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)

Sera were tested for autoantibodies in 98 patients with cryptogenic cirrhosis in Uganda and results correlated with serological tests for hepatitis B surface antigen (HBs Ag) and antibody to HBs Ag (HBs Ab). Smooth muscle antibodies (SMA) were detected in 23 (24%) of the patients but there was no difference in the incidence of SMA between HBs Ag-positive and negative cases. Antinuclear antibodies (ANA) were detected in five cases; mitochondrial, gastric and thyroid antibodies were not found in any patient. Unlike other geographical locations autoimmune mechanisms appear to play little part in the progression of chronic liver disease in Uganda Africans. Hepatitis B surface antigen was present in 36 (37%) and HBs Ab in 47 (48%) of the patients. Although evidence for past exposure to hepatitis B virus (as shown by detection of HBs Ab) was present in at least 30 out of the 62 HBs Ag-negative cases, there was no greater incidence of autoantibodies in HBs Ag-negative patients with or without HBs Ab. Persistent infection with hepatitis B virus and continuing liver damage may be an important factor but these results do not favor a role for the virus in causing chronic liver disease by triggering off an autoimmune reaction.
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PMID:Autoimmune factors in African cirrhosis. Correlation with hepatitis B surface antigen and antibody. 108 41

Persistent infection with hepatitis C virus (HCV) is associated with chronic hepatitis and cirrhosis which may eventually develop into primary hepatocellular carcinoma. The mechanism of pathogenesis is ill-defined and nothing is known of the distribution, frequency or type of infected cell in the liver of HCV-infected individuals. In this study we have examined liver tissue taken at autopsy from 2 anti-HCV-positive patients by in situ hybridization for the presence of HCV RNA. Viral RNA was detected by autoradiography after hybridization with 125I-labelled riboprobes, representing approximately 35% of the HCV genome. Only a few positive cells were identified in the HCV-infected liver samples, but not in a normal liver sample. Hybridization with an unrelated probe was negative in all samples. The HCV RNA-positive cells were detected with anti-sense but not sense RNA probes, suggesting that they contained a high ratio of genomic:antigenomic RNA. The appearance and distribution of the HCV RNA-positive cells suggested that they were not hepatocytes and were more likely to be lymphocytes or macrophages.
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PMID:Detection of hepatitis C virus RNA by in situ hybridization. 133 32

Persistent infection with hepatitis C virus (HCV) is associated with chronic hepatitis and cirrhosis which may eventually develop into hepatocellular carcinoma (HCC). As far, the pathogenesis mechanism of HCC is unclear and nothing is known of the distribution, frequency or type of infected cells in HCC. One-step reverse transcription in situ polymerase chain reaction (ORT-PCRIS) to detect HCV RNA in HCC samples was developed in our laboratory. Liver tissues from 27 patients with HCC were investigated by this technique for frozen or paraffin-embedded sections. Meanwhile, HCV RNA in sera and extracts of specimens with HCC were assayed by RT-PCR. The positive rate of HCV RNA by ORT-PCRIS was 81.5% (22/27) in the peritumor liver tissues and 77.8% (21/27) in the tumor tissues, significantly higher than 29.6% (8/27) in sera and 37.0% (10/27) in the extreats of HCC by RP-PCR (P < 0.01). HCV RNA positive signals were found mainly in the nuclei of tumor cell, and mainly both the nuclei and cytoplasms in peritumor cells and mainly both the nuclei and cytoplasms in peritumor cells (P < 0.05). Positive granules of HCV RNA were much more in peritumor cells than in the tumor cells. Positive cells were scattered mainly on the point-type in the cancer tissues and on the diffusion-type in the peritumor tissues. Our findings suggest that ORT-PCRIS for detecting HCV RNA in the cell with HCC remarkably prior to traditional RT-PCR. HCV infection plays a relatively important role in determination of HCC development and perhaps HCV replication and its genomic RNA integration with hepatocyte DNA are involved in the course of the malignant transformation of hepatocytes.
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PMID:[Detection of hepatitis C virus RNA in cells with hepatocellular carcinoma and its practical significance by in situ polymerase chain reaction]. 760 Aug 63

The hepatitis B virus is a member of an unusual family of noncytopathogenic, hepatotropic DNA viruses--the hepadnaviruses. The complete virus comprises a lipoprotein coat, the hepatitis B surface antigen, enveloping a nucleocapsid core that contains a small, circular DNA molecule. Four open reading frames have been identified on the hepatitis B virus DNA genome. They encode seven proteins, including a hepatitis B virus DNA polymerase molecule with reverse transcriptase activity. The replication of the virus resembles that of retroviruses and occurs predominantly but not exclusively in hepatocytes. Virus variants involving genomic mutations have been identified. Testing for hepatitis B surface antigen permits detection of many but not all acutely infected patients. Diagnosis of acute infection rests on the identification of IgM antibodies to the hepatitis B core antigen. Antibody to hepatitis B surface antigen appears in serum during the convalescent phase of hepatitis B virus infection. It is the neutralizing, protective antibody largely responsible for immunity to reinfection. In persistent infection hepatitis B surface antigen is present, antibody to hepatitis B core antigen is predominantly an IgG antibody, antibody to hepatitis B surface antigen is not detectable or is present in very low titers and viral replication may be active. Persistent infection leads to an asymptomatic carrier state, chronic hepatitis, cirrhosis and hepatocellular carcinoma. No specific treatment exists for acute hepatitis B virus infection. Current data indicate that approximately 50% of adults who have chronic infection achieve virologic, biochemical and histologic remission from treatment with alpha-2b-interferon.
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PMID:Hepatitis B today: clinical and diagnostic overview. 832 12

Persistent infection with hepatitis C virus (HCV) is associated with the development of liver cirrhosis and hepatocellular carcinoma. To examine the oncogenic potential of the HCV core gene product, primary rat embryo fibroblasts (REFs) were transfected with the core gene in the presence or absence of the H-ras oncogene. In contrast to a previous report (R. B. Ray, L. M. Lagging, K. Meyer, and R. Ray, J. Virol. 70:4438-4443, 1996), HCV core proteins from two different genotypes (type 1a and type 1b) were not found to transform REFs to tumorigenic phenotype in cooperation with the H-ras oncogene, although the core protein was successfully expressed 20 days after transfection. In addition, REFs transfected with E1A- but not core-expressing plasmid showed the phenotype of immortalized cells when selected with G418. The biological activity was confirmed by observing the transcription activation from two viral promoters, Rous sarcoma virus long terminal repeat and simian virus 40 promoter, which are known to be activated by the core protein from HCV-1 isolate. In contrast to the result with primary cells, the Rat-1 cell line, stably expressing HCV core protein, exhibited focus formation, anchorage-independent growth, and tumor formation in nude mice. HCV core protein was able to induce the transformation of Rat-1 cells with various efficiencies depending on the expression level of the core protein. These results indicate that HCV core protein has an oncogenic potential to transform the Rat-1 cell line but is not sufficient to either immortalize primary REFs by itself or transform primary cells in conjunction with the H-ras oncogene.
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PMID:Hepatitis C virus core from two different genotypes has an oncogenic potential but is not sufficient for transforming primary rat embryo fibroblasts in cooperation with the H-ras oncogene. 952 29

Hepatitis C virus (HCV), discovered in 1989, is the major causative agent of parenteral non-A, non-B hepatitis worldwide. Following the development of a method of diagnosing HCV infection, it became apparent that HCV frequently causes chronic hepatitis. Persistent infection with HCV is implicated in liver cirrhosis and hepatocellular carcinoma. Current worldwide estimations suggest that more than 170 million people have been infected with HCV, an enveloped positive single-stranded RNA (9.6-kilobases) virus belonging to the Flaviviridae. The HCV genome shows remarkable sequence variation, especially in the hypervariable region 1 of the E2 protein-encoding region, and globally, HCV appears to be distributed with more than 30 genotypes. Complicated "quasispecies" and frequent mutations of viral genomes have also emerged. The HCV genome encodes a large polyprotein precursor of about 3,000 amino acid residues, and this precursor protein is cleaved by the host and viral proteinases to generate at least 10 proteins in the following order: NH2-core-envelope (E1)-E2-p7-nonstructural protein 2 (NS2)-NS3-NS4A-NS4B-NS5A-NS5B-COOH. These viral proteins not only function in viral replication but also affect a variety of cellular functions. Although several explanations have been proposed, the mechanisms of HCV infection and replication in targeted cells, the mechanism of persistent viral infection, and the pathogenesis of hepatic diseases (hepatitis or hepatocellular carcinoma) are all poorly understood. A major reason why these mechanisms remain unclear is the lack of a good experimental HCV replication system. Although several classical trials using cultured cells have been reported, several new, more promising experimental strategies (generations of infectious cDNA clone, replicon, animal models, etc.) are currently being designed and tested, in order to resolve these problems. In addition, new therapies for chronic hepatitis have also been developed. The enormous body of information collected thus far in the field of HCV research is summarized below, and an overview of the current status of HCV molecular virology of HCV is provided.
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PMID:Molecular virology of hepatitis C virus. 1143 27

Hepatitis C was first recognized as a form of viral hepatitis that was distinct from disease caused by hepatitis A virus and hepatitis B virus. The etiologic agent of hepatitis C was proposed to be a small, enveloped virus based on demonstrations of its transmissibility to chimpanzees, electron microscopic studies, and sensitive to chloroform. Successful molecular cloning of viral genome in the late 1980's led to the development of assay for serological diagnosis of HCV and it is currently estimated that at least 170 million people are chronically infected with the hepatitis C virus. HCV evades host antiviral defenses by mechanisms that remain to be identified and establishes a persistent infection in a majority of patients. Persistent infection of HCV is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Therefore development of antiviral treatment for HCV is an urgent worldwide health problem. Although much has been learned about HCV genome organization, polyprotein processing, protein function and structure, many key questions remain to be answered. Major efforts of Japanese investigators should now be directed at establishing cellular system and animal models appropriate for dissecting the various steps in HCV replication cycle and strategies for blocking them.
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PMID:[Overview of hepatitis C virus from its discovery to now]. 1157 79

Persistent infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. All treatments known so far rely on the antiviral activity of interferon alfa (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, only a fraction of the patients clear the virus during therapy and for those who do not respond there is currently no alternative treatment. Selectable subgenomic HCV RNAs (replicons) have been recently used to investigate the effect of IFN-alpha on HCV replication. However, it has not yet been analyzed whether other cytokines also play a role in the innate immune response against HCV. Here we show that IFN-gamma inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons. We further show that the inhibitory action of IFN-gamma does not rely on the production of nitric oxide or the depletion of tryptophan. In conclusion, our results suggest that cytotoxic T cells and natural killer cells may contribute to HCV clearance not only by cell killing but also by producing IFN-gamma, thereby enhancing the intracellular inhibition of viral replication.
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PMID:Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. 1187 Mar 86

Persistent infection of hepatitis C virus (HCV) is a major cause of liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Searching for a substance with anti-HCV potential, we examined the effects of a variety of compounds on HCV replication using a HCV subgenomic replicon cell culture system. Consequently, the immunosuppressant cyclosporin A (CsA) was found to have a suppressive effect on the HCV replicon RNA level and HCV protein expression in these cells. CsA also inhibited multiplication of the HCV genome in a cultured human hepatocyte cell line infected with HCV using HCV-positive plasma. This anti-HCV activity of CsA appeared to be independent of its immunosuppressive function. In conclusion, our results suggest that CsA may represent a new approach for the development of anti-HCV therapy.
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PMID:Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. 1457 68

Persistent infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis in humans. In chronic carriers, the viral infection induces liver damage that predisposes the patient for cirrhosis and can lead to hepatocellular carcinoma. Current chemotherapies are limited to alpha interferon (IFN-alpha) used either alone or in combination with ribavirin (RBV). In addition to its limited efficacy, this treatment is frequently poorly tolerated because of its side effects. The urgently needed development of new drugs is made difficult by the lack of an in vitro or in vivo infectivity model, and no cell line has been found so far to reliably and reproducibly support HCV infection. For this reason, the closely related pestivirus bovine viral diarrhea virus (BVDV) has sometimes been used as a surrogate in vitro infectivity model. In this study we used an MDBK cell line persistently infected with noncytopathic BVDV to assess the antiviral effect of IFN-alpha and RBV, the two drugs currently in clinical use against HCV. The same system was then used to evaluate the potential of two classes of iminosugar derivates to clear noncytopathic BVDV infection from MDBK cells. We show that treatment with long-alkyl-chain deoxynojirimycin derivatives, which are inhibitors of the endoplasmic reticulum (ER)-resident alpha-glucosidases, can greatly reduce the amount of secreted enveloped viral RNA. Long-alkyl-chain deoxygalactonojirimycin derivatives, which do not inhibit ER alpha-glucosidases, were less potent but still more effective in this system than IFN-alpha or ribavirin.
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PMID:Effects of interferon, ribavirin, and iminosugar derivatives on cells persistently infected with noncytopathic bovine viral diarrhea virus. 1474 1


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