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7787326
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Primary malignant lymphoma of the liver associated with cirrhosis induced by hepatitis C viral infection.
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We present a case of primary malignant lymphoma of the liver of B cell origin with cirrhosis induced by hepatitis C viral infection. A 75-year-old Japanese woman with chronic liver dysfunction was admitted for hepatic tumors. The tumors were hypoechoic on ultrasonography and hypodense on computed tomography. Antibody to hepatitis C virus was positive. Ultrasonically guided biopsy was performed, and we diagnosed hepatic lymphoma with cirrhosis induced by hepatitis C virus clinically and immunohistochemically. This case may be the first report of the association of these two diseases, and may provide additional evidence of a predisposition to malignancy in cirrhosis.
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7787327
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Collagenous colitis.
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Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by colonic mucosal subepithelial collagen deposition. We report a 72-year-old woman who had collagenous colitis associated with chronic watery diarrhea. She received a non-steroidal anti-inflammatory agent (sulindac) because of rheumatoid arthritis. Histological examination of biopsy showed a thick subepithelial collagen layer with lymphocytes, plasma cells, and infiltration of a few eosinocytes in the lamina propria. These findings led to the diagnosis of collagenous colitis. After treatment with salazosulfapyridine, her bowel movement became normalized and mucosal subepithelial collagen deposition disappeared.
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7787325
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Involvement of the central nervous system in rheumatoid arthritis: its clinical manifestations and analysis by magnetic resonance imaging.
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A rheumatoid arthritis (RA) patient showed high signal intensity in the subcortical region of the frontal and occipital lobes on T2-weighted magnetic resonance imaging (MRI). Histopathological examination in the autopsy specimen revealed severe systemic vasculitis. Additional radiological and laboratory studies revealed that transient cerebral ischemia induced by vasculitis occurred in this patient.
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7787324
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Acromegalic gigantism with low serum level of growth hormone and elevated serum insulin-like growth factor-I.
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In a case of acromegalic gigantism with hyperprolactinemia is reported, the basal serum growth hormone (GH) levels ranged from 1.2 to 1.9 ng/ml. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood sampling showed non-pulsatile GH secretion. Serum prolactin and insulin-like growth factor-I (IGF-I) levels were elevated. After unsuccessful surgery, bromocriptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide with bromocriptine reduced serum GH and IGF-I levels. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and cause clinical acromegalic gigantism.
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7787323
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Appropriate intravenous doses of L-thyroxine and magnesium in a thyroidectomized patient with thyroid and parathyroid carcinomas receiving total parenteral nutrition during acute necrotizing pancreatitis.
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A totally thyroidectomized patient with thyroid and parathyroid carcinomas, which had developed after neck irradiation in childhood, became hypercalcemic due to pulmonary metastases. The hypercalcemia was ameliorated by intermittent iv administration of bisphosphonate for 3.5 years, but this gradually became refractory to the bisphosphonate treatment. After right thoracotomy for resection of pulmonary metastases, acute necrotizing pancreatitis developed. The patient was therefore placed on total parenteral nutrition supplemented with T4 and a restricted dose of magnesium. Thyroxine(T4) (30 micrograms/day, iv) was not sufficient to maintain euthyroidism, but a higher dose (60 micrograms/day) elicited mild hyperthyroidism to the same extent as that elicited by an oral dose of 100 micrograms/day. The present case showed that the appropriate iv dose of T4 in this thyroidectomized patient with acute pancreatitis was about 60% of the oral dose. Furthermore, bisphosphonates (pamidronate and alendronate) and magnesium depletion were very effective in controlling the hypercalcemia.
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7787322
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Coronary thrombosis induced by intracoronary acetylcholine injection in a patient with normal coronary myocardial infarction.
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A 67-year-old male was admitted with acute myocardial infarction. Coronary thrombolysis was carried out because complete occlusion of the obtuse marginal branch (OM) in the circumflex artery was detected in emergent coronary angiography, and recanalization of the OM was obtained at 3 hours after the onset of chest pain. No significant stenosis of the OM was found in coronary angiography performed at the recovery stage. After intracoronary acetylcholine injection to the left coronary artery, coronary spasm was induced and coronary thrombosis was observed in the left anterior descending artery thereafter. These findings indicate the possibility that the etiology of myocardial infarction is coronary thrombosis induced by coronary spasm.
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7787321
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Cytoplasmic body myopathy with hypertrophic cardiomyopathy.
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A patient with cytoplasmic body myopathy presented muscle hypotonia from birth and developed progressive muscular atrophy and weakness, scoliosis, contracture of joints and cardiorespiratory failure. At the age of 17, he died of heart failure. Post mortem examination revealed severe hypertrophy of cardiac walls and generalized muscular atrophy. Microscopic examination showed many cytoplasmic bodies in skeletal muscle fibers and myofiber disarray in myocardium. No cases of cytoplasmic body myopathy with hypertrophic cardiomyopathy have been reported previously. It is suggested that the Z-line component is related to the formation of the cytoplasmic body in skeletal muscle and disarray in the cardiac muscle.
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7787320
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Parvovirus infection and generalized edema in adults.
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We describe the clinical and laboratory findings of 7 adult patients with serological evidence of recent human parvovirus B19 (HPV) infection who presented with generalized edema. Six of the 7 patients had household contact with children with erythema infectiosum and had flu-like symptoms before visiting hospital. The interval between the flu-like episode and the development of edema ranged from 4 to 13 days (mean 7.0). In all 7 patients, there was serological confirmation of recent HPV infection, and all showed the development of edema following HPV infection without urine abnormalities or anemia. Two patients presented hypocomplementemia, and two patients showed signs of congestive heart failure. HPV may be considered a causative agent of generalized edema not only in the fetus but also in adults and HPV infection should be included in the differential diagnosis of generalized edema formation.
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7787319
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Thrombomodulin in exercise-induced asthma.
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Thrombomodulin (TM) is a membrane protein present in the vascular endothelium. It has also been found in human plasma, within which, however, its pathological functions have not been clearly described. In this study, the plasma TM concentrations in 19 asthmatic patients were determined by sandwich enzyme immunoassay using two monoclonal antibodies for human TM. The concentration of plasma TM in exercise-induced asthma (EIA)-positive asthmatic patients was significantly increased by exercise challenge. In addition, for these patients a positive correlation was found between the severity of EIA and the degree of change in plasma TM induced by exercise challenge. These findings suggest that the increase in influx of TM into the plasma in EIA-positive asthmatics may be due to generalized pulmonary endothelial damage following exercise challenge.
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7787318
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Portal hypertensive colopathy: endoscopic findings and the relation to portal pressure.
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Portal hypertensive colopathy (PHC) is a new clinical entity in patients with liver cirrhosis. In this study, colonoscopic findings and clinical features including upper gastrointestinal endoscopy and hepatic hemodynamics were prospectively investigated among 35 PH patients with a hepatic venous pressure gradient (HVPG) of greater than 12 mmHg due to chronic liver diseases. Colonoscopy was also performed in 100 patients without liver disease as non-PH controls. The colonoscopy revealed vascular ectasias, vascular irregularity, vascular dilatation, solitary red spots, diffuse red spots, and hemorrhoids in 26, 32, 30, 25, 10 and 25, respectively, of 35 PH patients compared to 3, 7, 3, 11, 0 and 19, respectively, in controls. PHC was endoscopically diagnosed in 27 of 35 PH patients according to our criteria. These patients with PHC were more frequently associated with esophageal varices and portal hypertensive gastropathy, and had higher HVPG than PH patients without PHC. Portal hypertension is an important factor in the etiology of PHC.
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7787317
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TRH stimulation test in healthy elderly: paradoxical response of growth hormone is abnormal in normal aging.
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The purpose of this study was to measure TSH (thyrotropin), PRL (prolactin) and GH (growth hormone) response to a TRH (thyrotropin releasing hormone) stimulation test in 37 healthy elderly male subjects and determine if these responses correlate with the incidence of mental decline; and also, to determine if these responses occur more frequently in the elderly than in the general population. A hyperresponse of TSH was documented in 7 of our 37 elderly male subjects, a delayed response of TSH in 4, a low response of PRL in 29 and a significant paradoxical response of GH in 2. Those subjects with a significant paradoxical response of GH were 82 and 83 years of age and their HDS was 20.0 and 25.5, respectively. We did not find a causal relationship between mental decline and the paradoxical response of GH, but our data suggests that the paradoxical response of GH is not normal in elderly older than 80 years old.
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7787315
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Hepatic role in the storage and utilization of fish oil fatty acids in humans: studies on liver surgery patients.
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Fish oil fatty acids (FOFA) were analyzed in fresh liver tissue and in subcutaneous and omental adipose tissue obtained from 5 patients who underwent partial hepatectomy. FOFA were also determined in plasma from 5 patients and in 10 healthy subjects. There was a high content of FOFA in the liver phospholipid (PL) fraction (twice that in our previous autopsy study) suggesting that these surgery patients had a hepatic FOFA content of at least 25g. In plasma, FOFA was predominantly found in the PL of high density lipoprotein (HDL) and partly in the PL of other lipoproteins. Since these lipoproteins are produced by the liver, the present findings indicate the role of the liver not only in storage but also in the utilization of FOFA to form the biologically important surface PL component of circulating lipoproteins.
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7787316
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Event-related potential components analysis of cognitive impairment in patients with multiple lacunar infarcts.
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We measured the visual event-related potentials (ERPs) and reaction time (RT) in 21 patients with multiple lacunar infarcts and in 8 age-equivalent normal subjects. The N2 latency of the infarct patients was significantly longer than that of the normal subjects, although the NA and the P3 latencies and RT did not differ between the two groups. The N2 latency was negatively correlated with the scores of Mini-Mental State Examination or the Hasegawa's dementia scale. These results suggest that the impairment of cognitive information processing in these patients arises from an uncertainty in the classification of a perceived event. In addition, the N2 latency may be more sensitive in detecting cognitive impairment in multiple infarct patients.
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7787314
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Molecular cloning of a cDNA for proctase B from Aspergillus niger var. macrosporus and sequence comparison with other aspergillopepsins I.
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A cDNA for proctase B from Aspergillus niger var. macrosporus was isolated and sequenced. The deduced amino acid sequence (394 residues) of the preproform of the enzyme was highly homologous (98% identify) with those of aspergillopepsins I from A. awamori and A. saitoi, and moderately homologous (68% identity) with that of A. oryzae. Most of the sequence differences were found in the carboxyl-terminal domain.
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7787313
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The phylogeny of Williopsis salicorniae Hinzelin, Kurtzman et Smith based on the partial sequences of 18S and 26S ribosomal RNAs (Saccharomycetaceae)
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Williopsis salicorniae IFO 10733 (type strain), which is characterized by the formation of saturn-shaped ascospores, by the incapability of assimilating nitrate, and by a lower DNA base composition (36.7 mol% G + C), was examined for its partial base sequences of 18S and 26S rRNAs. In the 18S rRNA partial base sequencings, it had an identical base sequence with the type strain of Ogataea glucozyma (identical to Pichia glucozyma, identical to Hansenula glucozyma), which produces hat-shaped ascospores and has the ability to assimilate nitrate and methanol and a higher DNA base composition (45.1 mol% G + C). In the 26S rRNA partial base sequencings, the base differences were four, and the percent similarity was 87 between the type strains of the two species. The data obtained are discussed phylogenetically and taxonomically.
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7787312
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Stimulatory factors for enzymatic biotin synthesis from dethiobiotin in cell-free extracts of Escherichia coli.
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The activity of biotin synthesis from dethiobiotin was found in cell-free extracts of an Escherichia coli bioB transformant. Among the sulfur compounds tested, only S-adenosyl-L-methionine (AdoMet) had a significant effect, while methionine and cysteine were inert. The activity was linearly stimulated by increasing protein concentration. When the dialyzed cell-free extracts were used for the reaction, NADP+, NADPH, and FAD among the well-known cofactors tested promoted the activity. Furthermore, in the presence of AdoMet, cysteine was apparently effective for biotin synthetic activity.
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7787309
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USF-19A, a new lipoxygenase inhibitor from Streptomyces sp.
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USF-19A, a soybean lipoxygenase (SBL) and human 5-lipoxygenase (5-LO) inhibitor, was isolated from Streptomyces sp. USF-19 strain. Its chemical structure was determined by spectroscopic evidence to be a new member of the antimycin antibiotic family. The IC50 value of USF-19A against 5-LO was 28.0 microM.
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7787311
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Binding of amino acid pyrolysates and aflatoxins to autoclaved cells of Enterococcus faecalis FK-23.
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There was significant binding in autoclaved cells of Enterococcus faecalis FK-23 toward Trp-P1 and Trp-P2. Although the binding ability towards aflatoxins B1, B2, G1, and G2 was less compared with the significant binding toward Trp-P1 and Trp-P2, higher percentage binding toward these aflatoxins was observed when the amount of the cell preparation was increased.
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7787308
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Functional distinction among structural subsections in the specific priming signal for DNA replication of the broad host-range plasmid RSF1010.
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To analyze the functional contribution to the ssiA function of subsections of the ssiA-determinant sequence based on their dimensions, we constructed ssiA mutants carrying insertions and deletions. Results of the examination of the ssiA mutants told us that, in addition to the base sequence, the dimensions were crucial factors for the functional contribution of the subsections of ssiA.
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7787307
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Purification and characterization of membrane-bound hydrogenase from a thermophilic hydrogen-oxidizing bacterium, Pseudomonas hydrogenothermophila strain TH-1.
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A membrane-bound hydrogenase was purified aerobically by one step using a hydroxyapatite column after solubilization by acetone treatment from a thermophilic hydrogen-oxidizing bacterium, Pseudomonas hydrogenothermophila strain TH-1. The enzyme consists of two polypeptides of 63 and 31 kDa, respectively. The amino-terminal amino acid sequences of both subunits were homologous to membrane-bound type [Ni-Fe] hydrogenases from other origins. The thermostability under a hydrogen gas atmosphere is highly stable at 50 degrees C, which is the optimum temperature for the cell growth.
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7787310
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Isolation of bacteria degrading carbazole under microaerobic conditions, i.e. nitrogen gas substituted conditions.
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Microorganisms degrading carbazole (CA), a model substrate of heterocyclic nitrogen compounds in crude petroleum oil, were screened under microaerobic conditions, i.e. nitrogen gas substituted conditions. Eight bacteria were isolated and identified. For example, Bacillus sp. KUKK-4 degraded 31% of CA when cultivated for 28 days in a medium initially containing CA at 1000 mg/l with shaking under the microaerobic conditions.
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7787305
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Cleavage of connectin by calpain and cathepsin D.
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mu-Calpain quickly split the alpha-connectin in myofibrils into beta-connectin, and then produced a 1700-kDa component. Cathepsin D also split alpha-connectin into beta-connectin, further degrading it to fragments smaller than the 1700-kDa component with increasing incubation time. The action of cathepsin D on the connectin molecule was distinctly different from that of mu-calpain in terms of the splitting rate and manner. When freshly excised muscle was exposed to a temperature of 37 degrees C, complete disappearance of connectin (alpha, beta and 1700-kDa component) was observed within 36 h. In contrast, at 2 degrees C, about 75% of connectin was retained as beta-form even after 3 weeks. The present data suggest that the degradation of connectin in muscle might be caused by mu-calpain in the early stage of aging, and then with time, this action is replaced by m-calpain or cathepsin D. However, the possibility of other intrinsic proteases participating in the degradation of connectin still remains.
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7787304
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Selective use of L-valine and L-isoleucine for the biosynthesis of branched-chain fatty acids in rat skin.
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Iso- and anteiso-fatty acids are detected in more than trace amounts in rat skin surface lipid. The terminal portion of even carbon number iso- and anteiso-fatty acids are synthesized respectively from valine (Val) and isoleucine (Ile) by essentially the same reaction sequences established for straight chain fatty acids. This paper describes the stereospecific biosynthesis of these branched chain fatty acids (BCFAs) and alcohols (BCFALs) in rat skin. Dependence of the concentration of these BCFAs on dietary L-Val and L-Ile was studied. Concentrations of even carbon number iso- and anteiso-fatty acid increased respectively with dietary L-Val and L-Ile. The saturation dose appeared to be 2% for L-Val and 1% for L-Ile. Supplementation of the diet with 2% D-Val, however, did not affect the concentration of even carbon number iso-fatty acid in rat skin surface lipid despite a comparable serum Val level to that of the 2% L-Val group. A similar experiment using 1% DL-Ile found that L-isomer, but not D-isomer, in the circulation was used for the biosynthesis of anteiso-fatty acids. This view was applicable to the incorporation of D-Val and DL-Ile into related BCFALs.
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7787303
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Pyromeconic acid and its glucosidic derivatives from leaves of Erigeron annuus, and the siderophile activity of pyromeconic acid.
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3'-O-Caffeylerigeroside (pyromeconic acid 3-O-beta-D-glucoside 3'-O-caffeyl ester) was obtained from the leaves of Erigeron annuus as a new pyromeconic acid derivative, and its structure was elucidated. Together with the gamma-pyrone derivative, pyromeconic acid (3-hydroxy-4H-pyran-4-one) and its beta-glucoside (erigeroside) were also isolated from the aerial parts of E. annuus. The siderophile activity of pyromeconic acid was also studied.
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7787302
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Promoinducin, a novel thiopeptide produced by Streptomyces sp. SF2741.
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Our continued screening to find tipA promoter-inducing substances resulted in the isolation of promoinducin from a mycelial extract of Streptomyces sp. SF2741. Based on various 1D- and 2D-NMR studies, including field gradient (FG)-COSY, HSQC, FG-HMBC, phase-sensitive 13C-decoupled HMBC and NOESY experiments, promoinducin's structure was established to be a thiopeptide composed of threonine, some unusual amino acids masked at their carboxyl groups by thiazole or methyloxazole rings, sulfomycinamate and five dehydroalanine residues. Promoinducin induced the tipA promoter at 40 ng/ml, and also exhibited strong antibacterial activity against some Gram-positive bacteria.
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7787301
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Comparison of o-phthalaldehyde modification of alpha-amylases from porcine pancreas and Bacillus subtilis with Taka-amylase A.
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A fluorescent reagent, o-phthalaldehyde (OPA), competitively inhibited porcine pancreatic alpha-amylase (PPA) with Ki values of 0.7-0.9 mM, while alpha-amylase from Bacillus subtilis (BS) was uncompetitively inhibited, with Ki values of 5.8-7.6 mM. In both cases, OPA gave a time-dependent irreversible inactivation, where the amylase activity was lost faster than the maltosidase activity. Zymograms of the course of OPA modification showed that PPA was converted into at least six, faster moving components and BS gave two components. The OPA modification was retarded by the addition of the substrate analog, cyclodextrins, and the OPA modified enzymes decreased in affinity for the substrate soluble starch. Stoichiometric measurement showed that both PPA and BS was inactivated by the incorporation of 1 mol of OPA per mol of enzyme. The role of OPA modification of alpha-amylases was discussed in relation to the regulation of catalytic activity of enzymes.
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7787300
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Effects of the lipid-saccharide complex and unsaponifiable matter from sunflowers on liver lipid metabolism and intestinal flora in rats.
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The effects of the flower lipid-saccharide complex and unsaponifiable matter (1 g/kg of diet) from the sunflower on liver lipid metabolism and intestinal flora was studied in rats given cholesterol-enriched diets. After six weeks of feeding, the microsomal cholesterol concentration in the liver had been significantly reduced with the sunflower diet. The ratio of cholesterol/phospholipid was also reduced by the sunflower diet. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the sunflower groups was significantly lower than that of the control group. There was no significant difference in the cholesterol 7 alpha-hydroxylase activity, although this tended to increase with dietary sunflower consumption. The number of Bacillus in the cecum flora was significantly higher in the lipid-saccharide complex group than in the other groups, while Bifidobacterium and Eubacterium in the cecum flora was significantly higher in the unsaponifiable matter group when compared to the control group. These results suggest that the lipid-saccharide complex and unsaponifiable matter in the sunflower are related to liver cholesterol synthesis and intestinal flora.
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7787299
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Rapid and simple procedure for purifying PAS-4 glycoprotein from bovine milk fat globule membrane.
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The isolation and partial characterization of PAS-4 glycoprotein (78 kDa) from bovine milk fat globule membrane (MFGM) is described. PAS-4 was selectively extracted with Triton X-114 nonionic detergent and then fractionated on DEAE-Sepharose at pH 7.5. The PAS-4 fraction that was not bound on DEAE-Sepharose gave a single band by SDS-PAGE. The recovery of PAS-4 was 57.4% from MFGM. An amino acid analysis found a high percentage of nonpolar residues. Approximately 7.2% of carbohydrate from PAS-4 was composed of mannose, galactose (Gal), N-acetylglucosamine, N-acetylgalactosamine (GalNAc), and sialic acid, most of the Gal and GalNAc in PAS-4 being released after mild alkaline hydrolysis. This indicated that PAS-4 contained both N- and O-linked sugar chains in concordance with the results of lectin affinity. PAS-4 had apparent isoelectric points of 7.45, 7.41, and 7.32, but these were shifted to pI 7.47 by a neuraminidase treatment. The apparent molecular weight of PAS-4 after deglycosylation with N-glycanase was approximately 57,000 by SDS-PAGE.
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7787297
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Alpha-subunit of beta-conglycinin, an allergenic protein recognized by IgE antibodies of soybean-sensitive patients with atopic dermatitis.
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One of the major allergenic proteins in the soybean 7S-globulin fraction, which was recognized by sera of about 25% soybean-sensitive patients with atopic dermatitis, was identified as alpha-subunit of beta-conglycinin. The IgE antibodies recognizing the alpha-subunit did not show a cross-reactivity against both alpha'- and beta-subunits known to be highly homologous to alpha-subunit, and also against other allergenic components identified in soybeans [Ogawa et al., J. Nutr. Sci. Vitaminol., 35, 555-565 (1993)]. The IgE-binding site(s) was estimated to be located on the peptide 232-283 of alpha-subunit.
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7787298
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The complete amino acid sequence of chitinase-B from the leaves of pokeweed (Phytolacca americana).
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The complete amino acid sequence of pokeweed leaf chitinase-B (PLC-B) has been determined by first sequencing all 19 tryptic peptides derived from the reduced and S-carboxymethylated (RCm-) PLC-B and then connecting them by analyzing the chymotryptic peptides from three fragments produced by cyanogen bromide cleavage of RCm-PLC-B. PLC-B consists of 274 amino acid residues and has a molecular mass of 29,473 Da. Six cysteine residues are linked by disulfide bonds between Cys20 and Cys67, Cys50 and Cys57, and Cys159 and Cys188. From 58-68% sequence homology of PLC-B with five class III chitinases, it was concluded that PLC-B is a basic class III chitinase.
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7787295
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Role of ornithine in urea synthesis in rats treated with thyroid hormone.
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The purpose of this study was to find whether the regulation of urea synthesis was mediated through the activation of N-acetyglutamate synthesis by ornithine when the thyroid status was manipulated. Experiments were done on three groups of rats, given 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without triiodothyronine (T3) treatment, treated with PTU + T3, or neither PTU nor T3 (control). Urinary excretion of urea and the liver concentrations of ornithine and N-acetylglutamate in rats given PTU + T3 were significantly lower than in rats given PTU alone. The liver concentration of N-acetylglutamate was correlated with the liver concentration of ornithine (r = 0.920, p < 0.001). Ornithine administration (0.5 mmol/100 g body wt) elevated the liver concentration of N-acetylglutamate in all three groups. The results suggest that the greater concentration of ornithine in the hypothyroid (PTU alone) rats is likely to increase the N-acetylglutamate concentration in liver and stimulate urea synthesis.
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7787296
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Measurement of superoxide dismutase-like activity of natural antioxidants.
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The superoxide dismutase (SOD)-like activity of natural antioxidants was evaluated by measuring the inhibition of pyrogallol autoxidation that is catalyzed by the superoxide radical. Among 22 water-soluble antioxidants tested, L-ascrobic acid, L-ascorbic acid 6-palmitate, glutathione (reduced form), (+)-catechin, and (-)-epicatechin showed effective SOD-like activity. To analyze lipophilic antioxidants, an optically clear organic system composed of diethyl ether, surfactant (dioctyl sulfosuccinate, AOT) and water, called reverse micelles, was developed. The optimum concentrations of AOT, water and pyrogallol for determining SOD-like activity were found to be 50 mM, 1.3 M, and 40 mM, respectively. After proving that pyrogallol autoxidation was mediated by the superoxide anion in that system, the SOD-like activity of 24 lipophilic antioxidants was measured. Cinnamon oil, gamma-oryzanol, extract of rosemary leaf, L-alpha-lecithin, and L-alpha-cephalin exhibited activity, although the activity of some antioxidants could not be measured because of the intense color or low solubility.
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7787294
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Change in the distribution of alpha-tocopherol stereoisomers in rats after intravenous administration.
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Synthetic alpha-tocopherol (alpha-Toc) contains equal amounts of eight different stereoisomers arising from three chiral centers in the phytyl tail. Of these, the four stereoisomers with the 2R configuration are generally more active than their corresponding 2S-isomers. We investigated the change in distribution of alpha-Toc stereoisomers in the plasma and tissues after intravenously administering all-rac- and SRR-alpha-Toc acetate. The concentration of 2R-isomers in the rat plasma after administering all-roc-alpha-Toc acetate was higher than that of the 2S-isomers. On the other hand, the concentration of 2R-isomers in the liver was lower than that of 2S-isomers up to 6 h. In the rat plasma after administering only SRR-alpha-Toc acetate, no SRR-alpha-Toc was detected after 6 h, although SRR-alpha-Toc in the liver was retained at a higher level than in the other tissues. We presume that the intravenously administered 2R- and 2S-isomers were easily transported into the liver from the plasma, the 2R-isomers being preferentially released from the liver into the blood, whereas the 2S-isomers remained in the liver for up to 6 h.
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7787292
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Effect of the viscosity or deacetylation degree of chitosan on fecal fat excreted from rats fed on a high-fat diet.
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Several chitosan preparations, either with a comparable degree of deacetylation but differing viscosity or with comparable viscosity but a differing degree of deacetylation, were examined for their effect on the fecal fat excreted from rats fed on a high-fat diet. As the viscosity or deacetylation degree of a chitosan preparation increased, the more its effect on the apparent fat digestibility by rats became conspicuous. A supplement of ascorbic acid to each chitosan diets resulted in a significant depression of fat digestion and absorption in the lumen. The chitosan intake caused a higher level of fat to be excreted in the feces of the corn oil-receiving rats than the lard-receiving ones, although the effect was strong with both diet groups.
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7787293
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Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate.
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We investigated the mechanism for the inhibition of fat digestion by chitosan, and the synergistic effect of ascorbate. The important inhibition characteristics of fat digestion by chitosan from observations of the ileal contents were that it dissolved in the stomach and then changed to a gelled form, entrapping fat in the intestine. The synergistic effect of ascorbate (AsA) on the inhibition of fat digestion by chitosan is thought not to be acid-dependent but due to the specificity of AsA itself, according to the data resulting from using preparations supplemented with sodium ascorbate (AsN). The mechanism for the synergistic effect is considered to be 1) viscosity reduction in the stomach, which implies that chitosan mixed with a lipid is better than chitosan alone, 2) an increase in the oil-holding capacity of the chitosan gel, and 3) the chitosan-fat gel being more flexible and less likely to leak entrapped fat in the intestinal tract.
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7787291
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Systemic release of mucosal mast-cell protease in primed brown Norway rats after feeding with beta-lactoglobulin.
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The plasma level of mucosal mast-cell protease was examined to find whether such measurements could be an indicator of allergic response to beta-lactoglobulin (beta-LG) challenged orally by rats. Brown Norway rats, which had been raised on a bovine milk-free diet, were systemically sensitized on day 0 with a low dose of beta-LG, and then by an oral administration of beta-LG for 3 h on day 14. The oral challenge with beta-LG in saline, when compared to saline alone, resulted in a systemic elevation of rat mast-cell protease II (RMCPII), one of the specific markers for gut mucosal mast-cell secretion. The challenge with beta-LG in a fat emulsion further increased the level of plasma RMCPII. This manipulation, however, was not successful for detecting any significant difference in mucosal leucotriene C4, another allergic mediator. An oral challenge with polymerized beta-LG did not induce any elevation of the protease, but resulted in a lower plasma level of beta-LG-specific IgG. This animal model is thus relevant to investigate the events regulating the mucosal hypersensitivity and humoral immunity to food proteins.
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7787289
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Pediatric heart transplantation.
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Studies from a number of centers have documented the growth and success of pediatric heart transplantation. The 1st year of life is the period of greatest mortality from congenital heart disease and has now become the single most frequent age of pediatric heart transplantation. Appropriately, congenital heart disease is the most common diagnosis leading to heart transplantation. Early mortality is still greatest in recipients who undergo transplantation during the 1st year of life. The patients at greatest risk are being identified and new maneuvers to lower early mortality are emerging. Long-term follow-up continues to indicate excellent late survival with low morbidity. This review focuses on key advances in knowledge reported in the last year.
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7787288
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Alternatives to human heart replacement.
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The continuing and increasing discrepancy between the number of available donor hearts and the number of patients who might benefit from cardiac transplantation has prompted efforts in the development of xenotransplantation, mechanical assist devices, and cardiomyoplasty techniques. We briefly review recent work in these three fields. The results of experimental xenotransplantation between closely related species are improving slowly with currently available drugs, and clinical trials in this field may be possible in the near future. Implantable ventricular assist devices are also at a stage of development where permanent implantation is likely to be followed by a reasonable and worthwhile period of patient survival. With regard to cardiomyoplasty, steady progress is being made in clarifying exact indications and patient selection, as well as confirming the potential benefits.
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7787287
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Immunosuppression in cardiac transplantation: a new era in immunopharmacology.
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During the past 5 years, there has been a concerted effort to identify new immunosuppressive agents for organ transplantation that have greater efficacy and fewer side effects than current therapies (corticosteroids, azathioprine, cyclosporine, anti-T cell antibodies). These new drugs can be generally classified according to their varying structures or mechanisms of action: xenobiotic molecules (FK506, rapamycin, cyclosporine analogues); antimetabolites (mycophenolate mofetil, mizoribine, brequinar sodium); and those agents with novel or incompletely defined mechanisms of action (leflunomide, 15-deoxyspergualin). Many of the newer agents offer better therapeutic indexes, and some even show promise in the treatment of two of the major obstacles currently facing cardiac allograft transplantation: antibody-mediated accelerated humoral rejection and chronic vascular rejection (also known as accelerated graft coronary artery disease). With the increasing shortage of donor organs in recent years, there has been a resurgence of interest in xenotransplantation; some of the new immunosuppressants demonstrate efficacy in prolonging xenograft survival. Most of these agents will probably find their niches as components of low-dose combination regimens designed to maximize effective immunosuppression and minimize drug toxicities and opportunistic infections.
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7787286
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Immunopathology of cardiac transplant rejection.
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Transplant rejection represents a diverse series of complex immunological events beginning with allorecognition and lymphocyte activation and differentiation, followed by interactions of antibodies and activated lymphocytes with the vascular endothelium and subsequent cellular infiltration into the allograft, and, finally, the inflammatory process leading to tissue injury. This paper reviews how these events contribute to the different types of cardiac transplant rejection, including cardiac allograft vasculopathy.
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7787285
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Clinical follow-up of the heart transplant recipient.
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Long-term survival of heart transplant recipients is now commonplace, due to improved perioperative care. It is thus appropriate to review recent studies concerning immunosuppression-related clinical problems in heart transplant recipients, including infections, malignancies, hypertension, hyperlipidemia, and osteoporosis. Hormonal and peripheral vascular responses of the denervated heart, exercise tolerance, pulmonary function, and parenting are also discussed.
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7787284
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Socioeconomic aspects of heart transplantation.
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Heart transplantation is an established treatment modality for end-stage cardiac disease. Unfortunately, relative to other health care priorities, heart transplantation has fallen into disrepute. Efforts to reform the health care system have focused on three fundamental issues--cost, quality, and access. On each count, heart transplantation is vulnerable to criticism. Managed care is an incremental approach to health care reform that imposes fiscal constraint on providers. This constraint is expressed in the form of capitation which, in turn, requires providers to assume risk and accept economic responsibility for clinical decisions. While the need for transplantation is considerable, there are both clinical and economic factors limiting the overall level of activity. In 1993, over 2200 heart transplants were performed in the United States on people who were dying of end-stage cardiac disease. The total demand for heart transplantation was estimated to be about 5900 persons, which was not met due to an insufficient supply of donor hearts. Absent donors, the fiscal consequences of heart transplantation are minimized. In 1993, actuaries estimated that the total charge per heart transplant was $209,100. By designating centers based on price and quality considerations, managed care plans have reduced this per procedure expense to less than $100,000. While the benefits of transplantation are noteworthy, there are still concerns. Sixty percent of patients report that they are able to work, but only 30% do so. Employers hope to improve upon this record by expanding the designated center approach. In conclusion, the future of heart transplantation is unclear. Opportunities for innovation are limited, although the management of heart failure is an area of increased interest.
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7787283
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Candidate evaluation and selection for heart transplantation.
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Because of the increasing discrepancy between the number of identified candidates for heart transplantation and available donor organs, appropriate selection of patients for heart transplantation is critical. The establishment of a cardiac prognosis that is significantly worse than that following heart transplant is central in the determination of candidacy for transplantation. However, with recent improvements in heart failure management, prognosis must be considered a dynamic state involving periodic reassessment to ensure an individual's ongoing suitability for transplantation. There have been many descriptions of prognostic indexes in heart failure, but care must be used when extrapolating observations collected from patients with a broad range of conditions to those with end-stage disease. The contraindications to heart transplantation have also evolved with the increasing success of the transplant process. Many conditions that precluded patients from heart transplant in the past are no longer regarded as absolute. Despite less stringent conditions for recipient candidacy, the need to achieve optimal results with an increasingly valuable donor resource will necessitate careful scrutiny of the posttransplant implications of the various conditions currently regarded as contraindications to heart transplant. Determination of heart transplantation candidacy therefore continues to remain a highly individualized process, requiring clinical judgment and experience.
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7787281
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New developments in infective endocarditis.
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Endocarditis as seen today differs significantly from that outlined by Sir William Osler in his famous Gulstonian lectures in 1885. The median age of the patients has increased; the spectrum of predisposing cardiac lesions has changed; more cases are due to unusual organisms, including gram-negative bacteria and fungi; and more cases present acutely and the classic findings of late endocarditis are seldom seen. Endocarditis was untreatable and uniformly fatal in 1885. Although continued advances in medical and surgical therapy have significantly increased survival, the recent appearance of multiresistant organisms in some cases is reminiscent of the Osler era. Recent advances in the diagnosis and management of endocarditis include the identification of a specific Staphylococcus aureus receptor protein on endothelial cells, better imaging of the cardiac structures using transesophageal echocardiography, improvement in clinical diagnostic criteria and surgical techniques, and the use of outpatient oral antibiotics for penicillin-sensitive streptococcal endocarditis.
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7787280
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Which prosthetic valve should we choose?
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In this review I concentrate on issues related to prosthetic valves themselves: their development, performance, and durability. For example, mechanical failure or tissue deterioration appear to be intrinsic properties of the valve and are therefore central to my topic, whereas the development, diagnosis, and management of endocarditis are largely independent of the type of prosthesis and are thus not dealt with here. Other outcomes such as stroke are also determined by factors other than the choice of valve, as was cogently argued in papers published during the past year. The papers on tissue valves have a common theme: they document the inevitability of tissue failure, too early for acceptable use other than in old age. The mechanical valves that have stood the test of time have done so because they do not fail.
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7787279
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Surgical repair and reconstruction of valvular lesions.
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Thirty-six years have passed since the inception of mitral valve repair by Lillehei and McGoon. In the period presently under review it is apparent that mitral valve repair and the late results have become more predictable. Previously, repair was not attempted because of concern that valve replacement, with its attendant problems, might be necessary. This attitude appears to be slowly changing. The current issue is whether patients who have severe mitral regurgitation but are relatively asymptomatic should be referred for repair before ventricular function deteriorates or atrial fibrillation develops. Current evidence suggests that approximately 10% of asymptomatic patients will progress sufficiently each year to require surgical intervention. Systolic anterior motion of the mitral valve causing left ventricular outflow tract obstruction, has, since the era of routine intraoperative transesophageal echocardiography, become a well-recognized occasional consequence of mitral valve repair. Numerous theories have been suggested as to its cause: the most plausible suggest that risk factors include the presence of excess valvular tissue, a bulging septum, a nondilated hyperdynamic left ventricle, and a narrow mitral-aortic angle. The fact that numerous annuloplasty techniques exist, each having its own proponent(s), suggests that different techniques or types of annuloplasty are equally effective. Reparative techniques for the aortic valve have lagged behind those for the mitral valve because of limited previous success. The type of valve pathology was recently classified in terms of repair and new techniques, which are briefly documented, have been tried.(ABSTRACT TRUNCATED AT 250 WORDS)
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7787278
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Recent developments in balloon valvuloplasty techniques.
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The long-term outcome after mitral valvuloplasty is excellent and compares well with surgical treatment of mitral stenosis. Compared with the double balloon technique, the Inoue method is technically easier and may reduce acute complications without any adverse effect on long-term outcomes. Excellent long-term outcome is also seen after balloon valvuloplasty of aortic stenosis in the young and in pulmonary stenosis at all ages. Finally, although balloon aortic valvuloplasty in the elderly may not change the terrible prognosis of such patients, it does improve functional status and is a useful bridge to surgery in selected patients.
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7787277
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Management of valvular regurgitation.
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The principles of the management of left-sided valvular regurgitation, which weigh watchful waiting against surgery, have crystallized over the past 15 years. While the timing of surgery once was enigmatic, it is now clear that surgery must be done prior to the development of prolonged left ventricular dysfunction. Fortunately, satisfactory indexes have been developed that allow the clinician to detect and avoid such dysfunction. Therefore, patients now undergo surgery sooner, resulting in reduced operative mortality and better long-term survival. However, there are still several unresolved issues regarding the management of valvular regurgitation. For instance, operations for mitral regurgitation that preserve the mitral apparatus improve postoperative left ventricular performance compared with conventional mitral valve replacement. However, the proper timing for these operations is still being examined. Another issue is whether vasodilators, which reduce the regurgitant overload, can delay the onset of ventricular dysfunction and thus also delay surgery. In contemplating vasodilator use there is a paradox between the principle of early surgery to prevent dysfunction and use of medical therapy to delay surgery. Several studies which have appeared in the literature in the past year help resolve some of these issues.
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7787276
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Management of valvular stenosis.
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The management of valvular stenosis has changed dramatically over the past 15 years, largely due to interventional cardiology. At the beginning of the 1980s, balloon valvuloplasty was thought by many to represent a definitive new treatment for calcific aortic stenosis in the elderly infirm. Before the end of the decade, this treatment had gone out of favor, but by that time we had learned that many of those same patients could undergo aortic valve replacement relatively safely and with excellent results. Unlike aortic stenosis, mitral stenosis is a disabling rather than a lethal disease, so the timing of intervention is much more difficult, particularly as there are treatment choices. Mortality, morbidity, and the possible bonus from proceeding earlier rather than later all need to be taken into consideration. Much to many people's surprise, mitral balloon valvuloplasty has grown and prospered, especially since the introduction of the Inoue balloon. It is the treatment of choice for young patients with mobile, noncalcified, stenosed valves, although still offering worthwhile palliation for older patients with higher echocardiographically determined valve scores. Echocardiography has gradually usurped cardiac catheterization for the assessment of valve stenosis and left ventricular function, but in patients with concomitant coronary disease that will be treated at the same time, the need for coronary angiography remains almost unchallenged.
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7787275
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Recent developments in the diagnosis and management of mitral valve prolapse.
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Mitral valve prolapse (MVP), which occurs in about 3% of adults, is usually a primary, dominantly inherited condition. MVP may be diagnosed by auscultation of a mid-systolic click and late-systolic murmur that move dynamically with postural maneuvers. M-mode echocardiography confirms MVP by demonstrating late-systolic prolapse and two-dimensional echocardiography reveals leaflet billowing into the left atrium. Echocardiography identifies severe forms of MVP by documenting significant mitral regurgitation, enlargement and thickening of the mitral leaflets and annulus, and loss of leaflet apposition. In contrast to early reports, true "MVP syndrome" as revealed by controlled studies consists of low body weight and blood pressure, minor skeletal abnormalities, orthostatic hypotension, palpitations, and mitral regurgitation that is usually mild. Complications of MVP include progressive mitral regurgitation, infective endocarditis, orthostatic syncope, and possible risks of neurologic ischemia and arrhythmic sudden death. Risk factors we have identified for complications among patients with MVP include older age, male gender, the presence of mitral regurgitation, and possibly, higher weight and blood pressure. The cumulative risk of all complications of MVP by age 75 is from 5% to 10% for affected men and 2% to 5% for affected women. Patients with MVP who have neither a murmur nor Doppler evidence of mitral regurgitation may be reassured that their condition is benign. For other patients with MVP we have shown that oral antibiotic prophylaxis is cost-effective. The presence and severity of mitral regurgitation govern the frequency and intensiveness of follow-up.
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7787274
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Advances in noninvasive assessment of valvular heart disease.
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Echocardiography continues to be the noninvasive method of choice in the evaluation of valvular heart disease. Important recent developments include clinical validation of approaches used to quantify valvular regurgitation, in particular the proximal flow convergence zone method; use of transesophageal imaging to monitor and evaluate surgical or percutaneous interventions in valvular heart disease, in particular mitral valve repair; insight into flow-related stretch of the orifice area in aortic stenosis; and validation of nuclear magnetic resonance imaging in small series for quantification of left-sided valvular stenotic and regurgitant lesions.
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7787271
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Adult congenital heart disease.
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Much of the literature published in 1993 on the topic of adult congenital heart disease described long-term follow-up of patients following repair in childhood. This report reviews the most important papers published during the past year related to long-term follow-up, and also describes new information on the noninvasive evaluation of congenital heart disease in adults as well as the interventional cardiologic techniques that are currently being applied to treat some defects in the catheterization laboratory.
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7787270
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Identification of patients with hypertrophic cardiomyopathy at high risk for sudden death.
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Patients with hypertrophic cardiomyopathy are at increased risk for sudden death. Recent studies have improved our ability to risk-stratify such patients and have elucidated several potential mechanisms of sudden death and syncope. Certain noninvasive tests, such as signal-averaged electrocardiography and measurements of cardiac autonomic function and QT/QT dispersion, are often abnormal in hypertrophic cardiomyopathy, but are not useful for risk stratification. Myocardial ischemia determined by exercise thallium scintigraphy, however, identifies young patients with hypertrophic cardiomyopathy who are at high risk for cardiac arrest and syncope. Nonsustained ventricular tachycardia on ambulatory Holter monitoring in the absence of symptoms of impaired consciousness is associated with a benign prognosis and is not predictive of sudden death. Conversely, ventricular tachycardia induced at electrophysiologic study identifies adult patients with hypertrophic cardiomyopathy who subsequently experience sudden death. Finally, characterization of the natural history of the genetic defects will increasingly become an integral part of risk evaluation in hypertrophic cardiomyopathy.
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7787269
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New perspectives in childhood blood pressure.
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Ambulatory blood pressure monitoring is a new technique available to the pediatric cardiologist, and several studies have investigated its usefulness. Investigators are now providing data for both normal values and reproducibility. Other authors have examined the effects of hypertension in mothers upon their offspring, which include small birthweight and possible developmental delay. New data, particularly from the Bergen Blood Pressure Study, indicate that maternal hypertension may be a precursor for future blood pressure elevation in offspring. It is known that obese people are more likely to be hypertensive. A study performed in China in a lean population, including individuals who were relatively obese, showed the positive relation of body weight to blood pressure. Furthermore, data now emerging indicate that both retinal vessels and renal arteries in children suffer changes with persistently elevated blood pressure. This clearly is something to follow. Other articles examined in this review investigate the relation of atherosclerosis to hypertensive disease.
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7787268
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Advances in acquired pediatric heart disease.
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Acquired heart disease in children may result in significant morbidity and mortality. Advances continue to be made in understanding Kawasaki disease, acute and chronic rheumatic heart disease, infective endocarditis, myocarditis, and dilated cardiomyopathy. The role of superantigens, particularly bacterial toxins, in the pathogenesis of Kawasaki disease continues to be defined. Intravascular ultrasound promises to improve the assessment of coronary arteries in Kawasaki disease. Current recommendations for the long-term management of Kawasaki disease are discussed. Significant changes in the epidemiology of acute rheumatic fever and endocarditis are noted. Updates on the role of echocardiography as well as current therapeutic issues in these diseases are addressed. The application of immunologic and molecular biologic techniques have implicated genetic and immune factors in the pathogenesis of myocarditis and cardiomyopathy. The relationship between viral infection and subsequent dilated cardiomyopathy, as well as the role of autoimmune mechanisms in the pathogenesis of these disorders, remains controversial.
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7787267
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Congenital cardiovascular disease and cardiac surgery in childhood: Part 2. Acyanotic congenital heart defects and interventional techniques.
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The literature for the period reviewed documents a significant reduction of morbidity and mortality for neonatal repairs of atrioventricular septal defects, coarctation of the aorta, and ventricular septal defects. Long-term follow-up of patients with coarctation of the aorta provides important suggesting that earlier repair of asymptomatic coarctation and complete elimination of obstruction in the arch as well as at the coarctation site are essential to better long-term results. Surgery for complete atrioventricular septal defect has evolved from palliation, with poor long-term results, to complete repair within the first 6 months of life, with minimal morbidity and mortality. Special emphasis is now placed on children with Down's syndrome who have complete atrioventricular septal defects; data confirm their tendency for earlier development of pulmonary vascular obstructive changes. Further refinements in surgical and interventional catheterization techniques have resulted in promising advances for many lesions--coarctation of the aorta (native and recurrent); valvular, subvalvular, and supravalvular aortic stenosis; valvular pulmonary stenosis; patent ductus arteriosus; and branch pulmonary artery stenosis--and have prompted provocative discourse between cardiologists and surgeons. These refinements in surgical and interventional techniques have initiated a new era in the clinical management of congenital heart disease in childhood.
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7787265
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Fetal arrhythmias, pediatric arrhythmias, and pediatric electrophysiology.
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The practice of pediatric electrophysiology has been altered drastically and irrevocably over the past 5 years. With the advent of widespread application of transcatheter radiofrequency ablative techniques in young patients, decision-making in the management of childhood arrhythmias has focused less on palliative medical therapies and more on the potential for curative, nonsurgical interventions. This review examines the published contributions in the area of pediatric catheter ablation, antiarrhythmic drug therapy, postoperative arrhythmias, fetal arrhythmias, and electrocardiographic phenomena after cardiac transplantation.
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7787266
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Congenital cardiovascular disease and cardiac surgery in childhood: Part 1. Cyanotic congenital heart defects.
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The management of congenital heart disease is in a state of evolution, with earlier surgical and/or catheter interventions dominating clinical decision-making. Recent advances in interventional cardiac catheterization techniques, as well as continuing advances in the surgical management of complex congenital defects, continue to be the focus of attention of cardiologists and surgeons. The majority of the papers reviewed document mid- and long-term results of specific operative procedures for and address the appropriate role of cardiac catheterization techniques in the management of transposition of the great vessels, tetralogy of Fallot, total anomalous pulmonary venous connection, truncus arteriosus, pulmonary atresia with intact ventricular septum, and the univentricular heart. Early definitive intervention has become the standard of care for almost all defects reviewed.
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7787264
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Recent insights into the regulation of cardiac Ca2+ flux during perinatal development and in cardiac failure.
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Systolic and diastolic cardiac function improve during the transition from fetus to newborn to adult. This perinatal maturation is temporally correlated with and at least partially dependent on subcellular changes in the expression of several gene products that regulate cytosolic Ca2+ concentration. Expression of the Na(+)-Ca2+ exchanger of the sarcolemma is highest in the fetus, whereas expression of the sarcoplasmic reticulum Ca2+ pump and the voltage-dependent Ca2+ channel of the sarcolemma increase in conjunction with the perinatal maturation of cardiac function. Whereas cardiac relaxation in the normal mature heart depends primarily on the sarcoplasmic reticulum Ca2+ pump, relaxation in the fetal heart appears to be more dependent on transsarcolemmal Ca2+ flux. Like the fetal heart during prolonged relaxation, the failing human heart exhibits impaired relaxation and abnormal Ca2+ flux regulation. Although altered expression of several gene products has been demonstrated in the failing heart, the responsible factor(s) remains unknown.
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7787263
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The molecular genetics of cardiovascular disease.
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The following consideration of this past year's published studies uses the cited reports as important examples of the ongoing characterization of the molecular basis of cardiac disease and the process of cardiac development. Mutations in cardiac troponin T and alpha-tropomyosin have been identified in familial hypertrophic cardiomyopathy, as have new beta-myosin heavy chain gene mutations. The general relation between beta-myosin heavy chain gene mutations that produce a charge change versus conservative amino acid replacements and sudden death remains unresolved. New fibrillin 1 gene mutations have been identified in patients with Marfan syndrome, the neonatal form of Marfan syndrome, and ectopia lentis. The same mutation is rarely found in more than one family. The association of supravalvar aortic stenosis and elastin gene mutations was further strengthened. The complexity of the relation between dystrophin mutations and the cell-specific loss of dystrophin expression can result in patients having cardiomyopathy and no myopathy. X-chromosome inactivation was shown to be the basis of cardiomyopathy in women with a single mutated dystrophin allele. New candidate genes that control cardiac morphogenesis and myocyte differentiation were proposed. New evidence to support 22q11 microdeletions as a common basis of nonsyndromic conotruncal malformations was published. These studies represent an important beginning. Although mutant genes have been recognized in affected individuals with various syndromes and congenital cardiac abnormalities, our understanding of how a genotype yields a given phenotype remains to be established.
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7787262
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New insights on anatomical location of components of the reentrant circuit and ablation therapy for atrioventricular junctional reentrant tachycardia.
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The success of radiofrequency catheter ablation in the treatment of atrioventricular junctional, or atrioventricular nodal, reentrant tachycardia has rekindled interest in the electrophysiological and anatomical characteristics of the reentrant circuit. We conclude that there is no evidence that within the atrioventricular nodal area, which contains both the compact node and transitional cells, there are anatomically delineated dual or multiple pathways. Rather, the two main atrial inputs into the atrioventricular nodal area (posterior and anterior) seem to be the anatomically relevant structures for "slow" and "fast" pathways. Two other inputs (sinus septum and left atrial) may be the cause for multiple pathways in some individuals. Nonuniform anisotropic properties of the zone of transitional cells may account for slow or fast conduction in the same area, depending on directional differences of wavefronts. We prefer the term atrioventricular junctional reentrant tachycardia rather than atrioventricular nodal reentrant tachycardia because of mounting evidence that perinodal tissue is involved in the reentrant circuit. Finally, the role and origin of double extracellular electrograms is discussed. Further research is required to establish whether an anatomical or an electrogram-guided approach for catheter ablation is preferred.
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7787259
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Catheter ablation of ventricular tachycardia.
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Endocardial lesions created by radiofrequency catheter ablation are relatively small and focal. The application of radiofrequency ablation to patients with structural heart disease and ventricular tachycardia is quite limited because the substrate for these tachycardias is often diffuse or difficult to localize. In contrast, idiopathic ventricular tachycardia often originates from a discrete focus and can usually be ablated using radiofrequency energy. The wider applicability of ablation therapy for ventricular tachycardia will depend on improvements in mapping techniques and the ability to create larger areas of injury in patients with coronary artery disease and ventricular tachycardia.
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7787258
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Arrhythmogenic right ventricular dysplasia.
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Arrhythmogenic right ventricular dysplasia is a relatively newly described clinical entity that is more and more frequently recognized. It may explain an increasing number of unexpected, sudden deaths in young adults that are or are not preceded by cardiac symptoms. A genetic transmission of the disease has been suggested by the study of familial cases. A location on chromosome 14 appears to be responsible for this disease. In some patients, a superimposed inflammatory process mixed with the pattern of arrhythmogenic right ventricular dysplasia may explain the progressive deterioration of left ventricular function. The systematic study of electrocardiograms demonstrates prolongation of the QRS complex and repolarization abnormalities in the right precordial leads due to a parietal block. Multiple therapeutic approaches are now available. The first line of therapy remains antiarrhythmic drugs, which are effective in most cases. Ablative techniques, implantable defibrillators, and heart transplantation have been used in the most severe examples of the disease.
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7787254
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Biological activity of human N-ras and K-ras genes containing the Asn17 dominant negative mutation.
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Substitution of asparagine for serine at position 17 of human H-ras results in an impaired GTP-binding activity, causing the mutant Ras protein to be locked in a constitutively inactive GDP-bound state. Expression of this mutant in NIH 3T3 cells inhibits cell proliferation by blocking endogenous ras function. Plasmids that encode the analogous dominant negative mutation at position 17 in human N- and K-ras were constructed. These mutant ras genes, driven by a heavy metal-inducible sheep metallothionein promoter, were introduced by transfection into a variety of animal cell lines. All three mutant ras genes displayed an inhibitory phenotype when expressed in NIH 3T3 cells. This inhibition could be overcome by cotransfection with either activated H-ras or v-raf. These data indicate that the three human Ras proteins probably act through the same signal transduction pathway in NIH 3T3 cells and suggest that these mutations may confer similar phenotypes to other GTP/GDP-binding proteins.
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7787252
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Effect of the local anesthetic bupivacaine on the energy metabolism of Ehrlich ascites tumor cells.
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The effect of the local anesthetic bupivacaine on the energy metabolism of Ehrlich ascites tumor cells has been investigated. Even at low concentrations, bupivacaine decreased the oxygen uptake rate, but its effect was remarkably higher on the uncoupled respiration. Experiments on specific segments of the respiratory chain have shown that bupivacaine did not inhibit electron transport from Q to oxygen. Spectroscopic evidences demonstrated a NAD(P)H oxidation in bupivacaine-treated cells respiring on endogenous substrates, indicating that the inhibition of oxygen depended on a reduced electron transport from site 1-entering substrates to respiratory chain. The aerobic glycolysis was stimulated by low and inhibited by high bupivacaine concentrations. The increased lactate production rate was due to an activation of mitochondrial ATPase, whereas its decrease was related to an inhibition of the hexokinase activity.
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7787253
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Whole-body autoradiographic study of [3H]-PK 11195 distribution in dunning AT-1 tumour-bearing rats.
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In vivo binding of [3H]-PK 11195 to peripheral benzodiazepine binding sites in Dunning AT-1 prostatic tumour-bearing rats was investigated by whole-body autoradiography. Distribution and retention of PK 11195 in tumour and other organs was examined at different time intervals. Autoradiograms indicated PK 11195 binding sites in the periphery of the tumour, whereas no or little binding was detected in the prostate. Among other organs, adrenal cortex was most intensely radiolabelled. Administration of nonradioactive PK 11195 before [3H]-PK 11195 blocked binding in all organs more completely than in tumour, kidney, and adrenal cortex, where low levels of radioactivity still were present. Radioactivity in the tumour, contrary to other organs, seemed to increase with time, indicating a slow uptake with large capacity. High performance liquid chromatography analysis of extracted radioactivity from the tumour showed that almost all radioactivity consisted of intact [3H]-PK 11195. These results indicate binding in vivo of PK 11195 to peripheral benzodiazepine receptors in Dunning AT-1 rat prostatic tumours and a large capacity for uptake and retention of [3H]-PK 11195 in tumours.
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7787251
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Enhanced cytotoxicity with interleukin-1 alpha and 5-fluorouracil in HCT116 colon cancer cells.
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Recombinant human interleukin-1 alpha (rIL-1 alpha), at concentrations that were not growth-inhibitory when given alone (100-10,000 U/ml), enhanced the growth inhibition resulting from a 72-h fluorouracil (FUra) exposure in HCT116 colon cancer cells. Median-effect analysis of clonogenic assays indicated that rIL-1 alpha, given 24 h prior to and following a 24-h exposure to FUra, increased lethality in a more than additive fashion. rIL-1 alpha did not appear to significantly affect [3H]-FUra metabolism, total [3H]-FUra-RNA incorporation or RNA retention after drug removal, inhibition of thymidylate synthase, or thymidine triphosphate pool depletion. During continuous exposure to rIL-1 alpha, transient stimulation of RNA and DNA synthesis was observed at 72 h, with a return to normal by 96 h. A 24-h exposure to 10 microM FUra altered the elution profile of newly synthesized DNA as monitored by pH step alkaline elution. An accumulation of lower-MW single-stranded DNA species was noted with FUra compared to control, accompanied by a significantly decreased proportion of DNA retained on the polycarbonate filter: 10% retained vs. 32% for control (P = 0.01). A 48-h exposure to rIL-1 alpha alone did not affect the elution profile of nascent DNA species, nor did it enhance the effects of FUra. Although FUra did not appreciably affect pulse [3H]-uridine incorporation into RNA for the initial 8-24 h of FUra exposure, progressive inhibition of net RNA synthesis was observed thereafter. FUra prevented the stimulatory effect of rIL-1 alpha on RNA synthesis, and net RNA synthesis was significantly inhibited (by 64-79% after 72 and 96 h) with the combination compared to rIL-1 alpha alone. Continuous exposure to 10 microM thymidine did not rescue cells from the lethality of FUra alone or the combination of FUra plus rIL-1 alpha, suggesting that depletion of deoxythymidine triphosphate as a consequence of thymidylate synthase inhibition was not the most important component of FUra toxicity. In contrast, 1 mM uridine provided partial protection against the toxicity of FUra alone or with rIL-1 alpha. Although uridine did not affect FUra metabolism, it decreased FUra-RNA incorporation by 42-60%, presumably as a consequence of the 2-fold expansion of UTP pools. [125I]-rIL-1 alpha binding was nonspecific; with a 24-h exposure, however, internalized [125I]-rIL-1 alpha exceeded cell surface-bound material by 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
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7787250
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p53 mutations in bladder carcinoma cell lines.
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Point mutations and deletions in the p53 tumor suppressor gene occur frequently in advanced stage bladder tumors. To extend these observations to an in vitro model of bladder tumorigenicity, we have evaluated the presence of p53 mutations in a panel of bladder carcinoma cell lines. p53 alleles were cloned using the reverse transcriptase-polymerase chain reaction method, and exons 2-11 were sequenced. Of 11 cell lines examined, 5 cell lines had missense point mutations, and each overexpressed p53 protein on western blot analysis. Except for the HT-1197 cell line, these point mutations occurred in evolutionarily conserved domains, which are characteristic hot spots for mutations. HT-1197 encodes an unusual C-terminal point mutation in codon 365, within the basic motif tetramerization domain, suggesting a linkage between induction of a mutant p53 conformation and alterations in protein oligomerization. Six of 11 cell lines had wild-type levels of p53 expression, with 4 producing p53 proteins having either internal deletions or truncations, and 2 producing wild-type p53. Presence of wild-type p53 was found only in cell lines derived from either a low-grade, papillary tumor (RT4) or fetal bladder (FHs 738Bl). The T24 cell line was found to contain a novel p53 mutant having an in-frame deletion of tyrosine 126. This p53 mutant does not bind SV40 large T antigen, yet is expressed at low levels, comparable to cell lines containing wild-type p53 alleles. Our findings characterize p53 mutations in a panel of bladder carcinoma cell lines, and provide a model for testing the role of wild-type or mutant p53 cDNA to suppress or induce tumorigenic properties.
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7787248
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The bulk of unpolymerized actin in Xenopus egg extracts is ATP-bound.
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Non-muscle cells contain 15-500 microM actin, a large fraction of which is unpolymerized. Thus, the concentration of unpolymerized actin is well above the critical concentration for polymerization in vitro (0.2 microM). This fraction of actin could be prevented from polymerization by being ADP bound (therefore less favored to polymerize) or by being ATP bound and sequestered by a protein such as thymosin beta 4, or both. We isolated the unpolymerized actin from Xenopus egg extracts using immobilized DNase 1 and assayed the bound nucleotide. High-pressure liquid chromatography analysis showed that the bulk of soluble actin is ATP bound. Analysis of actin-bound nucleotide exchange rates suggested the existence of two pools of unpolymerized actin, one of which exchanges nucleotide relatively rapidly and another that apparently does not exchange. Native gel electrophoresis of Xenopus egg extracts demonstrated that most of the soluble actin exists in complexes with other proteins, one of which might be thymosin beta 4. These results are consistent with actin polymerization being controlled by the sequestration and release of ATP-bound actin, and argue against nucleotide exchange playing a major role in regulating actin polymerization.
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7787247
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Phosphorylation and activation of the Xenopus Cdc25 phosphatase in the absence of Cdc2 and Cdk2 kinase activity.
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The M-phase inducer, Cdc25C, is a dual-specificity phosphatase that directly phosphorylates and activates the cyclin B/Cdc2 kinase complex, leading to initiation of mitosis. Cdc25 itself is activated at the G2/M transition by phosphorylation on serine and threonine residues. Previously, it was demonstrated that Cdc2 kinase is capable of phosphorylating and activating Cdc25, suggesting the existence of a positive feedback loop. In the present study, kinases other than Cdc2 that can phosphorylate and activate Cdc25 were investigated. Cdc25 was found to be phosphorylated and activated by cyclin A/Cdk2 and cyclin E/Cdk2 in vitro. However, in interphase Xenopus egg extracts with no detectable Cdc2 and Cdk2, treatment with the phosphatase inhibitor microcystin activated a distinct kinase that could phosphorylate and activate Cdc25. Microcystin also induced other mitotic phenomena such as chromosome condensation and nuclear envelope breakdown in extracts containing less than 5% of the mitotic level of Cdc2 kinase activity. These findings implicate a kinase other than Cdc2 and Cdk2 that may initially activate Cdc25 in vivo and suggest that this kinase may also phosphorylate M-phase substrates even in the absence of Cdc2 kinase.
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7787249
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Annexin II marks astrocytic brain tumors of high histologic grade.
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Annexin II is highly expressed in glioblastoma multiforme [Reeves, S. A.; Chavez-Kappel, C.; Davis, R.; Rosenblum, M.; Israel, M. A. Developmental regulation of annexin II (lipocortin 2) in human brain and expression in high grade glioma. Cancer Res. 52:6871-6876; 1992] and is a likely second messenger in mitogenic pathways known to be important for the growth of these tumors. We have examined tumor tissue from patients diagnosed with low-, intermediate-, or high-grade astrocytic tumors for expression of annexin II by immunohistochemistry, and found that annexin II levels varied significantly among these three tumors (P < 0.0005). Levels were highest in glioblastoma multiforme, intermediate in anaplastic astrocytomas, and lowest in astrocytomas. In contrast to the usual cytoplasmic localization of annexin II, distinct nuclear staining was found in many of the specimens. Reactive astrocytes found in gliotic brain also stained with anti-annexin II antibody. We examined matched specimens for a correlation between annexin II staining intensity and the bromodeoxyuridine labeling index and found that, while tumors with the most intense annexin II staining had highest bromodeoxyuridine labeling indexes, there was not a strong association between these two parameters. The association between annexin II staining and histologic grade in astrocytic malignancies indicates that annexin II may be an important marker of high-grade glial tumors, and suggests that this marker may be useful for the pathologic classification of glial tumors and the clinical evaluation of brain tumor patients.
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7787246
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Control of the Cdc2/cyclin B complex in Xenopus egg extracts arrested at a G2/M checkpoint with DNA synthesis inhibitors.
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Proliferating eukaryotic cells possess checkpoint mechanisms that block cell division in the presence of unreplicated or damaged DNA. Using cell-free extracts from Xenopus eggs, we have investigated the mechanisms underlying the inability of a recombinant Cdc2/cyclin B complex to induce mitosis in the presence of incompletely replicated DNA. We found that the activities of the kinases and phosphatases that regulate the major phosphorylation sites on Cdc2 (e.g., tyrosine 15, threonine 14, and threonine 161) are not altered significantly under conditions where Xenopus extracts remain stably arrested in interphase due to the presence of the replication inhibitor aphidicolin. However, at threshold concentrations, a Cdc2/cyclin B complex containing a mutant Cdc2 subunit that cannot be phosphorylated on either tyrosine 15 or threonine 14 displays a markedly reduced capacity to induce mitosis in the presence of aphidicolin. This observation indicates that the replication checkpoint in Xenopus egg extracts functions without the inhibitory tyrosine and threonine phosphorylation of Cdc2. We provide evidence that the checkpoint-dependent suppression of the Cdc2/cyclin B complex involves a titratable inhibitor that is regulated by the presence of unreplicated DNA.
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7787245
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The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
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The ubiquitin-mediated degradation of mitotic cyclins is required for cells to exit from mitosis. Previous work with cell-free systems has revealed four components required for cyclin-ubiquitin ligation and proteolysis: a nonspecific ubiquitin-activating enzyme E1, a soluble fraction containing a ubiquitin carrier protein activity called E2-C, a crude particulate fraction containing a ubiquitin ligase (E3) activity that is activated during M-phase, and a constitutively active 26S proteasome that degrades ubiquitinated proteins. Here, we identify a novel approximately 1500-kDa complex, termed the cyclosome, which contains a cyclin-selective ubiquitin ligase activity, E3-C. E3-C is present but inactive during interphase; it can be activated in vitro by the addition of cdc2, enabling the transfer of ubiquitin from E2-C to cyclin. The kinetics of E3-C activation suggest the existence of one or more intermediates between cdc2 and E3-C. Cyclosome-associated E3-C acts on both cyclin A and B, and requires the presence of wild-type N-terminal destruction box motifs in each cyclin. Ubiquitinated cyclins are then rapidly recognized and degraded by the proteasome. These results identify the cyclosome-associated E3-C as the component of the cyclin destruction machinery whose activity is ultimately regulated by cdc2 and, as such, the element directly responsible for setting mitotic cyclin levels during early embryonic cell cycles.
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7787244
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Characterization of kinectin, a kinesin-binding protein: primary sequence and N-terminal topogenic signal analysis.
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Kinectin is a kinesin-binding protein (Toyoshima et al., 1992) that is required for kinesin-based motility (Kumar et al., 1995). A kinectin cDNA clone containing a 4.7-kilobase insert was isolated from an embryonic chick brain cDNA library by immunoscreening with a panel of monoclonal antibodies. The cDNA contained an open reading frame of 1364 amino acids encoding a protein of 156 kDa. A bacterially expressed product of the full length cDNA bound purified kinesin. Transient expression in CV-1 cells gave an endoplasmic reticulum distribution that depended upon the N-terminal domain. Analysis of the predicted amino acid sequence indicated a highly hydrophobic near N-terminal stretch of 28 amino acids and a large portion (326-1248) of predicted alpha helical coiled coils. The 30-kDa fragment containing the N-terminal hydrophobic region was produced by cell-free in vitro translation and found to assemble with canine pancreas rough microsomes. Cleavage of the N terminus was not observed confirming its role as a potential transmembrane domain. Thus, the kinectin cDNA encodes a cytoplasmic-oriented integral membrane protein that binds kinesin and is likely to be a coiled-coil dimer.
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7787243
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Molecular cloning and characterization of human kinectin.
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We have identified a human cDNA that is homologous to the chicken kinectin, a putative receptor for the organelle motor kinesin. The human cDNA clone hybridized to a single 4.6-kb mRNA species that codes for a protein of 156 kDa molecular mass. The predicted primary translation product contains an N-terminal transmembrane helix followed by a bipartite nuclear localization sequence and two further C-terminal leucine zipper motifs. In addition, the aminoacid sequence revealed a large region (327-1362) of predicted alpha-helical coiled coils. A monoclonal antibody CT-1 raised against a GST-kinectin fusion protein produced a perinuclear, endoplasmic reticulum-like staining pattern in diverse cell types from different species, indicating evolutionary conservation. Monoclonal antibody CT-1 and anti-chicken kinectin antibodies cross-reacted both in Western blotting and immunoprecipitation with a 160-kDa protein, confirming the antigenic identity of this 160-kDa protein with chicken kinectin. Epitope tagging studies revealed that the nuclear localization sequence motif of kinectin is not functional. Furthermore, a truncated kinesin cDNA lacking the N-terminal hydrophobic domain revealed a nonspecific cytoplasmic staining pattern. Together the data suggest that kinectin is an integral membrane protein anchored in the endoplasmic reticulum via a transmembrane domain.
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7787242
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A fluorescent lipid analogue can be used to monitor secretory activity and for isolation of mammalian secretion mutants.
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The use of reporter proteins to study the regulation of secretion has often been complicated by posttranslational processing events that influence the secretion of certain proteins, but are not part of the cellular mechanisms that specifically regulate secretion. This has been a particular limitation for the isolation of mammalian secretion mutants, which has typically been a slow process. To provide a reporter of secretory activity independent of protein processing events, cells were labeled with the fluorescent lipid analogue C5-DMB-ceramide (ceramide coupled to the fluorophore boron dipyrromethene difluoride) and its secretion was followed by fluorescence microscopy and fluorescence-activated cell sorting. Brefeldin A, which severely inhibits secretion in Chinese hamster ovary cells, blocked secretion of C5-DMB-ceramide. At high temperature, export of C5-DMB-ceramide was inhibited in HRP-1 cells, which have a conditional defect in secretion. Using C5-DMB-ceramide as a reporter of secretory activity, several different pulse-chase protocols were designed that selected mutant Chinese hamster ovary cells that were resistant to the drug brefeldin A and others that were defective in the transport of glycoproteins to the cell surface. Mutant cells of either type were identified in a mutagenized population at a frequency of 10(-6). Thus, the fluorescent lipid C5-DMB-ceramide can be used as a specific marker of secretory activity, providing an efficient, general approach for isolating mammalian cells with defects in the secretory pathway.
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7787241
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Ultrastructural characterization of neurons recorded intracellularly in vivo and injected with lucifer yellow: advantages of immunogold-silver vs. immunoperoxidase labeling.
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Immunoperoxidase labeling of lucifer yellow provides a sensitive method for morphological characterization of neurons recorded intracellularly in vitro or in vivo. However, the reaction product is often so dense that it obscures ultrastructural details necessary for the analysis of synaptic contacts onto individually filled neurons. In the present study, we describe a silver intensification procedure using 1 nm gold labeling of lucifer yellow as an optimal means for immunocytochemically identifying single physiologically characterized neurons at the ultrastructural level. Single neurons in the frontal cortex of anesthetized rats were impaled in vivo and filled with lucifer yellow. The brains were then perfused with an acrolein fixative. Single vibratome sections through the recording site were reacted with a rabbit antibody directed against lucifer yellow followed by goat anti-rabbit 1 nm gold-labeled IgG and silver intensified. For comparison, additional sections were processed for immunoperoxidase detection of lucifer yellow. Labeled sections were processed for light microscopy or embedded in plastic for electron microscopy. The immunogold-silver label as well as peroxidase reaction product of lucifer yellow was readily detected in cell bodies, proximal and distal dendrites, and spines. However, in contrast to immunoperoxidase, the immunogold-silver reaction did not obscure subcellular organelles. Most importantly, the synaptic junctions formed by afferents to the filled neuron were more easily identifiable following the immunogold-silver procedure. This clear visualization of postsynaptic densities is essential for examining synaptic circuitry between afferents and physiologically characterized neurons.
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7787240
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Comparison of SEM processing methods for cultured human lens epithelial cells grown on flat and microcarrier bead substrates.
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The increasing importance of in vitro models has presented new challenges in SEM processing techniques. The present study has evaluated the quality of preservation of cultured human lens epithelial cells processed by critical point, Peldri II, and tert-butyl alcohol drying. Specimens processed by critical point drying produced specimens with severe cracking of cell processes and microcracks across cell membrane surfaces. Peldri II and tert-butyl alcohol drying eliminated breakage of the filopodia and lamellipodia as well as eliminating the microcracks across the apical membrane surface. The morphology of lens epithelial cells grown on Cytodex 3 beads appeared rounded with convoluted membrane surfaces. These morphological features were present for cells processed by all three methods. Cytodex 3 beads were subsequently shown to shrink 52% in diameter during dehydration, which results in an 89% reduction in volume for the bead. Cells grown on Biosilon beads, which do not shrink, had a morphology similar to the cells grown on a flat substrate. These results indicate that Peldri II and tert-butyl alcohol drying offer an attractive alternative to critical point drying when preparing cultured cells for SEM. Interpretation of cultured cell morphology must consider shrinkage of the substrate material as a possible contributor to artifact.
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7787236
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Development and postnatal regulation of adult myoblasts.
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The myogenic precursor cells of postnatal and adult skeletal muscle are situated underneath the basement membrane of the myofibers. It is because of their unique positions that these precursor cells are often referred to as satellite cells. Such defined satellite cells can first be detected following the formation of a distinct basement membrane around the fiber, which takes place in late stages of embryogenesis. Like myoblasts found during development, satellite cells can proliferate, differentiate, and fuse into myofibers. However, in the normal, uninjured adult muscle, satellite cells are mitotically quiescent. In recent years several important questions concerning the biology of satellite cells have been asked. One aspect has been the relationship between satellite cells and myoblasts found in the developing muscle: are these myogenic populations identical or different? Another aspect has been the physiological cues that control the quiescent, proliferative, and differentiative states of these myogenic precursors: what are the growth regulators and how do they function? These issues are discussed, referring to previous work by others and further emphasizing our own studies on avian and rodent satellite cells. Collectively, the studies presented indicate that satellite cells represent a distinct myogenic population that becomes dominant in late stages of embryogenesis. Moreover, although satellite cells are already destined to be myogenic precursors, they do not express any of the four known myogenic regulatory genes unless their activation is induced in the animal or in culture. Furthermore, multiple growth factors are important regulators of satellite cell proliferation and differentiation. Our work on the role of one of these growth factors [platelet-derived growth factor (PDGF)] during proliferation of adult myoblasts is further discussed with greater detail and the possibility that PDGF is involved in the transition from fetal to adult myoblasts in late embryogenesis is brought forward.
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7787239
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Computer graphics of SEM images facilitate recognition of chromosome position in isolated human metaphase plates.
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There is general agreement that at the time of mitosis chromosomes occupy precise positions and that these positions likely affect subsequent nuclear function in interphase. However, before such ideas can be investigated in human cells, it is necessary to determine first the precise position of each chromosome with regard to its neighbors. It has occurred to us that stereo images, produced by scanning electron microscopy, of isolated metaphase plates could form the basis whereby these positions could be ascertained. In this paper we describe a computer graphic technique that permits us to keep track of individual chromosomes in a metaphase plate and to compare chromosome positions in different metaphase plates. Moreover, the computer graphics provide permanent, easily manipulated, rapid recall of stored chromosome profiles. These advantages are demonstrated by a comparison of the relative position of group A-specific and groups D- and G-specific chromosomes to the full complement of chromosomes in metaphase plates isolated from a nearly triploid human-derived cell (HeLa S3) to a hypo-diploid human fetal lung cell.
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7787238
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Expression of myosin heavy chain isoforms and myogenesis of intrafusal fibres in rat muscle spindles.
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This review concerns the pattern of expression and regulation of myosin heavy chain (MHC) isoforms in intrafusal fibres of rat muscle spindles detected by immunocytochemistry. The three types of intrafusal fibres--nuclear bag1, nuclear bag2, and nuclear chain fibres--are unique in co-expressing several MHCs including special isoforms such as slow tonic and alpha cardiac-like MHC and isoforms typical of muscle development, such as embryonic and neonatal MHC. The distinct intrafusal fibre types appear sequentially during rat hind limb development, the nuclear bag2 precursors being first identifiable at 17-18 days in utero as the only primary myotubes expressing slow tonic MHC. Sensory innervation is required for the expression of "spindle-specific" MHC isoforms. Motor innervation contributes to the diversity in distribution of the different MHCs along the length of the nuclear bag fibres. It is suggested that unique populations of myoblasts are destined to become intrafusal fibres during development in the rat hind limb muscles and that the regional heterogeneity in MHC expression is related both to sensory and motor innervation and to the properties of the myoblast lineages. These distinct features make intrafusal fibres an attractive in situ model for investigating myogenesis, myofibrillogenesis, and the mechanisms regulating MHC expression.
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7787237
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Patterns of myosin isoforms in mammalian skeletal muscle fibres.
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The present article attempts to combine existing information on the distribution of fast and slow myosin isoforms in histochemically distinct muscle fibres. Four myosin heavy chain (MHC) isoforms, MHCI, MHCIIa, MHCIIb, and MHCIId(x), have been identified in small mammals and have been assigned to the histochemically defined fibre types I, IIA, IIB, and IID(X), respectively. These fibres express only one MHC isoform and are called pure fibre types. Hybrid fibres expressing two MHC isoforms are regarded as transitory between respective pure fibre types. The existence of pure and hybrid fibres even in normal muscles under steady state conditions creates a spectrum of fibre types. The multiplicity of fibre types is even greater when myosin light chains are taken into account. A large number of isomyosins results from the combinatorial patterns of various myosin light and heavy chains isoforms, further increasing the diversity of muscle fibres. As shown by comparative studies, the distribution of different fibre types varies in a muscle-specific, as well as a species-specific manner.
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7787235
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Muscle-specific gene expression during myogenesis in the mouse.
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Over the past decade, significant advances in molecular biological techniques have substantially increased our understanding of in vivo myogenesis, supplementing the information that previously had been obtained from classical embryological and morphological studies of muscle development. In this review, we have attempted to correlate morphogenetic events in developing murine muscle with the expression of genes encoding the MyoD family of myogenic regulatory factors and the contractile proteins. Differences in the pattern of expression of these genes in murine myotomal and limb muscle are discussed in the context of muscle cell lineage and environmental factors. The differences in gene expression in these two types of muscle suggest that no single coordinated pattern of gene activation is required during the initial formation of the muscles of the mouse.
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7787228
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Low-volume application by mist-blower compared with conventional compression sprayer treatment of houses with residual pyrethroid to control the malaria vector Anopheles albimanus in Mexico.
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Village-scale trials were carried out in southern Mexico to compare the efficacy of indoor-spraying of the pyrethroid insecticide lambda-cyhalothrin applied either as low-volume (LV) aqueous emulsion or as wettable-powder (WP) aqueous suspension for residual control of the principal coastal malaria vector Anopheles albimanus. Three indoor spray rounds were conducted at 3-month intervals using back-pack mist-blowers to apply lambda-cyhalothrin 12.5 mg a.i./m2 by LV, whereas the WP was applied by conventional compression sprayer at a mean rate of 26.5 mg a.i./m2. Both treatments caused mosquito mortality indoors and outdoors (collected inside house curtains) as a result of contact with treated surfaces before and after feeding, but had no significant impact on overall population density of An. albimanus resting indoors or assessed by human bait collections. Contact bioassays showed that WP and LV treatments with lambda-cyhalothrin were effective for 12-20 weeks (> 75% mortality) without causing excito-repellency. Compared to the WP treatment (8 houses/man/day), LV treatment (25 houses/man/day) was more than 3 times quicker per house, potentially saving 68% of labour costs. This is offset, however, by the much lower unit price of a compression sprayer (e.g. Hudson 'X-pert' at US$120) than a mist-blower (e.g. 'Super Jolly' at US$350), and higher running costs for LV applications. It was calculated, therefore, that LV becomes more economical than WP after 18.8 treatments/100 houses/10 men at equivalent rates of application, or after 7.6 spray rounds with half-rate LV applications.
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7787229
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Simulium metallicum cytospecies E larval habitat characterization in the Altamira focus of onchocerciasis, northern Venezuela.
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Simulium metallicum sibling species E was identified cytotaxonomically from an onchocerciasis focus at Altamira in northern Venezuela. S. metallicum E larvae were sampled monthly from two small mountain streams over a 15-month period (July 1990 to September 1991) and eleven habitat variables were measured at two altitudes. One stream consistently harboured much higher densities of S. metallicum E larvae than the other, with three annual peaks of abundance: during the dry season and at the beginning and end of the rainy season. These peak densities were correlated with high rainfall 4 months previously. Larvae were most abundant on submerged rocks and fallen leaves, in small shallow areas characterized by slow water current, high conductivity and sparse terrestrial vegetation cover. Stream variables which best explained the temporal changes in abundance were water discharge and conductivity. The population dynamics of S. metallicum E appeared to be influenced primarily by interactions between stream discharge and substrate stability. Relevance of these results to vector control with larvicides is discussed.
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7787227
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Anopheles culicifacies in Baluchistan, Iran.
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Anopheles culicifacies (probably species A) is the main vector of malaria in Baluchistan, southeastern Iran. Adult mosquitoes were collected during 1990-92 by five methods of sampling: knock-down pyrethrum space-spray indoors, human and animal bait (18.00-05.00 hours), pit shelters and CDC light traps, yielding 62%, 3%, 6%, 4% and 25% of specimens, respectively. Whereas spray-catches comprised c. 70% gravid and semi-gravid females, light trap catches were mostly (c. 60%) unfed females, while females from pit shelters comprised all abdominal stages more equally (13-36%). An.culicifacies populations peaked in April-May and rose again during August-November. Densities of indoor-resting mosquitoes were consistently greater in an unsprayed village than in villages subjected to residual house-spraying with propoxur, malathion or pirimiphos-methyl. Monthly malaria incidence generally followed fluctuations of An.culicifacies density, usually with a peak in May-June.
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7787226
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Malaria-induced reduction of fecundity during the first gonotrophic cycle of Anopheles stephensi mosquitoes.
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Anopheles stephensi mosquitoes which had fed upon mice infected with Plasmodium yoelii nigeriensis malaria parasites produced significantly fewer eggs than mosquitoes fed on an uninfected mouse. Fecundity reduction was more pronounced when the bloodmeal contained malaria gametocytes and the mosquitoes developed oocysts. Egg production and haematin excretion were correlated for uninfected bloodfed mosquitoes; the presence of P.y.nigeriensis in the blood affected this relationship. Reduced fecundity was associated with a significant reduction of bloodmeal size (measured by haematin excretion) in mosquitoes which ingested gametocytaemic blood. The bloodmeal size in mosquitoes fed on parasitaemic blood without gametocytes was not significantly reduced. The use of haematin assays for determination of bloodmeal size in mosquitoes is discussed.
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7787225
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Pyrethroid-impregnated hessian curtains for protection against mosquitoes indoors in south India.
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Hessian curtains impregnated with deltamethrin 50 mg/m2 were hung in the eaves and doorways of eight one-roomed huts in Madurai, Tamil Nadu State, South India. Statistically significant reductions of indoor-resting and man-biting densities of the mosquitoes Anopheles subpictus and Culex quinquefasciatus were observed for 14 weeks, in two field trials. Bioassays on curtains in the field showed over 50% mortality of Cx quinquefasciatus and An.stephensi for up to 8 weeks. The curtains were highly acceptable to the community, and cost approximately Rs.33.15 (US$1.05) for material and Rs.10 ($0.32) for delta-methrin per hut, totalling Rs 53.15 ($1.70) for two impregnations giving 6 months protection. Comparative costs of house-spraying with residual insecticides are estimated as Rs.1.92 ($0.06) for two rounds of DDT at 1 g/m2, or Rs.40 ($1.27) for three rounds of malathion at 2 g/m2. Therefore the relative annual cost of protection using deltamethrin-impregnated hessian curtains is 28 x or 1.3 x more than for house-spraying with DDT or malathion, respectively (excluding operational expenditure).
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7787222
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Mosquito control in Dar es Salaam. II. Impact of expanded polystyrene beads and pyriproxyfen treatment of breeding sites on Culex quinquefasciatus densities.
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In two contrasting areas of Dar es Salaam (Ilala and Mikocheni) all enclosed breeding sites of Culex quinquefasciatus, such as latrines and septic tanks, were treated with a floating layer of expanded polystyrene beads. 7 months later checks in both study areas revealed only one site (from which the polystyrene had been removed during emptying) containing immature stages of Cx quinquefasciatus. Open breeding sites such as areas of flooded land and blocked drains were treated with pyriproxyfen (an insect growth regulator) at a concentration of 0.1 ppm. Emergence of Cx quinquefasciatus adults from these sites was inhibited for 4 weeks during the rainy season and for up to 11 weeks during the dry season. The problem of mosquito breeding sites caused by bathroom sullage water was addressed through a combination of health education and indirect pressure from the Urban Malaria Control Project (UMCP) via local community leaders. Households responsible for these sites were encouraged to eliminate them by diverting the water into an enclosed drainage structure, usually a pit latrine. After two weekly visits 64.7% of households had complied and 93.4% had complied after five visits. 5 months later, only 15.7% had reverted to allowing sullage water to collect into puddles. Densities of Cx quinquefasciatus adults dropped by 76.7% in Mikocheni and by 46.2% in Ilala following intervention, but increased by 84.9% and 25.6% in two untreated comparison areas. The reasons for differential success of the combined interventions in the two treated areas are discussed.
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7787223
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Relationships between host blood factors and proteases in Glossina morsitans subspecies infected with Trypanosoma congolense.
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Host blood effects on Trypanosoma congolense establishment in Glossina morsitans morsitans and Glossina morsitans centralis were investigated using goat, rabbit, cow and rhinoceros blood. Meals containing goat erythrocytes facilitated infection in G.m.morsitans, whereas meals containing goat plasma facilitated infection in G.m.centralis. Goat blood effects were not observed in the presence of complementary rabbit blood components. N-acetyl-glucosamine (a midgut-lectin inhibitor) increased infection rates in some, but not all, blood manipulations. Cholesterol increased infection rates in G.m.centralis only. Both compounds together added to cow blood produced superinfection in G.m.centralis, but not in G.m.morsitans. Midgut protease levels did not differ 6 days post-infection in flies maintaining infections versus flies clearing infections. Protease levels were weakly correlated with patterns of infection, but only in G.m.morsitans. These results suggest that physiological mechanisms responsible for variation in infection rates are only superficially similar in these closely-related tsetse.
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7787221
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Mosquito control in Dar es Salaam. I. Assessment of Culex quinquefasciatus breeding sites prior to intervention.
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In preparation for a trial polystyrene beads and pyriproxyfen for the control of Culex quinquefasciatus mosquitoes, surveys of their breeding were carried out in two contrasting areas of Dar es Salaam, Mikocheni and Ilala, during the dry season. Sanitation structures (latrines, soakage pits, septic tanks and cess pits) were the most profilic breeding places, totalling 780 in Mikocheni and 1544 in Ilala. Those in Mikocheni were estimated to contain about 1.4 times more mosquito pupae, per site, than in such structures in Ilala. This was both because a higher proportion of sites contained visible water and because sites with water were more likely to contain pupae in Mikocheni. The relative importance of the different types of structure, in terms of productivity, was the same in both areas. Although septic tanks and cess pits made up only 10.5% of the on-site sanitation structures in Ilala, they contained 53% of the total number of pupae in enclosed sites; they were therefore particularly important targets for treatment with polystyrene beads. A survey during the rainy season of sites in Ilala revealed little change in the proportion that were wet, or in the frequency of breeding in those with visible water. The number, type and area of open breeding sites varied greatly between the two study areas. In Mikocheni the area of open breeding sites was 100 times greater than in Ilala, with 97% of the 13,000 m2 being flooded grassland. In Ilala all but four of the sixty-six open breeding sites were puddles of sullage water derived from bathrooms.(ABSTRACT TRUNCATED AT 250 WORDS)
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7787220
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Immunosuppression and feeding success of Ixodes ricinus nymphs on BALB/c mice.
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The effect of repeated infestations of Ixodes ricinus (L.) nymphs on BALB/c mice was studied. Four successive infectations resulted in an increase of tick feeding success. Tick yield and mean engorged weight increased and the length of the feeding period was reduced significantly (P < 0.05-0.01). The increase of specific anti-tick antibodies was not significant (P > 0.05). The blastogenic response of spleen lymphocytes to T-cell mitogens (Con A and PHA-P) was unimpaired or slightly enhanced, whereas the response to B-cell activators (LPS and PWM) was suppressed, as was the total antibody generation in vitro. The numbers of mast cells in murine skin at the tick attachment sites slightly decreased during the third infestation. The suppression of B-cell competence and of antibody generation, together with decrease of skin mast cell numbers in tick attachment sits, are considered to be responsible for enhancement of tick feeding success.
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7787224
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Dispersal of the Old World screw-worm fly Chrysomya bezziana.
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Dispersal of the Old World screw-worm fly, Chrysomya bezziana Villeneuve, was studied in Papua New Guinea by releasing radio-isotope labelled, laboratory-reared flies and collecting their labelled egg masses from sentinel cattle. A log-linear model was developed to describe recapture rate. Distance was found to dominate the model and was represented by a bilinear ('broken-stick') term as log-distance. Further terms in the model such as attractiveness of the site (estimated from the number of non-labelled egg masses), the season of the year and a time trend were statistically significant but of minor importance. From the model, the median distance females dispersed before depositing an egg mass was 10.8 km. The maximum distance from the release site that egg masses were recovered was 100 km. The dispersal ability of C. bezziana is discussed in terms of its impact on the prospects of eradicating this species using SIRM if an outbreak occurred in Australia.
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7787219
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An association between phlebotomine sandflies and aphids in the Peruvian Andes.
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As the composition of natural sugars in the diet of adult sandflies (Diptera: Psychodidae: Phlebotominae) may affect the development of Leishmania (Kinetoplastida: Trypanosomatidae) in sandfly guts, and so play an important role in the epidemiology of leishmaniasis, there is increasing interest in the sources of sugars for wild sandflies. Advanced chromatography techniques have provided indirect evidence that wild sandflies feed on honeydew, a substance released by aphids (Hemiptera: Aphididae) when feeding. Our objective was to determine whether sandfly density can be influenced directly by the local density of aphids. Aphid density was determined by counting absolute numbers of aphids on alfalfa stems in Purisima Valley, Peru, where sandflies transmit Leishmania peruviana causing Andean cutaneous leishmaniasis (uta). Sandfly relative abundance was measured using sticky trap sampling repeatedly in alfalfa fields. Lutzomyia verrucarum accounted for 92% of the total sandflies collected. As there was a female bias in sandflies collected close to houses, only the numbers of male sandflies were used in analysis. Most of the adult aphids found feeding on alfalfa were either Therioaphis trifolii forma maculata (97%) or Acyrthosiphon pisum (3%). By regression analysis, a significant relationship was found between the density of Lu.verrucarum males and the density of adults of both aphid species. This is the first ecological study to support the hypothesis that aphid honeydew may be a source of sugar for sandflies.
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7787216
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Oviposition aggregation pheromone in the Simulium damnosum complex.
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Communal oviposition by the Simulium damnosum complex of Afrotropical blackflies (Diptera: Simuliidae) was investigated under controlled laboratory conditions, using wild-caught flies in Sierra Leone. Volatile compounds emitted by Simulium eggs were trapped using a closed collection system, and their attractiveness to gravid flies was tested in a two-choice behavioural bioassay. Significantly more female blackflies oviposited on substrates baited with freshly laid eggs (100% chose the baited substrate), or with the volatiles collected from freshly laid eggs (85% chose the baited substrate), in preference to the relevant control substrates. Substrates baited with volatiles from 12-h-old eggs were not significantly more attractive than controls (only 31% chose the baited substrates; P = 0.33). Gas chromatographic analysis of the egg volatiles consistently showed two peaks emanating from fresh eggs, but significantly lower amounts from 12-h-old eggs (P < 0.05). A novel system for collecting the volatiles from this and other blackfly species, as they laid eggs on a substrate in flowing water, is described. Volatiles collected using this method showed identical gas chromatographic profiles to those of fresh eggs alone, indicating that the flies themselves produced no other volatile chemical signals during oviposition. Evidently communal oviposition by S. damnosum s.l. was mediated by a pheromone emanating from fresh eggs. The role of pheromone-mediated egg aggregation in blackfly ecology is discussed, and its possible manipulation is considered.
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7787218
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Isolation and characterization of a trypsin-like enzyme from the buffalo fly, Haematobia irritans exigua.
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The incorporation of soybean trypsin inhibitor (SBTI) into the diet of the buffalo fly, Haematobia irritans exigua (De Meijere), results in increased mortality and reduced fecundity. A trypsin-like enzyme which binds to SBTI was isolated by affinity chromatography on a Sepharose-SBTI column followed by ion-exchange chromatography. The enzyme was inhibited by benzamidine, phenylmethylsulfonyl fluoride, ovomucoid, leupeptin and alpha-2 macroglobulin. The enzyme was not inhibited by EDTA or p-chloromecuribenzoic acid and had a broad pH optimum of pH 7-9. Vaccination of sheep produced antibodies specific for the trypsin-like enzyme which inhibited enzyme activity in vitro but did not affect the survival of flies maintained in in vitro culture.
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7787217
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A cost-benefit analysis of feeding in female tsetse.
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Three models for feeding in female tsetse are considered. Model I: there is a prolonged non-feeding phase after each meal followed by feeding at a constant rate, with a constant probability of dying as a consequence of feeding. Model II: the feeding rate increases linearly after each meal. Model III: the feeding rate increases exponentially after each meal. In Models II and III the feeding hazard is a linear function of the probability of feeding. Production of viable female offspring is estimated under each model, making allowance for losses of adults due to starvation and to background and feeding mortality, losses of pupae due to predation and parasitization, and losses of young flies if their mothers take insufficient blood during pregnancy. Under Model I, if females require three meals to produce viable pupae in 9 days, then for a non-decreasing population with a background mortality of 1%/day, and 25% pupal losses due to predation and parasitism, the feeding risk must be < or = 5%/feed. At this maximum level the non-feeding phase should be 2-2.5 days for optimal productivity, with a mean feeding interval of 60-72 h. If the background mortality is 2%/day, feeding losses cannot exceed 1%/feed for a non-decreasing population. If four or five meals are required for the production of fully viable pupae, the optimal values of the non-feeding phase and mean feeding interval tend towards 1 and 2 days respectively. Under Models II and III the mean feeding interval is 50-60 h for optimal productivity (with variances 3 times as large as for Model I), in good agreement with estimates from recent models for feeding and digestion. Field evidence suggests that feeding tsetse take greater risks as their fat levels dwindle. This should result in feeding (and feeding mortality) rates which increase during the feeding phase--as assumed in Models II and III but not in Model I. These models allow greater flexibility than Model I, because flies can feed early in the hunger cycle, at low probability, as long as the feeding risk is also low.
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7787214
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Ultrastructural analysis of the development of human basophils and mast cells in vitro.
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The ultrastructural analysis of a variety of culture systems of human cord blood mononuclear cells (spanning a 10-year research effort) is reviewed. Human basophils, eosinophils and mast cells reliably developed from their agranular precursors that are present in human cord blood. Suspension cultures and cocultures with fibroblasts were used to examine the effects on differentiation and maturation of full (fibroblast), interleukin-2-depleted (human T cells), and murine inducer T cell culture supernatants, partially purified mouse fibroblast factor(s), recombinant human interleukins 3 and 5, and recombinant human and murine c-kit ligands (stem cell factor, mast cell growth factor). Together, these studies allowed us to define the differentiation and full maturation of the basophil and eosinophil lineages and provided evidence for the induction of a form of secretion (termed piecemeal degranulation) of the basophil and eosinophil lineages in interleukin-3- or -5-supplemented cultures. Mast cells were absent from interleukin-3- or -5-containing cultures. The development of fully mature mast cells occurred regularly in fibroblast-containing cocultures; partially mature mast cells developed in fibroblast culture supernatant-, partially purified mouse fibroblast factor(s)-, and either recombinant human or murine c-kit ligand-supplemented suspension cultures. Small numbers of basophils and eosinophils were present in the suspension cultures that received c-kit ligand in its recombinant or naturally occurring forms. Ultrastructural immunogold analyses confirmed that basophils and eosinophils contained the Charcot-Leyden crystal protein (in different subcellular locations) but that mast cells did not. In both cocultures and suspension cultures, the primary event recorded for mast cells was that of differentiation and maturation, with the ultrastructural correlates of synthetic activity and granule building prevailing. Spontaneous secretory events, recognizable by ultrastructural analysis, were not evident in either mature or partially mature mast cells developing in these cultures.
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7787215
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Cholecystokinin in the control of gastric acid and plasma gastrin and somatostatin secretion in healthy subjects and duodenal ulcer patients before and after eradication of Helicobacter pylori.
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Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown. In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays. In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.
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7787211
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Abundance of guanine, guanosine, inosine and adenosine in human seminal plasma.
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Guanine, guanosine, inosine and adenosine were found in large amounts in seminal plasma from 145 men, regardless of whether spermatozoa were present or not. The mean guanine level in 61 normozoospermic men was 89.7 +/- 93.1 mumol/l; this was significantly lower in 32 vasectomized men (18.9 +/- 31 mumol/l) suggesting the involvement of the epididymis in its secretion. Guanine and nucleoside levels were significantly higher in the seminal plasma of oligozoo- and azoospermic than normozoospermic men. Guanine and nucleoside levels were consistently inter-related in the seminal plasma of normozoospermic men with the best correlation between guanine and guanosine.
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