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)

To investigate the gene expression profile of a normal human liver, we performed serial analysis of gene expression (SAGE), which allows the quantitative and simultaneous analysis of thousands of genes expressed in tissue. Polyadenylated RNA was obtained from a bulk normal human liver sample and SAGE was performed. Reverse transcriptase-polymerase chain reaction (RT-PCR) was also performed in each of 3 different normal liver samples to evaluate the validity of the profile in each individual. A total of 30,982 tags were sequenced, 8,596 of which were unique. The genes highly expressed in the normal liver were those encoding plasma proteins (>21.8% of total transcripts), cytoplasmic proteins (>8.6%), enzymes (>4.8%), protease inhibitors (>1.7%), complements (>1.1%), and coagulation factors (>0.75%). About 13.9% of all transcripts encoded genes not reported in GenBank thus far. This study identifies candidate genes to be examined in relation to various human liver diseases, including viral hepatitis, liver cirrhosis, and hepatocellular carcinoma.
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PMID:Comprehensive gene expression profile of a normal human liver. 1069 86

A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.
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PMID:[An autopsy case of interstitial pneumonia probably induced by Sho-saiko-to]. 1070 45

Proteoglycans play key roles in the physiological assembly of extracellular matrices and in the modulation of growth factor activities. During liver regeneration there is a profound remodelling of the connective tissue network with a concurrent alteration in proteoglycan gene expression. In the present study we have analyzed in detail the biochemical and molecular properties of the proteoglycans associated with biliary cirrhosis. The three major proteoglycans of human liver, namely decorin, syndecan and perlecan, were markedly elevated in the cirrhotic parenchyma as compared to normal liver tissue. Particularly elevated (eight fold) was the perlecan. This proteoglycan had not only heparan sulfate but also chondroitin and dermatan sulfate. Reverse transcriptase PCR revealed a marked enhancement of decorin and syndecan expression and detectable message for perlecan was found only in the cirrhotic liver. These results indicate that significant proteoglycan alterations are associated with the development of biliary cirrhosis and provide basis for future studies aimed at the characterization of the molecular events involved in the regulation of extracellular matrix deposition in this common human disease.
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PMID:Altered Proteoglycan Gene Expression in Human Biliary Cirrhosis. 1117 26

Hepatitis C virus infection is a major health burden affecting an estimated 200 million people worldwide. Chronic hepatitis C is one of the leading causes of cirrhosis and end-stage liver cirrhosis; thus effective therapies are required. For many years interferon-alpha has been the treatment of choice for patients with chronic hepatitis C infection. However, in only 10%-15% of patients is interferon-alpha monotherapy successful, leading to sustained virological response. A combination of interferon-alpha and ribavirin significantly enhanced sustained virological response rates to 40%. Strategies to further improve response rates include modification of the interferon dosing schedule with induction dosing and daily interferon, new interferons such as consensus interferon, or interferon with longer half-life and more favorable pharmacokinetics such as pegylated interferons. Recent trials showed that a combination of pegylated interferons and ribavirin leads to sustained response rates of about 50% with an acceptable safety profile. Hopefully, new treatment modalities will be available in the near future. Helicase, protease and the RNA polymerase are potential targets to suppress HCV replication and several immunotherapeutic approaches are explored.
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PMID:Current and future treatment of hepatitis C. 1129 80

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The absence of culture systems permissive for HCV replication has presented a major bottleneck to antiviral development. We sought to recapitulate the early steps in the life cycle of HCV by means of DNA-based expression of viral genomic sequences. Here we report expression of replicating HCV RNA by using a, to our knowledge, novel binary expression system in which cells were transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis Delta ribozyme to control 3' cleavage, and infected with vaccinia-T7 polymerase. HCV genomic and replicative strand synthesis, in addition to protein synthesis, was detectable and depended on full-length HCV sequences. Moreover, the system was capable of generating HCV RNA quasispecies, consistent with the action of the low-fidelity HCV NS5B RNA polymerase. IFN-alpha, but not ribavirin, directly inhibited the viral replicative cycle in these cells, identifying the virus itself and not solely the immune system as a direct target of IFN action. The availability of a cell-based test for viral replication will facilitate screening of inhibitory compounds, analysis of IFN-resistance mechanisms, and analysis of virus-host cell interactions.
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PMID:Hepatitis C virus replication is directly inhibited by IFN-alpha in a full-length binary expression system. 1149 7

Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.
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PMID:Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses. 1159 79

Hepatitis C virus (HCV) is the most common cause of chronic viral hepatitis. The World Health Organization estimates that 170 million people world-wide are infected with HCV; 70% of them will develop chronic hepatitis and 20-30% cirrhosis in 10-30 years. Of those with cirrhosis, an estimated 25-30% will develop liver cancer. Since the identification and molecular characterization of HCV in 1989, a variety of diagnostic tests based on the detection of hepatitis virus antibodies or HCV RNA in the serum have been developed. The enzyme-linked immunosorbent assays (ELISA 3) and the recombinant immunoblot assays (RIBA 2nd and 3rd generation) exhibit improved sensitivity and specificity for HCV antibodies. Qualitative and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) has allowed clinicians to track the natural history of HCV and to monitor the progress of therapy. This article reviews the state-of-the-art tests and assays developed for the diagnosis and management of HCV infection.
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PMID:[Diagnostic strategies in Hepatitis C virus infection]. 1209 56

The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
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PMID:Course and outcome of hepatitis C. 1240 73

Vascular endothelial growth factor (VEGF) is involved in both development and progression of several epithelial tumours, but its role in hepatocellular carcinoma (HCC) is unclear. Assessment of liver and blood levels of VEGF may provide further insights on angiogenesis in HCC. Tissue mRNA of VEGF-165, VEGF-189 and their receptor KDR was assessed by a semi-quantitative retro-transcriptase polymerase chain reaction, and expressed as target transcript/beta-actin ratio, in 29 patients with HCC, 26 with cirrhosis and 15 with chronic hepatitis. VEGF-165 was also measured by ELISA in plasma samples obtained from both hepatic and femoral veins in additional 58 patients, including 15 with HCC. The liver expression of mRNA of VEGF-165, VEGF-189 and KDR was higher in HCC than in chronic liver diseases (1.54 +/- 0.89 vs 0.62 +/- 0.47, P < 0.0001; 1.09 +/- 0.65 vs 0.64 +/- 0.54, P = 0.003; 1.30 +/- 1.09 vs 0.69 +/- 0.72, P = 0.014). VEGF-165 was higher in HCC tissue than in extra-tumoural tissues (1.44 +/- 0.31 vs 1.03 +/- 0.21, P = 0.0009) and in the cirrhotic tissue of HCC patients than in HCC-free cirrhosis (1.03 +/- 0.23 vs 0.45 +/- 0.45, P = 0.0002). Tissue VEGF-189 mRNA inversely correlated with tumour size and degree of tumour cell proliferation. The hepatic and femoral vein levels of VEGF-165 protein were significantly higher in HCC patients than in cirrhotic patients (66.7 +/- 57.1 vs 24.2 +/- 16.4 pg/mL, P = 0.0001 and 37.1 +/- 42.2 vs 13.5 +/- 9.6 pg/mL, P = 0.001). There was a gradient of VEGF-165 between hepatic and femoral veins in both HCC and cirrhosis. In conclusion, VEGF appears to be involved in the development of HCC and it could be a predictor of HCC development in patients with cirrhosis.
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PMID:Increased expression of vascular endothelial growth factor in small hepatocellular carcinoma. 1724 53

Hepatitis C virus (HCV) is a major causative agent of liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Because the current standard therapy, interferon (IFN) or pegylated-IFN alone or in combination with ribavirin, is ineffective on approximately half of the HCV-infected patients, alternative therapeutics are greatly needed. The chemical genetics method is a useful strategy to elucidate molecular mechanisms of the viral life cycle and screen for anti-viral agents. This review focuses on the use of chemical genetics approach to virology, which could be called 'chemical virology', and introduces an example of such analysis. From a cell culture-based screening, an immunosuppressant cyclosporin A (CsA) was identified as an anti-HCV compound. Analysis using CsA as a bioprobe showed that cyclophilin (CyP) B, a cellular target of CsA, regulates the function of HCV RNA polymerase NS5B, which is essential for efficient viral genome replication. By targeting CyP, HCV genome replication was drastically suppressed. Thus, chemical genetics analysis identified CyPB as a cellular cofactor of HCV genome replication and a target for novel anti-HCV agents.
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PMID:Chemical genetics approach to hepatitis C virus replication: cyclophilin as a target for anti-hepatitis C virus strategy. 1729 3


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