Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of advanced recombinant DNA technology has provided an improved understanding of the human AAT deficiency phenotype by providing the amino acid sequence of several variant proteins and by allowing for the production of various cell and animal models to study the molecular and biochemical components of the retention, degradation, and accumulation of these variants in the hepatic ER. Human AAT deficiency will continue to serve as an excellent model for enhancing our current understanding of mechanisms utilized in regulating protein "traffic" in the ER and in elucidating the pathophysiologic components of AAT-related liver disease.
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PMID:Molecular biology and genetics of alpha 1-antitrypsin deficiency. 143 81

The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p < 0.001). The effects of copper loading (Cu, 3 g/kg diet); galactosamine (GalN, 0.85 g/kg i.p.); or carbon tetrachloride (CCl4, 10 mmol/kg i.p.) were examined. Serum aspartate transaminase activity was elevated slightly by vitamin E deficiency but not by hepatic copper accumulation. In vitamin E-replete (E+) and vitamin E-deficient (E-) rats, GalN or CCl4 caused a large and comparable elevation in serum AST and OCT activity. This effect on AST was markedly reduced by copper loading in vitamin E replete (E+) rats, but in E(-) rats copper had significantly less protective effect. Copper also diminished the OCT response to GalN in E+, though not E-, rats. A significant rise in total hepatic alpha-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(-) rats. Thus alpha-tocopherol deficiency (a) was not hepatotoxic per se; (b) failed to potentiate the toxicity of copper, GalN or CCL4; but (c) partially abolished the protection by copper against toxin-induced liver injury. Retention of hepatic alpha-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.
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PMID:Alpha-tocopherol deficiency fails to aggravate toxic liver injury but liver injury causes alpha-tocopherol retention. 148 10

The pharmacokinetics of trapidil (Rocornal, Deutsches Hydrierwerk Rodleben GmbH) were studied in 15 patients with chronic liver disease (12 patients with hepatic cirrhosis, 2 patients with alcoholic fatty liver, one patient with liver fibrosis). Trapidil was given orally (200 mg, Rocornal dragees 100 mg) as well as intravenously (100 mg) in random order. Serum samples were analyzed for trapidil by HPLC. The pharmacokinetic parameters were compared with the parameters of 12 healthy volunteers, investigated by Weiss [1991]. Total plasma clearance was decreased significantly in patients with hepatic cirrhosis (99.6 ml/min vs 273.1 ml/min in controls and 255.3 ml/min in patients with non cirrhotic liver disease). However, there was no difference in clearance between patients with compensated and patients with decompensated cirrhosis. Clearance and aspartate aminotransferase activity correlated inversely. In addition, in some of the patients suffering from portal hypertension delayed absorption was observed, but the difference did not reach statistical significance. The volumes of distribution were significantly lower in patients with non alcoholic cirrhosis (19.9 l vs 36.8 l in controls and 41.0 l in patients with alcoholic cirrhosis). It might be concluded from this study, that dosage adjustments are necessary in treatment of patients with cirrhosis. In patients suffering from portal hypertension an intravenous administration should be prefered.
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PMID:Pharmacokinetics of trapidil (Rocornal) in patients with chronic liver disease. 149 Aug 1

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.
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PMID:[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. 151 41

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol-enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 micrograms/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin-treated rats had significantly higher liver enzyme levels (ALT: 1064 +/- 355 IU/liter, AST: 2024 +/- 515 IU/liter) compared with isocaloric/endotoxin controls (ALT: 237 +/- 54 IU/liter, AST: 602 +/- 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 +/- 200 units/ml) compared with isocaloric/endotoxin controls (344 +/- 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 +/- 64 IU/liter, AST: 612 +/- 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/kg endotoxin produced significantly lower peak serum TNF concentrations (401 +/- 76 units/ml) than gavage with distilled water (1152 +/- 208 units/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor in alcohol enhanced endotoxin liver injury. 153 Jan 27

Serum human hepatocyte growth factor levels were measured using a newly developed enzyme-linked immunosorbent assay kit in patients with liver diseases. Serum human hepatocyte growth factor levels were increased in correlation with derangements of prothrombin time, total bilirubin and other parameters reflecting hepatocellular dysfunction in 112 patients with chronic liver disease. The levels were positively correlated with serum AST and ALT levels in 59 of these patients whose prothrombin times were within the normal range. Abnormally increased serum human hepatocyte growth factor levels were found in 100% of the determinations in 16 patients with fulminant hepatic failure and in 80% of the determinations in 16 patients with chronic hepatic failure. The levels greater than 1 ng/ml, however, were found in 94% of determinations in the former group, but only in 16% of the determinations in the latter group. This difference was seen irrespective of prothrombin time or hepatic coma grades. In patients with fulminant hepatic failure serum human hepatocyte growth factor levels were increased immediately after plasma exchange using heparin as the anticoagulant in 71% of the determinations. This increase disappeared 12 hr after discontinuation of plasma exchange. In 17 of 39 patients with chronic renal failure who had no liver disease, serum human hepatocyte growth factor levels were abnormally increased before hemodialysis using heparin, and the levels were elevated immediately after hemodialysis in all the patients. The increase of serum human hepatocyte growth factor levels in hepatic failure may be the result of hepatocellular dysfunction and necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of serum human hepatocyte growth factor levels in patients with hepatic failure. 153 Jul 86

The precise role of lipid peroxidation in the pathogenesis of alcoholic liver disease is still being debated. To explore the issue, this study was undertaken to investigate the status of lipid peroxidation, antioxidants and prooxidants at two discrete stages of experimental alcoholic liver disease. Male Wistar rats were intragastrically fed a high-fat diet plus ethanol for 5 or 16 wk (the duration that resulted in initiation of centrilobular liver necrosis or liver fibrosis, respectively). Lipid peroxidation was assessed in isolated microsomes and mitochondria with three parameters: malondialdehyde equivalents as determined by thiobarbituric acid assay, conjugated diene formation and 4-hydroxynonenal as a 2,4-dinitrophenylhydrazone derivative. To assess antioxidant systems, hepatic concentrations of glutathione, methionine and alpha-tocopherol were determined. The concentration of nonheme iron, a known prooxidant, was also measured. At wk 5, centrilobular liver necrosis was already evident in the ethanol-fed animals, with two- or threefold increases in plasma AST and ALT levels. At this stage, neither malondialdehyde equivalents nor conjugated diene values were elevated, and the 4-hydroxynonemal level was below 0.2 nmol/mg protein. Hepatic concentrations of methionine and alpha-tocopherol in these animals were increased two- and threefold, respectively, whereas the reduced glutathione level remained unchanged. When alcoholic liver disease had progressed to perivenular or bridging fibrosis at wk 16, all three parameters of lipid peroxidation showed consistent increases that were accompanied by significant reductions in the hepatic glutathione and methionine levels. Interestingly, the control animals pair-fed with the high-fat diet also had significantly elevated 4-hydroxynonenal levels at wk 16 compared to the wk 5 level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. 163 54

The recent cloning of the genome of hepatitis C virus (HCV) has allowed the detection of antibodies to HCV (anti-HCV) in human serum. The presence of serum antibodies to HCV often indicates active infection with HCV. We have assessed the serological and histological features in a group of alcoholic patients with chronic liver disease and have evaluated the possible etiologic role of HCV infection in the development of liver damage. Serum samples and liver biopsy specimens were obtained from 41 consecutive patients, all having a definite history of alcohol abuse and evidence of chronic hypertransaminasemia. Fifteen patients (37%) were positive for anti-HCV by ELISA, and 13 (86.6%) of them were also positive by RIBA. Eleven of these patients had histologic features of chronic active hepatitis (CAH), a lesion which is not known to be induced by excessive alcohol intake. No other possible causes of CAH were found, and CAH was not present in any of the anti-HCV negative patients. In patients with CAH, mean AST to ALT ratio was less than 1 (0.6), a finding which is characteristic of viral rather than alcoholic chronic liver disease. In conclusion, our study suggests that sporadic hepatitis C virus infection plays an etiologic role in the development of chronic active liver disease in a subgroup of alcoholic patients.
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PMID:Serological and histological aspects of hepatitis C virus infection in alcoholic patients. 166 17

In order to evaluate the seroprevalence of anti-hepatitis C virus (HCV) antibody in rheumatoid arthritis (RA), where a high prevalence of false-positive anti-HCV reactions is reported, we studied 79 patients affected with RA. In these subjects we recorded some clinical and anamnestic data (history of blood transfusion, risk factors of liver disease, therapy) and determined, besides a few routine laboratory parameters including rheumatoid factor (RF), AST and ALT, the anti-HCV serology using the 1st (EIA, Ortho and Abbott; Neutralization test, Abbott; RIBA, Chiron-Ortho) and the 2nd generation tests (EIA, Ortho; RIBA, Chiron-Ortho). Four patients (of whom three were RF seronegative) were anti-HCV reactive by the 1st generation EIA tests (5.1%). According to the results of the confirmatory tests, and particularly of the 2nd generation, two patients resulted infected by HCV. These results do not confirm the previously reported high prevalence of false-positive anti-HCV reactions in RA, and demonstrated the usefulness of the 2nd generation tests in diagnosing the HCV infection.
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PMID:[Prevalence of antibodies against hepatitis C virus in rheumatoid arthritis. Study using second-generation tests]. 166 11

This paper discusses the progress of enzyme diagnosis by different examples. These include: the requirement for improved enzymological screening, despite the introduction of a test for hepatitis C; the imbalance between the popularity of "unexplained chronic aminotransferase elevations" and efforts to solve the inherent problems; the inadequate attempts to use the metabolic changes in the hepatocytes to improve diagnosis, prognosis, and pathophysiological understanding of viral liver diseases; the remarkable investigations into the 2'-5'-oligoadenylate synthetase for better control of interferon therapy in chronic viral hepatitis; the use of enzymes as markers of etiology, particularly for the detection of alcohol induced liver diseases; the continuing preference for the aminotransferases in this scenario although the ratios of aspartate aminotransferase over alanine aminotransferase, or of mitochondrial aspartate aminotransferase over total aspartate aminotransferase activity, largely depend on the severity and intralobular localization of damage and the stage of the liver disease.
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PMID:Progress in the enzyme diagnosis of liver disease: reality or illusion? 170 67


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