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

Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.
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PMID:Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. 127 66

DNA from human hepatocellular carcinomas (HCC) were analysed for the presence of mutations in codons 12 and 61 of the K-ras, H-ras and N-ras genes. The relevant ras sequences were amplified in vitro using the polymerase chain reaction and point mutations detected by selective hybridisation using mutation-specific synthetic oligonucleotides. In one of the 19 HCCs a mutation in codon 61 of the K-ras gene was detected, whilst in 3/19 HCCs a mutation was found in codon 61 of the N-ras gene. The mutations were all heterozygous A-T transversions and were found in HCCs arising in patients with underlying cirrhosis. In two of these patients where the corresponding normal tissue was available only the wild-type ras gene was detected, indicating that oncogenic activation of the ras gene was a consequence of somatic mutation. In another patient the same mutation in codon 61 of the N-ras gene was found in cirrhotic liver tissue and in all four patients the same mutation was also detected in formalin-fixed, paraffin-embedded liver biopsy HCC tissue obtained at diagnosis. These results indicate that mutational activation of the ras genes at codon 61 is an infrequent but possibly early event in the development of HCC in Britain.
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PMID:Infrequent point mutations in codons 12 and 61 of ras oncogenes in human hepatocellular carcinomas. 132 1

Point-mutational activation of the c-Ki-ras proto-oncogene has been shown to be rare in human hepatocellular carcinoma, the most common primary liver cancer and one usually associated with chronic viral infection. To reveal the association of c-Ki-ras activation with cholangiocarcinogenesis under different etiological backgrounds, the incidence of point mutation at codons 12 and 13 of the c-Ki-ras proto-oncogene was examined in three groups of human liver cancers with differentiation to biliary epithelial cells: Group 1, cholangiocellular carcinoma in Japanese with normal livers; Group 2, cholangiocellular carcinoma in Thais who had lived in an area where the liver fluke Opisthorchis viverrini is endemic; and Group 3, combined hepatocellular-cholangiocellular carcinoma, a rare type showing features of both hepatocellular and biliary epithelial differentiation, in Japanese with chronic viral hepatitis with or without cirrhosis. The polymerase chain reaction and direct sequencing of its product were used to detect the mutation. Point mutation at codon 12 of the c-Ki-ras gene was detected in five (56%) of nine cases in Group 1. In contrast, the mutation was not detected in any of the cases in Groups 2 and 3. Therefore, point-mutational activation of c-Ki-ras did not seem to be involved in the development of primary liver cancers associated with apparent chronic irritation of liver cells or biliary epithelial cells caused by exogenous liver-fluke or viral infection. On the other hand, point-mutational activation of the c-Ki-ras proto-oncogene may be involved in cholangiocarcinogenesis in liver without preexisting liver-fluke or viral infection.
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PMID:Cholangiocarcinomas in Japanese and Thai patients: difference in etiology and incidence of point mutation of the c-Ki-ras proto-oncogene. 133 66

The localization of hepatitis C virus-infected hepatocytes in the human liver remains unclear despite the development of a serological assay for the antibody to hepatitis C virus. We studied their localization immunohistochemically with monoclonal antibodies to core, envelope and NS3 antigens of hepatitis C virus. We examined 48 liver biopsy samples from C100-3 antibody-positive patients with chronic liver disease (chronic persistent hepatitis, 5 cases; chronic active hepatitis, 41 cases; cirrhosis, 2 cases) and 12 liver biopsy samples from C100-3 antibody-negative patients with chronic liver disease (type B chronic hepatitis, 8 cases; alcoholic liver disease, 4 cases). In the C100-3 antibody-positive group, positive immunostaining for core antigen, envelope antigen and NS3 antigen was found in 23% (11 of 48), 24% (11 of 45) and 24% (11 of 46), respectively. Negative results were obtained in the C100-3 antibody-negative group. Hepatocytes with positive staining were scattered in the lobules, and they were found in the same regions irrespective of whether the antibody to core antigen, to envelope antigen or to NS3 antigen was used. Each positive cell was strongly stained in the cytoplasm; these decorations disappeared after absorption of the primary antibody with purified antigen. mean ALT levels in the patients with positive immunostaining for core, envelope or NS3 antigen (174.8 +/- 105.7 U/L) tended to be higher than in those with negative immunostaining (142.0 +/- 93.8 U/L). On histological evaluation of liver specimens with a scoring system of the histological activity index, intralobular inflammation and fibrosis had higher scores for samples with positive rather than negative immunostaining (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical detection of hepatitis C virus-infected hepatocytes in chronic liver disease with monoclonal antibodies to core, envelope and NS3 regions of the hepatitis C virus genome. 137 9

Determination of p21, a product of Ha-ras oncogene, and HBsAg in hepatocellular carcinoma (HCC) and liver cirrhosis etc. was carried out with ABC method. The results showed that HCC tissues exhibited enhancement of p21 expression with a positive rate of 72.4%, which was obviously higher than the expression of p21 in tissues from liver cirrhosis, chronic hepatitis and hepatoblastoma. The p21 positive rate of regenerative cirrhosis nodules close to the HCC was 87.2%. The p21 expression level in HBsAg positive regenerative nodules of cirrhosis close to the HCC was significantly high, and its positive rate reached 93.9%. The expression level of p21 protein in well-differentiated HCC was higher than that of poorly differentiated and undifferentiated HCC. Therefore, the result suggests that the expression level of p21 in liver cirrhosis is related to persistent infection of HBV. The elevated expression of p21 plays an important role in the development of regenerative nodules in liver cirrhosis towards HCC, and it is also an important factor in the early stage of HCC development.
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PMID:[Expression of p21 in hepatocellular carcinoma and liver cirrhosis and its relation with HBV infection]. 165 96

To elucidate the cell biological significance of ras oncogene, the expression of ras-p21 was analyzed in 53 cases of liver tissues including 34 cases of hepatocellular carcinoma (HCC), by using immunohistochemical method. In result, 22 (65%) cases of 34 HCC and 34 (79%) cases of 43 liver cirrhosis were positive for p21, whereas all of chronic hepatitis and normal livers were negative. Especially, comparative study between the expression of p21 and clinicopathological background of HCC revealed that p21 was prominently expressed in well differentiated form, nodular type, small liver cancer, and the cases showing AFP levels below 400 ng/ml. From these results, it was indicated that ras oncogene might play an important role in malignant transformation of hepatocytes or differentiation of HCC.
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PMID:[The expression of ras p21 product in hepatocellular carcinoma]. 170 Jan 76

A detection system was developed to distinguish the four different HCV genomes [HCV-J, HCV-US, HCV-K2 and group II HCV (HCV-GII)], involving reverse transcription followed by a nested polymerase chain reaction using specific primers for each HCV type. The putative non-structural (NS) 5 regions of HCV-J, HCV-US and HCV-K2 and the putative NS3 region of HCV-GII were amplified. Of 95 specimens from patients with acute hepatitis, chronic hepatitis, liver cirrhosis or hepatocellular carcinoma, 67 specimens were positive for HCV-J, 2 for HCV-US, 23 for HCV-K2 and 11 for HCV-GII. About half the specimens that were positive for HCV-K2 or HCV-GII were coinfected with HCV-J and all those that were positive for HCV-GII were also positive for HCV-K2. Nucleotide sequence analysis of several amplified cDNA products revealed that HCV-K2 and HCV-GII could each be classified into two groups, and the pattern of classification of HCV-K2 was identical with that of HCV-GII. Therefore, our results strongly suggest that HCV-K2 is the same as HCV-GII.
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PMID:Distribution of plural HCV types in Japan. 172 Mar 9

The expression of cellular oncogenes in nonneoplastic human liver tissue was examined to determine if there was a correlation between oncogene expression and physiologic regeneration in liver disease. Human liver tissue specimens from 70 patients with various histologic findings from almost normal to cirrhosis were examined (using northern blot analysis) for the expression of nine cellular oncogenes. With c-K-ras, four RNA bands (5.6-kilobase [kb], 2.1-kb, 1.5-kb, and 1.2-kb RNA species) were detected in all liver tissue examined. Expression of c-fos was also detected in a few samples examined when 50-micrograms samples of total RNA were applied. Other oncogenes such as H-ras, myc, erbB, raf, fms, fes, and myb were not detected. These results indicate that particular oncogene(s) may not be highly expressed during liver regeneration in human liver disease, or that populations of regenerating hepatocytes may be too small to show significant elevations of oncogene expression. The new finding of a constant expression of c-K-ras in human liver tissue suggests that it is linked to essential hepatocellular function rather than carcinogenesis.
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PMID:Oncogene expression in the liver tissue of patients with nonneoplastic liver disease. 201 59

In order to investigate how chronic liver diseases, including liver cirrhosis and chronic hepatitis, are associate with hepatocarcinogenesis in terms of gene alteration, the methylation states of the c-myc and c-Ki-ras genes were examined in 34 liver tissues from patients with chronic liver disease without hepatocellular carcinoma (HCC), 34 non-tumor liver tissues from patients with HCC, 18 HCC tissues and 31 control liver tissues. The methylation states were analyzed by the Southern hybridization method using the restriction endonuclease isoschizomers MspI and HpaII. The CCGG sites at the second exon of the c-myc gene tended to be more extensively hypomethylated both in chronic liver disease and in non-tumor tissues than in control livers. Whereas the CCGG sites of the c-Ki-ras, and the third exon of the c-myc gene tended to be hypomethylated only in HCC tissues in comparison with other tissue groups. These results suggest that chronic liver disease may be situated between normal liver and HCC based on the state of DNA methylation and associated with the development of HCC through hypomethylation of the c-myc and/or c-Ki-ras gene.
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PMID:Hypomethylation of the c-myc oncogene in liver cirrhosis and chronic hepatitis. 254 2

To elucidate the role of oncogene expression in hepatocarcinogenesis, we examined the expression of 8 cellular oncogenes by dot blot and/or northern blot analysis in neoplastic, cirrhotic and non-cirrhotic human liver tissues obtained at surgery. Significantly higher levels of c-myc gene expression were observed in tissues of hepatocellular carcinoma (HCC) and adjacent cirrhotic tissues than in apparently normal liver tissues or those of chronic hepatitis (normal-chronic hepatitis). There was a tendency to higher c-myc mRNA levels in HCC than in liver cirrhosis. However, when tumorous and adjacent cirrhotic tissues from the same patient were compared, c-myc mRNA levels were not consistently higher in HCC. No significant differences in mRNA levels of c-fos, N-myc, N-ras, Ha-ras, c-erbA, c-erbB and c-abl were observed among the HCC, cirrhosis and normal-chronic hepatitis groups. Although the significance of increased c-myc gene expression in liver cirrhosis and HCC is still not known, it is conceivable that the persistent elevation of c-myc gene expression in cirrhosis contributes to the development of HCC.
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PMID:Expression of oncogenes in human liver disease. 284 21


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