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)

Hepatocyte growth factor (HGF) has been reported to be a potent mitogen for hepatocytes in vivo and in vitro. Recent reports have shown that HGF has cytoprotective actions in acute liver injury models, but its mechanisms remain to be resolved. In the present study, we investigated whether HGF could work as an anti-hepatitis agent for acute liver injury caused by D-galactosamine (D-GalN) using transgenic (TG) mice expressing HGF in hepatocytes, compared with wild-type (WT) mice of their siblings. After administration of 3 g/kg body weight of D-GalN, elevated serum transaminase levels and severe liver damage that were observed in WT mice were significantly improved in TG mice. In TG mice, the percentage of proliferating cell nuclear antigen (PCNA)-positive hepatocytes was high at 0 hours after D-GalN treatment, and increased at 24 hours. The percentage of PCNA-positive cells in WT mice was very low at 0 hours and 24 hours after treatment, but increased at 48 hours. To clarify the mechanisms via which HGF acts, we measured hepatic HGF and prostaglandin E2 (PGE2) contents after D-GalN administration by an enzyme immunoassay. Total hepatic HGF contents, which were composed of murine (endogeneous) and human (derived from transgene) HGF, in TG mice were higher than those in WT mice at 0, 12, and 24 hours after administration of 3 g/kg body weight of D-GalN. Hepatic PGE2 contents in TG mice were also significantly higher than those in WT mice. Hepatic PGE2 contents had a positive correlation with total HGF contents at both 12 hours and 24 hours after the treatment. Moreover, an administration of 0.5 microg of anti-HGF antibody into the portal vein suppressed hepatic PGE2 contents of mice, compared with saline-injected mice in acute liver injury. Anti-PGE2 antibody administration caused more severe liver damage than saline solution. A survival rate of TG mice that were given 6 g/kg body weight of D-GalN-a lethal dose of D-GalN-was improved compared with WT mice. These results provided direct evidences that HGF worked as an anti-hepatitis agent against acute liver injury caused by D-GalN, and that this action might be exerted through accelerated hepatic PGE2 production.
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PMID:Protective action of hepatocyte growth factor for acute liver injury caused by D-galactosamine in transgenic mice. 936 68

In HBV related hepatitis it is generally accepted that the liver injury is mediated by an immune response to the virus, since HBV is not directly cytopathic. The first step in cytotoxic T lymphocyte mediated immune reaction in HBV infected mice is the induction of apoptosis. The role of BCL-2, p53 and PCNA (as the main regulators of cell cycle homeostasis) in this process has not been studied. The aim of this pilot study is to estimate immunohistochemically the expression of the BCL-2, p53 and PCNA in a group of HBV infected patients at various stages of the disease. Formalin fixed, paraffin embedded liver biopsies from 5 patients with HBsAG positivity in their serum were used for immunohistochemical study of the expression of BCL-2, PCNA (PC10) and P53 (DO1clone). As the chromogen we used both the DAB and AEC. The results were co-related with the 3 liver biopsies as controls. In the hepatocytes of the all cases (including controls) we did not found any positivity of BCL-2, p53 and PCNA. However the majority of the lymphocytes present in the liver of some cases of HBV infected patients were strongly BCL-2 positive. This preliminary results of very small group of patients could indicate that hepatocytes in the HBV infection are in the quiescent stage as in the controls and that the cell cycle regulation during infection could be controlled by other genes such as bax, bcl-Xs, FAS etc., but further studies are required.
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PMID:Immunohistochemical study of the expression of BCL-2, PCNA and P53 proteins in the patients with hepatitis B. The pilot study. 943

The discovery of Helicobacter hepaticus infection, H. hepaticus hepatitis, and increased incidence of liver tumors in control males from several recent National Toxicology Program B6C3F1 mouse carcinogenicity bioassays raised questions regarding the suitability of these bioassays for hazard identification. The purpose of this study was to determine if changes in cell proliferation and death at terminal sacrifice might be linked to the increased liver tumor incidences among control males. In control males, enhanced rates of hepatocyte proliferation, as assessed by immunostaining for proliferating cell nuclear antigen (PCNA), and apoptosis, as assessed from hematoxylin and eosin- and TUNEL-stained preparations, were seen in 3 bioassays with H. hepaticus hepatitis. One bioassay with H. hepaticus infection without attendant hepatitis and one bioassay without H. hepaticus or hepatitis did not have elevated rates of hepatocyte proliferation or apoptosis. There was no significant effect on PCNA cell proliferation indices or apoptosis in females. The present findings are indicative of a clear association between the presence of H. hepaticus infection with attendant hepatitis, increased cell proliferation and apoptosis, and increased incidences of hepatocellular neoplasia in males but not in females. Thus, the interpretation of liver tumor responses in H. hepaticus-infected studies is considered to be confounded in male mice. The lack of enhanced cell proliferation or hepatocellular neoplasia in control females suggests that bioassay results from females are valid for hazard identification. Furthermore, the absence of enhanced cell proliferation in lungs and kidneys of male and females suggests that neoplastic effects at these sites are not exacerbated by H. hepaticus infection.
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PMID:Alteration in cell kinetics in control B6C3F1 mice infected with Helicobacter hepaticus. 943 4

A 52 year old woman had autoimmune hepatitis and an increased concentration of serum carbohydrate antigen 19-9 (CA19-9). The origin of the raised CA19-9 was studied using immunohistochemistry. Liver biopsy section showed chronic active hepatitis with large numbers of proliferated bile ductules. Immunohistochemical analysis revealed that the proliferated bile ductule cells were positive for proliferating cell nuclear antigen (PCNA) and for CA19-9. It is speculated that the raised serum CA19-9 concentration was derived from proliferated bile ductule cells and these cells, which are positive for PCNA, may be able to produce high concentrations of CA19-9.
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PMID:Increased expression of proliferating cell nuclear antigen in autoimmune hepatitis in a patient with raised serum concentration of CA19-9. 960 95

The accumulation of oval cells is an early event in the development of hepatocellular carcinoma induced by certain experimental regimes involving hepatocarcinogens. Oval cells have also been observed during chronic hepatitis induced by alcohol and iron overload. In this study, livers of murine cytomegalovirus (MCMV) infected mice were examined to determine whether hepatitis induced by this virus could initiate oval cell proliferation. BALB/c and C57BL/6 mice were infected with MCMV and studied 4, 8, 10 and 12 months later, alongside control (uninfected) mice. The livers were examined histochemically, immunocytochemically and by in situ hybridization to identify oval cells, inflammatory cells and proliferating cells. Oval cells were seen in the periportal regions of livers from MCMV infected BALB/c mice. These increased in number from 4 to 12 months after infection in parallel with increases in the numbers of inflammatory cells, even though cells expressing MCMV antigens were no longer evident in these samples. Proliferating oval cells and hepatocytes were identified by PCNA staining, indicating an increased level of liver regeneration in the infected livers. C57BL/6 mice are less susceptible to persistent MCMV hepatitis and had fewer oval cells than BALB/c mice. Thus the study demonstrates an association between MCMV induced hepatitis, inflammation, and presence of oval cells.
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PMID:The association between murine cytomegalovirus induced hepatitis and the accumulation of oval cells. 1031 24

The mechanism of liver giant cell formation is not clarified. Some authors consider the giant cells regenerative, others, degenerative. Paraffin sections of 10 archival cases of idiopathic neonatal hepatitis (INH), 8 of extrahepatic biliary atresia (EHBA), and 5 normal liver samples were immunostained with two well-characterized cell proliferation markers: anti-PCNA monoclonal antibody (MAb) (clone PC-10) and MAb MIB-1, which detects Ki-67, a nuclear proliferation-related antigen. In addition, polyclonal antibody to carcinoembryonic antigen (CEA) was used to identify remnants of canalicular, therefore hepatocytic, membranes in giant cells. Quantitative analysis of immunostaining was done by estimating PCNA and Ki-67 indices separately in giant cells and in nongiant hepatocytes. In normal samples, mean PCNA and Ki-67 indices were 1. 22% and 0.74%, respectively. In the cases of INH and EHBA, only a small minority of giant cells showed PCNA or Ki-67 staining limited to occasional peripherally located nuclei. PCNA and Ki-67 indices were significantly higher in the non-giant cell compartment. CEA staining was seen only in rare giant cells as centrally located canalicular remnants bordered by polarized nuclei, suggesting that they had been formed from rosettes through dissolution of cell membranes. Other giant cells shared CEA-labeled canalicular membranes with mononuclear hepatocytes in rosettes. These findings indicate that the giant cells in INH and EHBA are not regenerative cells, they are not formed by amitotic division of nuclei in syncytia, and that fusion of rosette-forming hepatocytes is a possible mechanism of their formation.
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PMID:Infantile liver giant cells: immunohistological study of their proliferative state and possible mechanisms of formation. 1034 79

We used the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) method to detect apoptosis, and immunohistochemical staining for molecules related to apoptosis, a marker of cell proliferation, and surface markers of lymphocytes to examine 20 patients with autoimmune hepatitis (AIH). Confluent hepatic necrosis was frequently found, in which rosette formation of hepatocytes and ductular proliferation were common. TUNEL staining and staining for Lewis Y antigen, Bax protein, and Fas antigen were found in biliary epithelial cells in bile ducts and proliferating atypical bile ductules in regions of confluent necrosis with severe lymphocytic infiltration. TUNEL staining and staining for Lewis Y antigen and Bax protein were found in rosette-forming hepatocytes. Many hepatocytes in lobules without injury were stained for proliferating cell nuclear antigen (PCNA). bcl-2 oncoprotein was found in many lymphocytes surrounding proliferating atypical bile ductules and rosette-forming hepatocytes in regions of confluent necrosis, in which CD20 and OPD 4 were found. Apoptosis of both hepatocytes in rosette arrangement and biliary epithelial cells in bile ducts and proliferating atypical bile ductules may play a role in progression of AIH as well as confluent hepatic necrosis.
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PMID:Significant role of apoptosis in type-1 autoimmune hepatitis. 1072 2

Recent studies have shown that expression levels of the multidrug resistance gene MDR1, which encodes the drug transporter P-glycoprotein, correlate with prognostic outcomes of certain tumor types. These findings suggest that expression of MDR1 may affect tumor behaviors. To address this issue further, we investigated the expression of mdr1a, a human MDR1 homolog, on the development of hepatocellular carcinoma in a transgenic mouse model carrying the liver-targeted expression of human hepatitis-B virus (HBV) surface antigen. The pathogenetic program was compared in HBV mice carrying either mdr1a(+/+) or mdr1a(-/-). We found that the expressions of proliferative activity markers, Ki67 nuclear antigen, and proliferating cell nuclear antigen were elevated in mdr1a(-/-) mice younger than 10 wk in comparison with those in the same age group of wild-type animals. Replication in the hepatic population as determined by bromodeoxyuridine incorporation tended to support observation that mdr1a(-/-) mice exhibited elevated labeling indices in this age group. Moreover, histologic staining and flow-cytometric analysis showed that the mdr1a(-/-) animals exhibited a higher cell population with polyploidy than did the mdr1a(+/+) counterparts of the same age. However, no significant differences in the expression of the liver-injury markers serum alanine transaminase and aspartate transaminase were observed. Although our results showed that absence of mdr1a expression is correlated with modest enhanced proliferative characteristics in the livers at stage before the development of hepatocellular carcinoma, the overall life spans between these two strains of mice were not significantly different. The implication of these findings to the role of P-glycoprotein in tumor development and cancer chemotherapy is discussed.
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PMID:Elevated expression of hepatic proliferative markers during early hepatocarcinogenesis in hepatitis-B virus transgenic mice lacking mdr1a-encoded P-glycoprotein. 1107 7

Treatment of hepatitis B virus carriers with the nucleoside analog lamivudine suppresses virus replication. However, rather than completely eliminating the virus, long-term treatment often ends in the outgrowth of drug-resistant variants. Using woodchucks chronically infected with woodchuck hepatitis virus (WHV), we investigated the consequences of combining lamivudine treatment with immunotherapy mediated by an adenovirus superinfection. Eight infected woodchucks were treated with lamivudine and four were infected with approximately 10(13) particles of an adenovirus type 5 vector expressing beta-galactosidase. Serum samples and liver biopsies collected following the combination therapy revealed a 10- to 20-fold reduction in DNA replication intermediates in three of four woodchucks at 2 weeks after adenovirus infection. At the same time, covalently closed circular DNA (cccDNA) and viral mRNA levels both declined about two- to threefold in those woodchucks, while mRNA levels for gamma interferon and tumor necrosis factor alpha as well as for the T-cell markers CD4 and CD8 were elevated about twofold. Recovery from adenovirus infection was marked by elevation of sorbitol dehydrogenase, a marker for hepatocyte necrosis, as well as an 8- to 10-fold increase in expression of proliferating cell nuclear antigen, a marker for DNA synthesis, indicating significant hepatocyte turnover. The fact that replicative DNA levels declined more than cccDNA and mRNA levels following adenovirus infection suggests that the former decline either was cytokine induced or reflects instability of replicative DNA in regenerating hepatocytes. Virus titers in all four woodchucks were only transiently suppressed, suggesting that the effect of combination therapy is transient and, at least under the conditions used, does not cure chronic WHV infections.
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PMID:Combination therapy with lamivudine and adenovirus causes transient suppression of chronic woodchuck hepatitis virus infections. 1109 Jan 75

The effects of different doses of Interferon alpha 2b (IFN alpha 2b), alone and in combination with praziquantel (PZQ), on hepatic schistosomiasis were tested. An experimental murine model of hepatic schistosomiasis was used. Four parameters were assessed; hepatic fibrosis by estimation of OH-proline content/g dry weight liver, hepatocyte proliferative activity by the PCNA/LI, schistosomal egg load by digesting parts of the liver by KOH and hepatocyte function by measuring parenchymal liver enzyme levels. IFN alpha 2b was found to increase hepatic fibrosis in a dose dependent manner both alone and in combination with PZQ. An augmentation of the regenerative activity of the liver was observed. A reduction in the number of the granulomas and egg counts was observed only when PZQ was added. However, no effect on the size of the granulomas was observed apart from the normal process of modulation. Caution should be exercised when treating patients with concomitant hepatic schistosomiasis and hepatitis with IFN alpha 2b as it increases both hepatocyte regenerative activity and hepatic fibrosis; two main components of cirrhosis.
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PMID:Parasitological, pathological and functional studies on the effects of IFN alpha 2b in murine hepatic schistosomiasis. 1141 37


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