chemical",
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[
487,
496
]
],
"text": [
"celecoxib"
],
"normalized": []
},
{
"id": "9_T21",
"type": "Protein",
"offsets": [
[
470,
475
]
],
"text": [
"COX-2"
],
"normalized": []
},
{
"id": "9_T23",
"type": "Chemical",
"offsets": [
[
536,
551
]
],
"text": [
"(R,S)-ketorolac"
],
"normalized": []
},
{
"id": "9_T24",
"type": "Chemical",
"offsets": [
[
576,
587
]
],
"text": [
"acetic acid"
],
"normalized": []
},
{
"id": "9_T25",
"type": "Chemical",
"offsets": [
[
606,
617
]
],
"text": [
"carrageenan"
],
"normalized": []
},
{
"id": "9_T27",
"type": "Chemical",
"offsets": [
[
648,
659
]
],
"text": [
"carrageenan"
],
"normalized": []
},
{
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10 | 10027962 | [
{
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"Diazaborine and isoniazid are, at first sight, unrelated anti-bacterial agents that inhibit the enoyl-ACP reductase (ENR) of Escherichia coli and Mycobacterium tuberculosis respectively. The crystal structures of these enzymes including that of the diazaborine-inhibited E. coli ENR have been obtained at high resolution. Site-directed mutagenesis was used to study the importance of amino acid residues in diazaborine susceptibility and enzyme function. The results show that drug binding and inhibition require the presence of a glycine residue at position 93 of E. coli ENR or at the structurally equivalent position in the plant homologue, which is naturally resistant to the drug. The data confirm the hypothesis that any amino acid side-chain other than hydrogen at this position within the three-dimensional structure of these enzymes will affect diazaborine resistance by encroaching into the drug binding site. Substitutions of Gly-93 by amino acids with small side-chains, such as serine, alanine, cysteine and valine, hardly affected the catalytic parameters and rendered the bacterial host resistant to the drug. Larger amino acid side-chains, such as that of arginine, histidine, lysine and glutamine, completely inactivated the activity of the enzyme. \n"
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478,
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] | [] | [] | [
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] |
12 | 10028198 | [
{
"id": "13",
"type": "",
"text": [
"The aim of this study was to investigate the distribution, excretion and metabolism of 1,2-dimethylnaphthalene-[ring-U-3H] in rats. The experiments were performed on 54 male outbred IMP:Wist rats with body weight of 200 g +/- 20%. The compound was given i.p. in olive oil in a single dose of 28 mg/kg (about 6.2 MBq per animal). 3H radioactivity was traced in selected organs and tissues, blood, urine and faeces, 1-72 h following the administration. The main metabolites were isolated from urine and identified by the GC-MS method. Faeces and urine proved to be the main route of tritium elimination. Over 93% of the given compound was excreted during the first 72 h. Maximum level of tritium in plasma was observed during the 4th h after the compound administration. The accretion of 3H proceeded with kinetic constant of 0.7 h, followed by monophasic decline with the half-life of about 19h. In organs and tissue, the highest concentration during the first hours after administration were detected in the fat, adrenals, liver, spleen and kidneys. Then gradual decline of tritium was noticed in all examined tissues. The following urinary metabolites were identified: 1. 1,2-dimethylthionaphthalene, 2. 1,2-dimethylnaphthol, 3. 1-methylnaphthalene-2-methanol, 4. 1-methyl-2-naphthoic acid and 5. 1,2-dimethylmethylthionaphthalene. In conclusion, 1,2-dimethylnaphthalene has a relatively rapid turnover rate in the rat organism and does not form deposits in the tissue. The metabolism encompasses ring hydroxylation and glutathione conjugation leading to thionaphthol and oxygenation, and then to naphthoic acid. \n"
],
"offsets": [
[
0,
1620
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"olive oil"
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[
521,
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"GC-MS"
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},
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"id": "13_T8",
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[
583,
590
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"tritium"
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"id": "13_T9",
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330,
332
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"text": [
"3H"
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},
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"id": "13_T10",
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788,
790
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"text": [
"3H"
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{
"id": "13_T11",
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[
1077,
1084
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"tritium"
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"normalized": []
},
{
"id": "13_T12",
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[
1176,
1203
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"text": [
"1,2-dimethylthionaphthalene"
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},
{
"id": "13_T13",
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"offsets": [
[
1208,
1228
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"text": [
"1,2-dimethylnaphthol"
],
"normalized": []
},
{
"id": "13_T14",
"type": "Metabolite",
"offsets": [
[
1208,
1228
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],
"text": [
"1,2-dimethylnaphthol"
],
"normalized": []
},
{
"id": "13_T15",
"type": "Chemical",
"offsets": [
[
1233,
1263
]
],
"text": [
"1-methylnaphthalene-2-methanol"
],
"normalized": []
},
{
"id": "13_T16",
"type": "Metabolite",
"offsets": [
[
1233,
1263
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"text": [
"1-methylnaphthalene-2-methanol"
],
"normalized": []
},
{
"id": "13_T17",
"type": "Chemical",
"offsets": [
[
1268,
1294
]
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"text": [
"1-methyl-2-naphthoic acid"
],
"normalized": []
},
{
"id": "13_T18",
"type": "Metabolite",
"offsets": [
[
1268,
1294
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"1-methyl-2-naphthoic acid"
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"id": "13_T19",
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1302,
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"id": "13_T20",
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"offsets": [
[
1302,
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"text": [
"1,2-dimethylmethylthionaphthalene"
],
"normalized": []
},
{
"id": "13_T21",
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[
1420,
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"text": [
"rat"
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},
{
"id": "13_T22",
"type": "Chemical",
"offsets": [
[
1352,
1375
]
],
"text": [
"1,2-dimethylnaphthalene"
],
"normalized": []
},
{
"id": "13_T23",
"type": "Chemical",
"offsets": [
[
1526,
1537
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],
"text": [
"glutathione"
],
"normalized": []
},
{
"id": "13_T24",
"type": "Chemical",
"offsets": [
[
1561,
1573
]
],
"text": [
"thionaphthol"
],
"normalized": []
},
{
"id": "13_T25",
"type": "Chemical",
"offsets": [
[
1603,
1617
]
],
"text": [
"naphthoic acid"
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"normalized": []
},
{
"id": "13_T26",
"type": "Biological_Activity",
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[
1578,
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"text": [
"oxygenation"
],
"normalized": []
},
{
"id": "13_T27",
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[
1176,
1203
]
],
"text": [
"1,2-dimethylthionaphthalene"
],
"normalized": []
},
{
"id": "13_T6",
"type": "Chemical",
"offsets": [
[
688,
695
]
],
"text": [
"tritium"
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"normalized": []
},
{
"id": "13_T28",
"type": "Biological_Activity",
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[
73,
83
]
],
"text": [
"metabolism"
],
"normalized": []
},
{
"id": "13_T29",
"type": "Biological_Activity",
"offsets": [
[
1480,
1490
]
],
"text": [
"metabolism"
],
"normalized": []
}
] | [] | [] | [
{
"id": "13_R1",
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"arg2_id": "13_T7",
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{
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"type": "Associated_With",
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"arg2_id": "13_T7",
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"type": "Associated_With",
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"type": "Metabolite_Of",
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"arg2_id": "13_T1",
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"id": "13_R10",
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"arg1_id": "13_T14",
"arg2_id": "13_T1",
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"type": "Metabolite_Of",
"arg1_id": "13_T27",
"arg2_id": "13_T1",
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}
] |
14 | 10028199 | [
{
"id": "15",
"type": "",
"text": [
"Trimethylbenzene isomers (TMBs): 1,2,4-TMB (pseudocumene--PS), 1,2,3-TMB (hemimellitene--HM) and 1,3,5-TMB (mesitylene--MES) are important constituents of solvent mixtures. In the US, the adopted TLV-TWA value for TMBs is 125 mg/m3 or 25 ppm (ACGIH 1996). Recent experiments at our laboratory have revealed an impaired learning of passive and active avoidance responses and a longer persistence of an effect of footshock (increase in latency of the paw-lick response to heat) in rats tested several weeks after a four-week inhalation exposure (6h/day, five days/week) to PS at a concentration of 100 or 250 ppm (15). The concentration-effect relationship appeared to be nonlinear; the effect of 100 ppm HM was more pronounced than that of 250 ppm. In the present experiment we investigated the effects of a repeated four-week (6h/day, 5 days/week) inhalation exposure to HM at concentrations of 0, 25, 100 or 250 ppm on radial-maze performance, open-field activity, passive and active avoidance learning, and on the shock-induced changes in latency of the paw-lick response to heat (hot-plate test). The tests were performed between days 14 and 61 after the last exposure. No significant effects on radial-maze performance and open-field activity were noted in any of the dose groups. In the remaining tests effects of exposure were noted but, similarly as in the case of PS exposure, the concentration-effect relationship was not linear. In rats exposed to HM at 25 or 100 ppm, but not 250 ppm, learning of the passive avoidance, i.e. refraining from performance of a punished response (stepping off an elevated platform) was significantly impaired. Moreover, in rats exposed to 100, but not 250 ppm of HM, acquisition of the two-way active avoidance in the shuttle-box was slower and the footshock-induced increase in latency of the paw-lick response to heat persisted longer than in the unexposed animals. The results suggest that a low-level inhalation exposure to HM, just like low-level exposure to PS, may lead to long-lasting disturbances in the CNS functions. The nonlinear concentration-effect relationship observed in the case of both TMB-s requires clarification in further studies. \n"
],
"offsets": [
[
0,
2202
]
]
}
] | [
{
"id": "15_T1",
"type": "Chemical",
"offsets": [
[
0,
16
]
],
"text": [
"Trimethylbenzene"
],
"normalized": []
},
{
"id": "15_T2",
"type": "Chemical",
"offsets": [
[
26,
30
]
],
"text": [
"TMBs"
],
"normalized": []
},
{
"id": "15_T3",
"type": "Chemical",
"offsets": [
[
33,
42
]
],
"text": [
"1,2,4-TMB"
],
"normalized": []
},
{
"id": "15_T4",
"type": "Chemical",
"offsets": [
[
44,
56
]
],
"text": [
"pseudocumene"
],
"normalized": []
},
{
"id": "15_T5",
"type": "Chemical",
"offsets": [
[
58,
60
]
],
"text": [
"PS"
],
"normalized": []
},
{
"id": "15_T6",
"type": "Chemical",
"offsets": [
[
63,
72
]
],
"text": [
"1,2,3-TMB"
],
"normalized": []
},
{
"id": "15_T7",
"type": "Chemical",
"offsets": [
[
74,
87
]
],
"text": [
"hemimellitene"
],
"normalized": []
},
{
"id": "15_T8",
"type": "Chemical",
"offsets": [
[
89,
91
]
],
"text": [
"HM"
],
"normalized": []
},
{
"id": "15_T9",
"type": "Chemical",
"offsets": [
[
97,
106
]
],
"text": [
"1,3,5-TMB"
],
"normalized": []
},
{
"id": "15_T10",
"type": "Chemical",
"offsets": [
[
108,
118
]
],
"text": [
"mesitylene"
],
"normalized": []
},
{
"id": "15_T11",
"type": "Chemical",
"offsets": [
[
120,
123
]
],
"text": [
"MES"
],
"normalized": []
},
{
"id": "15_T12",
"type": "Chemical",
"offsets": [
[
214,
218
]
],
"text": [
"TMBs"
],
"normalized": []
},
{
"id": "15_T16",
"type": "Species",
"offsets": [
[
479,
483
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "15_T17",
"type": "Chemical",
"offsets": [
[
571,
573
]
],
"text": [
"PS"
],
"normalized": []
},
{
"id": "15_T18",
"type": "Chemical",
"offsets": [
[
704,
706
]
],
"text": [
"HM"
],
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},
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"id": "15_T19",
"type": "Chemical",
"offsets": [
[
872,
874
]
],
"text": [
"HM"
],
"normalized": []
},
{
"id": "15_T22",
"type": "Chemical",
"offsets": [
[
1375,
1377
]
],
"text": [
"PS"
],
"normalized": []
},
{
"id": "15_T23",
"type": "Chemical",
"offsets": [
[
1461,
1463
]
],
"text": [
"HM"
],
"normalized": []
},
{
"id": "15_T25",
"type": "Chemical",
"offsets": [
[
1708,
1710
]
],
"text": [
"HM"
],
"normalized": []
},
{
"id": "15_T28",
"type": "Chemical",
"offsets": [
[
1975,
1977
]
],
"text": [
"HM"
],
"normalized": []
},
{
"id": "15_T29",
"type": "Chemical",
"offsets": [
[
2011,
2013
]
],
"text": [
"PS"
],
"normalized": []
},
{
"id": "15_T31",
"type": "Chemical",
"offsets": [
[
2152,
2157
]
],
"text": [
"TMB-s"
],
"normalized": []
},
{
"id": "15_T13",
"type": "Species",
"offsets": [
[
1445,
1449
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "15_T14",
"type": "Species",
"offsets": [
[
1668,
1672
]
],
"text": [
"rats"
],
"normalized": []
}
] | [] | [] | [] |
16 | 10029225 | [
{
"id": "17",
"type": "",
"text": [
"OBJECTIVE: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). METHODS: A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. RESULTS: In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA-specific IgE. The air levels of MTHPA detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5-63.9 and 4.93-5.49 microg/m3, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the MTHPA levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15-22 microg/m3, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. CONCLUSIONS: These results suggest that MTHPA exposure at levels above 15 microg/m3 should be avoided to prevent the development of occupational allergic diseases in most workers. \n"
],
"offsets": [
[
0,
1780
]
]
}
] | [
{
"id": "17_T1",
"type": "Chemical",
"offsets": [
[
130,
164
]
],
"text": [
"methyltetrahydrophthalic anhydride"
],
"normalized": []
},
{
"id": "17_T2",
"type": "Chemical",
"offsets": [
[
166,
171
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T3",
"type": "Species",
"offsets": [
[
111,
118
]
],
"text": [
"workers"
],
"normalized": []
},
{
"id": "17_T4",
"type": "Species",
"offsets": [
[
203,
210
]
],
"text": [
"workers"
],
"normalized": []
},
{
"id": "17_T5",
"type": "Chemical",
"offsets": [
[
251,
262
]
],
"text": [
"epoxy resin"
],
"normalized": []
},
{
"id": "17_T6",
"type": "Chemical",
"offsets": [
[
268,
273
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T7",
"type": "Protein",
"offsets": [
[
549,
552
]
],
"text": [
"IgE"
],
"normalized": []
},
{
"id": "17_T8",
"type": "Chemical",
"offsets": [
[
534,
539
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T9",
"type": "Chemical",
"offsets": [
[
572,
577
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T10",
"type": "Protein",
"offsets": [
[
725,
728
]
],
"text": [
"IgE"
],
"normalized": []
},
{
"id": "17_T11",
"type": "Protein",
"offsets": [
[
894,
897
]
],
"text": [
"IgE"
],
"normalized": []
},
{
"id": "17_T12",
"type": "Chemical",
"offsets": [
[
1332,
1337
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T13",
"type": "Chemical",
"offsets": [
[
1424,
1429
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T14",
"type": "Chemical",
"offsets": [
[
1639,
1644
]
],
"text": [
"MTHPA"
],
"normalized": []
},
{
"id": "17_T16",
"type": "Species",
"offsets": [
[
502,
509
]
],
"text": [
"workers"
],
"normalized": []
},
{
"id": "17_T17",
"type": "Species",
"offsets": [
[
740,
747
]
],
"text": [
"workers"
],
"normalized": []
},
{
"id": "17_T18",
"type": "Species",
"offsets": [
[
960,
967
]
],
"text": [
"workers"
],
"normalized": []
},
{
"id": "17_T19",
"type": "Species",
"offsets": [
[
1109,
1116
]
],
"text": [
"persons"
],
"normalized": []
},
{
"id": "17_T20",
"type": "Species",
"offsets": [
[
1770,
1777
]
],
"text": [
"workers"
],
"normalized": []
},
{
"id": "17_T21",
"type": "Species",
"offsets": [
[
1181,
1188
]
],
"text": [
"workers"
],
"normalized": []
}
] | [] | [] | [] |
18 | 1002932 | [
{
"id": "19",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
20 | 10030438 | [
{
"id": "21",
"type": "",
"text": [
"All the benzodiazepines (BZDs) in clinical use have the capacity to promote the binding of the major inhibitory neurotransmitter, gamma-amino-butyric acid (GABA), to sub-types of GABA receptors which exist as multi-subunit ligand-gated chloride channels. Thus, the BZDs facilitate the actions of GABA in the brain. The BZDs in use as antiepileptic drugs are diazepam, clonazepam, clobazam, nitrazepam, and lately, also lorazepam and midazolam as emergency therapy. The BZDs have a wide-spectrum of proven clinical efficacy in the prevention of different kind of seizures. Clonazepam and clobazam, as well as nitrazepam in some cases, can be useful as an adjunct treatment in refractory epilepsies. However, the clinical use of BZDs for the prophylactic treatment of epilepsy is associated with two major problems which have limited the long-term use of these drugs: the potential for side-effects, especially sedative effects, and the high risk of development of tolerance. Despite the limitations of BZDs in the prophylactic treatment of epilepsies, these drugs play a prominent role in clinical practice in the emergency management of acute seizures and status epilepticus. Diazepam, clonazepam and lorazepam are all considered first-line agents in the emergency management of acute seizures and status epilepticus. Furthermore, the value of midazolam as an emergency therapy in epilepsy has been increasingly recognized in recent years. \n"
],
"offsets": [
[
0,
1445
]
]
}
] | [
{
"id": "21_T1",
"type": "Chemical",
"offsets": [
[
8,
23
]
],
"text": [
"benzodiazepines"
],
"normalized": []
},
{
"id": "21_T2",
"type": "Chemical",
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130,
154
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"text": [
"gamma-amino-butyric acid"
],
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},
{
"id": "21_T3",
"type": "Biological_Activity",
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[
112,
128
]
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"text": [
"neurotransmitter"
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"id": "21_T4",
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156,
160
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"id": "21_T5",
"type": "Chemical",
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266,
270
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"BZDs"
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"id": "21_T6",
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25,
29
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297,
301
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"type": "Chemical",
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320,
324
]
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"text": [
"BZDs"
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{
"id": "21_T9",
"type": "Biological_Activity",
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335,
348
]
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"text": [
"antiepileptic"
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"normalized": []
},
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"id": "21_T10",
"type": "Chemical",
"offsets": [
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359,
367
]
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"text": [
"diazepam"
],
"normalized": []
},
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"id": "21_T11",
"type": "Chemical",
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369,
379
]
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"clonazepam"
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"normalized": []
},
{
"id": "21_T12",
"type": "Chemical",
"offsets": [
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381,
389
]
],
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},
{
"id": "21_T13",
"type": "Chemical",
"offsets": [
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391,
401
]
],
"text": [
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"normalized": []
},
{
"id": "21_T14",
"type": "Chemical",
"offsets": [
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420,
429
]
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"text": [
"lorazepam"
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"normalized": []
},
{
"id": "21_T15",
"type": "Chemical",
"offsets": [
[
434,
443
]
],
"text": [
"midazolam"
],
"normalized": []
},
{
"id": "21_T18",
"type": "Chemical",
"offsets": [
[
470,
474
]
],
"text": [
"BZDs"
],
"normalized": []
},
{
"id": "21_T20",
"type": "Chemical",
"offsets": [
[
573,
583
]
],
"text": [
"Clonazepam"
],
"normalized": []
},
{
"id": "21_T21",
"type": "Chemical",
"offsets": [
[
588,
596
]
],
"text": [
"clobazam"
],
"normalized": []
},
{
"id": "21_T22",
"type": "Chemical",
"offsets": [
[
609,
619
]
],
"text": [
"nitrazepam"
],
"normalized": []
},
{
"id": "21_T24",
"type": "Chemical",
"offsets": [
[
728,
732
]
],
"text": [
"BZDs"
],
"normalized": []
},
{
"id": "21_T26",
"type": "Chemical",
"offsets": [
[
861,
866
]
],
"text": [
"drugs"
],
"normalized": []
},
{
"id": "21_T27",
"type": "Biological_Activity",
"offsets": [
[
911,
919
]
],
"text": [
"sedative"
],
"normalized": []
},
{
"id": "21_T28",
"type": "Chemical",
"offsets": [
[
1004,
1008
]
],
"text": [
"BZDs"
],
"normalized": []
},
{
"id": "21_T30",
"type": "Chemical",
"offsets": [
[
1179,
1187
]
],
"text": [
"Diazepam"
],
"normalized": []
},
{
"id": "21_T31",
"type": "Chemical",
"offsets": [
[
1189,
1199
]
],
"text": [
"clonazepam"
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"normalized": []
},
{
"id": "21_T32",
"type": "Chemical",
"offsets": [
[
1204,
1213
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"lorazepam"
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},
{
"id": "21_T35",
"type": "Chemical",
"offsets": [
[
1347,
1356
]
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"text": [
"midazolam"
],
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},
{
"id": "21_T38",
"type": "Metabolite",
"offsets": [
[
130,
154
]
],
"text": [
"gamma-amino-butyric acid"
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},
{
"id": "21_T39",
"type": "Protein",
"offsets": [
[
179,
193
]
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"text": [
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"normalized": []
},
{
"id": "21_T40",
"type": "Protein",
"offsets": [
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223,
254
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"text": [
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"normalized": []
},
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"id": "21_T41",
"type": "Metabolite",
"offsets": [
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297,
301
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"text": [
"GABA"
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},
{
"id": "21_T44",
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[
156,
160
]
],
"text": [
"GABA"
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"normalized": []
},
{
"id": "21_T16",
"type": "Chemical",
"offsets": [
[
349,
354
]
],
"text": [
"drugs"
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},
{
"id": "21_T17",
"type": "Chemical",
"offsets": [
[
1060,
1065
]
],
"text": [
"drugs"
],
"normalized": []
}
] | [] | [] | [
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"id": "21_R1",
"type": "Associated_With",
"arg1_id": "21_T10",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R2",
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"arg1_id": "21_T11",
"arg2_id": "21_T9",
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},
{
"id": "21_R3",
"type": "Associated_With",
"arg1_id": "21_T12",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R4",
"type": "Associated_With",
"arg1_id": "21_T13",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R5",
"type": "Associated_With",
"arg1_id": "21_T14",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R6",
"type": "Associated_With",
"arg1_id": "21_T15",
"arg2_id": "21_T9",
"normalized": []
},
{
"id": "21_R10",
"type": "Associated_With",
"arg1_id": "21_T10",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R11",
"type": "Associated_With",
"arg1_id": "21_T11",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R12",
"type": "Associated_With",
"arg1_id": "21_T12",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R13",
"type": "Associated_With",
"arg1_id": "21_T13",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R14",
"type": "Associated_With",
"arg1_id": "21_T14",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R15",
"type": "Associated_With",
"arg1_id": "21_T15",
"arg2_id": "21_T27",
"normalized": []
},
{
"id": "21_R20",
"type": "Associated_With",
"arg1_id": "21_T38",
"arg2_id": "21_T3",
"normalized": []
},
{
"id": "21_R21",
"type": "Associated_With",
"arg1_id": "21_T38",
"arg2_id": "21_T3",
"normalized": []
},
{
"id": "21_R9",
"type": "Binds_With",
"arg1_id": "21_T4",
"arg2_id": "21_T39",
"normalized": []
},
{
"id": "21_R16",
"type": "Binds_With",
"arg1_id": "21_T44",
"arg2_id": "21_T39",
"normalized": []
},
{
"id": "21_R7",
"type": "Binds_With",
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"arg2_id": "21_T39",
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},
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"id": "21_R8",
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"arg1_id": "21_T38",
"arg2_id": "21_T39",
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"id": "21_R17",
"type": "Associated_With",
"arg1_id": "21_T24",
"arg2_id": "21_T27",
"normalized": []
}
] |
22 | 1003703 | [
{
"id": "23",
"type": "",
"text": [
"Anti-ulcer effects of cetraxate, a new compound possessing anti-plasmin, anti-casein and anti-trypsin actions were investigated by using experimental gastric ulcer models in rats. Cetraxate, 300 mg/kg p.o. showed significant inhibitory effects of 65.3%, 70.0%, 30.2%, and 67.1% against aucte types of ulcers producing by aspirin, phenylbutazone, indomethacin, and pyloric ligature (Shay's ulcer), respectively. These effects were greater than those obtained by gefarnate and aluminum sucrose sulfate may be mainly attributed to the protecting action of this drug on gastric mucosa. Ctraxate further revealed remarkable inhibitory effects on chronic types of ulcers produced by acetic acid, clamping, and clamping-cortisone. In acetic acid ulcer in particular, cetraxate was found to have a dose-dependent inhibitory effect at doses over 50 mg/kg. Of test drugs including L-glutamine and methylmethionine sulfonium chloride, cetraxate showed the most remarkable inhibitory effect on beta-glucuronidase activity in ulcer tissue of these three types of ulcers. These findings suggest that cetraxate may prevent the connective tissue in the ulcer location from decomposition due to lysosomal enzymes such as beta-glucuronidase, thereby accelerating the recovery from ulcer. \n"
],
"offsets": [
[
0,
1274
]
]
}
] | [
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"id": "23_T1",
"type": "Biological_Activity",
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0,
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]
],
"text": [
"Anti-ulcer"
],
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},
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22,
31
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"cetraxate"
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"type": "Biological_Activity",
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59,
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"text": [
"anti-plasmin"
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"id": "23_T4",
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73,
84
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"text": [
"anti-casein"
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"id": "23_T5",
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89,
101
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"text": [
"anti-trypsin"
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},
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"id": "23_T6",
"type": "Protein",
"offsets": [
[
64,
71
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],
"text": [
"plasmin"
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"normalized": []
},
{
"id": "23_T9",
"type": "Protein",
"offsets": [
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94,
101
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"text": [
"trypsin"
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"normalized": []
},
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"id": "23_T11",
"type": "Species",
"offsets": [
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174,
178
]
],
"text": [
"rats"
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"normalized": []
},
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"id": "23_T12",
"type": "Chemical",
"offsets": [
[
180,
189
]
],
"text": [
"Cetraxate"
],
"normalized": []
},
{
"id": "23_T13",
"type": "Biological_Activity",
"offsets": [
[
225,
235
]
],
"text": [
"inhibitory"
],
"normalized": []
},
{
"id": "23_T14",
"type": "Chemical",
"offsets": [
[
321,
328
]
],
"text": [
"aspirin"
],
"normalized": []
},
{
"id": "23_T15",
"type": "Chemical",
"offsets": [
[
330,
344
]
],
"text": [
"phenylbutazone"
],
"normalized": []
},
{
"id": "23_T16",
"type": "Chemical",
"offsets": [
[
346,
358
]
],
"text": [
"indomethacin"
],
"normalized": []
},
{
"id": "23_T17",
"type": "Chemical",
"offsets": [
[
461,
470
]
],
"text": [
"gefarnate"
],
"normalized": []
},
{
"id": "23_T18",
"type": "Chemical",
"offsets": [
[
475,
499
]
],
"text": [
"aluminum sucrose sulfate"
],
"normalized": []
},
{
"id": "23_T19",
"type": "Chemical",
"offsets": [
[
582,
590
]
],
"text": [
"Ctraxate"
],
"normalized": []
},
{
"id": "23_T21",
"type": "Chemical",
"offsets": [
[
677,
688
]
],
"text": [
"acetic acid"
],
"normalized": []
},
{
"id": "23_T22",
"type": "Chemical",
"offsets": [
[
714,
723
]
],
"text": [
"cortisone"
],
"normalized": []
},
{
"id": "23_T23",
"type": "Chemical",
"offsets": [
[
728,
739
]
],
"text": [
"acetic acid"
],
"normalized": []
},
{
"id": "23_T24",
"type": "Chemical",
"offsets": [
[
761,
770
]
],
"text": [
"cetraxate"
],
"normalized": []
},
{
"id": "23_T25",
"type": "Biological_Activity",
"offsets": [
[
806,
815
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "23_T26",
"type": "Biological_Activity",
"offsets": [
[
619,
628
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "23_T20",
"type": "Chemical",
"offsets": [
[
873,
884
]
],
"text": [
"L-glutamine"
],
"normalized": []
},
{
"id": "23_T28",
"type": "Chemical",
"offsets": [
[
889,
924
]
],
"text": [
"methylmethionine sulfonium chloride"
],
"normalized": []
},
{
"id": "23_T29",
"type": "Chemical",
"offsets": [
[
926,
935
]
],
"text": [
"cetraxate"
],
"normalized": []
},
{
"id": "23_T31",
"type": "Protein",
"offsets": [
[
984,
1002
]
],
"text": [
"beta-glucuronidase"
],
"normalized": []
},
{
"id": "23_T33",
"type": "Chemical",
"offsets": [
[
1088,
1097
]
],
"text": [
"cetraxate"
],
"normalized": []
},
{
"id": "23_T35",
"type": "Protein",
"offsets": [
[
1207,
1225
]
],
"text": [
"beta-glucuronidase"
],
"normalized": []
},
{
"id": "23_T38",
"type": "Protein",
"offsets": [
[
1181,
1198
]
],
"text": [
"lysosomal enzymes"
],
"normalized": []
},
{
"id": "23_T39",
"type": "Protein",
"offsets": [
[
78,
84
]
],
"text": [
"casein"
],
"normalized": []
},
{
"id": "23_T40",
"type": "Biological_Activity",
"offsets": [
[
532,
542
]
],
"text": [
"protecting"
],
"normalized": []
},
{
"id": "23_T43",
"type": "Biological_Activity",
"offsets": [
[
963,
972
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "23_T7",
"type": "Chemical",
"offsets": [
[
558,
562
]
],
"text": [
"drug"
],
"normalized": []
},
{
"id": "23_T8",
"type": "Chemical",
"offsets": [
[
856,
863
]
],
"text": [
"drugs"
],
"normalized": []
},
{
"id": "23_T10",
"type": "Biological_Activity",
"offsets": [
[
989,
1002
]
],
"text": [
"glucuronidase"
],
"normalized": []
}
] | [] | [] | [
{
"id": "23_R1",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T1",
"normalized": []
},
{
"id": "23_R2",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T3",
"normalized": []
},
{
"id": "23_R3",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T4",
"normalized": []
},
{
"id": "23_R4",
"type": "Associated_With",
"arg1_id": "23_T2",
"arg2_id": "23_T5",
"normalized": []
},
{
"id": "23_R5",
"type": "Associated_With",
"arg1_id": "23_T12",
"arg2_id": "23_T13",
"normalized": []
},
{
"id": "23_R9",
"type": "Associated_With",
"arg1_id": "23_T17",
"arg2_id": "23_T13",
"normalized": []
},
{
"id": "23_R10",
"type": "Associated_With",
"arg1_id": "23_T18",
"arg2_id": "23_T13",
"normalized": []
},
{
"id": "23_R11",
"type": "Associated_With",
"arg1_id": "23_T19",
"arg2_id": "23_T26",
"normalized": []
},
{
"id": "23_R14",
"type": "Associated_With",
"arg1_id": "23_T24",
"arg2_id": "23_T25",
"normalized": []
},
{
"id": "23_R16",
"type": "Associated_With",
"arg1_id": "23_T12",
"arg2_id": "23_T40",
"normalized": []
},
{
"id": "23_R15",
"type": "Associated_With",
"arg1_id": "23_T29",
"arg2_id": "23_T43",
"normalized": []
},
{
"id": "23_R17",
"type": "Binds_With",
"arg1_id": "23_T2",
"arg2_id": "23_T6",
"normalized": []
},
{
"id": "23_R24",
"type": "Binds_With",
"arg1_id": "23_T2",
"arg2_id": "23_T39",
"normalized": []
},
{
"id": "23_R28",
"type": "Binds_With",
"arg1_id": "23_T2",
"arg2_id": "23_T9",
"normalized": []
},
{
"id": "23_R6",
"type": "Binds_With",
"arg1_id": "23_T20",
"arg2_id": "23_T31",
"normalized": []
},
{
"id": "23_R12",
"type": "Binds_With",
"arg1_id": "23_T28",
"arg2_id": "23_T31",
"normalized": []
},
{
"id": "23_R13",
"type": "Binds_With",
"arg1_id": "23_T29",
"arg2_id": "23_T31",
"normalized": []
}
] |
24 | 10037325 | [
{
"id": "25",
"type": "",
"text": [
"The induction of micronucleated erythrocytes by diisopropylcarbodiimide (DIC) and dicyclohexylcarbodiimide (DCC) was investigated as part of a U.S. National Toxicology Program (NTP) evaluation of the subchronic toxicity of these chemicals. Analysis of peripheral blood smears from male and female B6C3F1 mice exposed to 17.5-140.0 mg DIC/kg/day by skin painting for 13 weeks revealed dose-related increases in the frequency of micronucleated normochromatic erythrocytes (MN-NCE) in both sexes. Results of a similar 13-week peripheral blood micronucleus (MN) test with DCC (1.5-12.0 mg/kg/day) were also positive, although the increases in MN-NCE were not as great as those observed with DIC. In contrast to the positive results of the subchronic skin-painting studies in mice, acute bone marrow MN studies with DIC and DCC in male F344 rats, using intraperitoneal (i.p.) injection, yielded negative results. Both the acute and the subchronic exposures included doses that produced clinical signs of toxicity. Acute mouse bone marrow MN tests with DIC administered in single or triple i.p. injection protocols were subsequently conducted to determine if the differing responses between mice and rats were due to species or protocol differences. The results of these acute tests were negative or equivocal. Because the subchronic studies produced positive results, it was hypothesized that these carbodiimides required multiple treatments over an extended period of time to produce an increase in MN-erythrocytes. To confirm the original response, a second dermal subchronic study was conducted with DIC; the protocol was modified to include sequential blood samplings to permit monitoring MN frequencies over time. The data demonstrated a small but consistent induction of micronucleated erythrocytes in mice treated with DIC by skin painting. \n"
],
"offsets": [
[
0,
1845
]
]
}
] | [
{
"id": "25_T1",
"type": "Chemical",
"offsets": [
[
48,
71
]
],
"text": [
"diisopropylcarbodiimide"
],
"normalized": []
},
{
"id": "25_T2",
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"induction"
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26 | 10037456 | [
{
"id": "27",
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"text": [
"We investigated the protective effect of fluvastatin sodium on the oxidation of low-density lipoprotein (LDL) induced in vitro by copper ions. The extent of lipid peroxidation was assessed by monitoring the increase of UV absorbance at 234 nm, which is the peak absorbance of a conjugated diene. Fluvastatin sodium (1-30 microM) not only prolonged the lag time of oxidation in the initiation step, but also decreased the rate of oxidation in the propagation step, both concentration dependently. Fluvastatin sodium and alpha-tocopherol showed an additive effect when both compounds were added before oxidation. However, when the lag time was prolonged initially by alpha-tocopherol, and fluvastatin sodium and alpha-tocopherol, were further added into the reaction mixture at the end point of the lag phase, fluvastatin sodium still showed an antioxidative effect, whereas alpha-tocopherol showed a pro-oxidative effect. Therefore, the antioxidative property of fluvastatin sodium differs from that of alpha-tocopherol. In this experiment, as neither the double bond-reduced derivative of fluvastatin sodium nor pravastatin sodium showed any protective effect, we concluded that the antioxidative effect of fluvastatin sodium is not a common property of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but may be derived from its unique chemical structure. Since the oxidative modification of LDL plays an important role in the genesis of atherosclerosis, fluvastatin sodium may help reduce the risk of atherosclerosis, not only by reducing plasma LDL levels but also by protecting LDL from oxidative modification. \n"
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0,
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844,
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901,
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964,
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1004,
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105,
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20,
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1391,
1400
]
],
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] | [] | [] | [
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"normalized": []
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"type": "Associated_With",
"arg1_id": "27_T13",
"arg2_id": "27_T14",
"normalized": []
},
{
"id": "27_R4",
"type": "Associated_With",
"arg1_id": "27_T16",
"arg2_id": "27_T15",
"normalized": []
},
{
"id": "27_R5",
"type": "Associated_With",
"arg1_id": "27_T22",
"arg2_id": "27_T21",
"normalized": []
},
{
"id": "27_R6",
"type": "Associated_With",
"arg1_id": "27_T22",
"arg2_id": "27_T26",
"normalized": []
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{
"id": "27_R7",
"type": "Associated_With",
"arg1_id": "27_T31",
"arg2_id": "27_T34",
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{
"id": "27_R8",
"type": "Associated_With",
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"type": "Associated_With",
"arg1_id": "27_T1",
"arg2_id": "27_T19",
"normalized": []
}
] |
28 | 10048024 | [
{
"id": "29",
"type": "",
"text": [
"Sequence analysis reveals that the Bacillus subtilis 168 tuaABCDEFGH operon encodes enzymes required for the polymerization of teichuronic acid as well as for the synthesis of one of its precursors, the UDP-glucuronate. Mutants deficient in any of the tua genes, grown in batch cultures under conditions of phosphate limitation, were characterized by reduced amounts of uronate in their cell walls. The teichuronic acid operon belongs to the Pho regulon, as phosphate limitation induces its transcription. Placing the tuaABCDEFGH operon under the control of the inducible Pspac promoter allowed its constitutive expression independently of the phosphate concentration in the medium; the level of uronic acid in cell walls was dependent on the concentration of the inducer. Apparently, owing to an interdependence between teichoic and teichuronic acid incorporation into the cell wall, in examined growth conditions, the balance between the two polymers is maintained in order to insure a constant level of the wall negative charge. \n"
],
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[
0,
1034
]
]
}
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35,
56
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],
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"offsets": [
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127,
143
]
],
"text": [
"teichuronic acid"
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"normalized": []
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"id": "29_T3",
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"offsets": [
[
203,
218
]
],
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"UDP-glucuronate"
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"normalized": []
},
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[
307,
316
]
],
"text": [
"phosphate"
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"normalized": []
},
{
"id": "29_T5",
"type": "Chemical",
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[
370,
377
]
],
"text": [
"uronate"
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458,
469
]
],
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"phosphate"
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645,
654
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"phosphate"
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697,
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822,
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847,
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835,
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127,
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203,
218
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822,
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835,
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765,
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]
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"inducer"
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] |
30 | 10048138 | [
{
"id": "31",
"type": "",
"text": [
"Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered i.p. twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin > or = oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin approximately equal to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG. \n"
],
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0,
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]
}
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],
"normalized": []
},
{
"id": "31_T12",
"type": "Chemical",
"offsets": [
[
636,
645
]
],
"text": [
"cisplatin"
],
"normalized": []
},
{
"id": "31_T13",
"type": "Chemical",
"offsets": [
[
654,
665
]
],
"text": [
"oxaliplatin"
],
"normalized": []
},
{
"id": "31_T14",
"type": "Chemical",
"offsets": [
[
687,
695
]
],
"text": [
"platinum"
],
"normalized": []
},
{
"id": "31_T15",
"type": "Chemical",
"offsets": [
[
799,
808
]
],
"text": [
"cisplatin"
],
"normalized": []
},
{
"id": "31_T16",
"type": "Chemical",
"offsets": [
[
811,
822
]
],
"text": [
"oxaliplatin"
],
"normalized": []
},
{
"id": "31_T17",
"type": "Chemical",
"offsets": [
[
825,
835
]
],
"text": [
"ormaplatin"
],
"normalized": []
},
{
"id": "31_T18",
"type": "Chemical",
"offsets": [
[
922,
932
]
],
"text": [
"ormaplatin"
],
"normalized": []
},
{
"id": "31_T19",
"type": "Chemical",
"offsets": [
[
956,
967
]
],
"text": [
"oxaliplatin"
],
"normalized": []
},
{
"id": "31_T20",
"type": "Chemical",
"offsets": [
[
970,
979
]
],
"text": [
"cisplatin"
],
"normalized": []
},
{
"id": "31_T21",
"type": "Chemical",
"offsets": [
[
1025,
1033
]
],
"text": [
"platinum"
],
"normalized": []
},
{
"id": "31_T22",
"type": "Chemical",
"offsets": [
[
1050,
1060
]
],
"text": [
"ormaplatin"
],
"normalized": []
},
{
"id": "31_T23",
"type": "Chemical",
"offsets": [
[
1065,
1076
]
],
"text": [
"oxaliplatin"
],
"normalized": []
},
{
"id": "31_T24",
"type": "Chemical",
"offsets": [
[
1086,
1095
]
],
"text": [
"cisplatin"
],
"normalized": []
},
{
"id": "31_T25",
"type": "Chemical",
"offsets": [
[
1122,
1132
]
],
"text": [
"ormaplatin"
],
"normalized": []
},
{
"id": "31_T26",
"type": "Biological_Activity",
"offsets": [
[
1145,
1155
]
],
"text": [
"neurotoxic"
],
"normalized": []
},
{
"id": "31_T27",
"type": "Species",
"offsets": [
[
1195,
1205
]
],
"text": [
"Wistar rat"
],
"normalized": []
},
{
"id": "31_T28",
"type": "Chemical",
"offsets": [
[
1263,
1273
]
],
"text": [
"ormaplatin"
],
"normalized": []
},
{
"id": "31_T29",
"type": "Chemical",
"offsets": [
[
1278,
1289
]
],
"text": [
"oxaliplatin"
],
"normalized": []
},
{
"id": "31_T30",
"type": "Biological_Activity",
"offsets": [
[
1299,
1309
]
],
"text": [
"neurotoxic"
],
"normalized": []
},
{
"id": "31_T31",
"type": "Chemical",
"offsets": [
[
1315,
1324
]
],
"text": [
"cisplatin"
],
"normalized": []
},
{
"id": "31_T32",
"type": "Biological_Activity",
"offsets": [
[
1334,
1347
]
],
"text": [
"neurotoxicity"
],
"normalized": []
},
{
"id": "31_T33",
"type": "Chemical",
"offsets": [
[
1387,
1395
]
],
"text": [
"platinum"
],
"normalized": []
},
{
"id": "31_T35",
"type": "Spectral_Data",
"offsets": [
[
750,
767
]
],
"text": [
"mass spectrometry"
],
"normalized": []
}
] | [] | [] | [
{
"id": "31_R1",
"type": "Associated_With",
"arg1_id": "31_T11",
"arg2_id": "31_T10",
"normalized": []
},
{
"id": "31_R2",
"type": "Associated_With",
"arg1_id": "31_T12",
"arg2_id": "31_T10",
"normalized": []
},
{
"id": "31_R3",
"type": "Associated_With",
"arg1_id": "31_T13",
"arg2_id": "31_T10",
"normalized": []
},
{
"id": "31_R4",
"type": "Associated_With",
"arg1_id": "31_T25",
"arg2_id": "31_T26",
"normalized": []
},
{
"id": "31_R5",
"type": "Associated_With",
"arg1_id": "31_T28",
"arg2_id": "31_T30",
"normalized": []
},
{
"id": "31_R6",
"type": "Associated_With",
"arg1_id": "31_T29",
"arg2_id": "31_T30",
"normalized": []
},
{
"id": "31_R7",
"type": "Associated_With",
"arg1_id": "31_T31",
"arg2_id": "31_T30",
"normalized": []
},
{
"id": "31_R11",
"type": "Associated_With",
"arg1_id": "31_T14",
"arg2_id": "31_T35",
"normalized": []
}
] |
32 | 10048141 | [
{
"id": "33",
"type": "",
"text": [
"1,2-Dichlorobenzene (1,2-DCB) is a potent hepatotoxicant in male Fischer 344 (F344) rats and previous studies have suggested that reactive oxygen species may play a role in the development of hepatotoxicity. Since reactive oxygen species can damage lipid membranes, this study was conducted to determine the extent of lipid peroxidation after administration of 1,2-DCB by immuno-histochemical analysis of 4-hydroxynonenal (4-HNE) protein adduct formation in liver and conjugated diene formation in liver and serum. The contribution of Kupffer cells to the lipid peroxidation was also investigated. Male F344 rats were administered 1,2-DCB (3.6 mmol/kg i.p. in corn oil) and killed at selected times between 3 and 48 h. Time course studies revealed the greatest abundance of 4-HNE protein adducts in the centrilobular regions of the liver 24 h after 1,2-DCB administration, with much lower levels at 16 h. Adducts were present in necrotic and vacuolized centrilobular hepatocytes of 1,2-DCB treated rats but not in livers of controls. Further, conjugated dienes were significantly increased in liver and serum 16 and 24 h after 1,2-DCB administration, peaking at 24 h. These data correlated with hepatocellular injury, determined by serum alanine aminotransferase activity and histopathological evaluation, which was markedly elevated within 16 h and peaked at 24 h. When rats were pretreated with gadolinium chloride (GdCl3; 10 mg/kg i.v. 24 h prior to 1,2-DCB), an inhibitor of Kupffer cells, hepatotoxicity was decreased by 89 and 86%, at 16 and 24 h, respectively. Conjugated diene concentrations were decreased to control values at these times after 1,2-DCB administration. Moreover, no 4-HNE protein adducts were detected in livers of 1,2-DCB-treated rats pretreated with GdCl3. Finally, Kupffer cells isolated from 1,2-DCB-treated rats produced significantly more superoxide anion than Kupffer cells isolated from vehicle controls. These data, along with previous findings, suggest that lipid peroxidation associated with 1,2-DCB is mediated in part by Kupffer cell-derived reactive oxygen species. \n"
],
"offsets": [
[
0,
2110
]
]
}
] | [
{
"id": "33_T1",
"type": "Chemical",
"offsets": [
[
0,
19
]
],
"text": [
"1,2-Dichlorobenzene"
],
"normalized": []
},
{
"id": "33_T2",
"type": "Chemical",
"offsets": [
[
21,
28
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T3",
"type": "Biological_Activity",
"offsets": [
[
42,
53
]
],
"text": [
"hepatotoxic"
],
"normalized": []
},
{
"id": "33_T4",
"type": "Species",
"offsets": [
[
65,
76
],
[
84,
88
]
],
"text": [
"Fischer 344",
"rats"
],
"normalized": []
},
{
"id": "33_T5",
"type": "Chemical",
"offsets": [
[
130,
153
]
],
"text": [
"reactive oxygen species"
],
"normalized": []
},
{
"id": "33_T6",
"type": "Biological_Activity",
"offsets": [
[
193,
207
]
],
"text": [
"hepatotoxicity"
],
"normalized": []
},
{
"id": "33_T7",
"type": "Chemical",
"offsets": [
[
215,
238
]
],
"text": [
"reactive oxygen species"
],
"normalized": []
},
{
"id": "33_T8",
"type": "Chemical",
"offsets": [
[
362,
369
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T9",
"type": "Chemical",
"offsets": [
[
406,
422
]
],
"text": [
"4-hydroxynonenal"
],
"normalized": []
},
{
"id": "33_T10",
"type": "Chemical",
"offsets": [
[
424,
429
]
],
"text": [
"4-HNE"
],
"normalized": []
},
{
"id": "33_T11",
"type": "Chemical",
"offsets": [
[
469,
485
]
],
"text": [
"conjugated diene"
],
"normalized": []
},
{
"id": "33_T12",
"type": "Species",
"offsets": [
[
605,
614
]
],
"text": [
"F344 rats"
],
"normalized": []
},
{
"id": "33_T13",
"type": "Chemical",
"offsets": [
[
633,
640
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T14",
"type": "Chemical",
"offsets": [
[
662,
670
]
],
"text": [
"corn oil"
],
"normalized": []
},
{
"id": "33_T15",
"type": "Chemical",
"offsets": [
[
776,
781
]
],
"text": [
"4-HNE"
],
"normalized": []
},
{
"id": "33_T16",
"type": "Protein",
"offsets": [
[
431,
438
]
],
"text": [
"protein"
],
"normalized": []
},
{
"id": "33_T17",
"type": "Protein",
"offsets": [
[
782,
789
]
],
"text": [
"protein"
],
"normalized": []
},
{
"id": "33_T18",
"type": "Chemical",
"offsets": [
[
851,
858
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T19",
"type": "Chemical",
"offsets": [
[
985,
992
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T20",
"type": "Chemical",
"offsets": [
[
1046,
1063
]
],
"text": [
"conjugated dienes"
],
"normalized": []
},
{
"id": "33_T21",
"type": "Chemical",
"offsets": [
[
1130,
1137
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T23",
"type": "Species",
"offsets": [
[
1375,
1379
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "33_T24",
"type": "Chemical",
"offsets": [
[
1401,
1420
]
],
"text": [
"gadolinium chloride"
],
"normalized": []
},
{
"id": "33_T25",
"type": "Chemical",
"offsets": [
[
1422,
1427
]
],
"text": [
"GdCl3"
],
"normalized": []
},
{
"id": "33_T26",
"type": "Chemical",
"offsets": [
[
1457,
1464
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T27",
"type": "Biological_Activity",
"offsets": [
[
1470,
1479
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "33_T28",
"type": "Biological_Activity",
"offsets": [
[
1498,
1512
]
],
"text": [
"hepatotoxicity"
],
"normalized": []
},
{
"id": "33_T29",
"type": "Chemical",
"offsets": [
[
1572,
1588
]
],
"text": [
"Conjugated diene"
],
"normalized": []
},
{
"id": "33_T30",
"type": "Chemical",
"offsets": [
[
1658,
1665
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T31",
"type": "Chemical",
"offsets": [
[
1695,
1700
]
],
"text": [
"4-HNE"
],
"normalized": []
},
{
"id": "33_T32",
"type": "Protein",
"offsets": [
[
1701,
1708
]
],
"text": [
"protein"
],
"normalized": []
},
{
"id": "33_T33",
"type": "Chemical",
"offsets": [
[
1744,
1751
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T34",
"type": "Species",
"offsets": [
[
1760,
1764
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "33_T35",
"type": "Chemical",
"offsets": [
[
1781,
1786
]
],
"text": [
"GdCl3"
],
"normalized": []
},
{
"id": "33_T36",
"type": "Chemical",
"offsets": [
[
1825,
1832
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T37",
"type": "Species",
"offsets": [
[
1841,
1845
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "33_T38",
"type": "Chemical",
"offsets": [
[
1874,
1890
]
],
"text": [
"superoxide anion"
],
"normalized": []
},
{
"id": "33_T39",
"type": "Chemical",
"offsets": [
[
2032,
2039
]
],
"text": [
"1,2-DCB"
],
"normalized": []
},
{
"id": "33_T40",
"type": "Chemical",
"offsets": [
[
2084,
2107
]
],
"text": [
"reactive oxygen species"
],
"normalized": []
},
{
"id": "33_T45",
"type": "Species",
"offsets": [
[
78,
82
],
[
84,
88
]
],
"text": [
"F344",
"rats"
],
"normalized": []
},
{
"id": "33_T46",
"type": "Species",
"offsets": [
[
1001,
1005
]
],
"text": [
"rats"
],
"normalized": []
},
{
"id": "33_T22",
"type": "Biological_Activity",
"offsets": [
[
1250,
1266
]
],
"text": [
"aminotransferase"
],
"normalized": []
},
{
"id": "33_T41",
"type": "Protein",
"offsets": [
[
1242,
1266
]
],
"text": [
"alanine aminotransferase"
],
"normalized": []
}
] | [] | [] | [
{
"id": "33_R1",
"type": "Associated_With",
"arg1_id": "33_T1",
"arg2_id": "33_T3",
"normalized": []
},
{
"id": "33_R2",
"type": "Associated_With",
"arg1_id": "33_T2",
"arg2_id": "33_T3",
"normalized": []
},
{
"id": "33_R3",
"type": "Associated_With",
"arg1_id": "33_T5",
"arg2_id": "33_T6",
"normalized": []
},
{
"id": "33_R8",
"type": "Associated_With",
"arg1_id": "33_T24",
"arg2_id": "33_T27",
"normalized": []
},
{
"id": "33_R9",
"type": "Associated_With",
"arg1_id": "33_T25",
"arg2_id": "33_T27",
"normalized": []
}
] |
34 | 10048179 | [
{
"id": "35",
"type": "",
"text": [
"The crystal structure of gliclazide, N-[(perhydrocyclopenta [c]pyrrol-2-yl)aminocarbonyl]-p-toluenesulfonamide, C15H21B3O3S, a second-generation oral hypoglycemic agent, contains discrete molecules with normal molecular dimensions. Both of the five-membered fused rings adopt envelope conformations. The molecules are linked into chains by intermolecular hydrogen bonds involving amino-H atoms, with N...O separations of 2.967 (3) and 2.949 (3) A. \n"
],
"offsets": [
[
0,
450
]
]
}
] | [
{
"id": "35_T1",
"type": "Chemical",
"offsets": [
[
25,
35
]
],
"text": [
"gliclazide"
],
"normalized": []
},
{
"id": "35_T2",
"type": "Chemical",
"offsets": [
[
37,
110
]
],
"text": [
"N-[(perhydrocyclopenta [c]pyrrol-2-yl)aminocarbonyl]-p-toluenesulfonamide"
],
"normalized": []
},
{
"id": "35_T3",
"type": "Biological_Activity",
"offsets": [
[
150,
162
]
],
"text": [
"hypoglycemic"
],
"normalized": []
},
{
"id": "35_T4",
"type": "Chemical",
"offsets": [
[
304,
313
]
],
"text": [
"molecules"
],
"normalized": []
},
{
"id": "35_T5",
"type": "Spectral_Data",
"offsets": [
[
4,
21
]
],
"text": [
"crystal structure"
],
"normalized": []
},
{
"id": "35_T6",
"type": "Chemical",
"offsets": [
[
188,
197
]
],
"text": [
"molecules"
],
"normalized": []
},
{
"id": "35_T7",
"type": "Chemical",
"offsets": [
[
380,
385
]
],
"text": [
"amino"
],
"normalized": []
},
{
"id": "35_T8",
"type": "Chemical",
"offsets": [
[
386,
387
]
],
"text": [
"H"
],
"normalized": []
}
] | [] | [] | [
{
"id": "35_R1",
"type": "Associated_With",
"arg1_id": "35_T1",
"arg2_id": "35_T3",
"normalized": []
},
{
"id": "35_R2",
"type": "Associated_With",
"arg1_id": "35_T2",
"arg2_id": "35_T3",
"normalized": []
},
{
"id": "35_R3",
"type": "Associated_With",
"arg1_id": "35_T1",
"arg2_id": "35_T5",
"normalized": []
},
{
"id": "35_R4",
"type": "Associated_With",
"arg1_id": "35_T2",
"arg2_id": "35_T5",
"normalized": []
}
] |
36 | 10048567 | [
{
"id": "37",
"type": "",
"text": [
"Antibacterial antibiotics, diperamycin (1) was produced in the culture broth of Streptomyces griseoaurantiacus MK393-AF2. Various spectroscopic analyses of 1 suggested that 1 belonged to a member of cyclic hexadepsipeptide antibiotic. Antibiotic 1 had potent inhibitory activity against various Gram-positive bacteria including Enterococcus seriolicida and methicillin-resistant Staphylococcus aureus. \n"
],
"offsets": [
[
0,
403
]
]
}
] | [
{
"id": "37_T1",
"type": "Biological_Activity",
"offsets": [
[
0,
13
],
[
14,
25
]
],
"text": [
"Antibacterial",
"antibiotics"
],
"normalized": []
},
{
"id": "37_T2",
"type": "Biological_Activity",
"offsets": [
[
14,
25
]
],
"text": [
"antibiotics"
],
"normalized": []
},
{
"id": "37_T3",
"type": "Chemical",
"offsets": [
[
27,
38
]
],
"text": [
"diperamycin"
],
"normalized": []
},
{
"id": "37_T4",
"type": "Species",
"offsets": [
[
80,
120
]
],
"text": [
"Streptomyces griseoaurantiacus MK393-AF2"
],
"normalized": []
},
{
"id": "37_T5",
"type": "Chemical",
"offsets": [
[
199,
233
]
],
"text": [
"cyclic hexadepsipeptide antibiotic"
],
"normalized": []
},
{
"id": "37_T9",
"type": "Biological_Activity",
"offsets": [
[
235,
245
]
],
"text": [
"Antibiotic"
],
"normalized": []
},
{
"id": "37_T10",
"type": "Chemical",
"offsets": [
[
246,
247
]
],
"text": [
"1"
],
"normalized": []
},
{
"id": "37_T11",
"type": "Biological_Activity",
"offsets": [
[
259,
269
]
],
"text": [
"inhibitory"
],
"normalized": []
},
{
"id": "37_T12",
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357,
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27,
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"antibiotic"
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"1"
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"id": "37_T21",
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] |
38 | 10048572 | [
{
"id": "39",
"type": "",
"text": [
"\n"
],
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[
0,
1
]
]
}
] | [] | [] | [] | [] |
40 | 10048707 | [
{
"id": "41",
"type": "",
"text": [
"By assaying lactate dehydrogenase and malondialdehyde leakage from LLC-PK1 cells in culture, a study was conducted to clarify whether flavonoid compounds ameliorate renal cellular injury. The cells were cultured with various concentrations of samples under routine conditions. The results demonstrated that baicalin, cirsimaritin, 6-hydroxyluteolin, luteolin, plantaginin, rhoifolin, sorbarin, afzelin, hyperin, isoquercitrin, isorhamnetin, kaempferitrin, kaempferol-7-glucoside, oxyayanin A, quercetin, quercitrin, rhamnetin and rutin exerted marked protective effects on the cells, whereas acacetin, apigenin, apiin, cirsilineol, genkwanin, pectolinarin and tetramethylquercitin had virtually no effect. In the light of these findings, we propose that the general capability of these compounds is largely decided by the number and position of phenolic hydroxyl groups linked to the structural backbone. \n"
],
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0,
908
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]
}
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351,
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404,
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],
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],
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442,
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457,
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},
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481,
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494,
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517,
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],
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620,
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],
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]
],
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},
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644,
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],
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},
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661,
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]
],
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},
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847,
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]
],
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},
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67,
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],
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},
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552,
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]
],
"text": [
"protective"
],
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}
] | [] | [] | [
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},
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"arg2_id": "41_T2",
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},
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"id": "41_R25",
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},
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},
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},
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"id": "41_R28",
"type": "Associated_With",
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},
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"id": "41_R29",
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},
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"id": "41_R30",
"type": "Associated_With",
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"arg2_id": "41_T2",
"normalized": []
},
{
"id": "41_R31",
"type": "Associated_With",
"arg1_id": "41_T18",
"arg2_id": "41_T2",
"normalized": []
},
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"id": "41_R32",
"type": "Associated_With",
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},
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"id": "41_R33",
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},
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},
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"type": "Associated_With",
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"arg2_id": "41_T2",
"normalized": []
}
] |
42 | 100496 | [
{
"id": "43",
"type": "",
"text": [
"\n"
],
"offsets": [
[
0,
1
]
]
}
] | [] | [] | [] | [] |
44 | 10049714 | [
{
"id": "45",
"type": "",
"text": [
"Dopamine D4-like binding sites are abundant in human cerebral cortex as detected by [3H]nemonapride. The extremely low density of D4 mRNA in human cerebral cortex is inconsistent with the high amount of D4-like binding sites. To investigate the nature of the D4-like receptors, [3H]nemonapride binding sites in the nonhuman primate cerebral cortex were characterized. Although [3H]nemonapride binding sites were D4-like, displaceable by clozapine but not raclopride, [3H]nemonapride binding was not displaced by selective D4 antagonists but was displaced by the selective 5-HT2A antagonist MDL100907. Using [3H]ketanserin as a 5-HT2A ligand, nemonapride showed high affinity for monkey (Ki = 10.4 nM) and cloned human (Ki = 9.4 nM) 5-HT2A receptors, while its affinity for rat receptors was lower (Ki = 140 nM). The present study demonstrates that cerebral cortical D4-like binding sites labeled by [3H]nemonapride in nonhuman primates consist of a very small portion of D4, but a substantial portion of 5-HT2A receptors. The unexpectedly high affinity of nemonapride for primate 5-HT2A receptor suggests reconsidering previous data from other studies using [3H]nemonapride, particularly those on D4-like receptors. \n"
],
"offsets": [
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0,
1218
]
]
}
] | [
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],
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],
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],
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438,
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456,
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468,
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]
],
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580,
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]
],
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280,
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},
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],
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131,
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]
],
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},
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1005,
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},
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],
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},
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484,
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]
],
"text": [
"binding"
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},
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"type": "Protein",
"offsets": [
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849,
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]
],
"text": [
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],
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},
{
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"offsets": [
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1057,
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]
],
"text": [
"nemonapride"
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},
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]
],
"text": [
"primate"
],
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},
{
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"offsets": [
[
1159,
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]
],
"text": [
"[3H]nemonapride"
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},
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"id": "45_T52",
"type": "Protein",
"offsets": [
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]
],
"text": [
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},
{
"id": "45_T54",
"type": "Protein",
"offsets": [
[
204,
225
]
],
"text": [
"D4-like binding sites"
],
"normalized": []
},
{
"id": "45_T55",
"type": "Protein",
"offsets": [
[
378,
407
]
],
"text": [
"[3H]nemonapride binding sites"
],
"normalized": []
},
{
"id": "45_T56",
"type": "Species",
"offsets": [
[
142,
147
]
],
"text": [
"human"
],
"normalized": []
}
] | [] | [] | [
{
"id": "45_R2",
"type": "Associated_With",
"arg1_id": "45_T16",
"arg2_id": "45_T15",
"normalized": []
},
{
"id": "45_R3",
"type": "Binds_With",
"arg1_id": "45_T3",
"arg2_id": "45_T1",
"normalized": []
},
{
"id": "45_R5",
"type": "Binds_With",
"arg1_id": "45_T16",
"arg2_id": "45_T55",
"normalized": []
},
{
"id": "45_R4",
"type": "Binds_With",
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"arg2_id": "45_T55",
"normalized": []
},
{
"id": "45_R1",
"type": "Associated_With",
"arg1_id": "45_T13",
"arg2_id": "45_T46",
"normalized": []
},
{
"id": "45_R6",
"type": "Binds_With",
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"arg2_id": "45_T23",
"normalized": []
},
{
"id": "45_R8",
"type": "Binds_With",
"arg1_id": "45_T19",
"arg2_id": "45_T42",
"normalized": []
},
{
"id": "45_R7",
"type": "Binds_With",
"arg1_id": "45_T49",
"arg2_id": "45_T39",
"normalized": []
}
] |
46 | 10052027 | [
{
"id": "47",
"type": "",
"text": [
"The concentrations of adrenaline, noradrenaline, dopamine, aldosterone, the atrial natriuretic hormone, and plasma renin activity were investigated in 50 patients with mild chronic heart failure. The patients received oral digoxin chronically in a daily dose of 0.125 mg. On the basis of the estimate of the dosing of digoxin these patients were divided into two groups: the first with therapeutic and the second with subtherapeutic concentrations of digoxin in serum. The therapeutic concentration of digoxin in serum was found in 23 patients (46%), while subtherapeutic levels were found in 27 patients (54%). The concentrations of noradrenaline, dopamine, the renin activity of plasma, aldosterone and the atrial natriuretic hormone in the blood serum in the group of patients in whom the presence of subtherapeutic concentrations of digoxin was found, did not differ essentially from the concentration that was observed in the group with therapeutic concentrations. Only the concentration of adrenaline was higher (p < 0.05) in the group of patients with therapeutic concentrations of digoxin. The above results reveal that the neuroendocrine activity of plasma (except for the concentration of adrenaline) is alike in both ranges of digoxin concentrations in serum. \n"
],
"offsets": [
[
0,
1272
]
]
}
] | [
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"id": "47_T1",
"type": "Chemical",
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[
22,
32
]
],
"text": [
"adrenaline"
],
"normalized": []
},
{
"id": "47_T2",
"type": "Chemical",
"offsets": [
[
34,
47
]
],
"text": [
"noradrenaline"
],
"normalized": []
},
{
"id": "47_T3",
"type": "Chemical",
"offsets": [
[
49,
57
]
],
"text": [
"dopamine"
],
"normalized": []
},
{
"id": "47_T4",
"type": "Chemical",
"offsets": [
[
59,
70
]
],
"text": [
"aldosterone"
],
"normalized": []
},
{
"id": "47_T8",
"type": "Species",
"offsets": [
[
154,
162
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T9",
"type": "Species",
"offsets": [
[
200,
208
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T10",
"type": "Chemical",
"offsets": [
[
223,
230
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T5",
"type": "Biological_Activity",
"offsets": [
[
95,
102
]
],
"text": [
"hormone"
],
"normalized": []
},
{
"id": "47_T7",
"type": "Metabolite",
"offsets": [
[
22,
32
]
],
"text": [
"adrenaline"
],
"normalized": []
},
{
"id": "47_T12",
"type": "Metabolite",
"offsets": [
[
34,
47
]
],
"text": [
"noradrenaline"
],
"normalized": []
},
{
"id": "47_T13",
"type": "Metabolite",
"offsets": [
[
49,
57
]
],
"text": [
"dopamine"
],
"normalized": []
},
{
"id": "47_T14",
"type": "Metabolite",
"offsets": [
[
59,
70
]
],
"text": [
"aldosterone"
],
"normalized": []
},
{
"id": "47_T15",
"type": "Chemical",
"offsets": [
[
318,
325
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T16",
"type": "Chemical",
"offsets": [
[
451,
458
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T17",
"type": "Chemical",
"offsets": [
[
502,
509
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T18",
"type": "Species",
"offsets": [
[
332,
340
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T19",
"type": "Species",
"offsets": [
[
535,
543
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T20",
"type": "Species",
"offsets": [
[
596,
604
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T21",
"type": "Chemical",
"offsets": [
[
634,
647
]
],
"text": [
"noradrenaline"
],
"normalized": []
},
{
"id": "47_T22",
"type": "Metabolite",
"offsets": [
[
634,
647
]
],
"text": [
"noradrenaline"
],
"normalized": []
},
{
"id": "47_T23",
"type": "Metabolite",
"offsets": [
[
649,
657
]
],
"text": [
"dopamine"
],
"normalized": []
},
{
"id": "47_T24",
"type": "Chemical",
"offsets": [
[
649,
657
]
],
"text": [
"dopamine"
],
"normalized": []
},
{
"id": "47_T25",
"type": "Protein",
"offsets": [
[
663,
668
]
],
"text": [
"renin"
],
"normalized": []
},
{
"id": "47_T27",
"type": "Chemical",
"offsets": [
[
689,
700
]
],
"text": [
"aldosterone"
],
"normalized": []
},
{
"id": "47_T28",
"type": "Metabolite",
"offsets": [
[
689,
700
]
],
"text": [
"aldosterone"
],
"normalized": []
},
{
"id": "47_T29",
"type": "Chemical",
"offsets": [
[
709,
735
]
],
"text": [
"atrial natriuretic hormone"
],
"normalized": []
},
{
"id": "47_T30",
"type": "Biological_Activity",
"offsets": [
[
728,
735
]
],
"text": [
"hormone"
],
"normalized": []
},
{
"id": "47_T31",
"type": "Species",
"offsets": [
[
771,
779
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T33",
"type": "Chemical",
"offsets": [
[
996,
1006
]
],
"text": [
"adrenaline"
],
"normalized": []
},
{
"id": "47_T34",
"type": "Metabolite",
"offsets": [
[
996,
1006
]
],
"text": [
"adrenaline"
],
"normalized": []
},
{
"id": "47_T35",
"type": "Chemical",
"offsets": [
[
1089,
1096
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T37",
"type": "Metabolite",
"offsets": [
[
1199,
1209
]
],
"text": [
"adrenaline"
],
"normalized": []
},
{
"id": "47_T38",
"type": "Chemical",
"offsets": [
[
1199,
1209
]
],
"text": [
"adrenaline"
],
"normalized": []
},
{
"id": "47_T39",
"type": "Chemical",
"offsets": [
[
1238,
1245
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T40",
"type": "Chemical",
"offsets": [
[
837,
844
]
],
"text": [
"digoxin"
],
"normalized": []
},
{
"id": "47_T11",
"type": "Chemical",
"offsets": [
[
76,
102
]
],
"text": [
"atrial natriuretic hormone"
],
"normalized": []
},
{
"id": "47_T32",
"type": "Species",
"offsets": [
[
1045,
1053
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "47_T41",
"type": "Protein",
"offsets": [
[
115,
120
]
],
"text": [
"renin"
],
"normalized": []
}
] | [] | [] | [
{
"id": "47_R1",
"type": "Isolated_From",
"arg1_id": "47_T7",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R2",
"type": "Isolated_From",
"arg1_id": "47_T12",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R3",
"type": "Isolated_From",
"arg1_id": "47_T13",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R4",
"type": "Isolated_From",
"arg1_id": "47_T14",
"arg2_id": "47_T8",
"normalized": []
},
{
"id": "47_R5",
"type": "Isolated_From",
"arg1_id": "47_T22",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R6",
"type": "Isolated_From",
"arg1_id": "47_T23",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R7",
"type": "Isolated_From",
"arg1_id": "47_T28",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R8",
"type": "Isolated_From",
"arg1_id": "47_T29",
"arg2_id": "47_T31",
"normalized": []
},
{
"id": "47_R9",
"type": "Isolated_From",
"arg1_id": "47_T34",
"arg2_id": "47_T32",
"normalized": []
}
] |
48 | 10052973 | [
{
"id": "49",
"type": "",
"text": [
"Three series of cycloalkanecarboxylic esters derived from the naturally occurring clavine alkaloids lysergol, dihydrolysergol-I, and elymoclavine were synthesized to study their interaction with 5-HT2A receptors and alpha1-adrenoceptors in rat tail artery and aorta, respectively. Especially cycloalkanecarboxylic esters derived from lysergol showed complex behavior as partial agonists and antagonists of the contractile effect of 5-HT. Within this group, partial 5-HT2A receptor agonist activity was most potent for cyclopropanecarboxylic ester 6a (pKP = 7.67, alpha = 0.21) and decreased as the volume requirement of the alicyclic ring increased. This tendency was echoed in experiments where the compounds were used as antagonists of the contractile effect of 5-HT. From the structure-activity study, the N-1-isopropyl homologue of 6a, compound 6b, emerged as the ligand with the highest affinity for rat 5-HT2A receptors (pA2 = 8.74). For cycloalkanecarboxylic esters derived from dihydrolysergol-I and elymoclavine, no clear structure-affinity relationship could be deduced, although those compounds that had smaller cycloalkyl rings in the acyl portion and an isopropyl substituent at N-1 showed the highest 5-HT2A receptor affinity. On the other hand, cycloalkanecarboxylic esters derived from lysergol, dihydrolysergol-I, and elymoclavine displayed low or marginal affinity at alpha1-adrenoceptors. A further aim of the study was to examine to what extent the complete removal of the acyl portion of the esters would affect 5-HT2A receptor affinity. The parent alcohols of the three series of N-1-isopropyl homologues, 1-isopropyllysergol (1b), 1-isopropyldihydrolysergol-I (2b), and 1-isopropylelymoclavine (3b), displayed higher affinity for 5-HT2A receptors (pA2 = 9.15, 8.50, 9.14) than the corresponding esters. Compounds 1b-3b had no contractile effects by themselves and displayed low affinity at guinea-pig 5-HT1B receptors and rat alpha1-adrenoceptors. The high affinity for rat 5-HT2A receptors was retained when clavines even more simple in structure than 1b-3b, compounds 4b and 5b, were examined as 5-HT2A receptor antagonists. The nanomolar antagonist activity of simple clavines (1b-5b) in the rat suggests that the indolo[4,3-fg]quinoline system of the ergolines is the molecular fragment that is responsible for 5-HT2A receptor affinity, and not the substituent at position C-8. \n"
],
"offsets": [
[
0,
2415
]
]
}
] | [
{
"id": "49_T1",
"type": "Chemical",
"offsets": [
[
100,
108
],
[
110,
127
],
[
133,
145
],
[
16,
44
]
],
"text": [
"lysergol",
"dihydrolysergol-I",
"elymoclavine",
"cycloalkanecarboxylic esters"
],
"normalized": []
},
{
"id": "49_T2",
"type": "Chemical",
"offsets": [
[
82,
99
]
],
"text": [
"clavine alkaloids"
],
"normalized": []
},
{
"id": "49_T3",
"type": "Chemical",
"offsets": [
[
100,
108
]
],
"text": [
"lysergol"
],
"normalized": []
},
{
"id": "49_T4",
"type": "Chemical",
"offsets": [
[
110,
127
]
],
"text": [
"dihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T5",
"type": "Chemical",
"offsets": [
[
133,
145
]
],
"text": [
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T6",
"type": "Metabolite",
"offsets": [
[
100,
108
]
],
"text": [
"lysergol"
],
"normalized": []
},
{
"id": "49_T7",
"type": "Metabolite",
"offsets": [
[
110,
127
]
],
"text": [
"dihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T8",
"type": "Metabolite",
"offsets": [
[
133,
145
]
],
"text": [
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T9",
"type": "Protein",
"offsets": [
[
196,
212
]
],
"text": [
"5-HT2A receptors"
],
"normalized": []
},
{
"id": "49_T11",
"type": "Protein",
"offsets": [
[
217,
237
]
],
"text": [
"alpha1-adrenoceptors"
],
"normalized": []
},
{
"id": "49_T13",
"type": "Species",
"offsets": [
[
241,
244
]
],
"text": [
"rat"
],
"normalized": []
},
{
"id": "49_T14",
"type": "Chemical",
"offsets": [
[
294,
322
],
[
336,
344
]
],
"text": [
"cycloalkanecarboxylic esters",
"lysergol"
],
"normalized": []
},
{
"id": "49_T15",
"type": "Chemical",
"offsets": [
[
336,
344
]
],
"text": [
"lysergol"
],
"normalized": []
},
{
"id": "49_T16",
"type": "Metabolite",
"offsets": [
[
336,
344
]
],
"text": [
"lysergol"
],
"normalized": []
},
{
"id": "49_T17",
"type": "Biological_Activity",
"offsets": [
[
380,
388
]
],
"text": [
"agonists"
],
"normalized": []
},
{
"id": "49_T18",
"type": "Biological_Activity",
"offsets": [
[
393,
404
]
],
"text": [
"antagonists"
],
"normalized": []
},
{
"id": "49_T19",
"type": "Chemical",
"offsets": [
[
434,
438
]
],
"text": [
"5-HT"
],
"normalized": []
},
{
"id": "49_T20",
"type": "Biological_Activity",
"offsets": [
[
483,
490
]
],
"text": [
"agonist"
],
"normalized": []
},
{
"id": "49_T22",
"type": "Protein",
"offsets": [
[
467,
482
]
],
"text": [
"5-HT2A receptor"
],
"normalized": []
},
{
"id": "49_T23",
"type": "Chemical",
"offsets": [
[
520,
551
]
],
"text": [
"cyclopropanecarboxylic ester 6a"
],
"normalized": []
},
{
"id": "49_T24",
"type": "Chemical",
"offsets": [
[
626,
640
]
],
"text": [
"alicyclic ring"
],
"normalized": []
},
{
"id": "49_T25",
"type": "Biological_Activity",
"offsets": [
[
726,
737
]
],
"text": [
"antagonists"
],
"normalized": []
},
{
"id": "49_T26",
"type": "Chemical",
"offsets": [
[
767,
771
]
],
"text": [
"5-HT"
],
"normalized": []
},
{
"id": "49_T27",
"type": "Chemical",
"offsets": [
[
812,
841
]
],
"text": [
"N-1-isopropyl homologue of 6a"
],
"normalized": []
},
{
"id": "49_T29",
"type": "Species",
"offsets": [
[
908,
911
]
],
"text": [
"rat"
],
"normalized": []
},
{
"id": "49_T31",
"type": "Protein",
"offsets": [
[
912,
928
]
],
"text": [
"5-HT2A receptors"
],
"normalized": []
},
{
"id": "49_T33",
"type": "Chemical",
"offsets": [
[
947,
975
]
],
"text": [
"cycloalkanecarboxylic esters"
],
"normalized": []
},
{
"id": "49_T34",
"type": "Metabolite",
"offsets": [
[
989,
1006
]
],
"text": [
"dihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T35",
"type": "Metabolite",
"offsets": [
[
1011,
1023
]
],
"text": [
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T36",
"type": "Chemical",
"offsets": [
[
989,
1006
]
],
"text": [
"dihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T37",
"type": "Chemical",
"offsets": [
[
1011,
1023
]
],
"text": [
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T38",
"type": "Chemical",
"offsets": [
[
947,
1023
]
],
"text": [
"cycloalkanecarboxylic esters derived from dihydrolysergol-I and elymoclavine"
],
"normalized": []
},
{
"id": "49_T39",
"type": "Chemical",
"offsets": [
[
1128,
1143
]
],
"text": [
"cycloalkyl ring"
],
"normalized": []
},
{
"id": "49_T40",
"type": "Chemical",
"offsets": [
[
1152,
1164
]
],
"text": [
"acyl portion"
],
"normalized": []
},
{
"id": "49_T41",
"type": "Chemical",
"offsets": [
[
1172,
1193
]
],
"text": [
"isopropyl substituent"
],
"normalized": []
},
{
"id": "49_T42",
"type": "Protein",
"offsets": [
[
1220,
1235
]
],
"text": [
"5-HT2A receptor"
],
"normalized": []
},
{
"id": "49_T45",
"type": "Chemical",
"offsets": [
[
1265,
1293
],
[
1307,
1315
],
[
1317,
1334
],
[
1341,
1353
]
],
"text": [
"cycloalkanecarboxylic esters",
"lysergol",
"dihydrolysergol-I",
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T46",
"type": "Metabolite",
"offsets": [
[
1307,
1315
]
],
"text": [
"lysergol"
],
"normalized": []
},
{
"id": "49_T47",
"type": "Metabolite",
"offsets": [
[
1317,
1334
]
],
"text": [
"dihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T48",
"type": "Metabolite",
"offsets": [
[
1341,
1353
]
],
"text": [
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T49",
"type": "Chemical",
"offsets": [
[
1307,
1315
]
],
"text": [
"lysergol"
],
"normalized": []
},
{
"id": "49_T50",
"type": "Chemical",
"offsets": [
[
1317,
1334
]
],
"text": [
"dihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T51",
"type": "Chemical",
"offsets": [
[
1341,
1353
]
],
"text": [
"elymoclavine"
],
"normalized": []
},
{
"id": "49_T52",
"type": "Chemical",
"offsets": [
[
1265,
1353
]
],
"text": [
"cycloalkanecarboxylic esters derived from lysergol, dihydrolysergol-I, and elymoclavine"
],
"normalized": []
},
{
"id": "49_T54",
"type": "Protein",
"offsets": [
[
1392,
1412
]
],
"text": [
"alpha1-adrenoceptors"
],
"normalized": []
},
{
"id": "49_T55",
"type": "Chemical",
"offsets": [
[
1499,
1503
]
],
"text": [
"acyl"
],
"normalized": []
},
{
"id": "49_T56",
"type": "Chemical",
"offsets": [
[
1519,
1525
]
],
"text": [
"esters"
],
"normalized": []
},
{
"id": "49_T58",
"type": "Protein",
"offsets": [
[
1539,
1554
]
],
"text": [
"5-HT2A receptor"
],
"normalized": []
},
{
"id": "49_T62",
"type": "Chemical",
"offsets": [
[
1569,
1585
],
[
1606,
1633
]
],
"text": [
"parent alcohols",
"of N-1-isopropyl homologues"
],
"normalized": []
},
{
"id": "49_T63",
"type": "Chemical",
"offsets": [
[
1635,
1654
]
],
"text": [
"1-isopropyllysergol"
],
"normalized": []
},
{
"id": "49_T64",
"type": "Chemical",
"offsets": [
[
1661,
1689
]
],
"text": [
"1-isopropyldihydrolysergol-I"
],
"normalized": []
},
{
"id": "49_T65",
"type": "Chemical",
"offsets": [
[
1700,
1723
]
],
"text": [
"1-isopropylelymoclavine"
],
"normalized": []
},
{
"id": "49_T66",
"type": "Protein",
"offsets": [
[
1760,
1776
]
],
"text": [
"5-HT2A receptors"
],
"normalized": []
},
{
"id": "49_T69",
"type": "Species",
"offsets": [
[
1921,
1931
]
],
"text": [
"guinea-pig"
],
"normalized": []
},
{
"id": "49_T70",
"type": "Protein",
"offsets": [
[
1932,
1947
]
],
"text": [
"5-HT1B receptor"
],
"normalized": []
},
{
"id": "49_T72",
"type": "Species",
"offsets": [
[
1953,
1956
]
],
"text": [
"rat"
],
"normalized": []
},
{
"id": "49_T75",
"type": "Protein",
"offsets": [
[
1957,
1977
]
],
"text": [
"alpha1-adrenoceptors"
],
"normalized": []
},
{
"id": "49_T77",
"type": "Species",
"offsets": [
[
2001,
2004
]
],
"text": [
"rat"
],
"normalized": []
},
{
"id": "49_T79",
"type": "Protein",
"offsets": [
[
2005,
2021
]
],
"text": [
"5-HT2A receptors"
],
"normalized": []
},
{
"id": "49_T80",
"type": "Metabolite",
"offsets": [
[
2040,
2048
]
],
"text": [
"clavines"
],
"normalized": []
},
{
"id": "49_T84",
"type": "Chemical",
"offsets": [
[
1656,
1658
]
],
"text": [
"1b"
],
"normalized": []
},
{
"id": "49_T85",
"type": "Chemical",
"offsets": [
[
1691,
1693
]
],
"text": [
"2b"
],
"normalized": []
},
{
"id": "49_T86",
"type": "Chemical",
"offsets": [
[
1725,
1727
]
],
"text": [
"3b"
],
"normalized": []
},
{
"id": "49_T87",
"type": "Chemical",
"offsets": [
[
1834,
1846
],
[
1847,
1849
]
],
"text": [
"Compounds 1b",
"3b"
],
"normalized": []
},
{
"id": "49_T89",
"type": "Chemical",
"offsets": [
[
2040,
2048
]
],
"text": [
"clavines"
],
"normalized": []
},
{
"id": "49_T90",
"type": "Chemical",
"offsets": [
[
2084,
2086
],
[
2087,
2089
]
],
"text": [
"1b",
"3b"
],
"normalized": []
},
{
"id": "49_T92",
"type": "Chemical",
"offsets": [
[
2091,
2099
],
[
2101,
2103
]
],
"text": [
"compound",
"4b"
],
"normalized": []
},
{
"id": "49_T94",
"type": "Protein",
"offsets": [
[
2129,
2144
]
],
"text": [
"5-HT2A receptor"
],
"normalized": []
},
{
"id": "49_T95",
"type": "Biological_Activity",
"offsets": [
[
2145,
2156
]
],
"text": [
"antagonists"
],
"normalized": []
},
{
"id": "49_T96",
"type": "Biological_Activity",
"offsets": [
[
2172,
2182
]
],
"text": [
"antagonist"
],
"normalized": []
},
{
"id": "49_T97",
"type": "Chemical",
"offsets": [
[
2202,
2210
]
],
"text": [
"clavines"
],
"normalized": []
},
{
"id": "49_T99",
"type": "Species",
"offsets": [
[
2226,
2229
]
],
"text": [
"rat"
],
"normalized": []
},
{
"id": "49_T100",
"type": "Chemical",
"offsets": [
[
2212,
2214
],
[
2215,
2217
]
],
"text": [
"1b",
"5b"
],
"normalized": []
},
{
"id": "49_T101",
"type": "Chemical",
"offsets": [
[
2248,
2271
]
],
"text": [
"indolo[4,3-fg]quinoline"
],
"normalized": []
},
{
"id": "49_T102",
"type": "Chemical",
"offsets": [
[
2286,
2295
]
],
"text": [
"ergolines"
],
"normalized": []
},
{
"id": "49_T103",
"type": "Metabolite",
"offsets": [
[
2286,
2295
]
],
"text": [
"ergolines"
],
"normalized": []
},
{
"id": "49_T104",
"type": "Chemical",
"offsets": [
[
2248,
2295
]
],
"text": [
"indolo[4,3-fg]quinoline system of the ergolines"
],
"normalized": []
},
{
"id": "49_T106",
"type": "Metabolite",
"offsets": [
[
82,
99
]
],
"text": [
"clavine alkaloids"
],
"normalized": []
},
{
"id": "49_T81",
"type": "Chemical",
"offsets": [
[
2091,
2099
],
[
2108,
2110
]
],
"text": [
"compound",
"5b"
],
"normalized": []
},
{
"id": "49_T28",
"type": "Protein",
"offsets": [
[
2346,
2362
]
],
"text": [
"5-HT2A receptor"
],
"normalized": []
},
{
"id": "49_T10",
"type": "Chemical",
"offsets": [
[
843,
854
]
],
"text": [
"compound 6b"
],
"normalized": []
}
] | [] | [] | [
{
"id": "49_R1",
"type": "Associated_With",
"arg1_id": "49_T23",
"arg2_id": "49_T20",
"normalized": []
},
{
"id": "49_R16",
"type": "Associated_With",
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"arg2_id": "49_T95",
"normalized": []
},
{
"id": "49_R17",
"type": "Associated_With",
"arg1_id": "49_T92",
"arg2_id": "49_T95",
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},
{
"id": "49_R18",
"type": "Binds_With",
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"arg2_id": "49_T22",
"normalized": []
},
{
"id": "49_R10",
"type": "Binds_With",
"arg1_id": "49_T27",
"arg2_id": "49_T31",
"normalized": []
},
{
"id": "49_R2",
"type": "Binds_With",
"arg1_id": "49_T10",
"arg2_id": "49_T31",
"normalized": []
},
{
"id": "49_R3",
"type": "Binds_With",
"arg1_id": "49_T86",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R4",
"type": "Binds_With",
"arg1_id": "49_T65",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R5",
"type": "Binds_With",
"arg1_id": "49_T85",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R6",
"type": "Binds_With",
"arg1_id": "49_T64",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R11",
"type": "Binds_With",
"arg1_id": "49_T84",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R13",
"type": "Binds_With",
"arg1_id": "49_T63",
"arg2_id": "49_T66",
"normalized": []
},
{
"id": "49_R14",
"type": "Binds_With",
"arg1_id": "49_T81",
"arg2_id": "49_T94",
"normalized": []
},
{
"id": "49_R19",
"type": "Binds_With",
"arg1_id": "49_T92",
"arg2_id": "49_T94",
"normalized": []
}
] |
50 | 100603 | [
{
"id": "51",
"type": "",
"text": [
"Subcutaneous tumor induction with three dose levels of 3-methylcholanthrene (MCA), benzo[a]pyrene (BP), and 7,12-dimethylbenz[a]anthracene (DMBA) in two vehicles was studied in C3H/Anf Cum, C57BL/6 Cum, DBA/2J, and (C57BLXC3H/Anf)F1 (BC3F1/Cum) mice. Median tumor dose levels were significantly lower when the three carcinogens were suspended in trioctanoin. When beeswax: trioctanoin (B:T) was used as a vehicle, the three carcinogens differed in their abilities to be absorbed or solubilized from the vehicle by the three strains of mice and the hybrid. In C3H/Anf mice, BP in B:T failed to produce tumors. In BC3F1 mice, no tumors were produced by MCA, BP, or DMBA in B:T. In C57BL/6 mice, no tumors were produced with DMBA or MCA in B:T. In DBA/2 mice, no tumors were produced by BP or MCA in B:T. These results indicated that the interpretation of tumor induction results obtained with B:T vehicle may be related to the conditions of bioassay rather than to the carcinogenic potential of a compound. \n"
],
"offsets": [
[
0,
1008
]
]
}
] | [
{
"id": "51_T2",
"type": "Chemical",
"offsets": [
[
55,
75
]
],
"text": [
"3-methylcholanthrene"
],
"normalized": []
},
{
"id": "51_T3",
"type": "Chemical",
"offsets": [
[
77,
80
]
],
"text": [
"MCA"
],
"normalized": []
},
{
"id": "51_T4",
"type": "Chemical",
"offsets": [
[
83,
97
]
],
"text": [
"benzo[a]pyrene"
],
"normalized": []
},
{
"id": "51_T5",
"type": "Chemical",
"offsets": [
[
99,
101
]
],
"text": [
"BP"
],
"normalized": []
},
{
"id": "51_T6",
"type": "Chemical",
"offsets": [
[
108,
138
]
],
"text": [
"7,12-dimethylbenz[a]anthracene"
],
"normalized": []
},
{
"id": "51_T7",
"type": "Chemical",
"offsets": [
[
140,
144
]
],
"text": [
"DMBA"
],
"normalized": []
},
{
"id": "51_T8",
"type": "Species",
"offsets": [
[
245,
249
]
],
"text": [
"mice"
],
"normalized": []
},
{
"id": "51_T9",
"type": "Chemical",
"offsets": [
[
346,
357
]
],
"text": [
"trioctanoin"
],
"normalized": []
},
{
"id": "51_T10",
"type": "Biological_Activity",
"offsets": [
[
316,
326
]
],
"text": [
"carcinogen"
],
"normalized": []
},
{
"id": "51_T11",
"type": "Biological_Activity",
"offsets": [
[
425,
435
]
],
"text": [
"carcinogen"
],
"normalized": []
},
{
"id": "51_T12",
"type": "Chemical",
"offsets": [
[
364,
371
]
],
"text": [
"beeswax"
],
"normalized": []
},
{
"id": "51_T13",
"type": "Chemical",
"offsets": [
[
373,
384
]
],
"text": [
"trioctanoin"
],
"normalized": []
},
{
"id": "51_T14",
"type": "Species",
"offsets": [
[
536,
540
]
],
"text": [
"mice"
],
"normalized": []
},
{
"id": "51_T15",
"type": "Species",
"offsets": [
[
568,
572
]
],
"text": [
"mice"
],
"normalized": []
},
{
"id": "51_T16",
"type": "Chemical",
"offsets": [
[
574,
576
]
],
"text": [
"BP"
],
"normalized": []
},
{
"id": "51_T17",
"type": "Species",
"offsets": [
[
619,
623
]
],
"text": [
"mice"
],
"normalized": []
},
{
"id": "51_T18",
"type": "Chemical",
"offsets": [
[
652,
655
]
],
"text": [
"MCA"
],
"normalized": []
},
{
"id": "51_T19",
"type": "Chemical",
"offsets": [
[
657,
659
]
],
"text": [
"BP"
],
"normalized": []
},
{
"id": "51_T20",
"type": "Chemical",
"offsets": [
[
664,
668
]
],
"text": [
"DMBA"
],
"normalized": []
},
{
"id": "51_T21",
"type": "Species",
"offsets": [
[
688,
692
]
],
"text": [
"mice"
],
"normalized": []
},
{
"id": "51_T22",
"type": "Species",
"offsets": [
[
753,
757
]
],
"text": [
"mice"
],
"normalized": []
},
{
"id": "51_T23",
"type": "Chemical",
"offsets": [
[
724,
728
]
],
"text": [
"DMBA"
],
"normalized": []
},
{
"id": "51_T24",
"type": "Chemical",
"offsets": [
[
732,
735
]
],
"text": [
"MCA"
],
"normalized": []
},
{
"id": "51_T25",
"type": "Chemical",
"offsets": [
[
786,
788
]
],
"text": [
"BP"
],
"normalized": []
},
{
"id": "51_T26",
"type": "Chemical",
"offsets": [
[
792,
795
]
],
"text": [
"MCA"
],
"normalized": []
},
{
"id": "51_T27",
"type": "Biological_Activity",
"offsets": [
[
969,
979
]
],
"text": [
"carcinogen"
],
"normalized": []
},
{
"id": "51_T28",
"type": "Biological_Activity",
"offsets": [
[
855,
870
]
],
"text": [
"tumor induction"
],
"normalized": []
},
{
"id": "51_T29",
"type": "Chemical",
"offsets": [
[
386,
389
]
],
"text": [
"B:T"
],
"normalized": []
},
{
"id": "51_T30",
"type": "Chemical",
"offsets": [
[
672,
675
]
],
"text": [
"B:T"
],
"normalized": []
},
{
"id": "51_T31",
"type": "Chemical",
"offsets": [
[
739,
742
]
],
"text": [
"B:T"
],
"normalized": []
},
{
"id": "51_T32",
"type": "Chemical",
"offsets": [
[
799,
802
]
],
"text": [
"B:T"
],
"normalized": []
},
{
"id": "51_T33",
"type": "Chemical",
"offsets": [
[
893,
896
]
],
"text": [
"B:T"
],
"normalized": []
},
{
"id": "51_T1",
"type": "Biological_Activity",
"offsets": [
[
13,
28
]
],
"text": [
"tumor induction"
],
"normalized": []
}
] | [] | [] | [
{
"id": "51_R1",
"type": "Associated_With",
"arg1_id": "51_T2",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R2",
"type": "Associated_With",
"arg1_id": "51_T3",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R3",
"type": "Associated_With",
"arg1_id": "51_T4",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R4",
"type": "Associated_With",
"arg1_id": "51_T5",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R5",
"type": "Associated_With",
"arg1_id": "51_T6",
"arg2_id": "51_T10",
"normalized": []
},
{
"id": "51_R6",
"type": "Associated_With",
"arg1_id": "51_T7",
"arg2_id": "51_T10",
"normalized": []
}
] |
52 | 10064158 | [
{
"id": "53",
"type": "",
"text": [
"Exposure of Clone 9 cells, a nontransformed rat liver cell line expressing only the Glutl glucose transporter isoform, to the guanylyl cyclase inhibitor LY-83583 was found to stimulate the rate of glucose transport (approximately 7- to 8-fold in 1 h). A similar response to LY-83583 was found in NIH 3T3 fibroblasts, 3T3-L1 pre-adipocytes, and C2C12 myoblasts. Neither the rate of glucose transport in cells under control conditions nor the effect of LY-83583 on glucose transport was altered by 10, 50, or 100 microM 8-bromo-cGMP or by addition of cGMP phosphodiesterase inhibitors, zaprinast, or dipyridamole suggesting that glucose transport and the response to LY-83583 is independent of cGMP levels. In addition, the effect of LY-83583 on glucose transport was not mediated by inhibition of oxidative phosphorylation, since exposure to the agent resulted in no increase in lactate production. Incubation of Clone 9 cells in the presence of the phospholipase C inhibitor U73122, however, attenuated the glucose transport response to LY-83583. Moreover, exposure to LY-83583 resulted in a rise in cell diacylglycerol content, and preincubation with U73122 significantly diminished this rise as well as the glucose transport response to LY-83583. The stimulatory effect of LY-83583 on glucose transport was significantly blocked by thapsigargin. Down-regulation of protein kinase C activity, resulting from 24 h pre-incubation in the presence of 160 nM phorbol-12-myristate 13-acetate, did not attenuate the glucose transport response to LY-83583. It is concluded that the stimulation of glucose transport in response to LY-83583 is independent of changes in cGMP levels, is not mediated by inhibition of oxidative phosphorylation, and is mediated, at least in part, through stimulation of the phospholipase C pathway. \n"
],
"offsets": [
[
0,
1827
]
]
}
] | [
{
"id": "53_T1",
"type": "Protein",
"offsets": [
[
84,
109
]
],
"text": [
"Glutl glucose transporter"
],
"normalized": []
},
{
"id": "53_T2",
"type": "Biological_Activity",
"offsets": [
[
143,
152
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "53_T3",
"type": "Protein",
"offsets": [
[
126,
142
]
],
"text": [
"guanylyl cyclase"
],
"normalized": []
},
{
"id": "53_T5",
"type": "Chemical",
"offsets": [
[
153,
161
]
],
"text": [
"LY-83583"
],
"normalized": []
},
{
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785,
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1109,
1123
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1156,
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1380,
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] |
54 | 10064560 | [
{
"id": "55",
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"Retinaldehyde (RAL), a key intermediate in retinoid metabolism, acts as a retinoic acid (RA) precursor, but is also reduced to retinol (ROH), which can subsequently be esterified to retinyl esters, the storage form of vitamin A. Limited information is available on the metabolism of geometric isomers of RAL as well as on the transplacental distribution of their metabolites, including RA isomers. Such information would be very helpful for the assessment of the teratogenic potency of RAL isomers, as teratogenesis represents a major side effect of retinoid use in pharmacotherapy. In the present study we examined concentrations of retinoids in plasma, maternal tissues, and embryos of pregnant rats 2 h after a single oral dose (100 mg/kg body weight) of all-trans-, 13-cis-, or 9-cis-RAL on gestational day 13. The main findings of this study were the very similar patterns of retinoid metabolites (consisting of retinoids with mainly the all-trans-configuration) after administration of all-trans- and 13-cis-RAL, and the high concentrations of 9-cis-RA, 9,13-dicis-RA, and 9-cis-retinoyl-beta-D-glucuronide after dosing with 9-cis-RAL. In addition, all-trans-RA as a RAL metabolite reached the embryos to a much greater extent than any of its cis-isomers. The results are discussed in view of in vitro data on enzymes involved in the biotransformation of RAL isomers. \n"
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218,
227
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304,
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502,
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550,
558
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634,
643
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43,
51
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698,
702
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768
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789,
792
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778
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792
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789,
791
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759,
769
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789,
792
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778
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789,
792
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783,
792
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783,
792
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"id": "55_T35",
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783,
792
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"normalized": []
},
{
"id": "55_T36",
"type": "Chemical",
"offsets": [
[
882,
902
]
],
"text": [
"retinoid metabolites"
],
"normalized": []
},
{
"id": "55_T37",
"type": "Metabolite",
"offsets": [
[
882,
902
]
],
"text": [
"retinoid metabolites"
],
"normalized": []
},
{
"id": "55_T38",
"type": "Chemical",
"offsets": [
[
918,
926
]
],
"text": [
"retinoid"
],
"normalized": []
},
{
"id": "55_T39",
"type": "Metabolite",
"offsets": [
[
918,
927
]
],
"text": [
"retinoids"
],
"normalized": []
},
{
"id": "55_T40",
"type": "Chemical",
"offsets": [
[
1015,
1018
],
[
993,
1003
]
],
"text": [
"RAL",
"all-trans-"
],
"normalized": []
},
{
"id": "55_T41",
"type": "Chemical",
"offsets": [
[
1008,
1018
]
],
"text": [
"13-cis-RAL"
],
"normalized": []
},
{
"id": "55_T42",
"type": "Chemical",
"offsets": [
[
1051,
1059
]
],
"text": [
"9-cis-RA"
],
"normalized": []
},
{
"id": "55_T43",
"type": "Metabolite",
"offsets": [
[
1051,
1059
]
],
"text": [
"9-cis-RA"
],
"normalized": []
},
{
"id": "55_T44",
"type": "Metabolite",
"offsets": [
[
1061,
1074
]
],
"text": [
"9,13-dicis-RA"
],
"normalized": []
},
{
"id": "55_T45",
"type": "Chemical",
"offsets": [
[
1061,
1074
]
],
"text": [
"9,13-dicis-RA"
],
"normalized": []
},
{
"id": "55_T46",
"type": "Chemical",
"offsets": [
[
1080,
1113
]
],
"text": [
"9-cis-retinoyl-beta-D-glucuronide"
],
"normalized": []
},
{
"id": "55_T47",
"type": "Metabolite",
"offsets": [
[
1080,
1113
]
],
"text": [
"9-cis-retinoyl-beta-D-glucuronide"
],
"normalized": []
},
{
"id": "55_T48",
"type": "Chemical",
"offsets": [
[
1132,
1141
]
],
"text": [
"9-cis-RAL"
],
"normalized": []
},
{
"id": "55_T49",
"type": "Chemical",
"offsets": [
[
1156,
1168
]
],
"text": [
"all-trans-RA"
],
"normalized": []
},
{
"id": "55_T50",
"type": "Metabolite",
"offsets": [
[
1156,
1168
]
],
"text": [
"all-trans-RA"
],
"normalized": []
},
{
"id": "55_T51",
"type": "Chemical",
"offsets": [
[
1174,
1177
]
],
"text": [
"RAL"
],
"normalized": []
},
{
"id": "55_T52",
"type": "Metabolite",
"offsets": [
[
1174,
1177
]
],
"text": [
"RAL"
],
"normalized": []
},
{
"id": "55_T53",
"type": "Chemical",
"offsets": [
[
1362,
1373
]
],
"text": [
"RAL isomers"
],
"normalized": []
},
{
"id": "55_T54",
"type": "Protein",
"offsets": [
[
1317,
1324
]
],
"text": [
"enzymes"
],
"normalized": []
},
{
"id": "55_T55",
"type": "Biological_Activity",
"offsets": [
[
52,
62
]
],
"text": [
"metabolism"
],
"normalized": []
},
{
"id": "55_T56",
"type": "Biological_Activity",
"offsets": [
[
269,
279
]
],
"text": [
"metabolism"
],
"normalized": []
}
] | [] | [] | [
{
"id": "55_R1",
"type": "Metabolite_Of",
"arg1_id": "55_T7",
"arg2_id": "55_T2",
"normalized": []
},
{
"id": "55_R2",
"type": "Metabolite_Of",
"arg1_id": "55_T11",
"arg2_id": "55_T2",
"normalized": []
},
{
"id": "55_R3",
"type": "Metabolite_Of",
"arg1_id": "55_T13",
"arg2_id": "55_T10",
"normalized": []
},
{
"id": "55_R4",
"type": "Metabolite_Of",
"arg1_id": "55_T50",
"arg2_id": "55_T51",
"normalized": []
},
{
"id": "55_R5",
"type": "Associated_With",
"arg1_id": "55_T21",
"arg2_id": "55_T20",
"normalized": []
},
{
"id": "55_R6",
"type": "Associated_With",
"arg1_id": "55_T21",
"arg2_id": "55_T23",
"normalized": []
},
{
"id": "55_R7",
"type": "Associated_With",
"arg1_id": "55_T24",
"arg2_id": "55_T23",
"normalized": []
},
{
"id": "55_R8",
"type": "Isolated_From",
"arg1_id": "55_T25",
"arg2_id": "55_T27",
"normalized": []
}
] |
56 | 10066805 | [
{
"id": "57",
"type": "",
"text": [
"UDP-glucose: anthocyanin 5-O-glucosyltransferase (5-GT) is responsible for the modification of anthocyanins to more stable molecules in complexes for co-pigmentation, supposedly resulting in a purple hue. The cDNA encoding 5-GT was isolated by a differential display applied to two different forms of anthocyanin production in Perilla frutescens var. crispa. Differential display was carried out for mRNA from the leaves of reddish-purple and green forms of P. frutescens, resulting in the isolation of five cDNA clones predominantly expressed in the red form. The cDNA encoded a polypeptide of 460 amino acids, exhibiting a low homology with the sequences of several glucosyltransferases including UDP-glucose: anthocyanidin 3-O-glucosyltransferase. By using this cDNA as the probe, we also isolated a homologous cDNA clone from a petal cDNA library of Verbena hybrida. To identify the biochemical function of the encoded proteins, these cDNAs were expressed in Saccharomyces cerevisiae cells. The recombinant proteins in the yeast extracts catalyzed the conversion of anthocyanidin 3-O-glucosides into the corresponding anthocyanidin 3,5-di-O-glucosides using UDP-glucose as a cofactor, indicating the identity of the cDNAs encoding 5-GT. Several biochemical properties (optimum pH, Km values, and sensitivity to inhibitors) were similar to those reported previously for 5-GTs. Southern blot analysis indicated the presence of two copies of 5-GT genes in the genome of both red and green forms of P. frutescens. The mRNA accumulation of the 5-GT gene was detected in the leaves of the red form but not in those of the green form and was induced by illumination of light, as observed for other structural genes for anthocyanin biosynthesis in P. frutescens. \n"
],
"offsets": [
[
0,
1763
]
]
}
] | [
{
"id": "57_T1",
"type": "Protein",
"offsets": [
[
0,
48
]
],
"text": [
"UDP-glucose: anthocyanin 5-O-glucosyltransferase"
],
"normalized": []
},
{
"id": "57_T4",
"type": "Protein",
"offsets": [
[
50,
54
]
],
"text": [
"5-GT"
],
"normalized": []
},
{
"id": "57_T5",
"type": "Metabolite",
"offsets": [
[
95,
107
]
],
"text": [
"anthocyanins"
],
"normalized": []
},
{
"id": "57_T6",
"type": "Chemical",
"offsets": [
[
95,
107
]
],
"text": [
"anthocyanins"
],
"normalized": []
},
{
"id": "57_T7",
"type": "Chemical",
"offsets": [
[
123,
132
]
],
"text": [
"molecules"
],
"normalized": []
},
{
"id": "57_T8",
"type": "Protein",
"offsets": [
[
223,
227
]
],
"text": [
"5-GT"
],
"normalized": []
},
{
"id": "57_T10",
"type": "Metabolite",
"offsets": [
[
301,
312
]
],
"text": [
"anthocyanin"
],
"normalized": []
},
{
"id": "57_T11",
"type": "Species",
"offsets": [
[
328,
358
]
],
"text": [
"Perilla frutescens var. crispa"
],
"normalized": []
},
{
"id": "57_T12",
"type": "Species",
"offsets": [
[
328,
346
]
],
"text": [
"Perilla frutescens"
],
"normalized": []
},
{
"id": "57_T13",
"type": "Species",
"offsets": [
[
459,
472
]
],
"text": [
"P. frutescens"
],
"normalized": []
},
{
"id": "57_T14",
"type": "Protein",
"offsets": [
[
582,
593
]
],
"text": [
"polypeptide"
],
"normalized": []
},
{
"id": "57_T15",
"type": "Protein",
"offsets": [
[
670,
690
]
],
"text": [
"glucosyltransferases"
],
"normalized": []
},
{
"id": "57_T16",
"type": "Protein",
"offsets": [
[
701,
751
]
],
"text": [
"UDP-glucose: anthocyanidin 3-O-glucosyltransferase"
],
"normalized": []
},
{
"id": "57_T17",
"type": "Species",
"offsets": [
[
856,
871
]
],
"text": [
"Verbena hybrida"
],
"normalized": []
},
{
"id": "57_T18",
"type": "Species",
"offsets": [
[
965,
989
]
],
"text": [
"Saccharomyces cerevisiae"
],
"normalized": []
},
{
"id": "57_T19",
"type": "Protein",
"offsets": [
[
1001,
1021
]
],
"text": [
"recombinant proteins"
],
"normalized": []
},
{
"id": "57_T20",
"type": "Species",
"offsets": [
[
1029,
1034
]
],
"text": [
"yeast"
],
"normalized": []
},
{
"id": "57_T21",
"type": "Chemical",
"offsets": [
[
1072,
1100
]
],
"text": [
"anthocyanidin 3-O-glucosides"
],
"normalized": []
},
{
"id": "57_T22",
"type": "Chemical",
"offsets": [
[
1124,
1157
]
],
"text": [
"anthocyanidin 3,5-di-O-glucosides"
],
"normalized": []
},
{
"id": "57_T23",
"type": "Metabolite",
"offsets": [
[
1124,
1157
]
],
"text": [
"anthocyanidin 3,5-di-O-glucosides"
],
"normalized": []
},
{
"id": "57_T24",
"type": "Chemical",
"offsets": [
[
1164,
1175
]
],
"text": [
"UDP-glucose"
],
"normalized": []
},
{
"id": "57_T25",
"type": "Protein",
"offsets": [
[
1237,
1241
]
],
"text": [
"5-GT"
],
"normalized": []
},
{
"id": "57_T9",
"type": "Protein",
"offsets": [
[
1375,
1379
]
],
"text": [
"5-GT"
],
"normalized": []
},
{
"id": "57_T26",
"type": "Species",
"offsets": [
[
1501,
1514
]
],
"text": [
"P. frutescens"
],
"normalized": []
},
{
"id": "57_T27",
"type": "Protein",
"offsets": [
[
1545,
1549
]
],
"text": [
"5-GT"
],
"normalized": []
},
{
"id": "57_T28",
"type": "Metabolite",
"offsets": [
[
1719,
1730
]
],
"text": [
"anthocyanin"
],
"normalized": []
},
{
"id": "57_T29",
"type": "Species",
"offsets": [
[
1747,
1760
]
],
"text": [
"P. frutescens"
],
"normalized": []
},
{
"id": "57_T30",
"type": "Chemical",
"offsets": [
[
1719,
1730
]
],
"text": [
"anthocyanin"
],
"normalized": []
},
{
"id": "57_T35",
"type": "Biological_Activity",
"offsets": [
[
1181,
1189
]
],
"text": [
"cofactor"
],
"normalized": []
},
{
"id": "57_T2",
"type": "Chemical",
"offsets": [
[
301,
314
]
],
"text": [
"anthocyanin"
],
"normalized": []
},
{
"id": "57_T3",
"type": "Chemical",
"offsets": [
[
601,
612
]
],
"text": [
"amino acids"
],
"normalized": []
}
] | [] | [] | [
{
"id": "57_R1",
"type": "Associated_With",
"arg1_id": "57_T24",
"arg2_id": "57_T35",
"normalized": []
},
{
"id": "57_R2",
"type": "Metabolite_Of",
"arg1_id": "57_T23",
"arg2_id": "57_T21",
"normalized": []
},
{
"id": "57_R3",
"type": "Isolated_From",
"arg1_id": "57_T10",
"arg2_id": "57_T11",
"normalized": []
}
] |
58 | 10069359 | [
{
"id": "59",
"type": "",
"text": [
"The cephalosporins are a large group of related beta-lactam antimicrobial agents. Favorable attributes of the cephalosporins include low rates of toxicity, relatively broad spectrum of activity, and ease of administration. Various cephalosporins are effective for treatment of many conditions, including pneumonia, skin and soft tissue infections, bacteremia, and meningitis. Differences among the numerous cephalosporin antimicrobial agents are sometimes subtle; however, an understanding of these differences is essential for optimal use of these agents. As a result of widespread use of cephalosporins, bacterial resistance to these drugs is increasingly common. New, fourth-generation agents (such as cefepime) offer an alternative for the treatment of infections caused by some drug-resistant microorganisms. \n"
],
"offsets": [
[
0,
815
]
]
}
] | [
{
"id": "59_T1",
"type": "Chemical",
"offsets": [
[
4,
18
]
],
"text": [
"cephalosporins"
],
"normalized": []
},
{
"id": "59_T2",
"type": "Chemical",
"offsets": [
[
48,
59
]
],
"text": [
"beta-lactam"
],
"normalized": []
},
{
"id": "59_T3",
"type": "Biological_Activity",
"offsets": [
[
60,
73
]
],
"text": [
"antimicrobial"
],
"normalized": []
},
{
"id": "59_T4",
"type": "Chemical",
"offsets": [
[
110,
124
]
],
"text": [
"cephalosporins"
],
"normalized": []
},
{
"id": "59_T5",
"type": "Biological_Activity",
"offsets": [
[
146,
154
]
],
"text": [
"toxicity"
],
"normalized": []
},
{
"id": "59_T7",
"type": "Chemical",
"offsets": [
[
231,
245
]
],
"text": [
"cephalosporins"
],
"normalized": []
},
{
"id": "59_T8",
"type": "Chemical",
"offsets": [
[
407,
420
]
],
"text": [
"cephalosporin"
],
"normalized": []
},
{
"id": "59_T9",
"type": "Biological_Activity",
"offsets": [
[
421,
434
]
],
"text": [
"antimicrobial"
],
"normalized": []
},
{
"id": "59_T10",
"type": "Chemical",
"offsets": [
[
590,
604
]
],
"text": [
"cephalosporins"
],
"normalized": []
},
{
"id": "59_T11",
"type": "Chemical",
"offsets": [
[
705,
713
]
],
"text": [
"cefepime"
],
"normalized": []
},
{
"id": "59_T13",
"type": "Chemical",
"offsets": [
[
636,
641
]
],
"text": [
"drugs"
],
"normalized": []
},
{
"id": "59_T12",
"type": "Chemical",
"offsets": [
[
783,
787
]
],
"text": [
"drug"
],
"normalized": []
}
] | [] | [] | [
{
"id": "59_R1",
"type": "Associated_With",
"arg1_id": "59_T1",
"arg2_id": "59_T3",
"normalized": []
},
{
"id": "59_R3",
"type": "Associated_With",
"arg1_id": "59_T8",
"arg2_id": "59_T9",
"normalized": []
},
{
"id": "59_R4",
"type": "Associated_With",
"arg1_id": "59_T11",
"arg2_id": "59_T9",
"normalized": []
}
] |
60 | 10069454 | [
{
"id": "61",
"type": "",
"text": [
"DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP) are activated by DNA strand breaks and participate in DNA repair. We investigated the interactive effects of inhibitors of these enzymes [wortmannin (WM), which inhibits DNA-PK, and 8-hydroxy-2-methylquinazolin-4-one (NU1025), a PARP inhibitor] on cell survival and DNA double-strand break (DSB) and single-strand break (SSB) rejoining in Chinese hamster ovary-K1 cells following exposure to ionizing radiation (IR) or temozolomide. WM (20 microM) or NU1025 (300 microM) potentiated the cytotoxicity of IR with dose enhancement factors at 10% survival (DEF10) values of 4.5 +/- 0.6 and 1.7 +/- 0.2, respectively. When used in combination, a DEF10 of 7.8 +/- 1.5 was obtained. WM or NU1025 potentiated the cytotoxicity of temozolomide, and an additive effect on the DEF10 value was obtained with the combined inhibitors. Using the same inhibitor concentrations, their single and combined effects on DSB and SSB levels following IR were assessed by neutral and alkaline elution. Cells exposed to IR were post-incubated for 30 min to allow repair to occur. WM or NU1025 increased net DSB levels relative to IR alone (DSB levels of 1.29 +/- 0.04 and 1.20 +/- 0.05, respectively, compared with 1.01 +/- 0.03 for IR alone) and the combination had an additive effect. WM had no effect on SSB levels, either alone or in combination with NU1025. SSB levels were increased to 1.27 +/- 0.05 with NU1025 compared with IR alone, 1.02 +/- 0.04. The dose-dependent effects of the inhibitors on DSB levels showed that they were near maximal by 20 microM WM and 300 microM NU1025. DSB repair kinetics were studied. Both inhibitors increased net DSB levels over a 3 h time period; when they were combined, net DSB levels at 3 h were identical to DSB levels immediately post-IR. The combined use of DNA repair inhibitors may have therapeutic potential. \n"
],
"offsets": [
[
0,
1914
]
]
}
] | [
{
"id": "61_T1",
"type": "Protein",
"offsets": [
[
0,
28
]
],
"text": [
"DNA-dependent protein kinase"
],
"normalized": []
},
{
"id": "61_T2",
"type": "Protein",
"offsets": [
[
30,
36
]
],
"text": [
"DNA-PK"
],
"normalized": []
},
{
"id": "61_T3",
"type": "Protein",
"offsets": [
[
42,
69
]
],
"text": [
"poly(ADP-ribose) polymerase"
],
"normalized": []
},
{
"id": "61_T5",
"type": "Protein",
"offsets": [
[
71,
75
]
],
"text": [
"PARP"
],
"normalized": []
},
{
"id": "61_T4",
"type": "Biological_Activity",
"offsets": [
[
132,
142
]
],
"text": [
"DNA repair"
],
"normalized": []
},
{
"id": "61_T11",
"type": "Chemical",
"offsets": [
[
216,
226
]
],
"text": [
"wortmannin"
],
"normalized": []
},
{
"id": "61_T12",
"type": "Chemical",
"offsets": [
[
228,
230
]
],
"text": [
"WM"
],
"normalized": []
},
{
"id": "61_T13",
"type": "Biological_Activity",
"offsets": [
[
239,
247
]
],
"text": [
"inhibits"
],
"normalized": []
},
{
"id": "61_T14",
"type": "Chemical",
"offsets": [
[
260,
294
]
],
"text": [
"8-hydroxy-2-methylquinazolin-4-one"
],
"normalized": []
},
{
"id": "61_T15",
"type": "Chemical",
"offsets": [
[
296,
302
]
],
"text": [
"NU1025"
],
"normalized": []
},
{
"id": "61_T16",
"type": "Biological_Activity",
"offsets": [
[
312,
321
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "61_T17",
"type": "Species",
"offsets": [
[
417,
432
]
],
"text": [
"Chinese hamster"
],
"normalized": []
},
{
"id": "61_T18",
"type": "Chemical",
"offsets": [
[
497,
509
]
],
"text": [
"temozolomide"
],
"normalized": []
},
{
"id": "61_T21",
"type": "Chemical",
"offsets": [
[
511,
513
]
],
"text": [
"WM"
],
"normalized": []
},
{
"id": "61_T22",
"type": "Chemical",
"offsets": [
[
529,
535
]
],
"text": [
"NU1025"
],
"normalized": []
},
{
"id": "61_T23",
"type": "Biological_Activity",
"offsets": [
[
565,
577
]
],
"text": [
"cytotoxicity"
],
"normalized": []
},
{
"id": "61_T24",
"type": "Chemical",
"offsets": [
[
755,
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"WM"
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"id": "61_T26",
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"cytotoxicity"
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800,
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1133,
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1139,
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1682,
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914,
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},
{
"id": "61_T38",
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187,
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]
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},
{
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1544,
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},
{
"id": "61_T42",
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248,
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]
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"DNA-PK"
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},
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"id": "61_T43",
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[
307,
311
]
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"text": [
"PARP"
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},
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"id": "61_T6",
"type": "Biological_Activity",
"offsets": [
[
887,
896
]
],
"text": [
"inhibitor"
],
"normalized": []
}
] | [] | [] | [
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"id": "61_R1",
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"arg2_id": "61_T13",
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},
{
"id": "61_R2",
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"arg2_id": "61_T13",
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},
{
"id": "61_R3",
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},
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"id": "61_R4",
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"arg2_id": "61_T16",
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},
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"id": "61_R7",
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},
{
"id": "61_R10",
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},
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"id": "61_R14",
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"normalized": []
},
{
"id": "61_R15",
"type": "Binds_With",
"arg1_id": "61_T11",
"arg2_id": "61_T1",
"normalized": []
},
{
"id": "61_R16",
"type": "Binds_With",
"arg1_id": "61_T12",
"arg2_id": "61_T1",
"normalized": []
},
{
"id": "61_R18",
"type": "Binds_With",
"arg1_id": "61_T14",
"arg2_id": "61_T3",
"normalized": []
},
{
"id": "61_R11",
"type": "Binds_With",
"arg1_id": "61_T15",
"arg2_id": "61_T3",
"normalized": []
},
{
"id": "61_R17",
"type": "Binds_With",
"arg1_id": "61_T14",
"arg2_id": "61_T43",
"normalized": []
},
{
"id": "61_R19",
"type": "Binds_With",
"arg1_id": "61_T15",
"arg2_id": "61_T43",
"normalized": []
},
{
"id": "61_R5",
"type": "Associated_With",
"arg1_id": "61_T24",
"arg2_id": "61_T6",
"normalized": []
},
{
"id": "61_R6",
"type": "Associated_With",
"arg1_id": "61_T25",
"arg2_id": "61_T6",
"normalized": []
}
] |
62 | 10070780 | [
{
"id": "63",
"type": "",
"text": [
"The FM4-64, a member of the family of fluorescent dyes, has been applied to the cerebellar cortex to evaluate its properties as an intracellular stain and intracortical tracer. Slabs of hamster cerebellum, 1-2 mm thick, were incubated in 10, 30, and 100 microns solutions of FM4-64 in sodium phosphate buffer and observed in a slow scan confocal laser scanning microscope. Mossy and climbing fibers were traced in the cerebellar white and gray substances. They exhibited a high fluorescence signal at the level of the myelin sheath. Mossy fibers were identified in the granular layer by their typical rosette formation and dichotomous bifurcation pattern. Climbing fiber bundles were observed crossing the granular layer and giving collateral branches around Golgi cell bodies. They ascend to the Purkinje cell layer on their way to the molecular layer. Cerebellar macroneurons (Golgi and Purkinje cells) and microneurons (granule, basket, and stellate cells) showed optimal intracellular staining of cell soma, axonal, and dendritic processes. The z-series of stacks of optodigital sections allowed us to explore in depth the cytoarchitectonic arrangement, nerve and glial cell morphology, and the topographic relationship with the afferent fibers. \n"
],
"offsets": [
[
0,
1253
]
]
}
] | [
{
"id": "63_T1",
"type": "Chemical",
"offsets": [
[
4,
10
]
],
"text": [
"FM4-64"
],
"normalized": []
},
{
"id": "63_T4",
"type": "Species",
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[
186,
193
]
],
"text": [
"hamster"
],
"normalized": []
},
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"id": "63_T5",
"type": "Chemical",
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[
285,
308
]
],
"text": [
"sodium phosphate buffer"
],
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},
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"id": "63_T6",
"type": "Chemical",
"offsets": [
[
275,
281
]
],
"text": [
"FM4-64"
],
"normalized": []
}
] | [] | [] | [] |
64 | 10071923 | [
{
"id": "65",
"type": "",
"text": [
"A comparative study of various procedures for tryptophanyl peptide bond cleavage by BNPS-skatole [2-(2-nitrophenyl)-3-methyl-3-bromoindolenine] was carried out on native and on reduced and alkylated bovine beta-lactoglobulin (BLG). The reaction yield and the composition of the derived products were studied in acetic acid, trifluoroacetic acid (TFA), and ethanol/TFA. For BNPS-skatole removal, extraction by water or ethyl ether was compared with dialysis and gel filtration. The three expected peptides (1-19, 20-61, 62-162) and incomplete cleaved fragments (1-61, 20-162) were separated and characterized by electrophoresis, reverse-phase high-performance liquid chromatography, and mass spectrometry. The highest hydrolysis yield (67.4%) occurred with native BLG cleaved in 88% acetic acid at 47 degrees C for 60 min. Subsequent water extraction and gel filtration led to total recovery of the material, but reagent elimination was only quantitative after gel filtration. Cleavage specificity was ensured by mass spectrometry and the amino acid composition of peptides 1-19 and 62-162. The chemical side reactions identified are discussed. \n"
],
"offsets": [
[
0,
1147
]
]
}
] | [
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"id": "65_T1",
"type": "Chemical",
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85,
97
]
],
"text": [
"BNPS-skatole"
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},
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"id": "65_T2",
"type": "Chemical",
"offsets": [
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99,
143
]
],
"text": [
"2-(2-nitrophenyl)-3-methyl-3-bromoindolenine"
],
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},
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"id": "65_T4",
"type": "Protein",
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[
207,
225
]
],
"text": [
"beta-lactoglobulin"
],
"normalized": []
},
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"id": "65_T5",
"type": "Species",
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[
200,
206
]
],
"text": [
"bovine"
],
"normalized": []
},
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"id": "65_T6",
"type": "Chemical",
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[
312,
323
]
],
"text": [
"acetic acid"
],
"normalized": []
},
{
"id": "65_T7",
"type": "Chemical",
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[
325,
345
]
],
"text": [
"trifluoroacetic acid"
],
"normalized": []
},
{
"id": "65_T8",
"type": "Chemical",
"offsets": [
[
347,
350
]
],
"text": [
"TFA"
],
"normalized": []
},
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"id": "65_T9",
"type": "Chemical",
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[
357,
364
]
],
"text": [
"ethanol"
],
"normalized": []
},
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"id": "65_T10",
"type": "Chemical",
"offsets": [
[
365,
368
]
],
"text": [
"TFA"
],
"normalized": []
},
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"id": "65_T11",
"type": "Chemical",
"offsets": [
[
374,
386
]
],
"text": [
"BNPS-skatole"
],
"normalized": []
},
{
"id": "65_T12",
"type": "Chemical",
"offsets": [
[
410,
415
]
],
"text": [
"water"
],
"normalized": []
},
{
"id": "65_T13",
"type": "Chemical",
"offsets": [
[
419,
430
]
],
"text": [
"ethyl ether"
],
"normalized": []
},
{
"id": "65_T14",
"type": "Protein",
"offsets": [
[
227,
230
]
],
"text": [
"BLG"
],
"normalized": []
},
{
"id": "65_T15",
"type": "Protein",
"offsets": [
[
765,
768
]
],
"text": [
"BLG"
],
"normalized": []
},
{
"id": "65_T16",
"type": "Chemical",
"offsets": [
[
784,
795
]
],
"text": [
"acetic acid"
],
"normalized": []
},
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"id": "65_T17",
"type": "Chemical",
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[
835,
840
]
],
"text": [
"water"
],
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},
{
"id": "65_T18",
"type": "Chemical",
"offsets": [
[
1040,
1050
]
],
"text": [
"amino acid"
],
"normalized": []
},
{
"id": "65_T19",
"type": "Spectral_Data",
"offsets": [
[
688,
705
]
],
"text": [
"mass spectrometry"
],
"normalized": []
},
{
"id": "65_T20",
"type": "Chemical",
"offsets": [
[
498,
506
],
[
508,
512
]
],
"text": [
"peptides",
"1-19"
],
"normalized": []
},
{
"id": "65_T21",
"type": "Spectral_Data",
"offsets": [
[
1014,
1031
]
],
"text": [
"mass spectrometry"
],
"normalized": []
},
{
"id": "65_T22",
"type": "Chemical",
"offsets": [
[
1066,
1079
]
],
"text": [
"peptides 1-19"
],
"normalized": []
}
] | [] | [] | [
{
"id": "65_R3",
"type": "Associated_With",
"arg1_id": "65_T20",
"arg2_id": "65_T19",
"normalized": []
},
{
"id": "65_R4",
"type": "Associated_With",
"arg1_id": "65_T22",
"arg2_id": "65_T21",
"normalized": []
}
] |
66 | 10072406 | [
{
"id": "67",
"type": "",
"text": [
"We conducted a study of the patterns and dynamics of oxidized fatty acid derivatives (oxylipins) in potato leaves infected with the late-blight pathogen Phytophthora infestans. Two 18-carbon divinyl ether fatty acids, colneleic acid and colnelenic acid, accumulated during disease development. To date, there are no reports that such compounds have been detected in higher plants. The divinyl ether fatty acids accumulate more rapidly in potato cultivar Matilda (a cultivar with increased resistance to late blight) than in cultivar Bintje, a susceptible cultivar. Colnelenic acid reached levels of up to approximately 24 nmol (7 microgram) per g fresh weight of tissue in infected leaves. By contrast, levels of members of the jasmonic acid family did not change significantly during pathogenesis. The divinyl ethers also accumulated during the incompatible interaction of tobacco with tobacco mosaic virus. Colneleic and colnelenic acids were found to be inhibitory to P. infestans, suggesting a function in plant defense for divinyl ethers, which are unstable compounds rarely encountered in biological systems. \n"
],
"offsets": [
[
0,
1119
]
]
}
] | [
{
"id": "67_T1",
"type": "Chemical",
"offsets": [
[
53,
84
]
],
"text": [
"oxidized fatty acid derivatives"
],
"normalized": []
},
{
"id": "67_T2",
"type": "Chemical",
"offsets": [
[
86,
95
]
],
"text": [
"oxylipins"
],
"normalized": []
},
{
"id": "67_T3",
"type": "Metabolite",
"offsets": [
[
53,
84
]
],
"text": [
"oxidized fatty acid derivatives"
],
"normalized": []
},
{
"id": "67_T4",
"type": "Metabolite",
"offsets": [
[
86,
95
]
],
"text": [
"oxylipins"
],
"normalized": []
},
{
"id": "67_T5",
"type": "Species",
"offsets": [
[
100,
106
]
],
"text": [
"potato"
],
"normalized": []
},
{
"id": "67_T6",
"type": "Species",
"offsets": [
[
153,
175
]
],
"text": [
"Phytophthora infestans"
],
"normalized": []
},
{
"id": "67_T7",
"type": "Chemical",
"offsets": [
[
181,
216
]
],
"text": [
"18-carbon divinyl ether fatty acids"
],
"normalized": []
},
{
"id": "67_T8",
"type": "Chemical",
"offsets": [
[
218,
232
]
],
"text": [
"colneleic acid"
],
"normalized": []
},
{
"id": "67_T9",
"type": "Metabolite",
"offsets": [
[
218,
232
]
],
"text": [
"colneleic acid"
],
"normalized": []
},
{
"id": "67_T10",
"type": "Chemical",
"offsets": [
[
237,
252
]
],
"text": [
"colnelenic acid"
],
"normalized": []
},
{
"id": "67_T11",
"type": "Metabolite",
"offsets": [
[
237,
252
]
],
"text": [
"colnelenic acid"
],
"normalized": []
},
{
"id": "67_T12",
"type": "Chemical",
"offsets": [
[
385,
410
]
],
"text": [
"divinyl ether fatty acids"
],
"normalized": []
},
{
"id": "67_T13",
"type": "Species",
"offsets": [
[
438,
444
],
[
525,
540
]
],
"text": [
"potato",
"cultivar Bintje"
],
"normalized": []
},
{
"id": "67_T14",
"type": "Chemical",
"offsets": [
[
567,
582
]
],
"text": [
"Colnelenic acid"
],
"normalized": []
},
{
"id": "67_T15",
"type": "Metabolite",
"offsets": [
[
567,
582
]
],
"text": [
"Colnelenic acid"
],
"normalized": []
},
{
"id": "67_T16",
"type": "Chemical",
"offsets": [
[
730,
750
]
],
"text": [
"jasmonic acid family"
],
"normalized": []
},
{
"id": "67_T17",
"type": "Chemical",
"offsets": [
[
805,
819
]
],
"text": [
"divinyl ethers"
],
"normalized": []
},
{
"id": "67_T18",
"type": "Species",
"offsets": [
[
876,
883
]
],
"text": [
"tobacco"
],
"normalized": []
},
{
"id": "67_T19",
"type": "Species",
"offsets": [
[
889,
909
]
],
"text": [
"tobacco mosaic virus"
],
"normalized": []
},
{
"id": "67_T20",
"type": "Metabolite",
"offsets": [
[
805,
819
]
],
"text": [
"divinyl ethers"
],
"normalized": []
},
{
"id": "67_T21",
"type": "Chemical",
"offsets": [
[
911,
920
],
[
936,
940
]
],
"text": [
"Colneleic",
"acid"
],
"normalized": []
},
{
"id": "67_T22",
"type": "Chemical",
"offsets": [
[
925,
940
]
],
"text": [
"colnelenic acid"
],
"normalized": []
},
{
"id": "67_T23",
"type": "Metabolite",
"offsets": [
[
925,
940
]
],
"text": [
"colnelenic acid"
],
"normalized": []
},
{
"id": "67_T24",
"type": "Metabolite",
"offsets": [
[
911,
920
],
[
936,
940
]
],
"text": [
"Colneleic",
"acid"
],
"normalized": []
},
{
"id": "67_T25",
"type": "Biological_Activity",
"offsets": [
[
960,
969
]
],
"text": [
"inhibitor"
],
"normalized": []
},
{
"id": "67_T26",
"type": "Species",
"offsets": [
[
974,
986
]
],
"text": [
"P. infestans"
],
"normalized": []
},
{
"id": "67_T27",
"type": "Chemical",
"offsets": [
[
1031,
1045
]
],
"text": [
"divinyl ethers"
],
"normalized": []
},
{
"id": "67_T29",
"type": "Species",
"offsets": [
[
438,
461
]
],
"text": [
"potato cultivar Matilda"
],
"normalized": []
},
{
"id": "67_T30",
"type": "Metabolite",
"offsets": [
[
730,
750
]
],
"text": [
"jasmonic acid family"
],
"normalized": []
}
] | [] | [] | [
{
"id": "67_R1",
"type": "Associated_With",
"arg1_id": "67_T24",
"arg2_id": "67_T25",
"normalized": []
},
{
"id": "67_R2",
"type": "Associated_With",
"arg1_id": "67_T23",
"arg2_id": "67_T25",
"normalized": []
},
{
"id": "67_R4",
"type": "Isolated_From",
"arg1_id": "67_T9",
"arg2_id": "67_T5",
"normalized": []
},
{
"id": "67_R5",
"type": "Isolated_From",
"arg1_id": "67_T11",
"arg2_id": "67_T5",
"normalized": []
},
{
"id": "67_R6",
"type": "Isolated_From",
"arg1_id": "67_T30",
"arg2_id": "67_T5",
"normalized": []
},
{
"id": "67_R7",
"type": "Isolated_From",
"arg1_id": "67_T9",
"arg2_id": "67_T18",
"normalized": []
},
{
"id": "67_R8",
"type": "Isolated_From",
"arg1_id": "67_T11",
"arg2_id": "67_T18",
"normalized": []
}
] |
68 | 10073739 | [
{
"id": "69",
"type": "",
"text": [
"AIMS: Cysteamine, the only drug available for the treatment of cystinosis in paediatric patients, is available as the hydrochloride, the bitartrate and as sodium phosphocysteamine salts. It has been suggested that cysteamine bitartrate and phosphocysteamine are better tolerated and may have a better bioavailability than cysteamine hydrochloride. This has, however, never been demonstrated. METHODS: We compared the pharmacokinetics and tolerance of these three formulations of cysteamine in 18 healthy adult male volunteers in a double-blind, latin-square, three-period, single oral dose cross-over relative bioavailability study. RESULTS: No statistical difference was found between relative bioavailabilities, AUC (0, infinity) (geometric mean and s.d. in micromol l(-1) h: 169+/-51, 158+/-46, 173+/-49 with cysteamine hydrochloride, phosphocysteamine and cysteamine bitartrate respectively), Cmax (geometric mean and s.d. in micromol l(-1); 66+/-25.5, 59+/-12, 63+/-20) and tmax (median and range in h: 0.88 (0.25-2), 1.25 (0.25-2), 0.88 (0.25-2)) with each of the three forms of cysteamine tested. Bioequivalence statistics (90% confidence intervals) showed non equivalence of Cmax of cysteamine base as the only non equivalence of pharmacokinetics between the three formulations: 90% CI for Cmax relative ratios to cysteamine hydrochloride were [75.6-105.81 for phosphocysteamine and [74.2-124.2] for cysteamine bitartrate. The only significant adverse event was vomiting whose frequency was inversely correlated with body weight (Spearman's r=-0.76, P<0.001). The nature of the salt tested did not influence vomiting. CONCLUSIONS: While none of the three forms of cysteamine tested has a clear advantage over the others in terms of pharmacokinetics and tolerance profile, this should now however be addressed in patients treated for cystinosis during repeat administrations. \n"
],
"offsets": [
[
0,
1889
]
]
}
] | [
{
"id": "69_T1",
"type": "Chemical",
"offsets": [
[
118,
131
],
[
137,
147
],
[
6,
16
]
],
"text": [
"hydrochloride",
"bitartrate",
"Cysteamine"
],
"normalized": []
},
{
"id": "69_T2",
"type": "Chemical",
"offsets": [
[
118,
131
]
],
"text": [
"hydrochloride"
],
"normalized": []
},
{
"id": "69_T4",
"type": "Chemical",
"offsets": [
[
155,
179
]
],
"text": [
"sodium phosphocysteamine"
],
"normalized": []
},
{
"id": "69_T5",
"type": "Chemical",
"offsets": [
[
6,
16
]
],
"text": [
"Cysteamine"
],
"normalized": []
},
{
"id": "69_T3",
"type": "Chemical",
"offsets": [
[
214,
235
]
],
"text": [
"cysteamine bitartrate"
],
"normalized": []
},
{
"id": "69_T6",
"type": "Chemical",
"offsets": [
[
241,
258
]
],
"text": [
"phosphocysteamine"
],
"normalized": []
},
{
"id": "69_T9",
"type": "Species",
"offsets": [
[
88,
96
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "69_T10",
"type": "Chemical",
"offsets": [
[
324,
334
]
],
"text": [
"cysteamine"
],
"normalized": []
},
{
"id": "69_T11",
"type": "Chemical",
"offsets": [
[
324,
348
]
],
"text": [
"cysteamine hydrochloride"
],
"normalized": []
},
{
"id": "69_T12",
"type": "Chemical",
"offsets": [
[
481,
491
]
],
"text": [
"cysteamine"
],
"normalized": []
},
{
"id": "69_T13",
"type": "Species",
"offsets": [
[
506,
527
]
],
"text": [
"adult male volunteers"
],
"normalized": []
},
{
"id": "69_T14",
"type": "Chemical",
"offsets": [
[
815,
839
]
],
"text": [
"cysteamine hydrochloride"
],
"normalized": []
},
{
"id": "69_T15",
"type": "Chemical",
"offsets": [
[
841,
858
]
],
"text": [
"phosphocysteamine"
],
"normalized": []
},
{
"id": "69_T16",
"type": "Chemical",
"offsets": [
[
864,
885
]
],
"text": [
"cysteamine bitartrate"
],
"normalized": []
},
{
"id": "69_T17",
"type": "Chemical",
"offsets": [
[
1089,
1099
]
],
"text": [
"cysteamine"
],
"normalized": []
},
{
"id": "69_T18",
"type": "Chemical",
"offsets": [
[
1195,
1205
]
],
"text": [
"cysteamine"
],
"normalized": []
},
{
"id": "69_T19",
"type": "Chemical",
"offsets": [
[
1195,
1210
]
],
"text": [
"cysteamine base"
],
"normalized": []
},
{
"id": "69_T20",
"type": "Chemical",
"offsets": [
[
1327,
1351
]
],
"text": [
"cysteamine hydrochloride"
],
"normalized": []
},
{
"id": "69_T21",
"type": "Chemical",
"offsets": [
[
1374,
1391
]
],
"text": [
"phosphocysteamine"
],
"normalized": []
},
{
"id": "69_T22",
"type": "Chemical",
"offsets": [
[
1413,
1434
]
],
"text": [
"cysteamine bitartrate"
],
"normalized": []
},
{
"id": "69_T23",
"type": "Chemical",
"offsets": [
[
1677,
1687
]
],
"text": [
"cysteamine"
],
"normalized": []
},
{
"id": "69_T24",
"type": "Species",
"offsets": [
[
1825,
1833
]
],
"text": [
"patients"
],
"normalized": []
},
{
"id": "69_T7",
"type": "Chemical",
"offsets": [
[
27,
31
]
],
"text": [
"drug"
],
"normalized": []
},
{
"id": "69_T8",
"type": "Biological_Activity",
"offsets": [
[
1457,
1470
]
],
"text": [
"adverse event"
],
"normalized": []
}
] | [] | [] | [
{
"id": "69_R1",
"type": "Associated_With",
"arg1_id": "69_T20",
"arg2_id": "69_T8",
"normalized": []
},
{
"id": "69_R2",
"type": "Associated_With",
"arg1_id": "69_T21",
"arg2_id": "69_T8",
"normalized": []
},
{
"id": "69_R3",
"type": "Associated_With",
"arg1_id": "69_T22",
"arg2_id": "69_T8",
"normalized": []
}
] |
70 | 10073910 | [
{
"id": "71",
"type": "",
"text": [
"Tyrosinaemia type I is caused by a deficiency of fumarylacetoacetate hydrolase and mainly affects the liver. This disease is characterized by the presence of a high level of succinylacetone. This metabolite has been used for prenatal diagnosis from amniotic fluid samples. One case with a normal level of succinylacetone in amniotic fluid has recently been described (Grenier et al., 1996). Here, we report that this patient is a compound heterozygote for two known mutations: E364X and IVS6-1g-->t. The low level of succinylacetone cannot be explained by these mutations. \n"
],
"offsets": [
[
0,
575
]
]
}
] | [
{
"id": "71_T2",
"type": "Protein",
"offsets": [
[
49,
78
]
],
"text": [
"fumarylacetoacetate hydrolase"
],
"normalized": []
},
{
"id": "71_T4",
"type": "Chemical",
"offsets": [
[
175,
190
]
],
"text": [
"succinylacetone"
],
"normalized": []
},
{
"id": "71_T5",
"type": "Metabolite",
"offsets": [
[
175,
190
]
],
"text": [
"succinylacetone"
],
"normalized": []
},
{
"id": "71_T6",
"type": "Metabolite",
"offsets": [
[
306,
321
]
],
"text": [
"succinylacetone"
],
"normalized": []
},
{
"id": "71_T7",
"type": "Chemical",
"offsets": [
[
306,
321
]
],
"text": [
"succinylacetone"
],
"normalized": []
},
{
"id": "71_T8",
"type": "Chemical",
"offsets": [
[
518,
533
]
],
"text": [
"succinylacetone"
],
"normalized": []
},
{
"id": "71_T1",
"type": "Metabolite",
"offsets": [
[
518,
533
]
],
"text": [
"succinylacetone"
],
"normalized": []
}
] | [] | [] | [] |
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Dataset Card for CHEBI Corpus
The ChEBI corpus contains 199 annotated abstracts and 100 annotated full papers. All documents in the corpus have been annotated for named entities and relations between these. In total, our corpus provides over 15000 named entity annotations and over 6,000 relations between entities.
Citation Information
@inproceedings{Shardlow2018,
title = {
A New Corpus to Support Text Mining for the Curation of Metabolites in the
{ChEBI} Database
},
author = {
Shardlow, M J and Nguyen, N and Owen, G and O'Donovan, C and Leach, A and
McNaught, J and Turner, S and Ananiadou, S
},
year = 2018,
month = may,
booktitle = {
Proceedings of the Eleventh International Conference on Language Resources
and Evaluation ({LREC} 2018)
},
location = {Miyazaki, Japan},
pages = {280--285},
conference = {
Eleventh International Conference on Language Resources and Evaluation
(LREC 2018)
},
language = {en}
}
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