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)

We studied the copper concentrations in the non-cancerous and cancerous liver tissues of LEC rats with hereditary hepatitis and spontaneous hepatoma by atomic absorption spectrophotometry. Copper concentration in the non-cancerous livers of 29-month-old male LEC rats was comparable to that in the livers of LEC rats aged 2, 3 and 8 months whose hepatic copper concentrations were more than 40 times those of normal LEA rats. Copper concentration in spontaneously developed hepatocellular carcinomas of the 29-month-old male LEC rats was lower than that in the surrounding non-cancerous liver tissues, but was still more than 39 times that of 8-month-old male LEA rats. These findings suggest that in LEC rats an abnormal copper metabolism may be maintained during the process of hepatic carcinogenesis.
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PMID:Abnormal copper accumulation in non-cancerous and cancerous liver tissues of LEC rats developing hereditary hepatitis and spontaneous hepatoma. 190 94

In 30- and 80-day-old LEC rats, hepatic Cu and Cu-metallothionein (MT) concentrations were much higher than those in control Fischer rats. The gross deposition was accompanied with enhancements of Zn and Fe concentrations. In LEC rats, more than half of the hepatic Cu was located in the cytosol fraction. Most of cytosolic Cu was bound to MT. In organs other than the liver, sharp depositions of Cu were not found. Both groups of LEC rats showed significantly low serum Cu concentrations and ceruloplasmin activity. The great accumulation of hepatic Cu with the increase of age is due to the inherent depression of the release of Cu from the liver. The deposition may be closely related to the onset of the sudden hepatitis observed in LEC rats.
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PMID:Copper metabolism in LEC rats aged 30 and 80 days old: induction of Cu-metallothionein and status of zinc and iron. 194 38

The LEC rat is a mutant inbred strain isolated from Long-Evans rats, which spontaneously develops hepatitis and hepatoma with high frequency. In this study, copper profiles of LEC rats, including copper concentration in the liver and concentrations of copper and ceruloplasmin in the serum, were investigated. It was found that copper accumulated in the liver of LEC rats immediately prior to the onset of hepatitis with a concentration of more than 50 times that of normal LEA rats, and serum concentrations of copper and ceruloplasmin decreased markedly, which resembled biochemically characteristic features of human Wilson's disease. Administration of d-penicillamine (100 mg/Kg/day p. o), a chelating agent, reduced the hepatic copper level and completely inhibited the development of hepatitis in LEC rats. Copper also accumulated in both cancerous and non-cancerous liver tissues of three 29-month old male LEC rats which had spontaneously developed hepatocellular carcinomas. These findings suggest that the hepatitis in LEC rats is caused by copper toxicity, and that the abnormal copper metabolism may be involved in hepatic carcinogenesis in the LEC rats. Therefore, it is considered that the LEC rat will provide a promising animal model for not only elucidating the pathogenesis of Wilson's disease and developing treatment strategies of the disease, but also for studying the role of copper in hepatic carcinogenesis.
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PMID:[Abnormal hepatic copper accumulation and its significance in LEC rats developing spontaneous hepatitis and hepatoma]. 195 41

An altered expression of the Yc subunit gene of rat glutathione S-transferase (GST) in the liver of the LEC rat, which is a mutant strain with spontaneous hereditary hepatitis associated with severe jaundice, has been reported. To provide further information concerning the structure of the Yc subunit gene, we carried out the Southern blot hybridization analysis of DNA samples from rats of eight different inbred strains including LEC with cDNA complementary to mRNA specific for the Yc subunit of rat liver GST as a probe. The hybridization patterns of the DNA samples from rats belonging to the different inbred strains showed interstrain variation in the length of restriction fragments with four restriction endonucleases. Since the DNA samples prepared from several rats of one inbred strain gave an identical hybridization pattern, the restriction fragment patterns for the Yc gene could be used as markers for genetic monitoring of inbred rat strains. Although the altered expression of Yc-Yc activity of GST has been observed in the liver of the LEC rat, the characteristic changes in the gene structure of the Yc subunit of LEC rat were not detected in the present hybridization analysis.
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PMID:Restriction fragment length polymorphism for the Yc subunit gene of rat liver glutathione S-transferase. 197 46

The LEC rat, which suffers from hereditary hepatitis, was examined for elucidation of its clinicopathological characteristics during development of the acute phase of hepatitis by quantitative analyses of histological observations of the liver in combination with laboratory data on various serum enzymes. The progression of acute hepatitis in the LEC rat was observed to begin insidiously early in life, i.e., a few enlarged hepatocytes and Councilman bodies appeared at around 8 weeks of age without clinical signs. Furthermore, it was revealed that the acute phase of hepatitis started with a remarkable increase of Councilman bodies, large nuclei and hepatocytes in mitosis in the liver 3 to 4 weeks before the onset of fulminant hepatitis, which is characterized by the elevation of serum enzyme activities such as GOT, GPT and gamma-GTP, and the onset of jaundice. From those observations, three stages were proposed for the progression of acute hepatitis in the LEC rat.
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PMID:Clinico-pathological studies of LEC rats with hereditary hepatitis and hepatoma in the acute phase of hepatitis. 217 Jul 50

Isozyme patterns of S-adenosylmethionine synthetase have been measured with or without dimethylsulfoxide in liver of LEC rat hereditary hepatitis. The activities of the alpha- and beta-forms are decreased with age after birth, and decreased to a half level of 36 weeks after birth. Concentration of S-adenosylmethionine in the liver is almost a half level of control rat. However, the activity of glycine- and tRNA-methyltransferases in the liver shows no significant change.
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PMID:Decreased activities of S-adenosylmethionine synthetase isozymes in hereditary hepatitis in Long-Evans rats. 236 43

LEC strain rats predisposed to hereditary hepatitis and liver cancer were examined for hepatic drug-metabolizing ability and the inducibility of chromosome damage by cyclophosphamide (CP) in somatic cells. Whereas the hepatic cytochrome P-450 contents and the activities of cytochrome P-450-catalyzed monooxygenases were lower in females than in males of both LEC and control LEA strains, male LEC rats exhibited significantly reduced cytochrome P-450 contents and monooxygenase activities compared with male LEA rats. When exposed to CP, a promutagen/procarcinogen requiring P-450-dependent metabolic activation, the frequencies of chromosome aberrations and sister-chromatid exchanges (SCEs) in bone marrow cells tended to be lower in females than in males of each strain and lower in LEC than in LEA rats of the same sex. In particular, the CP-induced SCEs were substantially lower in LEC rats. However, no such sex and strain differences were found in the SCE frequencies in regenerating hepatocytes of partially hepatectomized rats exposed to CP.
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PMID:Cytochrome P-450 and chromosome damage by cyclophosphamide in LEC strain rats predisposed to hereditary hepatitis and liver cancer. 238 46

A remarkably high incidence of hepatocellular carcinomas was observed in long-surviving LEC rats with hereditary hepatitis. Among the 60 LEC rats examined between 12 and 28 months of age from F29 and F30, 55 (92%) developed putative preneoplastic and neoplastic lesions such as hyperplastic foci and nodules, and hepatocellular carcinomas. Of these, hepatocellular carcinomas were observed with a high frequency (46/55; 84%). All rats of advanced age that survived more than 18 months developed hepatocellular carcinomas. These results suggest that the development of liver tumors in LEC rats is an age-associated phenomenon with serial hepatic alterations after the subsidence of acute hepatitis. The long-surviving rats had no normal tissue and showed chronic hepatitis in nontumorous tissues of the liver. Cholangiofibrosis was also found in most rats with hepatic lesions. Metastasis of hepatocellular carcinomas was found in four rats. Histologically, the hepatocellular carcinomas were of a well-differentiated type with a typical trabecular structure. Thus, LEC rats seem to be a promising animal model for studying the pathogenesis of hepatitis and hepatocellular carcinoma.
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PMID:High susceptibility to hepatocellular carcinoma development in LEC rats with hereditary hepatitis. 245 92

Alpha-fetoprotein (AFP) in the sera of 35 LEC (Long-Evans with a cinnamon-like coat color) rats between 7 and 25 weeks of age was evaluated by enzyme-linked immunosorbent assay (ELISA). Elevation of serum AFP and proliferation of oval cells in the liver were observed in most LEC rats, which suffered from acute hepatitis. On the other hand, the serum AFP level was within the normal range before the onset of hepatitis. Immunohistochemical staining for AFP revealed that some of the proliferating oval cells produced AFP. Morphometric analysis of AFP-positive cells and ELISA for serum AFP demonstrated that there was a statistically significant correlation between the number of AFP-positive cells in the liver and the concentration of AFP in the serum. Histological examination revealed the transition and differentiation of the oval cells to small hepatocytes. These results suggested that the phenomena which occurred in LEC rats suffering from acute hepatitis were similar to those that occurred during the early stage of azo dye hepatocarcinogenesis, although the extent of the oval cell proliferation and the elevation of serum AFP in LEC rats were not as great as those in rats treated with azo dye. This is the first report on a rat strain with proliferation of AFP-producing oval cells during its natural history.
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PMID:Elevation of serum alpha-fetoprotein and proliferation of oval cells in the livers of LEC rats. 245 91

We investigated the effect of salt on the fluorescence staining procedure for quantification of the amount of DNA in cell nuclei in situ. For this, NaCl was added at various concentrations to the Hoechst 33258 fluorochrome (Hoe) medium for staining DNA. The fluorescence intensity of free DNA-Hoe solution was not changed by the addition of NaCl, but that of the nuclei-Hoe complex in situ increased 4-fold on increasing the NaCl concentration up to 1 M. SDS polyacrylamide gel electrophoresis showed that histones H1, H2A, and H2B dissociated from cell nuclei in the presence of 1 M NaCl, resulting in increasing accessibility of DNA to the fluorochrome. The applicability of the NaCl-aided fluorescence staining method was evaluated by measuring the ploidy classes of various cells. The amount of DNA in spermatozoa is half that in 2 n hepatocytes, but by the conventional Hoe staining procedure the fluorescence intensity of spermatozoa is higher than that of 2 n hepatocytes, due to differences in accessibility of the dye to DNA. In contrast, by the NaCl-aided procedure, the fluorescence intensity of 2 n hepatocytes was twice that of spermatozoa. The effectiveness of the NaCl-aided Hoe staining method was checked using cultivated human gingival cells and hepatocytes of LEC rats with hereditary hepatitis. In all cases, reasonable proportionality between the fluorescence intensity and the amount of DNA was observed.
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PMID:NaCl-aided Hoechst 33258 staining method for DNA quantification and its application. 247 69


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