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)

Peripheral blood mononuclear cells (PBMC, n = 26), formalin-fixed paraffin-embedded liver tissues (n = 11) and saliva (n = 15) of primary biliary cirrhosis (PBC) patients were used for the detection of Epstein-Barr virus (EBV) sequences by polymerase chain reaction (PCR) assay. The semiquantitative analysis of EBV-DNA was also carried out in a reconstructive experiment using an EBV-infected cell line. The PBMCs of PBC patients showed increased levels of EBV-DNA (61%) in contrast to chronic active hepatitis patients (19%), liver cirrhosis patients (14%) and healthy individuals (11%). Furthermore, formalin-fixed paraffin-embedded liver tissues, as well as saliva from PBC patients, also demonstrated increased levels of EBV-DNA when compared to healthy individuals and those with other liver diseases. The increased levels of EBV-DNA in the PBMC, liver tissue and saliva of the PBC patients suggest that those patients may have a depressed immune function against EBV infection.
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PMID:Increased expression of Epstein-Barr virus in primary biliary cirrhosis patients. 133 91

Chronic infections with hepatitis B virus (HBV) of humans and animal hepadnavirus infections in their natural hosts are strongly associated with primary hepatocellular carcinoma (HCC). Although viral integrations are found in cells of many HCC, no general viral-specific hepatocarcinogenic mechanism for hepadnaviruses has been identified. In approximately one half of HCC in woodchuck hepatitis virus (WHV) infected woodchucks, viral integrations near the c-myc or N-myc genes have been reported which result in enhanced expression of the respective gene. Such host gene-specific insertional mutagenesis has not been found in HCC of other hepadnavirus infected hosts. Thus in humans, ground squirrels and ducks hepadnaviral integrations appear to be at different host chromosomal DNA sites in each HCC and few integrations have been found within or near any cellular gene. Other possible hepadnavirus-specific carcinogenic mechanisms that are being investigated include transactivation of cellular gene expression by an hepadnavirus gene product (e.g. the X-gene), and mutation of host genes by unknown hepadnavirus-specific mechanisms. It should be noted, however, that chronic hepadnavirus infection is associated with chronic necroinflammatory liver disease with hepatocellular necrosis and regeneration (sometimes leading to cirrhosis in humans), a pathological process that is common to numerous other risk factors for HCC. This suggests the possibility that this pathological process is hepatocarcinogenic irrespective of the inciting agent and the role of hepadnavirus infection is no different from that of other risk factors in causing chronic necroinflammatory liver disease.
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PMID:The role of hepatitis B virus in the development of primary hepatocellular carcinoma: Part I. 133 78

The DNA-HBV was investigated in 109 serum samples from 75 patients with different forms of infection with the HB virus, using an RIA hybridization technique (Genostic-Abott). DNA-HBV was present in 12 of 18 cases of acute hepatitis, 1 of 3 patients with fulminant disease, 11 of 14 patients with chronic hepatitis and/or cirrhosis, 2 of 10 patients with hepatoma and 6 of 30 asymptomatic chronic carriers. Presence of DNA-HBV beyond 60 days in 7 patients with acute hepatitis established the chronic state. The highest levels were found in patients with chronic hepatitis or cirrhosis (mean 41 +/- 11 pg/ml) and the lowest in chronic carriers and patients with hepatoma. High levels of DNA-HBV denote persistent viral replication and would support antiviral treatment. Thus, investigation of DNA-HBV has diagnostic, prognostic and therapeutic implications in patients with Hepatitis B.
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PMID:[Significance of investigating viral DNA in serum from patients with hepatitis B]. 134 Sep 75

Hepatitis B virus (HBV) serological markers were investigated in 40 incident cases of hepatocellular carcinoma (HCC) and in two age and sex matched control groups, comprising 40 patients with other cancers and 80 healthy individuals, resident in Bahia, Brazil. Serologic tests were done by radioimmunoassay. The study observed high proportion of seropositivity to HBsAg (42.5%) and of those presenting HBsAg or antiHBc (65.0%) among HCC cases, higher in men than women and in those aged 17 to 30 years old. HBsAg seropositivity among HCC patients was greater than in the control group with other cancers (7.5%) and in healthy controls (2.5%), corresponding to odds ratio estimates of 15.0 (95% CI 3.29, 68.30) and 33.0 (95% CI 9.13, 119.28), both statistically significant. HBeAg was not observed and antiHBe was present in 41.2% of cases, suggesting the absence of viral replication, possibly with viral DNA integration into the hepatocyte genome. The presence of cirrhosis was associated with HBsAg seropositivity among HCC cases. A history of chronic alcoholism is shown to be more frequently related to those cases with cirrhosis. This study highlights the relevant association between HCC and HBV in Northeast Brazil, particularly for young individuals, and the high risk of development of HCC for HBsAg carriers.
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PMID:A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in northeast Brazil. 134 17

DNA strand breaks (nicks) in non-parenchymal cells (NPCs) in CCl4-induced acute or chronic liver injury in rats were detected using an in situ nick translation method; their dynamic changes were analysed in relation to the proliferation pattern of hepatocytes and NPCs, as revealed by bromodeoxyuridine (BrdU)-uptake. In acute injury, hepatocyte proliferation started before centrilobular necrosis had occurred, whereas BrdU-labeled sinusoidal NPCs markedly increased only after centrilobular necrosis was apparent. DNA breakages in NPCs paralleled the proliferation pattern of these cells, suggesting that nicks are physiological, and reflect proliferation and activated gene expression. In chronic injury, liver cirrhosis developed after 9 weeks, but BrdU-labeling of hepatocytes was almost the same level as that in untreated liver. The number of BrdU-labeled NPCs showed only a slight increase, while those with DNA breakages were much more frequent in the cirrhotic stage, suggesting a significant role for NPCs in the fibrotic process. These results indicate that DNA strand breaks in NPCs act as a marker for activation states such as proliferation, differentiation and/or activated gene expression.
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PMID:Changes in DNA strand breaks in non-parenchymal cells following hepatocyte regeneration in CCl4-induced rat liver injury. 136 17

Type 1 collagen is the predominant collagen in cirrhotic livers. Each type 1 collagen molecule contains three subunits, two are identical (the alpha 1 chains) and the sequence of the third (alpha 2) is very similar. They are encoded at the non-synthenic loci, COL1A1 and COL1A2 and restriction site dimorphisms have been described at each locus. Genetic factors have been invoked as a basis for increased susceptibility to alcoholic cirrhosis. One hypothesis is that genetically determined differences in type 1 collagen may be involved in this predisposition. We have examined this by analysing restriction fragment length polymorphisms at each type 1 collagen locus in leucocyte DNA from 56 unrelated patients with alcoholic cirrhosis and 74 local unrelated healthy controls. Based on the presence or absence of these restriction site dimorphisms four possible haplotypes were generated at COL1A1 and COL1A2. We found no significant difference in allele frequencies between alcoholic cirrhotics and controls and, unlike a previous small study, we found no particular haplotype of either gene was associated with alcoholic cirrhosis. Our study provides no evidence for involvement of type 1 collagen structural genes in a genetic predisposition to cirrhosis in alcoholics.
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PMID:No evidence for involvement of type 1 collagen structural genes in 'genetic predisposition' to alcoholic cirrhosis. 136 77

Hereditary tyrosinemia (HT) is an autosomal recessive disorder of tyrosine metabolism that results in cirrhosis and hepatocellular carcinoma early in life, and that may be a useful model of early malignant transformation. This is the first report of DNA ploidy in this disease. The authors studied formalin-fixed liver tissue in three cases (two chronic and one acute) of HT for the presence of DNA aneuploidy by flow cytometric (FCM) analysis and image analysis (IA). In the chronic cases, the authors found DNA aneuploidy by FCM in 2/20 cirrhotic nodules in one case and 1/21 tissue sections in the other. Questionable minor aneuploid peaks were detected by FCM in 2/20 and 2/21 sections in these two cases, respectively. Static DNA measurements by IA were performed on those sections having abnormal histograms as well as in some sections having diploid DNA distribution. By this method, the authors confirmed the results of FCM studies and found additional small aneuploid nodules not detected by FCM, frequently associated with various forms of hepatocellular dysplasia as well as steatosis. In one case of acute HT (autopsy), no definite aneuploid peaks were present in five blocks. By immunohistochemical analysis, the authors found frequent positive staining for alpha-fetoprotein (AFP) in the cirrhotic nodules of the two chronic cases as well as in the steatotic regenerative nodules of the acute case. The expression of AFP may represent disturbed regeneration and maturation of liver cells in this disease. This study shows that DNA ploidy may be a useful marker for early malignant transformation in HT and supports the preneoplastic nature of the hepatocellular dysplasia in this disease.
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PMID:DNA ploidy abnormalities in the liver of children with hereditary tyrosinemia type I. Correlation with histopathologic features. 137 92

Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.
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PMID:Hepatitis C: a possible etiology for cryoglobulinaemia type II. 138 2

Three patients with submassive hepatic necrosis developed acute liver failure during the severe reactivation of chronic hepatitis B. The activity of hepatitis B virus (HBV) DNA polymerase increased in all three patients immediately before the onset of hepatic failure. Liver biopsy specimens obtained before and after the episode of submassive hepatic necrosis showed progression to advanced liver cirrhosis. The nucleotide sequences of the precore and core regions of HBV-DNA were investigated in two of the three patients and in another two patients with piecemeal and bridging necrosis. The nucleotide and amino acid sequences of the HBV-DNA core region changed after reactivation in the the two patients with submassive hepatic necrosis, while the sequences in the other two patients with piecemeal necrosis remained unchanged before and after reactivation. These results suggest that the antigenicity of the HBV-DNA core region may have been changed before and after severe reactivation. Due to mutation at the core region, a different type of epitope would be expressed on the hepatocytes after submassive hepatic necrosis, which would not be a target for the cytotoxic T cell. This was evident by the continuation of the normal serum GPT for 5 and 9 years, respectively.
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PMID:Mutation of the core region of HBV-DNA and submassive hepatic necrosis in patients with anti-HBe-positive chronic hepatitis B. 139 28

Assessment of liver regeneration with endogenous genes that are expressed during DNA replication is physiological, specific and direct. To determine whether H3 histone messenger RNA expression (which is tightly coupled with DNA synthesis) could be used for this purpose, we initially examined liver regeneration in a mouse model. After partial hepatectomy, RNA transblot studies showed induction of H3 histone messenger RNA expression in regenerating mouse livers. In situ molecular hybridization demonstrated that the overall pattern of H3 histone messenger RNA expression correlated with [3H]thymidine labeling of hepatocytes. After partial hepatectomy, H3 histone messenger RNA expression in hepatocytes peaked at 48 hr (greater than 60 times greater than at 24 hr; p less than 0.001) and then rapidly declined. Although hepatocyte labeling with [3H]thymidine showed similar kinetics of liver regeneration, use of this parameter resulted in overestimation of the proliferative compartment when it was compared with H3 histone messenger RNA expression. Next we determined whether H3 histone messenger RNA expression could be used to study hepatocellular proliferation in archival human material. H3 histone messenger RNA-expressing hepatocytes were identified on in situ hybridization in patients with acute or chronic active hepatitis and active cirrhosis, but not inactive cirrhosis. These studies demonstrate that H3 histone messenger RNA is expressed in a phasic manner during liver regeneration. Use of H3 histone messenger RNA expression to evaluate hepatocellular proliferation should facilitate clinical studies and greatly advance our understanding of the pathophysiology of liver regeneration.
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PMID:Analysis of hepatocellular proliferation: study of archival liver tissue is facilitated by an endogenous marker of DNA replication. 139 4


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