Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the major antecedent factors preceding the development of hepatocellular carcinoma is chronic hepatitis B virus infection. Also, recent molecular studies have shown that activation of c-oncogenes might be responsible for the malignant transformation in some cases of hepatocellular carcinoma. We used immunohistochemical methods to investigate the correlation of ras and c-myc oncogene expression with the presence of HBsAg in human liver disease. Our material consisted of 23 chronic active hepatitis B needle liver biopsies and surgical specimens from 11 cases of cirrhosis, 23 hepatocellular carcinoma and 10 normal adult livers. Direct, three-step and streptavidin-biotin-complex immunoperoxidase techniques using polyclonal (anti-HBsAg) and monoclonal antibodies (anti-ras p21, anti-myc p62), were performed. Normal liver tissues were negative for all antibodies used. In HBsAg+ chronic active hepatitis B cases enhancement of c-myc, and less frequently of ras oncogene expression, was a common observation. Increased myc p62 and ras p21 expression was a finding not restricted to HBsAg+hepatocytes, which occasionally were negative for oncoprotein immunostaining. All HBsAg-chronic active hepatitis B cases were negative for ras p21 and myc p62 specific staining. Cirrhotic livers showed more frequently enhanced c-myc expression. Most of the immunostained cells were negative for HBsAg. HBsAg- cases of hepatocellular carcinoma more often showed ras p21 than myc p62 overexpression. HBsAg+ hepatocellular carcinomas presented only ras p21-positive immunostaining, which was not detected in HBsAg+ hepatocytes. Our recent data supports the view that continued expression of HBsAg in human liver disease is not necessary for the enhancement of ras and c-myc oncogene expression.
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PMID:Expression of ras and c-myc oncoproteins and hepatitis B surface antigen in human liver disease. 846 26

Immunoblot analysis on serum samples from 90 patients with chronic hepatitis C virus infection revealed four putative immunogenic regions within the NS3 protein of the virus: E (around aa 1250/ 1251), A (within aa 1250-1334), A/B (around aa 1323 and 1334), and B/C (around aa 1407 and 1412). Among them, region E was most immunodominant, and region A was recognized much less frequently by patients with cirrhosis than by those with chronic hepatitis (10% vs. 46%, chi 2 = 12.05, P < .01). The results suggest that region A might be a potential prognostic marker to differentiate chronic hepatitis from cirrhosis.
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PMID:Identification of humoral antigenic determinants in the hepatitis C virus NS3 protein. 865 88

Hepatitis C virus (HCV) is the major etiological agent of both parenterally transmitted and sporadic non-A, non-B hepatitis. The disease is a major health problem with an estimated 50 million people infected worldwide, a high percentage of whom become chronically infected and are at high risk for liver cirrhosis. The serine protease contained within the N-terminal region of the nonstructural protein 3 (NS3 protease) of HCV is considered a promising target for the development of an antiviral therapy. A prime requisite to study in detail the biochemistry of the protease as well as develop inhibitors is the availability of a fast and sensitive in vitro assay of enzyme activity. However, due to their low kcat/Km values, synthetic peptide substrates based on the natural cleavage sites appear unsuitable for this purpose. We show here that appropriate substrates can be obtained by substituting the scissile amide bond with an ester linkage. The resulting depsipeptides show >100-fold improvement in kcat/Km values, up to 13,000 M-1 s-1, enabling detection of activity with subnanomolar NS3 concentrations. The ester substrates are obtained in high yield entirely by solid-phase synthesis using commercially available materials, without the need for any preassembled building blocks.(c) 1996 Academic Press, Inc.
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PMID:Synthetic depsipeptide substrates for the assay of human hepatitis C virus protease. 866 May 72

The recent cloning and genomic identification of hepatitis C virus (HCV) by sensitive and specific immune techniques has allowed a better definition of both histopathological and clinical features of the previously not well defined non-A, non-B hepatitis. In this regard, antibodies to different HCV antigens are usually found during infection, even if some of them such as anti-E1 and anti-E2/NS1 have been shown to be associated with significant viraemic levels. Acute hepatitis C is self-limiting in a minority of cases only. Over 60% of acute hepatitis becomes in fact chronic and may progress towards cirrhosis. In about 10% of cases, hepatocellular carcinoma may develop in cirrhotic livers. The occurrence of a strict relationship between immunoresponsiveness and disease activity is suggested by the observation that peripheral blood mononuclear cell (PBMC) proliferation induced by NS3 structure is associated with self-limiting acute hepatitis, while PBMC stimulation by core antigen characterizes chronic C hepatitis. The demonstration of lymphoid aggregates, bile duct lesions, intraportal lymphocyte infiltration, increased adhesion molecule expression and augmented cytokine release clearly emphasizes the involvement of immune-mediated reactions in the development of liver damage, even if a direct cytopathic effect cannot be excluded. Finally, it is likely that HCV may favour, through immune-mediated mechanisms, autoantibody generation and/or the appearance of some extrahepatic autoimmune manifestations during the course of HCV chronic infection.
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PMID:Hepatitis C virus infection. Biological and immunological features. 876 58

The purpose of the present study was to analyse lymphocyte proliferative responses to recombinant hepatitis C virus (HCV) antigens in chronic hepatitis C. Four recombinant peptides derived from the NS3, core, E1 and E2/NS1 regions of the HCV genome were used as antigens in lymphocyte proliferative responses. Forty-two patients, classified into various sub-groups, and 17 healthy control subjects were tested and the specific response was expressed as a stimulation index. Responses were analysed with alanine aminotransferase (ALT) level and histological diagnosis. NS3- and core-antigen specific responses in all patient groups were significantly higher than in the healthy control group. E1- and E2/NS1-antigen-specific responses in the patient group with ALT levels exceeding 100 IU/L were significantly higher than those in other patient groups. Histological diagnosis was not correlated to the intensity of the core- and NS3-specific responses. E1- and E2/NS1-antigens induced significantly elevated responses in patients with chronic active hepatitis and liver cirrhosis compared with results in the healthy control group and in patients with chronic persistent hepatitis. In conclusion, the significantly elevated responses to core- and NS3-antigens may be related to HCV infection and such responses to E1- and E2/NS1-antigens could be related to the severity and activity of the disease.
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PMID:Lymphocyte proliferative responses to recombinant hepatitis C virus antigens in patients with chronic hepatitis C. 887 64

We tested HGV RNA in serum in addition to HBV DNA and HCV RNA to study the causative agents involved in chronic non-B, non-C hepatitis. Twenty five patients diagnosed as having chronic non-B, non-C hepatitis(negative for HBsAg and HCV-Ab), were investigated in this study. HGV RNA was detected by nested RT-PCR using primers in 5'-untranslated, NS3 and NS5 regions. Of the 25 patients, 4(16%) were positive for HGV RNA, only 1(4%) was positive for HBV DNA and none were positive for HCV RNA. Of the 4 patients with HGV RNA, 2 histologically has mild fibrosis and the remaining 2 had cirrhosis. One patient with cirrhosis also had hepatocellular carcinoma; HBV DNA was positive in this patient. All 3 patients with only the HGV infection had a mild histological grade. In conclusion, HGV infection was involved in 16% of Japanese patients with chronic non-B, non-C hepatitis. Chronic hepatitis G seemed to exhibit mild hepatitis activity.
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PMID:[GB virus C/hepatitis G virus infection in patients with chronic non-B, non-C hepatitis]. 908 58

By using reverse transcription and PCR for NS3 and 5'-untranslated regions (5'UTR) of the viral genome, prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection in Chiang Mai, Thailand, was studied. High prevalence of GBV-C/HGV infection was observed among intravenous drug users (32%) and hemodialyzed patients (25%). The prevalence was also considerably high among patients with chronic liver disease, such as chronic hepatitis (9%), liver cirrhosis (12%) and hepatocellular carcinoma (10%). On the other hand, the prevalence among healthy blood donors (1%) was significantly lower than that of the above high-risk groups. GBV-C/HGV RNA positivity was significantly higher in individuals with antibodies against hepatitis C virus (24%) than in those without (5%). Phylogenetic analysis of the 5'UTR sequences classified Thai GBV-C/HGV isolates into three groups; (i) a group of isolates that are commonly found in the United States and Europe, (ii) a group of isolates that are commonly found in Asia, and (iii) a group of novel sequence variants.
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PMID:GB virus C/hepatitis G virus (GBV-C/HGV) infection in Chiang Mai, Thailand, and identification of variants on the basis of 5'-untranslated region sequences. 967 5

Hepatitis C virus (HCV) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma in a substantial number of infected individuals, estimated to be 100-200 million worldwide. Unfortunately, immunotherapy or other effective treatments for HCV infection are not yet available, and interferon administration has limited efficacy. Different approaches to HCV therapy are being explored, and these include inhibition of the viral proteinase, helicase, and RNA-dependent RNA polymerase and development of a vaccine. Here we present the design of selective inhibitors with nanomolar potencies of HCV NS3 proteinase based on eglin c. These eglin c mutants were generated by reshaping the inhibitor active site-binding loop, and the results emphasize the role played by residues P5-P4' in enzyme recognition. In addition, alanine scanning experiments provide evidence that the N terminus of eglin c also contributes to NS3 binding. These eglin inhibitors offer a unique tool for accurately assessing the requirements for effective inhibition of the enzymatic activity of NS3 and at the same time can be considered lead compounds for the identification of other NS3 inhibitors in targeted design efforts.
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PMID:Design of selective eglin inhibitors of HCV NS3 proteinase. 970 81

Expression of p21 and c-myc protein in hepatocellular carcinomas and their surrounding liver tissue was detected on serial sections by immunohistochemical method. The results showed that the positive rates of p21 expression were 53.3% (16/30) and 96.7% (29/30) in hepatocellular carcinomas and pericarcinomatous liver tissue, and 40% (12/30) and 86.7% (26/30) and 86.7% (26/30) for c-myc protein expression respectively. Their incidences in pericarcinomatous liver tissue were higher than that in cancer tissue (P < 0.01). The patterns of p21 and c-myc protein in cells were cytoplasm, membrane and/or nuclear types. Their expression was more intensive in pericarcinomatous hepatocytes, especially in liver cirrhosis nodes. The results indicate that abnormal activiation and expression of oncogene ras and c-myc may be related to hepatocellular carcinogenesis.
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PMID:[Comparative study of expression of p21 and c-myc protein in hepatocellular carcinoma with pericarcinomatous liver tissue]. 986 83

To evaluate the clinical feasibility of the antibody titer against a chimeric polypeptide (named Core 518), in which a domain of Core and NS3 of hepatitis C virus (HCV) was fused, ELISA was performed in a total of 76 serum samples. Each serum was serially diluted using two-fold dilution method with distilled water into 10 concentrations. They were all positive for second generation anti-HCV assay (HCV EIA II; Abbott Laboratories). Genotyping RT-PCR, quantitative competitive RT-PCR, and RIBA (Lucky Confirm; LG Biotech) were also assayed. Anti-Core 518 antibody was detected in x 12800 or higher dilutions of sera from 35 of 43 chronic hepatitis C (81.4%) and nine of 16 hepatocellular carcinoma sera (56.3%), one of four cirrhosis (25%), 0 of four acute hepatitis C, and one of nine healthy isolated anti-HCV-positive subjects (p=0.0000). The anti-Core 518 antibody titers were well correlated with the presence of HCV RNA in serum (p=0.002). The anti-Core 518 antibody titers decreased significantly in nine of ten responders to IFN-alpha treatment. Monitoring anti-Core 518 titers may be helpful not only for differentiating the status of HCV infection among patients with various type C viral liver diseases, but also for predicting responses to IFN-alpha treatment.
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PMID:Monitoring antibody titers to recombinant Core-NS3 fusion polypeptide is useful for evaluating hepatitis C virus infection and responses to interferon-alpha therapy. 1033 62


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