Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum gamma-glutamyl transferase (GGT, EC. 2.3.2.2. was measured in 173 patients with diseases of the hepatobiliary system (including metastatic cancer) and in 90 patients who were subsequently shown to have primary diseases of other etiology. All patients had been selected because they had abnormal alkaline phosphatase, aspartate aminotransferase or bilirubin on SMA 12/60 screening. Serum GGT was elevated in 97% of patients with primary hepatobiliary disease. The magnitude of the increase in GGT was variable in all groups and was unhelpful in differential diagnosis, even between medical and surgical cases. Moreover, GGT was abnormal in 69 patients who did not have primary hepatobiliary disease (77%), an incidence higher than that for other enzyme tests performed. We conclude that because GGT was more susceptible than other tests to spurious elevation in the absence of hepatobiliary disease and was unhelpful in differential diagnosis, it has little value apart from monitoring alcohol abuse and enzyme induction.
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PMID:Lack of value of serum gamma-glutamyl transferase in the diagnosis of hepatobiliary disease. 3 86

One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.
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PMID:No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion. 849 17

New biologically active compounds (BAC) created on the basis of nicotinic acid possess hepatoprotective action. The preparations were introduced preventively in doses of 10 mg/kg during 14 days. Litonit and nicogamol increased survival of experimental animals by 36.8% and nicotinic acid by 26.8%. ALT, AST, GGT activity in the blood serum was reduced. The activity of the main antioxidant enzymes (SOD and catalase) grew in the rat liver tissue in parallel with inhibition of DK and MDA activity. Morphological picture of the rat liver, most evident after application of litonit improved. Hepatoprotective action of these BAC are attributed to their membrano stabilizing effects.
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PMID:[Mechanisms of hepatoprotective action of new nicotinic acid derivatives in experimental CCL4-induced liver injury]. 142 11

This study was performed to investigate modifications in the serum bilirubin forms, hepatobiliary enzymes, and some glycoproteic substances in patients during the course of extrahepatic cholestasis (stage A) and following its clinical resolution (stage B). The series consisted of 16 patients: 11 had main bile duct stones; two, benign stenosis of the main bile duct; and three, main bile duct cancer. Cholestasis resolved spontaneously in one case, under endoscopy in two, and following surgery in 13. Five patients with liver cirrhosis and a picture of intrahepatic cholestasis following anesthesia were also investigated. Serum bilirubin forms were measured using van den Bergh's method and the alkaline methanolysis-HPLC procedure; the mono- and di-conjugated forms were considered together in the overall evaluation of the results. The hepatobiliary enzymes (ALP, GGT, and AST) were increased at stage A and significantly decreased at stage B. Similar patterns were observed in total (TB), unconjugated (UB), and conjugated bilirubin (CB) and in the percentage of CB out of TB (% CB). In the majority of patients, % CB at stage B was lower than at stage A, whereas in subjects with a high initial UB value, a different % CB pattern was observed. The direct bilirubin percentage (% DB), on the other hand, had a different pattern, and the variations between stages A and B were not significant. The pathophysiological bilirubin pattern was similar in patients with intrahepatic cholestasis. At stage A, in a number of patients the levels of glycoproteic substances (CA 19-9, TPA and ferritin) were raised, but at stage B they tended to decrease towards the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis. 160 Mar 31

The role of clinical (biliary pain and/or jaundice), laboratory (discriminant function (DF) calculated using AST, ALT, AlkPh and GGT serum values) and ultrasonographic (US)(dilation and/or stone of common bile duct (CBD)) findings in identification of the biliary etiology of acute pancreatitis (AP) was studied in 60 patients. AP biliary etiology was defined by ERCP executed in the early phase of the disease (lithiasis and/or stenosis of CBD; endoscopic features of forced papilla in patients with gallstone). US showed the best values of sensitivity (84.6%) and diagnostic efficacy (76.7%); DF showed the best results of specificity (62.5%) and of test positive predictive value (92.8%). The statistical evaluation (McNemar test) showed a significant increase of sensitivity for US vs clinical findings and of specificity for DS vs clinical findings (p less than 0.05). The sensitivity, specificity, accuracy, test negative and positive predictive value were improved to 96.1, 87.5, 96.6, 77.1 and 92% by the combination of US and DF. Therefore the association of US and DF can provide the best non invasive method in rapidly detecting CBD pathology as an etiological factor in AP and then the enough accurate indication to early operative ERCP.
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PMID:[The role of clinical, biochemical and echographic data in identifying the biliary pathogenesis of acute pancreatitis]. 162 15

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.
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PMID:Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet. 163 55

Extracts of homologous organs (liver, muscle) and of colostrum were infused intravenously in cattle of two different age groups: heifers (n = 9, each preparation was infused in 3 animals) and calves (n = 6, preparations from liver and muscle were infused in 3 animals each). Parameters of elimination kinetics were determined for some clinically relevant enzymes. Enzyme elimination was quicker in the younger animals. The volume of enzyme distribution was comparable to plasma volume. Biological half-lives in calves and heifers respectively were: CK from muscle 3.46 +/- 0.65 h and 8.27 +/- 3.27 h, AST from muscle 9.74 +/- 1.38 h and 33.48 +/- 3.74 h, AST from liver 14.99 +/- 0.81 h and 16.71 +/- 0.58 h, GLDH from liver 14.61 +/- 1.88 h and 25.09 +/- 4.13 h, SDH from liver 13.95 +/- 2.25 h and 17.68 +/- 0.81 h, GGT from colostrum 1.69 +/- 0.95 h (only heifers).
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PMID:[Elimination kinetics of several clinically relevant enzymes in the blood plasma of cattle after intravenous bolus infusion of homologous preparations]. 163 72

Cytotoxic T lymphocyte (CTL)-mediated cytolysis is induced via the interaction of the specific T-cell antigen receptor and the peptidic viral antigen associated with the major histocompatibility complex class I antigen. Here we demonstrate in vitro that lymphocytic choriomeningitis virus (LCMV) can escape the cytotoxic activity of LCMV-specific cloned CTLs by single amino acid changes within the recognized T-cell epitope defined by residues 275-289 of the LCMV glycoprotein [LCMV-GP-(275-289)]. LCMV-infected fibroblasts at a multiplicity of infection of 10(-3) exposed to virus-specific CTL at an effector-to-target cell ratio of 4:1 4 hr after infection was optimal for virus mutant selection. The selections were carried out with three LCMV-GP-(275-289)-specific CTL clones expressing T-cell antigen receptors containing the identical variable gene segments V alpha 4 and V beta 10 but different junctional regions; selection was also possible with LCMV-GP-(275-289)-specific cytotoxic polyclonal T cells. The most common escape mutation was an amino acid change of asparagine (AAT) to aspartic acid (GAT) at position 280; an additional mutation was glycine (GGT) to aspartic acid (GAT) at position 282. The results presented show that relevant point mutations within the T-cell epitope of LCMV-GP-(275-289) occur frequently and that they are selectable in vitro by CTLs.
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PMID:In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes. 172 16

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.
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PMID:Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies. 172 78

A study was carried out on 65 male workers heavily exposed to lead in the ceramic tile manufacturing industry in order to assess the effects of alcohol on the biological indicators of lead (PbB, ALA-D, ALA-U, ZPP). All subjects selected for the study had PbB levels greater than or equal to 60 micrograms/dl, normal levels of serum iron and no haemoglobin disorders. The subjects were divided into three groups according to alcohol intake checked by anamnestic investigation, mean corpuscular volume (MCV) values and liver function parameters, as follows: Group A--27 subjects, controls, with daily alcohol intake less than 80 ml, MCV less than or equal to 95 mu 3, normal GGT, AST and ALT levels; Group B--20 subjects, heavy drinkers, with daily alcohol intake greater than or equal to 80 ml, MCV greater than 95 mu 3, occasionally high GGT, but normal AST and ALT values; Group C--18 subjects, heavy drinkers, with daily alcohol intake greater than or equal to 80 ml, MCV greater than 95 mu 3, abnormal GGT, AST and ALT levels. The length of lead exposure did not significantly differ in the three groups. The well-known effects of ethanol intake on PbB, ALA-D and ALA-U values were confirmed, with the following mean values in the three groups: Group A: PbB = 66.0 (micrograms/dl), ALA-D = 10.3 (mU/ml r.c.), ALA-U = 8.4 (mg/l); Group B: PbB = 68.3 (micrograms/dl), ALA-D = 6.7 (mU/ml r.c.), ALA-U = 9.1 (mg/l); Group C: PbB = 71.5 (micrograms/dl), ALA-D = 4.6 (mU/ml r.c.), ALA-U = 12.7 (mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Influence of alcohol on the behavior of dose and effect indicators in workers exposed to inorganic lead: unexpected behavior of ZPP]. 180 15


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