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)

Changes in the synthesis of type I collagen, a major extracellular matrix component in skin and bones, are associated with both normal growth or repair processes and with several pathological conditions such as lung fibrosis and liver cirrhosis. The expression of the alpha 1(I) collagen gene is regulated by transcriptional and post-transcriptional mechanisms. Regulation at both these levels are usually utilised when extensive changes occur in collagen synthesis. We constructed plasmids carrying the whole or partially deleted 3'-UTR sequences of the alpha 1(I) collagen gene, fused to two hGH exons and to the promoter of the alpha 1(I) collagen gene. A control plasmid contained the 3'-UTR of the hGH gene. In transient transfections into Rat-1 fibroblasts, no significant differences between plasmids were found, which suggests that although 3'-end of the gene has been shown in previous studies to contain DNaseI hypersensitive sites and to bind sequence-specific nuclear proteins it does not seem to function as a transcriptional regulator. This was further supported by the finding that TGF-beta treatment induced a 2.5-fold expression of hGH mRNA from plasmids containing collagen promoter and either hGH or alpha 1(I) collagen 3'-UTR. In stable transfections, mRNAs using the first polyadenylation site were not as stable as those transcribed from the endogenous alpha 1(I) collagen gene. We suggest that the 3'-UTR alone may not be sufficient to determine the stability of the shorter alpha 1(I) collagen mRNA species.
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PMID:Effect of the 3'-untranslated region on the expression levels and mRNA stability of alpha 1(I) collagen gene. 787 3

The prevalence of different genotypes of Hepatitis C virus may vary between geographic areas and it is possible that various genotypes have different pathogenic characteristics. Therefore, 90 consecutive Italian patients anti-Hepatitis C Virus positive with a broad spectrum of chronic liver disease, have been analysed to observe prevalence of various genotypes of Hepatitis C Virus. Genotyping was performed by polymerase chain reaction with a set of nested biotinylated primers, located in 5'UTR region. Genotype 1b and genotype 2a were the most commonly encountered (respectively, 50% and 37%) whereas other genotypes were rare. The unexpected high prevalence of genotype 2a allowed direct comparison of clinical characteristics and response to therapy between patients with genotype 2a and those with 1b. Genotype 1b was more prevalent than 2a in patients over 60 years (29 vs 12) and in those with more severe liver disease (34 vs 16). In a univariate analysis, genotype 2a was associated with less severe liver disease (p = 0.02) and younger age (p = 0.018), in comparison with genotype 1b. Patients with genotype 2a responded to interferon alpha therapy better than those with 1b (p = 0.007). In a multivariate analysis, only younger age was associated with genotype 2a. Genotype 2a (in comparison with 1b) and absence of cirrhosis were independent predictors of response to interferon alpha. In conclusion, genotype 2a is playing an emerging role in younger Italian patients and seems more sensitive than 1b to interferon alpha therapy.
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PMID:High prevalence of hepatitis C virus (HCV) genotype 2 in Italian patients with chronic liver disease. 903 88

Infection with HGBV-C was surveyed in 286 patients with chronic liver disease. HGBV-C RNA was detected in 19 patients (6.6%), by nested RT-PCR with 5'UTR-derived primers. There were no appreciable differences in clinical and virological features between patients with and without HGBV-C RNA in serum. HGBV-C RNA was detected in three of 83(4%) patients with HBV infection, 15(8%) of 188 patients with HCV infection, and one of 12(8%) patients without evidence of ongoing infection with HBV or HCV, suggesting that the contribution of HGBV-C to non-B non-C hepatitis would not be high. HGBV-C RNA was detected more frequently in the patients with liver cirrhosis or hepatocellular carcinoma than in those with chronic hepatitis. This could reflect a possible role of HGBV-C in aggravating liver disease in co-operation with the other hepatitis viruses.
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PMID:[HGBV-C infection in patients with chronic liver disease]. 908 59

Hepatitis C virus (HCV) represents one of the major causes of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) around the world. Our knowledge of the life cycle of HCV, however, is limited. Current studies are hampered by the lack of a reproducible, high-level in vitro replication system of HCV. We sought to establish HCV replication in HepG2 cells by gene transfer of in vitro transcribed HCV RNA. In preliminary experiments, diethylaminoethyl-dextran led to more efficient gene transfer than cationic liposomes (lipofectin, lipofectamine, and DOTAP). Therefore, in subsequent experiments, HepG2 cells were transfected with full-length (9.6-kb) and near-full-length (9.4-kb) HCV RNA using diethylaminoethyl-dextran. Transfection with subgenomic HCV RNA and mock transfection were used as controls. Positive- and negative-strand HCV RNA sequences were detected by reverse transcription polymerase chain reaction (KT-PCR) for 60 days in the infectious HCV RNA transfected HepG2 cells. The presence of negative-strand HCV RNA, presumably representing replicative intermediates, was confirmed by ribonuclease protection assay. The intracellular levels of HCV RNA were measured by quantitative competitive RT-PCR from 10 to 50 days after transfection and were stable over this time period at moderately high levels (10(8) to 10(10) genomes per mg of total RNA). Expression of viral core and nonstructural proteins was detected in the cytoplasm of transfected cells by immunostaining. Virus-like particles measuring 50 to 60 nm in diameter were found by electron microscopy in cytoplasmic vesicles and conditioned media of the cells transfected with infectious HCV RNA but not in cells transfected with truncated HCV RNA. Culture supernatants of infectious HCV RNA transfected HepG2 cells were infectious for Daudi cells for three passages tested. The truncated HCV RNA lacking NS5 and 3' untranslated region (3' UTR) of HCV was replication incompetent. This is the first demonstration of HCV particles in HepG2 cells after transfection with infectious HCV RNA. We conclude that we have established a reproducible HCV replication system in HepG2 cells that can be used to study the life cycle of HCV and to test anti-HCV agents.
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PMID:Transfection of HepG2 cells with infectious hepatitis C virus genome. 925 Jan 50

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

This is the first study of HCV infection performed in Romania by reverse transcription-polymerase chain reaction (RT-PCR). We set up our own protocol, using "nested" primers located in the 5' UTR of HCV. Thirty two patients, 16 with chronic hepatitis, 7 with hepatic cirrhosis and 9 without chronic hepatic disease were investigated. The assignment of each patient to one of the groups was based on clinical and laboratory criteria, especially transaminase levels and hepatic biopsy findings. In 14 out of 16 (87.5%) chronic hepatitis cases and in 6 cases of hepatic cirrhosis out of 7 (85.7%), there was good agreement between RT-PCR and ELISA results. Transaminase levels were concordant with RT-PCR results in 27 of 29 cases (93.1%) but in only 21 of 29 cases (72.4%) transaminase levels were in agreement with ELISA results. In two patients treated with interferon, transaminase levels and the other clinical and laboratory parameters fell in the normal range in parallel with the disappearance of viremia, whereas anti-HCV antibodies were still detectable. RT-PCR has a higher specificity in detecting the etiology of hepatic diseases if compared to ELISA and an at least equal sensitivity. The method proves to be the best means for the confirmation of HCV infection, and for the monitoring of interferon therapy.
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PMID:Comparison between reverse transcription-polymerase chain reaction and immune enzyme assays in the diagnosis of hepatitis C virus infection. 1066 Sep 69

We present here a comprehensive review of the current literature plus our own findings about in vivo and in vitro analysis of hepatitis C virus (HCV) infection, viral pathogenesis, mechanisms of interferon action, interferon resistance, and development of new therapeutics. Chronic HCV infection is a major risk factor for the development of human hepatocellular carcinoma. Standard therapy for chronic HCV infection is the combination of interferon alpha and ribavirin. A significant number of chronic HCV patients who cannot get rid of the virus infection by interferon therapy experience long-term inflammation of the liver and scarring of liver tissue. Patients who develop cirrhosis usually have increased risk of developing liver cancer. The molecular details of why some patients do not respond to standard interferon therapy are not known. Availability of HCV cell culture model has increased our understanding on the antiviral action of interferon alpha and mechanisms of interferon resistance. Interferons alpha, beta, and gamma each inhibit replication of HCV, and the antiviral action of interferon is targeted to the highly conserved 5'UTR used by the virus to translate protein by internal ribosome entry site mechanism. Studies from different laboratories including ours suggest that HCV replication in selected clones of cells can escape interferon action. Both viral and host factors appear to be involved in the mechanisms of interferon resistance against HCV. Since interferon therapy is not effective in all chronic hepatitis C patients, alternative therapeutic strategies are needed to treat chronic hepatitis C patients not responding to interferon therapy. We also reviewed the recent development of new alternative therapeutic strategies for chronic hepatitis C, which may be available in clinical use within the next decade. There is hope that these new agents along with interferon will prevent the occurrence of hepatocellular carcinoma due to chronic persistent hepatitis C virus infection. This review is not inclusive of all important scientific publications due to space limitation.
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PMID:HCV-hepatocellular carcinoma: new findings and hope for effective treatment. 1627 14

Hepatitis C virus shows substantial nucleotide sequence diversity distributed throughout the viral genome. In the present study genotyping for Hepatitis C virus (HCV) infected patients was based on RFLP analysis of 5' UTR and using type specific primers of NS5B regions. It was observed that 60% of the patients (30 patients with chronic hepatitis) were infected with variants of genotype 1 and 40% of the patients (4 chronic hepatitis patients, 12 patients with chronic renal failure and 4 cirrhosis) were infected with variants of type 3 of HCV. None of the cirrhotic patients and patients with chronic renal failure, in the present study, were infected with type 1 of HCV. While PCR-RFLP, typing was rapid in conjunction with the primers used for RT-PCR, NS5 typing was helpful in determining the subtype. There was good correlation between the two typing methods and this method can be used as a cost-effective method for studying large number of samples. The study shows that predominant genotypes of HCV in South India include type 1 and 3. Type 3 seems to be transmitted nosocomially as suggested by the results in patients with chronic renal failure, as these patients are exposed to multiple medical interventions.
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PMID:Genotyping of Hepatitis C virus (HCV) in infected patients from South India. 1754 Jun 21

Studies have indicated that protective effects of statins (HMG-CoA reductase inhibitor) are associated with the regulation of endothelial nitric oxide synthase (eNOS) or inducible NOS (iNOS) in heart and liver diseases. Statins have been reported to enhance hepatic NO production and decrease the vascular tone in patients with cirrhosis. However, it is unclear which NOS contributes to the increased NO production. We hypothesized that statins are involved in the up-regulation of iNOS in inflammatory liver, resulting in decreased hepatic resistance. Primary cultured rat hepatocytes were treated with pro-inflammatory cytokine interleukin (IL)-1beta in the presence or absence of pitavastatin. Pretreatment of cells with pitavastatin resulted in up-regulation of iNOS induction by IL-1beta, followed by increased NO production. Pitavastatin had no effects on the degradation of IkappaB or activation of NF-kappaB. However, pitavastatin super-induced the up-regulation of type I IL-1 receptor (IL-1RI), which is essential for iNOS induction in addition to the IkappaB/NF-kappaB pathway. Mevalonate and geranylgeranylpyrophosphate blocked the stimulatory effects of pitavastatin on iNOS and IL-1RI induction. Transfection experiments revealed that pitavastatin increased the stability of iNOS mRNA rather than its promoter transactivation. In support of this observation, pitavastatin increased the antisense-transcript corresponding to the 3'-UTR of iNOS mRNA, which stabilizes iNOS mRNA by interacting with the 3'-UTR- and RNA-binding proteins. These findings demonstrate that pitavastatin up-regulates iNOS by the stabilization of its mRNA, presumably through the super-induction of IL-1RI and antisense-transcript. This implies that statins may contribute to a novel potentiated treatment in liver injuries including cirrhosis.
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PMID:Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes. 1793 42

The identification of target mRNAs is a key step for assessing the role of aberrantly expressed microRNAs in human cancer. MiR-221 is upregulated in human hepatocellular carcinoma (HCC) as well as in other malignancies. One proven target of miR-221 is CDKN1B/p27, whose downregulation affects HCC prognosis. Here, we proved that the cyclin-dependent kinase inhibitor (CDKI) CDKN1C/p57 is also a direct target of miR-221. Indeed, downregulation of both CDKN1B/p27 and CDKN1C/p57 occurs in response to miR-221 transfection into HCC-derived cells and a significant upregulation of both CDKN1B/p27 and CDKN1C/p57 occurs in response to antimiR-221 transfection. A direct interaction of miR-221 with a target site on the 3' UTR of CDKN1C/p57 mRNA was also demonstrated. By controlling these two CDKIs, upregulation of miR-221 can promote growth of HCC cells by increasing the number of cells in S-phase. To assess the relevance of these studies in primary tumors, matched HCC and cirrhosis samples were assayed for miR-221, for CDKN1B/p27 and CDKN1C/p57 expression. MiR-221 was upregulated in 71% of HCCs, whereas CDKN1B/p27 and CDKN1C/p57 proteins were downregulated in 77% of cases. A significant inverse correlation between miR-221 and both CDKN1B/p27 and CDKN1C/p57 was found in HCCs. In conclusion, we suggest that miR-221 has an oncogenic function in hepatocarcinogenesis by targeting CDKN1B/p27 and CDKN1C/p57, hence promoting proliferation by controlling cell-cycle inhibitors. These findings establish a basis toward the development of therapeutic strategies aimed at blocking miR-221 in HCC.
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PMID:MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. 1852 Oct 80


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