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)

Insulin secretion in response to glucose, glucose-stimulated insulin biosynthesis and insulin content was studied in pancreatic islets freshly isolated from male Wistar rats (150-200 g) with galactosamine-induced hepatitis. Animals were sacrificed by decapitation 3, 6, 12 and 24 hours after a single intraperitoneal injection of 500 mg/kg of galactosamine. Isolated islets prepared by collagenase method were perifused in Swim's medium with 20 mM glucose at 37 degrees C up to 30 minutes. Samples were taken at 2-10 min intervals for insulin assay. Insulin biosynthesis was assessed by the incorporation of [3H]-leucine into immunoprecipitable products (insulin and proinsulin) in pancreatic islets after 120 min incubation with 20 mM glucose. Glucose-stimulated insulin secretion was significantly increased at 6, 12 and 24 hours following the administration of galactosamine compared to control. The rate of insulin biosynthesis was stimulated to 170, 138 and 185% of control level 3, 6 and 12 hours after galactosamine-treatment, respectively. Significant increase in insulin content of islets was found 24 hours after galactosamine treatment, following the increased insulin biosynthesis. The present results indicate that pancreatic B cell function is activated in early stage of acute liver injury.
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PMID:Increase in glucose-stimulated insulin release and insulin biosynthesis in isolated pancreatic islets from D-galactosamine-treated rats. 219 63

Monolayer cell cultures of primary woodchuck hepatocytes, prepared by perfusing the liver in situ with collagenase type I, yielded hepatocytes with a viability of greater than 90% which could be held in culture for up to 3 months. Cultures of primary woodchuck hepatocytes were infected one day after plating with hepatitis delta virus (HDV) which had been passaged five times in woodchucks and was therefore identified as woodchuck hepatitis delta virus (WHDV). Replication of WHDV was demonstrated by the appearance of genomic WHDV RNA of ca. 1.7 kb beginning 7 days after infection, with an increase of copy numbers up to 2 weeks after inoculation. Synthesis of hepatitis delta virus-associated antigen (HDAg) in hepatocytes was detected by immunofluorescence staining of hepatocytes. Preincubation of the inoculum with rabbit sera containing antibodies against woodchuck hepatitis virus surface antigen (anti-WHs) reduced the infectivity of WHDV to an undetectable level compared with inocula which were treated with anti-WHs negative sera.
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PMID:Propagation of woodchuck hepatitis delta virus in primary woodchuck hepatocytes. 320 48

Primary cultures of non-proliferating hepatocytes isolated by the two-step collagenase perfusion method from woodchuck naturally infected with hepatitis virus (WHV) were used to study WHV propagation in vitro. Hepatocytes carrying WHV DNA exhibited a very high level of survival and retained their morphological characteristics for 2 to 3 months. Over this time, they were found to produce virus-specific proteins and release viral particles with DNA polymerase activity into the medium. Using Southern blot analysis and a recombinant hepatitis B virus DNA plasmid probe, intracellular and extracellular viral DNA was consistently detected. Only extrachromosomal forms of WHV DNA were observed and no integration could be demonstrated in the DNA of the cells. The WHV DNA patterns were repeatedly identical with a characteristic smear starting from 3.3 kb associated with other smaller DNA fragments which presumably represented intermediate replicative forms of viral DNA. Furthermore, dot blot hybridization of the total RNA revealed the presence of WHV-specific transcripts in cells after 3 weeks of culture. All these results are compatible with the maintenance of active WHV replication in vitro although it was somewhat reduced after the first day of culture. This provides a mammalian model for hepadnavirus replication studies in stable primary hepatocyte cultures.
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PMID:Maintenance of woodchuck hepatitis virus activity in woodchuck hepatocyte primary culture. 357 56

Impairment of the phagocytic capacities of Kupffer cells, as is found in Frog Virus 3 hepatitis of mice, allows the endothelial liver cells to take up intravenously inoculated latex particles of 1.0 micron diameter. In vitro experiments with cultivated endothelial cells isolated by collagenase perfusion of the liver and purified by centrifugal elutriation demonstrate that uptake occurs via a typical mechanism of phagocytosis involving pseudopodia. Ingestion of latex is inhibited by incubation of the cells at 4 degrees C and by treatment with cytochalasin B, whereas colchicine has no effect. These results demonstrate that: the Kupffer cells are not the only cells of the hepatic sinusoid capable of phagocytosis; and under conditions where the phagocytosis in Kupffer cells is impaired, the endothelial cells may participate in the clearance of large particles from the blood.
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PMID:Phagocytosis, an unrecognized property of murine endothelial liver cells. 375 36

Lysyl oxidase and collagenase activities were measured in experimental acute and chronic liver injury in mice and rats, and correlated with collagen synthesis and accumulation. Acute liver injury was induced in mice and rats by a single dose of carbon tetrachloride given by gavage, and also in mice by a single injection of murine hepatitis virus. Chronic liver injury was induced in rats by repeated injections of carbon tetrachloride. Elevated plasma glutamic oxaloacetic transaminase levels, increased hepatic prolyl hydroxylase activity, and increased synthesis of collagen-bound hepatic hydroxyproline occurred in animals with acute as well as with chronic liver injury. However, only chronic liver injury appeared to be associated with fibrosis, increased collagen-bound hydroxyproline content, increased hepatic lysyl oxidase and collagenase activities, as well as with increased serum lysyl oxidase activity. These data suggest that lysyl oxidase and collagenase may play an important role in the collagen accumulation associated with hepatic fibrosis.
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PMID:Lysyl oxidase and collagenase in experimental acute and chronic liver injury. 611 72

The Tyzzer's disease organism was grown in primary monolayer cultures of adult mouse hepatocytes prepared by collagenase perfusion. The organisms produced a plaque-like cytopathic effect involving almost the whole culture around 72 h post-infection when the bacterial growth reached a maximum. The organisms showed specific immunofluorescence, and electron microscopy revealed that intracellular organisms had peritrichous flagella and underwent cell division. After intravenous inoculation of the infected cell culture into mice, necrotic hepatitis was produced and the organisms, recovered from the liver lesion, could be propagated in primary culture of mouse hepatocytes.
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PMID:Growth of Tyzzer's organism in primary monolayer cultures of adult mouse hepatocytes. 634 4

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

Decorin is a small extracellular matrix proteoglycan. It binds and modulates transforming growth factor (TGF)-beta 1 action, the major stimulator of fibrogenesis. Its role in the pathogenesis of human liver cirrhosis is unknown. Therefore, we studied the relationship of the 2 proteins in normal human liver and in 43 chronic hepatitis and liver cirrhosis specimens. To understand the mechanism that maintains matrix deposition in stage IV hepatitis, we studied expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, as well as the activities of type IV collagenases. Gene expression was analyzed on messenger RNA and protein level by morphologic and biochemical approaches. Decorin proved to be an early marker of fibrogenesis, and its deposition increased parallel to that of TGF-beta 1 and to inflammatory activity. Liver fibrosis progressed despite high temporospatial expression of decorin with TGF-beta 1. Neither decorin nor TGF-beta 1 protein deposition increased further in cirrhosis with low inflammatory activity, suggesting that impaired extracellular matrix catabolism rather than active production plays a role in this stage. This possibility was supported by high message levels of metalloproteinase inhibitors, no 72-kd collagenase activities, and low 92-kd collagenase activities.
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PMID:Expression of decorin, transforming growth factor-beta 1, tissue inhibitor metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis. 1134 37

Alcoholic liver disease is a major cause of illness and death in the United States. In the initial stages of the disease, fat accumulation in hepatocytes leads to the development of fatty liver (steatosis), which is a reversible condition. If alcohol consumption is continued, steatosis may progress to hepatitis and fibrosis, which may lead to liver cirrhosis. Alcoholic fatty liver has long been considered benign; however, increasing evidence supports the idea that it is a pathologic condition. Blunting of the accumulation of fat within the liver during alcohol consumption may block or delay the progression of fatty liver to hepatitis and fibrosis. To achieve this goal, it is important to understand the underlying biochemical and molecular mechanisms by which chronic alcohol consumption leads to fat accumulation in the liver and fatty liver progresses to hepatitis and fibrosis. In addition to alcohol consumption, dietary fatty acids and obesity have been shown to affect the degree of fat accumulation within the liver. Again, it is important to know how these factors modulate the progression of alcoholic liver disease. The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of Fatty Liver, Dietary Fatty Acid Supplements, and Obesity in the Progression of Alcoholic Liver Disease" in Bethesda, Maryland, USA, October 2003. The following is a summary of the symposium. Alcoholic fatty liver is a pathologic condition that may predispose the liver to further injury (hepatitis and fibrosis) by cytochrome P450 2E1 induction, free radical generation, lipid peroxidation, nuclear factor-kappa B activation, and increased transcription of proinflammatory mediators, including tumor necrosis factor-alpha. Increased acetaldehyde production and lipopolysaccharide-induced Kupffer cell activation may further exacerbate liver injury. Acetaldehyde may promote hepatic fat accumulation by impairing the ability of peroxisome proliferator-activated receptor alpha to bind DNA, and by increasing the synthesis of sterol regulatory binding protein-1. Unsaturated fatty acids (corn oil, fish oil) exacerbate alcoholic liver injury by accentuating oxidative stress, whereas saturated fatty acids are protective. Polyenylphosphatidylcholine may prevent liver injury by down-regulating cytochrome P450 2E1 activity, attenuating oxidative stress, reducing the number of activated hepatic stellate cells, and up-regulating collagenase activity. Nonalcoholic steatohepatitis may develop through several mechanisms, such as oxidative stress, mitochondrial dysfunction and associated impaired fat metabolism, dysregulated cytokine metabolism, insulin resistance, and altered methionine/S-adenosylmethionine/homocysteine metabolism. Obesity (adipose tissue) may contribute to the development of alcoholic liver disease by generating free radicals, increasing tumor necrosis factor-alpha production, inducing insulin resistance, and producing fibrogenic agents, such as angiotensin II, norepinephrine, neuropeptide Y, and leptin. Finally, alcoholic fatty liver transplant failure may be linked to oxidative stress. In vitro treatment of fatty livers with interleukin-6 may render allografts safer for clinical transplantation.
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PMID:Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. 1567 Jun 59

As chronic liver disease progresses, an imbalance occurs between synthesis and breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs) prevent their fibrolytic action. In the present study, serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were investigated as non-invasive parameters for the diagnosis of hepatic fibrosis in patients with HCV related chronic liver disease. Their diagnostic potential was evaluated in comparison to hepatic histology and standard liver function tests. A sandwich enzyme immunoassay technique was used to study circulating values of MMP-2 and TIMP-1 in forty-one patients with HCV antibodies in their sera (27 patients with biopsy ascertained chronic hepatitis C and 14 patients with histologically proven liver cirrhosis. Hepatic histology was evaluated using the hepatitis-activity-index according to Ishak et al. (1995), quantifying separately inflammatory activity and fibrosis. Ten healthy individuals were also included in the study as controls. Serum levels of MMP-2 were similar in controls and in chronic hepatitis C patients with (n = 15) and without (n = 12) fibrosis, but increased significantly in cirrhosis. TIMP-1 serum values showed a steady increase from normal controls to chronic hepatitis C without fibrosis, hepatitis C with fibrosis, and cirrhosis. The diagnostic potential of MMP-2 to detect fibrosis was low with a sensitivity of 7% and a diagnostic efficiency of 56%. The diagnostic potential of circulating MMP-2 to detect cirrhosis was higher with a sensitivity of 83% and a specificity of 96% resulting in a diagnostic efficiency of 92%. Serum TIMP-1 values detected fibrosis with a sensitivity of 67% and a specificity of 69% resulting in an efficiency rate of 70%. TIMP-1 values detected cirrhosis with 100% sensitivity but only 75% specificity. The diagnostic potential of circulating TIMP-1 was higher than that of serum ALT, AST or albumin values. In conclusion, serum values of MMP-2 and TIMP-1 are able to detect cirrhosis with a high sensitivity. Moreover, TIMP-1 values can detect fibrosis with comparable efficiency. Regular determinations of both TIMP-1 and MMP-2 in patients with chronic hepatitis C may be used as indicators of increasing fibrosis and the development of cirrhosis.
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PMID:Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease. 1571 20


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