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)

The gangliosides in the livers of various inbred strains of rats and hepatoma of LEC rats were purified and analyzed by thin-layer chromatography. The patterns of ganglioside distribution in these rat livers were classified into three phenotypes depending on the strain, that is, a-type (ACI, LEA, LEW, BUF), b-type (WKAH, SHR/SP), and LEC type, which are characterized by dominance of a- or b-series of gangliosides, or a variation of a-type, respectively. A sex difference was also recognized in the molar ratio of GM3 which was much higher in males (60-75%) than in females (33-56%) except in LEC rats. In addition, the content of a-series gangliosides was lower and the content of b-series gangliosides was higher in a-type male rats than in a-type female rats. The opposite was true in b-type rats. LEC rats were an exception, characterized by no sex difference and a quite low content of b-series gangliosides. The LEC rat is a mutant strain that spontaneously develops fulminant hepatitis around 14 to 20 weeks of age and hepatoma at 1 to 1.5 years old. The gangliosides of the hepatoma were characterized by the appearance of the newly synthesized gangliosides, fucosyl-GM1 and alpha-galactosyl alpha-fucosyl GM1 (BGM1). In particular, BGM1 ganglioside accumulated in the hepatoma of female rats.
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PMID:Ganglioside distribution in the liver of inbred strains of rats and the cancerous liver of LEC rats. 846 32

The LEC rat is a mutant strain displaying hereditary hepatitis, and shows abnormal accumulation of copper (Cu) similar to that occurring in Wilson's disease. We prepared a multicellular spheroid composed of LEC rat liver cells to investigate the mechanism for abnormal accumulation of Cu. These multicellular spheroids were prepared by detaching the monolayer on the collagen-conjugated thermo-responsive polymer coated culture dish at a temperature below the critical solution temperature and culturing on the non-adhesive substratum. Long-term cultured spheroids of LEC rat liver cells as well as SD rat liver cells were attempted. Non-parenchymal cells obtained by collagenase perfusion from the LEC liver were fewer than those from the SD liver. Cells from the LEC rat, over 11 weeks of age, did not form a cell sheet; however, a mixture of parenchymal cells from LEC rats over aged 11 weeks and non-parenchymal cells from SD rats of any age yielded intact spheroids. We examined the toxicity, the accumulation and distribution of Cu in spheroids. The accumulation of Cu in LEC spheroids was higher than that in SD spheroids. Results suggest that spheroids consisting of LEC liver cells are useful as an alternative model to in vivo tests to investigate the mechanism for abnormal accumulation of Cu in liver.
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PMID:Abnormal hepatic copper accumulation of spheroid composed of liver cells from LEC rats in vitro. 874 89

In the present study, neurotransmitters related to the regulation of food intake were investigated in hypothalamus of LEC rats. The experiment was conducted using LEC and LEA (control) rats aged 4, 10 and 20 weeks. Cu concentration in hypothalamus of LEC rats aged 4 weeks was lower than that in the control, and similar to the control in 10 weeks of age. In contrast, Cu concentration of LEC rats aged 20 weeks was significantly higher (p < 0.01) than that in the control. The acetylcholine release from lateral hypothalamus of LEC rats aged 4 weeks was significantly higher (p < 0.05) than that in the control, but no significant difference of acetylcholine release was found between LEC and control rats aged 10 and 20 weeks. The metabolism of serotonin (5-HT) in hypothalamus of LEC rats was facilitated in 20 weeks of age. Furthermore, the 5-hydroxytryptophan, precursor of 5-HT in LEC rats aged 10 weeks was significantly higher (p < 0.05) than that in the control. No significant difference was found in norepinephrine (NE), dopamine (DA), 3, 4-dihydroxyphenyl acetic acid and homovanilic acid concentrations in each age of hypothalamus, except a significant decrease in NE concentration in LEC rats aged 10 weeks (p < 0.05). The daily and total food intake were suppressed in LEC rats from a young age. Furthermore, blood glucose, albumin and total cholesterol concentrations in LEC rats were lower than those in the control rats. The present study demonstrated that age dependent changes in Cu concentration and the metabolism of neurotransmitters related to the regulation of food intake occurred in hypothalamus of LEC rats. These results suggest that suppression of the food intake observed in LEC rats is not only due to hepatitis but also due to suppressive effects of feeding regulation center in central nervous system.
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PMID:Changes in brain neurotransmitters in hypothalamus related to feeding behavior in LEC rat. 875 32

The LEC strain of rats (LEC rats), originally developed as a model for hereditary fulminant hepatitis, is highly sensitive to whole-body X-irradiation when compared to WKAH strain of rats (WKAH rats). The present results showed that frequencies of certain types of chromosome aberrations induced by in vitro X-irradiation in the fibroblasts of LEC rats were higher than those of WKAH rats. In particular, frequencies of chromatid gaps and chromosome exchanges in LEC cells were higher approximately 4- to 5-fold and 6- to 8-fold, respectively, than those of WKAH cells.
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PMID:A high frequency of induction of chromosome aberrations in the fibroblasts of LEC strain rats by X-irradiation. 887 83

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family and is highly expressed in hepatoma tissues but not in normal liver. However, it is unknown when HB-EGF is induced during hepatocarcinogenesis and what are the mechanisms underlying its high expression in hepatoma. To address this issue, the expression of HB-EGF was investigated during hepatocarcinogenesis in LEC (Long-Evans with a cinnamon-like coat color) rats, which spontaneously develop hepatitis and hepatoma. LEA (Long-Evans with an agouti coat color) rats were used as controls. Furthermore, the induction of HB-EGF mRNA by various agents was investigated in a rat hepatoma cell line and hepatocytes in primary culture. Expression of HB-EGF mRNA in the liver was very low at the stage of acute and chronic hepatitis and markedly increased at the stage of hepatoma in LEC rats. Non-involved tissues adjacent to hepatoma showed low expression of HB-EGF mRNA. Immunochemical studies revealed positive staining in hepatoma tissues. Induction of HB-EGF mRNA by several growth factors was observed in a hepatoma cell line but not in normal hepatocytes. Our results suggest that HB-EGF is associated with the early progression steps of hepatoma.
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PMID:High expression of heparin-binding EGF-like growth factor in rat hepatocarcinogenesis. 890 Apr 31

In the present study we demonstrated the protective effects of the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PBN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PBN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PBN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TBARS) in livers of PBN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PBN-administered rats. The protective effect of PBN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PBN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PBN potentially has therapeutic value for the treatment of hepatitis.
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PMID:The effects of alpha-phenyl-tert-butyl nitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice. 890 21

Alpha-1-6 fucosylated alpha-fetoprotein (AFP) is known to be elevated in patients with primary hepatoma and has been suggested as being useful as an early indicator and predictor of the poor prognosis for hepatoma. Although GDP-L-fucosyl-N-acetyl-beta-D-glucosaminide alpha-1-6 fucosyltransferase (alpha-1-6 FucT), is the key enzyme involved in alpha-1-6 fucosylation of AFP, when and how the expression of alpha-1-6 FucT is enhanced during hepatocarcinogenesis is unknown. Recently, we established a convenient assay method for this enzyme and were successful in the purification and cDNA cloning of alpha-1-6 FucT from human gastric cancer, as well as from porcine brain. In the present study, levels of alpha-1-6 FucT activity and mRNA expression have been determined during hepatocarcinogenesis in LEC rats which spontaneously develop hereditary hepatitis and hepatoma. The fetal liver contained the highest enzymatic activity, which tended to increase in inverse proportion to gestation. The enzymatic activity was significantly increased in hepatoma tissues as compared with uninvolved adjacent tissues. Northern-blot analysis revealed high expression of alpha-1-6 FucT mRNA in hepatoma tissues, whereas the expression was fairly low in normal, hepatitis and uninvolved adjacent liver tissues. While the fetal liver had the highest enzymatic activity, the expression of alpha-1-6 FucT mRNA was low, suggesting that another alpha-1-6 FucT is induced in fetal liver or that post-translational modification occurs. High expression of alpha-1-6 FucT was also observed in 3'-MeDAB-induced rat hepatomas and some rat hepatoma cell lines. Collectively, alpha-1-6 FucT was strongly enhanced from an early stage of hepatocarcinogenesis and was maintained at a high level in rat hepatomas.
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PMID:High expression of alpha-1-6 fucosyltransferase during rat hepatocarcinogenesis. 945 7

Etheno adducts in DNA are formed from the carcinogens vinyl chloride and urethane, and also from products of lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal. Using an ultrasensitive detection method, the formation of etheno-DNA adducts in the liver was demonstrated in LEC rats (a strain with hereditary abnormal copper metabolism) that develop hepatitis and hepatocellular carcinoma. Wilson's disease and primary haemochromatosis are human genetic disorders that cause copper or iron accumulation resulting in a high risk for primary liver cancers. Levels of etheno adducts were also significantly elevated in the liver of these patients. In a group of male and female volunteers kept on a controlled diet, the effect of dietary fatty acid composition on the endogenous formation of lipid peroxidation-derived DNA adducts was determined in DNA from white blood cells. Dietary omega-6-polyunsaturated fatty acids greatly increased LPO-derived etheno-DNA adducts in vivo, in females. Thus, exocyclic DNA adducts are promising biomarkers for elucidating the effect of dietary fat intake, oxidative stress and protective dietary antioxidants on endogenous DNA damage and thus may provide a possible mechanistic link with elevated risk for diet-related cancers.
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PMID:Etheno-DNA base adducts as tools in human cancer aetiology and chemoprevention. 949 54

The hepatic concentrations of copper, zinc, magnesium, calcium, and selenium were measured in LEC rats, which develop a spontaneous form of hepatitis at 3-4 months of age, and compared to trace metal concentrations in the LEA rat, its asymptomatic congenic strain. Consistent with results found by other groups, copper was found to accumulate within the liver of LEC rats to levels more than 50 times those measured in LEA rats. In addition, liver selenium concentration in LEC rats was found to be around 50% of that in LEA rats. The enzyme activity, and RNA for the selenium dependent enzyme, glutathione peroxidase, was also found to be reduced in LEC rat liver. These results indicate that hepatic selenium in the LEC rat is depleted and that, as a result of this, the capacity to protect cells from copper-induced free-radical damage is reduced.
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PMID:The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis. 951 49

Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T1 and T2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the T1 and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.
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PMID:MR imaging of hepatic injury in the LEC rat under a high magnetic field (7.05 T). 1033 Nov 95


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