Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with hepatocellular carcinoma (HCC), gastrointestinal, lung, and ovarian cancers were shown to have autoantibodies to nuclear and nucleolar antigens as detected by immunofluorescence on cell substrates. The frequency of antinuclear antibodies (ANAs) was significantly higher (P less than 0.001) in patients with HCC (57/184 = 31%) than in patients with chronic hepatitis or liver cirrhosis (25/187 = 13%). Although a range of fluorescence patterns was observed, a higher percentage of nucleolar fluorescence was detected in HCC, and three of these nucleolar antigens were identified. They were NOR-90, nucleolus organizer region doublet polypeptides of 93 and 89 kDa involved in RNA polymerase I transcription; fibrillarin, a 34 kDa protein of the nucleolar U3 ribonucleoprotein particle which is engaged in preribosomal RNA processing; and nucleophosmin/protein B23, a 37 kDa polypeptide which is associated with ribosome maturation and cellular proliferation. All these antigens are nucleolar components that are engaged in some aspect of ribosome biosynthesis. Since autoantibodies to these nucleolar antigens have also been found in systemic autoimmune diseases, they do not represent autoimmune reactions unique to cancer but might reflect reaction pathways related to immune responses that are antigen-driven. The ANA response in HCC appears to be dynamic reactions to this antigen-drive since some patients with chronic liver disease showed seroconversion to ANA positivity, marked increase in titer and/or change in antibody specificity preceding or coincident with clinical detection of HCC. These changes in ANA showed a close temporal relationship with transformation from long-established chronic liver disease to HCC.
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PMID:Nucleolar antigens and autoantibodies in hepatocellular carcinoma and other malignancies. 131 27

A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two.
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PMID:Acute hepatitis C infection after sexual exposure. 789 Feb 21

Sera from 39 out of 40 patients with chronic hepatitis C virus (HCV) infection who had been treated for 60 weeks with interferon alfa-2b proved initially HCV RNA positive by reversed transcriptase polymerase chain reaction (PCR). These patients were analysed for genotype and quantitatively for HCV RNA levels prior to treatment by using a competitive PCR method with colorimetric detection of the amplified products. HCV RNA levels were correlated to outcome of treatment, mode of acquisition, histology and HCV genotype. The median pretreatment HCV RNA level in sustained responders (n = 15) with eradication of the viremia and normalization of serum ALT levels lasting 24 weeks post treatment was significantly lower than that in the combined group of non-sustained responders (n = 9) and non-responders (n = 15), 2.52 x 10(5) vs 8.90 x 10(5) genome equivalents per ml serum, p < 0.0125, respectively. 10 out of 17 patients with HCV RNA levels lower than the median level (5.64 x 10(5) genome equivalents per ml serum) had a sustained response to interferon treatment versus only 5/22 with levels equal to or higher than the median level, p = 0.04. No significant pretreatment differences in median HCV RNA levels according to mode of acquisition, genotype, or liver histology prior to treatment were seen. It is concluded that a low pretreatment HCV RNA level seems to be indicative of a sustained response to interferon alfa-2b treatment, whereas a high level seems to be indicative of a non-sustained or non-response. In the individual patient, however, the levels varied widely irrespective of response category.
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PMID:Serum hepatitis C virus RNA levels in chronic hepatitis C--importance for outcome of interferon alfa-2b treatment. 793 25

A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy.
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PMID:Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease. 819 99

The significance of a positive hepatitis C virus (HCV) screening test in asymptomatic blood donors with normal or near normal aminotransferases was studied along with the usefulness of HCV RNA polymerase chain reaction (PCR) testing for predicting chronic hepatitis in these individuals. One hundred and thirty-nine volunteer blood donors who were found positive by second generation ELISA for antibodies to HCV agreed to participate in the study. Thirty-one of them were supplemental test positive, had ALT values less than twice normal, and were followed over a minimum of 12 months. Thirteen consented to percutaneous liver biopsy and also had HCV RNA determination by PCR. Ten of the 13 subjects were positive for HCV RNA by PCR. Of the nine who were positive for HCV RNA and had adequate tissue for evaluation, seven had evidence of chronic hepatitis, three with limiting plate necrosis. Lobular inflammation was similar in severity to that found in the portal region. In addition, two had periportal fibrosis, and one had bridging fibrosis. Of the three subjects who were negative for HCV RNA, only one had portal inflammation which was limited to the portal region. None of these three had lobular changes, or periportal or bridging fibrosis. Of the three normal biopsies, two were from subjects who were negative for HCV RNA. The sensitivity and specificity of HCV RNA testing for chronic hepatitis was 87.5% and 50%, respectively, yielding an overall accuracy of 75%. We conclude that asymptomatic blood donors with antibodies to HCV, normal or mildly elevated liver tests, and HCV RNA may have abnormal liver histology indicating the potential for progressive liver disease. HCV RNA testing by PCR may be clinically useful as a noninvasive means to discriminate between those with and without chronic liver disease.
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PMID:Liver histology in anti-HCV-positive persons with normal or minimally elevated aminotransferases. 858 5

Because current standard therapy of chronic hepatitis C with alpha interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to alpha interferon therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemical improvement (decrease in serum alanine aminotransferase), but not with virological improvement. Iron reduction has been reported to increase the therapeutic response to alpha interferon. Most studies of this combination have been conducted in patients who had not responded to interferon alone; in these patients, improved responsiveness has been observed in some, but not all studies. In patients not previously treated, iron reduction was found in a recent trial to improve the sustained biochemical and virological response rate from 5% to 29%. Hepatic iron and chronic hepatitis C increase oxidative stress in the liver and are associated with decreases in hepatic glutathione levels. In one report, administration of N-acetyl cysteine, a sulfhydryl donor, led to improved response to interferon in chronic hepatitis C. Several cytokines and immunomodulators have undergone limited study; perhaps the most promising of these is thymosin alpha-1. In one small study, amantadine was found to produce some response in patients who previously had failed to respond to interferon. Ursodiol improves serum aminotransferase levels in chronic hepatitis C but has no antiviral effect, nor has it been found to improve histologic abnormalities. The future of therapy of chronic hepatitis C will likely include measures to decrease oxidative stress and injury and multidrug combinations, including inhibitors of the hepatitis C viral protease and RNA polymerase.
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PMID:Therapy of hepatitis C: other options. 930 80

The present study was designed to determine whether changes in DNA methyltransferase (DNA MTase) expression are involved in hepatocarcinogenesis. We examined DNA MTase expression in normal liver tissue (with no remarkable histological findings), liver tissue showing chronic hepatitis or cirrhosis, which are generally thought to be precancerous conditions, and hepatocellular carcinomas (HCCs) using the reverse-transcriptase polymerase chain reaction assay. DNA MTase mRNA levels were significantly higher in liver tissue showing chronic hepatitis and cirrhosis (DNA MTase mRNA/beta-actin mRNA ratio = 0.30 +/- 0.22, n = 24, P < 0.01) than in normal liver tissue either from patients with liver metastatic lesions of colonic cancer (0.14 +/- 0.05, n = 6) or from patients with HCCs (0.16 +/- 0.07, n = 3). DNA MTase mRNA levels were even higher in HCC tissue (0.34 +/- 0.18, n = 29). These results suggest that increased DNA MTase expression may be an early event during hepatocarcinogenesis. DNA MTase is a potential target for HCC preventive therapy.
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PMID:Increased DNA methyltransferase expression is associated with an early stage of human hepatocarcinogenesis. 947 34

The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-alpha) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-alpha n1 or recombinant IFN-alpha2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response at end of treatment was 35.3% for IFN-alpha n1 and 37.9% for IFN-alpha2b (P = .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent with IFN-alpha n1 than with IFN-alpha2b. Thus, sustained ALT responses (SR) to IFN-alpha n1 were significantly more frequent than SR to IFN-alpha2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3% vs. 6.7% at 72 weeks, P = .04). SR were associated with viral loss and histological improvement, and more patients treated with IFN-alpha n1 were HCV RNA negative at week 72 compared with patients treated with IFN-alpha2b (P = .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative to type 1, but the improved long-term efficacy of IFN-alpha n1 compared with IFN-alpha2b was evident for all major HCV genotypes. It is concluded that IFN-alpha n1 and IFN-alpha2b have similar end-of-treatment response rates and safety profiles but the sustained response rate is higher with IFN-alpha n1. SR to IFN-alpha treatment are associated with clearance of HCV RNA, and histological improvement was maximal in patients who exhibited sustained ALT normalization and clearance of HCV RNA.
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PMID:Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: results of an international randomized controlled trial. Clinical Advisory Group for the Hepatitis C Comparative Study. 953 53

Two research groups recently and independently, isolated a hepatotropic flavivirus from human sera. The two viruses, named GB virus C and hepatitis G virus (HGV), were subsequently discovered to represent the same virus, which was associated with acute and chronic hepatitis of the non-A-E type. The prevalences of infection with HGV have now been investigated in various groups of the Thai population, some of which [e.g. thalassaemic children, patients with chronic liver disease, carriers of antibodies to hepatitis B virus and/or hepatitis C virus (HCV), prostitutes and intravenous-drug users (IVDU)] were assumed to be at high risk. Samples of sera were investigated by reverse-transcriptase PCR, using four primers created from the 5' untranslated region of HGV. The prevalence of HGV infection among the healthy controls (1%-5%) was found to be much less than that among thalassaemic children (32.6%), asymptomatic carriers of anti-HCV (20.4%), IVDU (18.2%), aplastic anaemia patients (14.3%) and prostitutes (10%), although similar to that in patients with chronic liver disorders. These results confirm a parenteral route of transmission for HGV and emphasise the need for further research to determine the clinical significance of this virus.
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PMID:Prevalence of infection with hepatitis G virus among various groups in Thailand. 961 58

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.
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PMID:Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group. 979 29


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