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)

Liver tissues of LEC rats, which develop fulminant hepatitis and hepatocellular carcinoma (hepatoma), were examined by Northern blot analysis using a cDNA probe of rat placental glutathione S-transferase (GST-P). GST-P gene expression was observed not only during hepatocarcinogenesis but also in fulminant hepatitis before development of chronic hepatitis and hepatoma in LEC rats. Cholangiofibrosis in LEC rats also showed high GST-P expression. A transplantable cell line derived from spontaneous LEC hepatoma exhibited a remarkably high expression. By contrast, very weak expression was observed in the livers of young LEC rats before development of hepatitis and control strain rats. Thus, spontaneous hepatic lesions in LEC rats may provide a new clue to elucidate the mechanism of GST-P gene expression.
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PMID:Gene expression of placental glutathione S-transferase in hereditary hepatitis and spontaneous hepatocarcinogenesis of LEC strain rats. 248 61

Enlarged hepatocytes with huge nuclei were found in LEC rats with hereditary hepatitis. Flow cytometric analysis of the DNA content of nuclei from jaundiced LEC rats revealed the presence of very high polyploids, such as 32n and 64n. At the age of 12 weeks, before the onset of hepatitis, 8n polyploid nuclei were more frequent in LEC rats than in LEA rats, a sibling line of LEC rats. Binucleated hepatocytes were also more frequent in LEC rats than in LEA rats at week 4. Bi-, tri- and tetra-nucleated cells whose nuclei were sometimes different in size were observed when jaundice became manifest. The number of proliferating liver cells, determined by pulse labeling with 5-bromo-2'-deoxyuridine (BrdU), was higher in LEC rats than in LEA rats at 2, 4, 8, 12 and 14 weeks, with a maximum at week 4. A remarkable increase of BrdU uptake was observed at week 16, when jaundice developed. The possible involvement of abnormal cytokinesis and kariokinesis in the manifestation of hepatitis was suggested.
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PMID:Accumulation of abnormally high ploid nuclei in the liver of LEC rats developing spontaneous hepatitis. 249 58

The LEC (Long-Evans with a cinnamon-like coat color) rat is a new mutant strain with hereditary hepatitis. The rate of DNA synthesis, the relative amounts of binucleated cells, and the polyploidizations of LEC hepatocytes have been analyzed. Markedly high polyploidy, such as 32n and 64n, were detected after manifestation of hepatitis; however, no aneuploidy was detected. Bi-, tri- and tetranucleated cells whose nuclei occasionally differed in size were observed after the manifestation of hepatitis. In addition to small hepatocytes and oval cells in the periportal area of the hepatic lobule, enlarged cells with huge nuclei were also labeled with BrdU, indicating that in LEC rats suffering from hepatitis abnormal mitosis may be relevant to high polyploidization and multinucleation. Polypeptide analysis using 2D-PAGE detected the apparent lack of expression of two polypeptides, p29.5 and p30, in LEC liver cells; however, linkage analysis indicated no correlation between these peptide defects and the manifestation of hepatitis.
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PMID:Hereditary hepatitis in LEC rats: accumulation of abnormally high ploid nuclei. 262 Mar 8

We have reported an inbred strain LEC rats with high frequency of spontaneous hepatitis. In this paper, we study a possible involvement of hepatitis virus, hereditary background, and correlation between serum IgG level and onset of hepatitis in LEC rats. Neither electron microscopy nor indirect immunofluorescent test could detect hepatitis virus article or antigen. Furthermore, we could not succeed in inducing hepatitis of LEA and WKA/H rats by injecting the serum, plasma and liver homogenates of the affected IEC rats, nor in promoting/developing hepatitis of LEC and LEA rats under the immunosuppressed condition by administration of steroid hormone. When we made a mating between LEC and non-hepatitis rats to investigate the hereditary mode, F1s had no hepatitis, but F2s and backcrosses developed hepatitis. We observed, in particular, the lower the serum IgG level was, the higher the rate of developing hepatitis was. From these results, we speculate that the involvement of hepatitis virus is not likely, but that a genetic mutation might cause low level of IgG and be also correlated with development of hepatitis.
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PMID:[Pathogenesis of spontaneous hepatitis in an inbred strain of LEC (Long Evans cinnamon) rats]. 279 45

We investigated LEC rats immunopathologically which spontaneously developed hepatitis to find out the genesis, in comparison with non-hepatitis LEA (Long Evans Agouti) rats. 1) Wet weights of the spleen and thymus of 6-week old LEC rats were significantly lighter than those of LEA rats of the same age. 2) Serum IgG (Immunoglobulin G) in LEC rats remained markedly low after the age of two months and IgG antibody formation to SRBC (Sheep Red Blood Cell) as detected by plaque assay was also significantly suppressed. On the other hand, IgM antibody formation to SRBC was significantly suppressed through serum IgM level in LEC rats was normal or rather increased. 3) Blastogenic responses of spleen cells to PHA and Con A were much more suppressed in LEC rats than in LEA rats. 4) Cytostatic activity of intraperitoneal macrophages against tumor cells was more evident in LEC rats than in LEA rats, but there was no difference in NK (natural killer) activity between the two rat strains. From these results, it is speculated that spontaneously hepatitis-developing LEC rats possess T and B cell deficiency (combined immunodeficiency) and that the increase of macrophage and NK cell activities are linked to the genesis of developing hepatitis.
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PMID:[Combined immunodeficiency in LEC (Long Evans Cinnamon) rats with spontaneous hepatitis]. 279 59

The Long-Evans rat with a cinnamon-like coat color (LEC rat) is a mutant strain displaying hereditary hepatitis with severe jaundice. The age related difference in microsomal dealkylation of pentoxyresorufin and ethoxyresorufin was examined. The enzyme activity levels of pentoxyresorufin O-depentylase in LEC rats were decreased to 25% of the levels in control [Long-Evans rats with an agouti coat color (LEA rats)]. In contrast, ethoxyresorufin O-deethylase exhibited a much less marked difference between the strains. In parallel with these strain differences in enzyme activities, a decrease in phenobarbital (PB) inducible P450 isozymes, mainly P450b and P450e, was observed by Western blot analysis. The level of P450PB in LEC rats was more markedly depressed than in the LEA strain. On the other hand, microsomes from uninduced LEC rat liver had more 3-methylcholanthrene (MC) inducible P450MC, mainly P450c and P450d, than microsomes from LEA rat liver and these isozymes in the LEC were markedly induced by 3-methylcholanthrene treatment. The great difference in cytochrome P450PB content of the liver microsomes between LEC and LEA rats and the maintained constitutive levels of hepatic cytochrome P450MC in the LEC rats suggest a possible role of these cytochrome isozymes in the onset of spontaneous hepatitis and hepatoma.
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PMID:Selective expression and induction of cytochrome P450PB and P450MC during the development of hereditary hepatitis and hepatoma of LEC rats. 280 35

1. The LEC rats, a novel animal model of hepatitis and liver tumor, were found to have charge variants of serum alpha 1-antitrypsin (alpha 1AT) at the stage of liver tumor as judged by isoelectric focusing. 2. Treatment of the sera with neuraminidase showed that acidic variants of alpha 1AT in LEC rats seemed to be highly sialylated forms. 3. The concentration and enzymatic activity of serum alpha 1AT in LEC rats were not affected before the onset of hepatitis and even during the development of fulminant hepatitis and hepatocarcinogenesis. This indicates that hereditary hepatitis and subsequent liver tumor in LEC rats do not appear to be associated with alpha 1AT deficiency.
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PMID:Hepatoma-associated alterations of serum alpha 1-antitrypsin in hereditary hepatitis LEC rats as a new animal model of liver disease. 285 94

Spontaneous occurrence of placental glutathione S-transferase (GST-P)-positive foci was observed in the livers of 5-month-old LEC rats. Quantitative studies revealed that GST-P foci appeared after the onset of hepatitis. The number and size of GST-P foci increased with age and more foci were induced in males than in females. No sex difference, however, was found in the incidence of hepatitis. Although hepatitis is necessary for the induction of GST-P foci, it is insufficient for their further growth. Since hereditary hepatitis first appears at around 4 months of age, leading to a high incidence of hepatocellular carcinomas in later life, the spontaneous occurrence of the foci may be related to the development of hepatocellular carcinoma.
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PMID:Spontaneous occurrence of placental glutathione S-transferase-positive foci in the livers of LEC rats. 289 58

Previously we established that 'LEC rats' have displayed spontaneous fulminant hepatitis with severe jaundice, which progressed to liver cancer, and a single autosomal recessive gene is responsible for the cause of the diseases. The activities of drug metabolizing enzymes were assayed in livers from LEC and control (LEA) rats at 4 weeks and 3 months before the onset of liver cancer. At 4 weeks the cytochrome P-450 content of the LEC rat livers was 43% of the control (LEA) value. At 3 months the level was 65% of the control. Epoxide hydrolase, gamma-glutamyltranspeptidase and UDP-glucuronyltransferase activities were 2.6-, 6.9- and 2.4-times higher than those in the LEA rats at 4 weeks, respectively, while glutathione S-transferase activity was not significantly different between the two strains. The enzyme changes in the LEC rats are quite similar to those observed in hyperplastic foci and nodules in chemical carcinogenesis of hepatocytes.
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PMID:Metabolic predisposition of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma: alterations of the drug metabolizing enzymes. 290 Jul 2

A serially transplantable rat hepatocellular carcinoma (HCC) line was established. The primary spontaneous HCC which developed in a 506-day-old male hereditary hepatitis LEC rat was inoculated into young LEC rats. Only this HCC of 18 primary HCCs was successful in serial transplantation. The established cell line was histologically identical to the primary HCC showing a well-differentiated type with a trabecular structure of tumorous hepatocytes. The characteristic of albumin production was maintained. Chromosome analysis revealed rather widely dispersed polyploid chromosome numbers with a modal value at 96. Every metaphase contained two to five unusually large marker chromosomes.
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PMID:A transplantable cell line derived from spontaneous hepatocellular carcinoma of the hereditary hepatitis LEC rat. 313 Mar 60


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