Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-hepatitis effect of the olean-9(11),12-diene-3 b, 30-diol 3 b, o-hemisuccinate Na Salt (III b), a glycyrrhetinic acid derivative, was studied in CCl4 induced mouse. The mouse was administered i.p. with 0.1 mole/kg or 0.2 mole/kg of III b, then followed by 31.4 microliters/kg of CCl4. III b was shown to promote the activity of the glucose-6-phosphatase, lower the content of malondialdehyde, and prevent the activity from the soluble enzyme(i.e. GPT, GOT, LDH) from flowing out in the serum enzyme and liver homogenate. III b had the similar anti-peroxidation effect as vitamin E and can maintain the liver function.
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PMID:Effect of olean-9(11), 12-diene-3 beta, 30-diol 3 beta, o-hemisuccinate Na salt, a glycyrrhetinic acid derivative, on peroxidation in CCl4 induced mouse acute hepatitis. 166 46

Antibodies against cytochrome P-450 are found in some children with autoimmune hepatitis (antiliver/kidney microsome 1) and in patients with ticrynafen hepatitis (antiliver/kidney microsome 2). For an immune reaction against cytochrome P-450 to possibly destroy the hepatocytes, one must assume that cytochrome P-450 is present on the plasma membrane surface of hepatocytes. In a first series of experiments, plasma membranes were prepared with a technique based on the electrostatic attachment of isolated hepatocytes to polyethyleneimine-coated beads. After vortexing, beads were coated with a very pure plasma membrane fraction. Microsomal contamination, judged from the specific activities of glucose-6-phosphatase or NADH-cytochrome c reductase, was less than 1%. Nevertheless, the specific content (per milligram of protein) of CO-binding cytochrome P-450 was 20% of that in microsomes; the specific benzo(a)pyrene hydroxylase activity was 25%, and ethoxycoumarin deethylase 11%. Immunoblots showed the presence of cytochromes P-450 UT-A, UT-H, PB-B, ISF-G and PCN-E, the last three isoenzymes being inducible by, respectively, phenobarbital, 3-methylcholanthrene and dexamethasone. In a second series of experiments, nonpermeabilized isolated hepatocytes from untreated rats were incubated with anticytochrome P-450 antibodies. Immunofluorescence and immunoperoxidase staining confirmed the presence of cytochromes P-450 UT-A, PB-B and ISF-G on the membrane. In a last series of experiments, human antiliver-kidney microsomal 1 antibodies were found to react specifically with rat liver plasma membrane cytochrome P-450 UT-H (IID subfamily). We conclude that several cytochrome P-450 isoenzymes are present, active and inducible on the plasma membrane surface of hepatocytes. It is therefore conceivable that immunization against plasma membrane cytochrome P-450 might lead to the immunological destruction of hepatocytes in some patients.
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PMID:Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane. 211 12

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediate-cell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) and gamma-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplastic transformation of the hepatocytes.
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PMID:Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. 215 41

Two cynomolgus monkeys were inoculated with a stool extract originally derived from patients suffering from enterically transmitted non-A, non-B hepatitis. Subsequently, the primates developed self-limiting acute hepatitis and their liver tissues were obtained sequentially by needle biopsy or at sacrifice. Histologically, the liver tissues exhibited necroinflammation which appeared in parallel, both in time and magnitude, with elevation in serum aminotransferases. Necroinflammation was characterized by focal dropout of hepatocytes with accumulation of lymphocytes and macrophages. These lymphocytes were positive for a cytotoxic/suppressor immunophenotype. The hepatocytes surrounding these focal necroses showed depletion of glycogen granules and decrease in glucose-6-phosphatase and succinic dehydrogenase activities. Ultrastructurally, damaged hepatocytes around the focal necroses revealed marked dilatation of both rough and smooth endoplasmic reticula, swelling and disruption of the mitochondria and leakage of nuclear materials into the cytoplasm. Frequently, direct contact between the damaged hepatocytes and lymphocytes was noted. Virus-like particles measuring about 27 nm in diameter were observed singly or in small groups within the cytoplasm of damaged hepatocytes. Primary hepatocyte culture of a cynomolgus monkey, inoculated with a transmissible stool extract did not show any cytopathic change, although similar virus-like particles were recognized ultrastructurally in the cultured hepatocytes. Morphological analysis of in vitro and in vivo transmission studies in cynomolgus monkeys strongly supported the hypothesis of immune-mediated hepatocytolysis rather than a direct cytopathic effect of this hepatitis virus.
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PMID:Enterically transmitted non-A, non-B hepatitis in cynomolgus monkeys: morphology and probable mechanism of hepatocellular necrosis. 250 12

The zonal distribution of enzyme activities was measured by quantitative cytochemistry in cryosections of liver from three normal children and five infants with idiopathic hepatitis of infancy. Optimal conditions for cytochemical reactions were first validated in rat liver and subsequently used in human livers to quantify zonal activities of acid phosphatase (AP), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), glucose-6-phosphatase (G6P) and NADPH-dehydrogenase (ND). In normal rat and human livers, activities were greater for SDH and G6P in periportal and for GDH and ND in perivenular hepatocytes, while AP was evenly distributed along the sinusoids. In five infants with idiopathic hepatitis of infancy (IHI), a similar trend of distribution was observed for the two mitochondrial (SDH and GDH) and the two microsomal (G6P and ND) enzymes, although the distribution gradient was less pronounced than, in normal livers. AP showed a mildly greater periportal than perivenular activity. This preliminary study shows that a similar metabolic zonation exists for these enzymes in human livers as is observed in rats.
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PMID:The application of quantitative cytochemistry to study the acinar distribution of enzymatic activities in human liver biopsy sections. 254 21

Woodchucks free from woodchuck hepatitis virus were treated with diethylnitrosamine in vivo for 2 months, and then hepatocytes obtained by enzymatic perfusion were cultured with the hepatopromoter phenobarbital. This in vivo-in vitro procedure gave rise to proliferating epithelial cell foci, from one of which the presently described hepatocyte cell line (WLC-3) was established and characterized. WLC-3 cells possess morphological and biochemical features of differentiated hepatocytes, including glucose-6-phosphatase activity and albumin production. Histopathological analysis of the tumor which developed transitorily in nude mouse subcutis after inoculation of the cell line revealed glandular structures comprising cells of hepatocellular-like morphology. This is the first established woodchuck hepatocyte cell line free from woodchuck hepatitis virus and is therefore expected to be useful for studying the mode of gene expression and viral proliferation of woodchuck hepatitis virus and the mechanisms underlying woodchuck hepatitis virus-related hepatocarcinogenesis.
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PMID:Establishment and characterization of a diethylnitrosamine-initiated woodchuck hepatocyte cell line. 288 13

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.
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PMID:Enzyme-altered liver cell foci in woodchucks infected with woodchuck hepatitis virus. 289 65

Hepatocyte membranes destruction in experimental toxic hepatitis caused by heliotrine administration was accompanied by a 10-fold increase in blood serum activity of aldolase fructose-I-monophosphate, a decrease in cytochrome P-450 content, an increase in the rate of cytochrome P-450 inactivation, as well as a decrease in microsomal glucose-6-phosphatase activity. Administration of phosphatidylcholine liposomes decreased the activity of aldolase twofold, which indirectly shows partial reconstitution of liver cell membranes. Phosphatidylcholine protective action is also manifested in an increase in the activity of glucose-6-phosphatase, a microsomal marker enzyme, up to its control level and in a 20% reduced rate of cytochrome P-450 inactivation. It has been shown that destroyed liver cell membranes may be repaired by the introduction of phosphatidylcholine in the form of multilayer liposomes.
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PMID:[Phosphatidylcholine-induced repair of damaged hepatocyte membranes in heliotrine poisoning]. 303

Previous studies have demonstrated that sera from patients with severe liver damage after halothane anesthesia ("halothane hepatitis") contain antibodies reacting with novel antigenic determinants expressed on hepatocytes from rabbits exposed previously to halothane. To determine the structure of the halothane-induced antigen(s), immunoblotting experiments were performed using patient sera and rabbit liver subcellular fractions. Three polypeptide antigens (Mr 100,000, 76,000 and 57,000) expressed in liver fractions from animals sacrificed 16 hr after exposure to 1% halothane in oxygen for 45 min, but not in fractions from unexposed animals, were identified. Analysis of fractions prepared by differential and sucrose density gradient centrifugation, and characterized by enzyme marker analysis, localized all three antigens to a microsomal subfraction relatively enriched in glucose-6-phosphatase activity, therefore, presumably derived from the endoplasmic reticulum. Antibodies to these antigens were detected in 19 of 24 sera from patients with halothane hepatitis, and four distinct patterns of antibody specificity were observed: 100,000 + 76,000 (seven patients), 100,000 alone (seven patients), 76,000 alone (three patients) and 57,000 alone (two patients). Such antibodies were not detectable in sera from 24 normal blood donors or 36 control patients. Thus, halothane induces expression of three distinct polypeptide antigens in liver, and patients with halothane hepatitis differ in patterns of recognition of these antigens by circulating antibodies.
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PMID:Identification by immunoblotting of three halothane-induced liver microsomal polypeptide antigens recognized by antibodies in sera from patients with halothane-associated hepatitis. 330 10

Cytochemical analysis at the ultrastructural level was performed to characterize expression of catalase and glucose-6-phosphatase (G6Pase) activity as possible differentiation markers in oval cells proliferating during hepatocarcinogenesis induced in woodchucks by chronic infection with the woodchuck hepatitis virus (WHV) and additional treatment with aflatoxin B1 (AFB1). Oval cells from WHV-carriers treated with AFB1 showed two types of catalase-positive organelles: 1) microperoxisomes appearing as small strongly osmiophilic bodies corresponding to those present in biliary cells from control woodchucks, 2) peroxisomes with a hepatic staining pattern resembling those of mature hepatocytes but lacking a nucleoid. While in oval cells penetrating into the parenchyma a catalase-positive reaction product was restricted to rare microperoxisomes, in close vicinity to the portal tract about 30% of the oval cells produced peroxisomes with a hepatic staining pattern, indicating the existence of two different populations within the oval cell compartment. Peroxisomes with a hepatic staining pattern formed clusters and exhibited pleomorphism with marked variation in shape and size, the size sometimes coming up to that of normal hepatocellular peroxisomes. Serial sections revealed the complex organization of these peroxisomes. They consisted of several interconnected segments forming a peroxisomal reticulum. These findings are consistent with the hypothesis that a subpopulation of oval cells represents committed precursor cells capable of differentiating into hepatocytes. Activity of G6Pase was not demonstrable in this subpopulation of oval cells and became positive only in transitional cells. Differential expression of catalase and G6Pase activity in a stepwise fashion within the oval cell compartment appear to mark differentiation of oval cells into hepatocytes. Thus, elevated expression of catalase may be a useful early marker for the distinction of different subpopulations of oval cells committed to hepatic cell lineages before definitely changing their phenotype, whereas expression of G6Pase activity seems to begin later, accompanying morphological changes towards the phenotype of mature hepatocytes.
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PMID:Changes in catalase and glucose-6-phosphatase distribution patterns within oval cell compartment as possible differentiation markers during viral hepatocarcinogenesis in woodchucks. 876 96


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