Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum gamma-glutamyltransferase activity (GGT) has been measured in 150 patients with a variety of hepatobiliary disorders. GGT concentration was significantly higher in patients with "cholestatic" liver disease than in those with "hepatic" disorders, although there was considerable overlap. Measurement of GGT alone did not allow differentiation of intrahepatic cholestasis from extrahepatic cholestasis. However, GGT/serum bilirubin ratios were significantly higher in patients with intrahepatic cholestasis when compared with patients with extrahepatic biliary obstruction. Estimation of serum concentration of GGT appears to be a sensitive screening test both for alcohol consumption and for hepatobiliary disease. However, measurement of GGT concentration has only limited value in the differential diagnosis of hepatobiliary disease, although it may help in the differentiation of "hepatitic" and "cholestatic" liver disease.
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PMID:Value of serum gamma-glutamyltransferase activity in the diagnosis of hepatobiliary disease. 612 72

In experimental bile obstruction the serum activities of the membrane-bound liver enzymes, alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase are greatly increased, whereas in the liver only the alkaline phosphatase activity is elevated. After partial hepatectomy or tetrachloride poisoning the alkaline phosphatase activity in the regenerating live is increased to the same extent as in cholestasis without an accompanying elevation in serum activity. The following results support the hypothesis of a bile salt-mediated solubilization of membrane-bound enzymes in cholestatic liver: (1) 30 min after bile duct ligation the total bile acids in the liver were increased 5-fold, 2 h later as much as 10-fold. After 1 day, the bile acid concentration was still 4 times above normal. (2) Isolated plasma membranes from normal and obstructed livers were incubated in vitro with increasing amounts of tri- and dihydroxycholanic acids. At a final concentration of 1 mmol/l taurochenodeoxycholate significant amounts of membrane-bound enzymes were released into the 12,000-g supernatant. (3) In the regenerating liver, where tissue phsophatase activity was high and serum phosphatase activity unchanged, the bile salt concentration was not increased.
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PMID:Studies on the mechanism of the increase in serum alkaline phosphatase activity in cholestasis: significance of the hepatic bile acid concentration for the leakage of alkaline phosphatase from rat liver. 612 56

The association of gamma-glutamyltransferase activity with lipoproteins was investigated in serum from hepatobiliary diseased patients. From 60 to 80% of the total activity in such sera was bound in lipoprotein complexes. These complexes or multiple forms of gamma-glutamyltransferase could be separated into two main fractions by gel filtration or agarose gel electrophoresis. One fraction was characterized by gamma-glutamyltransferase of high molecular mass (Mr greater than 600,000) and beta-mobility and was detected in increased amounts in serum from patients with cholestasis. The main part of this activity was associated with lipoprotein-X and this complex could amount to 50% in some sera. The other fraction contained gamma-glutamyltransferase eluting in the molecular mass range of 250,000 to 450,000 and migrating with alpha 1 alpha 2-mobility. In this fraction complexes of gamma-glutamyltransferase and high-density lipoprotein were detected which could amount to 70% in non-icteric sera. However, heterogeneity in size, charge and density could be demonstrated in both fractions.
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PMID:Multiple forms of serum gamma-glutamyltransferase. Association of the enzyme with lipoproteins. 612 75

Serum gamma-glutamyltransferase (EC 2.3.2.2) showed microheterogeneity on electrofocusing, owing to variations in sialic acid content. We investigated the isoform patterns of papain-treated serum samples on agarose gels containing nonionic detergent and ampholytes in the low pH range. Serum from cases of cholestasis show seven bands with gamma-glutamyltransferase activity. These same bands were also found in liver tissue similarly treated, and they had pl values ranging from 3.8 to 4.2. Papain-treated sera that also had been neuraminidase digested showed only a single band, still enzymatically active and with a pl of 5.9. Increased gamma-glutamyltransferase in serum as a result of alcohol abuse was combined with a abnormally high degree of sialylation of the enzyme, giving more anodal isoforms. The decline in the concentration of this enzyme during several weeks of abstinence was accompanied by a gradual decrease in gamma-glutamyltransferase sialyation and the appearance of more cathodal fractions.
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PMID:Evaluation of serum gamma-glutamyltransferase by electrofocusing, and variations in isoform patterns. 613 55

We studied the association between gamma-glutamyltransferase (GGT) and apolipoproteins A or B in serum of 42 patients with various hepatobiliary diseases. Binding of the enzyme to apolipoprotein A is not related to a clearly defined disease, but appears to be mainly influenced by the ratio of total cholesterol to GGT activity. An important fraction of GGT activity is associated with apolipoprotein B in patients with icteric or anicteric cholestasis. Conversely, in noncholestatic patients, the percentage of apolipoprotein B-bound GGT activity is low. Addition of the "heavy" form of GGT, obtained by solubilizing the membrane-bound enzyme with detergents, to a serum with low GGT activity led to the binding of the enzyme only to apolipoprotein A. The "light" form of GGT, obtained by limited proteolysis of the "heavy" form and added to the same serum, did not bind to either apolipoprotein A or apolipoprotein B. Thus, the association between the serum enzyme and apolipoprotein A apparently results from nonspecific aggregation of the amphiphilic "heavy" form of the enzyme. The origin of the apolipoprotein B-GGT complexes found in cholestatic patients needs further investigation.
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PMID:Associations between serum gamma-glutamyltransferase and apolipoproteins: relationships with hepatobiliary diseases. 614 10

Distribution of plasma gamma-glutamyltransferase (GGT) activity among lipoproteins was studied by ultracentrifugation and polyacrylamide gradient gel electrophoresis of plasma from 2 normal controls, 7 patients with intrahepatic cholestasis, and 5 patients with biliary obstruction. Half the total plasma activity was associated with lipoproteins, and more than 90 per cent of the residue activity with macromolecular lipid-protein complex. Healthy subjects had the highest GGT activity in HDL, intermediate activity in LDL, and the lowest in VLDL. In cholestasis, GGT activity increased mainly by the following two mechanisms: 1) the appearance of cholestatic lipoproteins carrying GGT, such as lipoprotein X or Slow-Migrating HDL, or increase in concentration of lipid-protein complex with GGT activity and 2) increase in GGT activity per unit weight of HDL.
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PMID:Association of gamma-glutamyltransferase with plasma lipoprotein and lipid-protein complex in cholestasis. 615 Aug 87

Possible liver damage induced by chemicals or drugs must be detected early during drug development or industrial exposure, although damage is still difficult to predict, especially when immunotoxicity is involved. Liver toxicity may result from cytolysis, steatosis, cholestasis, phospholipidosis, or vascular lesions, most the outcome of a disadvantageous balance between chemicals or metabolites vs protective mechanisms, resulting from chemical dosage, genetic factors, or the immunoallergic status of the patient. Drug metabolism, lipid peroxidation, and thiol oxidation are frequently involved in liver toxicities. Classical guidelines in toxicology propose many methods for liver toxicity assessment: histology; chemical changes in hepatic tissue (lipids, glutathione, enzymes); physiological changes in biosynthesis (proteins, glycoproteins); excretion function (fructose); drug metabolism; and concentrations of related enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase) in blood. In vitro studies in human or animal hepatocytes or tumor-derived cell lines are useful in detecting hepatocellular lesions by cell viability, glutathione concentration, amount of lactate dehydrogenase released, cellular ATP, morphology (blebs), and drug metabolism.
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PMID:Manifestations of chemically induced liver damage. 749 49

Serum bile acid concentrations were measured after food had been withheld for 12 hours (fasting serum bile acid [FSBA] concentration) and 2 hours after a meal (post-prandial serum bile acid [PSBA] concentration) using a direct enzymatic procedure in 108 cats clinically suspected of having hepatobiliary disease. In all cats, liver tissue was examined histologically to confirm the diagnosis. Twenty-six cats did not have histologic evidence of hepatobiliary disease and served as controls. The remaining 82 cats had hepatobiliary disease including hepatic lipidosis (n = 20), portosystemic vascular anomaly (n = 24), hepatic necrosis (n =13), hepatic neoplasia (n = 8), or cholestatic hepatic disease(n = 17). Sensitivity and specificity of measuring FSBA and PSBA concentrations were calculated for each test alone and when results were interpreted in combination (ie, in series and in parallel), and were compared with sensitivity and specificity of routinely used serum biochemical tests, including measuring serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase, and measuring serum concentrations of cholesterol, BUN, and total bilirubin. When tests were considered individually, determination of FSBA and PSBA concentrations had higher specificity than did the other tests (using a cutoff of 15 mumol/L for FSBA concentration and of 20 mumol/L for PSBA concentration). Determination of PSBA concentration had the highest sensitivity of all single tests in cats with hepatic lipidosis, portosystemic vascular anomaly, or cholestasis; determination of alanine aminotransferase activity or PSBA concentration had the highest sensitivity for cats with hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measurement of serum bile acids concentrations for diagnosis of hepatobiliary disease in cats. 755 44

Hyperplastic nodular cirrhosis was induced in rats by long-term (6 month) i.p. administration of thioacetamide at doses of 2.66 mmol/kg body wt, three times per week. The survival rate of animals at the end of the treatment was 90%. To follow the temporal changes samples at 0, 7, 15, 30, 45, 60, 90, 150 and 180 days from rats during thioacetamide intoxication and from chronological controls were obtained. The cirrhogenic ability of this treatment was assessed on the basis of morphological changes: the development of macronodular cirrhosis and the appearance of fibrous septa of collagen through portal spaces. Parameters of liver injury and cholestasis were obtained by assaying the serum activities of isocitrate dehydrogenase and gamma-glutamyltransferase. Enzymes and metabolites related to glutathione redox systems, as well as other antioxidant enzymes, were tested. Catalase and glutathione peroxidase, the two enzymes involved in the elimination of peroxides, and glutathione reductase decreased significantly at the end of the 6 months of intoxication, while Cu-Zn and Mn superoxide dismutases increased progressively during the long-term thioacetamide treatment. Protein thiol levels profile showed a biphasic change increasing from the 7th day and were insensitive to the 30% depletion of intracellular glutathione (GSH). To study the relationship of the intracellular thiols on the mechanisms of cell proliferation and differentiation during the cirrhogenic process, DNA content was assayed by flow cytometry in isolated hepatocytes, and DNA ploidy and distribution between G0-G1, S and G2 + M phases were determined. Remarkable changes in relation to a sharp increase in diploid population from 7 to 180 days (24.5%-->85.5%), a pronounced decrease in polyploid populations (tetraploid+octoploid) in the same period (73.7%-->12.3%), and elevations in the populations in S phase (S1 + S2) were observed in thioacetamide-treated rats. The results obtained indicate that hepatocytes isolated from thioacetamide-treated rats showed a marked tendency to diploidy, an enhancement in DNA replication parallel to the hepatic content of protein sulphydryl groups and a significant decline in antioxidant enzyme activities. The increase in protein thiols was independent of GSH level and of the thiol redox state.
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PMID:Relationship between antioxidant systems, intracellular thiols and DNA ploidy in liver of rats during experimental cirrhogenesis. 761 93

Cattle in 2 herds developed type-3 photosensitization after eating moldy alfalfa hay. Clinical signs included severe epidermal necrosis of unpigmented skin and marked decrease of milk production (herd 1). One herd had 18% mortality. Values for serum gamma-glutamyltransferase, lactate dehydrogenase, aspartate transaminase, and serum bilirubin were high in affected cows. Biliary epithelial degeneration and necrosis affecting the smaller bile ductules is the most consistent histologic lesion. Biliary hyperplasia, early portal fibroplasia, hepatocellular vacuolar degeneration and necrosis, and cholestasis were commonly seen. Mold growth on the alfalfa hay associated with prolonged wet weather prior to harvest was common to both herds. The cases reported here document hepatoxicosis and photosensitization associated with feeding moldy alfalfa hay grown in southeastern United States.
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PMID:Toxic hepatopathy and photosensitization in cattle fed moldy alfalfa hay. 790 82


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