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:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 47-year-old man with acute hepatitis B virus (HBV) infection who had been receiving immunosuppressants after renal transplantation developed progressive liver failure. During the clinical course (approximately 7 months), anti-HBc IgM antibody and HBV-DNA polymerase levels remained high, but the serum alanine aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic examination of the liver showed submassive hepatic necrosis without significant inflammation accompanied by marked fibrosis. Most hepatocytes showed strong nuclear expression of HBc antigen by immunohistochemical staining and electron microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus infection in immunosuppressed individuals occasionally insidiously progresses, resulting in liver failure. The clinical course of such patients thus merits close scrutiny.
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PMID:Fatal acute hepatitis B virus infection while receiving immunosuppressants after renal transplantation. 828 32

Amplification of RNA by the polymerase chain reaction (PCR) is normally a two-step process requiring separate enzymes and buffer conditions. We describe a combined reverse transcription-PCR (RT-PCR) assay for hepatitis C virus (HCV) RNA amplification in which a single enzyme and buffer condition are used. In this assay, both the RT and PCR steps are carried out with the thermoactive DNA polymerase of Thermus thermophilus. A transcription vector containing HCV sequences has also been constructed to generate quantifiable HCV RNA templates that can be used to optimize reaction conditions and to assess the efficiency of amplification. Amplification from < or = 100 copies of RNA was detected reproducibly by gel electrophoresis. The assay sensitivity was increased to 10 RNA copies by hybridization to a probe. The patterns of viremia in three individuals infected with HCV were examined by amplification of HCV RNA from plasma samples collected serially over a period of 1 year. These results were correlated with the times of seroconversion and the onset of rise in levels of alanine aminotransferase in serum. In all three subjects, HCV RNA was detected prior to seroconversion and the initial rise in levels of alanine aminotransferase in serum. Upon seroconversion, HCV RNA fell to a level below the detection limit of the assay. This pattern of transient viremia appears to be characteristic of acute, resolving HCV infections. The combined RT-PCR assay is a sensitive method which circumvents the problems associated with PCR amplification of RNA. Using this assay, we demonstrated that three donors infected by the same index case all have similar patterns of viremia.
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PMID:Detection of hepatitis C virus RNA by a combined reverse transcription-polymerase chain reaction assay. 838 51

The aim of this study was to compare the sensitivity and specificity of conventional procedures (in-house one-stage polymerase chain reaction (PCR) and in-house nested PCR) and of new technologies (rTth DNA polymerase (Amplicor), branched-DNA, NASBA (nucleic acid amplification system)) for the qualitative detection of hepatitis C virus (HCV) RNA in serum of HCV-infected individuals. Serum samples from 37 anti-HCV-positive individuals (15 with a normal alanine aminotransferase (ALT) level, 22 with an elevated ALT level) and 10 anti-HCV-negative individuals as negative controls were studied. A second panel, including 9 diluted serum samples (from 1/10 to 1/100,000) was constituted to establish the differences of sensitivity of the 5 procedures with small quantities of HCV RNA in the serum. The anti-HCV-positive individuals with elevated ALT gave positive results with all 5 procedures. In patients with a normal ALT level, the assays with the highest sensitivity were Amplicor, NASBA and nested RT-PCR, followed by one-stage RT-PCR, then branched-DNA. One false-positive result was observed with Amplicor, and two with in-house nested PCR. On diluted samples, Amplicor, NASBA and nested PCR appeared more sensitive than one-stage PCR and branched-DNA. It is concluded that new procedures have satisfactory sensitivity and specificity and could advantageously replace the conventional PCR procedures for the routine qualitative detection of serum HCV RNA.
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PMID:Comparative study of conventional and novel strategies for the detection of hepatitis C virus RNA in serum: amplicor, branched-DNA, NASBA and in-house PCR. 853 May 67

To study the clinical significance of hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B, sera from five patients with chronic hepatitis B HBsAg levels were measured quantitatively by counting immunoassay (CIA). CIA is an immunoassay that combines the latex agglutination method and particle counting technique. The results were as follow: 1) In four patients with chronic active hepatitis, the increases of HBsAg levels were earlier than that of alanine aminotransferase levels, and HBsAg levels had approximately the same changes as hepatitis B virus associated DNA polymerase (HBV DNA-p) activities. 2) In four patients treated with interferon-alpha or beta, HBsAg levels after treatment decreased in the same manner as HBV DNA-p activities. 3) In a patient with chronic inactivate hepatitis. HBsAg levels were the same changes as HBV DNA-p activities. These results suggested that quantitative analysis of HBsAg levels is useful to evaluate the prognosis and exacerbation for chronic hepatitis B.
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PMID:[Change of hepatitis B surface antigen in serum from patients with chronic hepatitis B]. 858 88

Clinical and molecular biological characteristics were compared between patients who presented with fulminant hepatic failure following acute infection with hepatitis B virus (HBV) and those who developed hepatic failure during they carried HBV. The 11 patients with acute HBV infection had higher levels of alanine aminotransferase (mean +/- SD: 4943 +/- 2867 vs 1157 +/- 678 IU/L, P < 0.01), more often with a single peak (91% vs. 0%, P < 0.001), and lower total bilirubin level (15.3 +/- 4.4 vs 28.1 +/- 14.3 mg/1000 ml, P < 0.01) than the 13 patients with chronic HBV infection. Hepatitis B surface antigen was detected less often (55% vs. 100%, P < 0.05) and viral DNA polymerase less frequently (0% vs. 46%, P < 0.05) in the patients with acute than chronic HBV infection. Hepatitis B e antigen was detected in one (9%) patient with acute infection, less frequently than in six (46%) patients with chronic infection (P < 0.05). Mutations in the precore region was detected in HBV DNA clones from ten (91%) patients with acute infection and only in those from eight (62%) patients with chronic infection. All HBV DNA clones from the five (38%) patients with chronic infection that did not have precore mutations, however, possessed mutations in the core promoter. These results indicate that HBV mutants incapable of translating hepatitis B e antigen would play a major role in fulminant hepatic failure occurring after acute HBV infection. In contrast, HBV variants with core promoter mutations for reducing the transcription of hepatitis B e antigen would play an additional role in fulminant hepatic failure developing during chronic infection.
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PMID:Clinical and molecular virological differences between fulminant hepatic failures following acute and chronic infection with hepatitis B virus. 958 Aug 84

Active liver disease has been detected in chronic hepatitis B after seroconversion from positive HBe antigen to positive anti-HBe antibody. Active replication of HB virus (HBV) containing a precore stop-codon mutation has been implicated in this condition. The usual methods, such as direct sequencing, to characterize the responsible mutant of HBV are not suitable for routine clinical use. Here we employed the competitive mutation site specific assay (CMSSA) to detect precore mutant HBV-DNA in patients with positive HB surface antigen. In patients with HBe antigen, precore mutant HBV-DNA was significantly higher than in patients with HBe antibody. The level of precore mutant HBV-DNA in patients with elevated serum ALT was significantly higher than in patients with normal serum ALT. Sex, age and the level of serum HBV-associated DNA polymerase levels were not correlated with levels of precore mutant HBV-DNA. Ten of 11 negative patients for the precore mutant by polymerase chain reaction followed by restriction fragment length polymorphism assay (PCRRFLP) were positive for the precore mutant by CMSSA. These results suggest that the precore mutant has already emerged in the HBeAg-positive phase as determined by CMSSA, which is more sensitive than PCR-RFLP and is useful for evaluating the clinical course of patients with chronic hepatitis B.
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PMID:Quantitative analysis of hepatitis B virus precore mutant in hepatitis type B. 1032 64

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% +/- 18.6% of the patients, had sustained HBV-DNA suppression. All the 22 tested patients with HBV resistance developed mutation at position 550 in the YMDD motif of the DNA polymerase. None of the following variables were associated with an increased risk of lamivudine resistance: age, associated protease inhibitor therapy, Center for Disease Control (CDC) stage C, known HIV-infection duration, serum HBV-DNA level at baseline, CD4 cell count and serum alanine transaminase levels at baseline and at HBV-replication suppression (2 months of lamivudine). Lamivudine (300 mg/d) is effective for the inhibition of HBV replication in HIV-infected patients. However, emergence of lamivudine-resistant HBV may occur in 20% of patients per year.
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PMID:Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. 1077 55

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log(10) reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV.
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PMID:Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. 1086

In chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) is seroconverted from positive to negative. HBeAg is associated with active replication of the HBV and a high disease activity. To elucidate the relation between HBV X-precore region mutation and HBeAg status, HBV replication and liver function were surveyed in chronic hepatitis B patients. HBV DNA was isolated from fifteen serum samples of seven patients with chronic hepatitis B, and the X-precore region was amplified by PCR and sequenced. Each sequence was compared with the consensus sequence of each patient. The most frequently observed mutations were A to T at nt. 1762 and G to A at nt. 1764 in the core promoter region and G to A at nt. 1896 in the precore region. These mutations were more commonly found in HBeAg-negative serum samples than in HBeAg-positive (p < 0.001, respectively). Of 7 serum samples with the wild type or wild/mutant mixed type in the precore region, 6 were HBeAg-positive and had a high HBV DNA polymerase (DNA-p) activity and serum alanine aminotransferase (ALT) elevation. On the other hand, 6 serum samples with the mutant type only were HBeAg-negative and had a low DNA-p activity and normal ALT level. Interestingly, 2 serum samples with the mutant type only had a high DNA-p activity and serum ALT elevation, despite being HBeAg-negative. Core promoter region mutation was not associated with HBV markers or serum ALT level. In conclusion, mutation at nt. 1896 in the precore region causes seroconversion from HBeAg-positive to -negative and is accompanied by reductions of viral replication and hepatitis activity.
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PMID:[Nucleotide sequence analysis of the hepatitis B virus X-precore region in chronic hepatitis B]. 1149 82

Lamivudine, the negative enantiomer of 2'-deoxy-3'-thiacytidine, is a dideoxynucleoside analog that prevents hepatitis B virus (HBV) DNA synthesis by competitively inhibiting the viral reverse transcriptase and DNA polymerase stages of HBV replication and by terminating proviral DNA chain extension. A dose-ranging study established that once daily oral lamivudine 3 mg/kg up to a maximum of 100 mg/day has the optimum efficacy and tolerability profile for achieving a maximal reduction in serum HBV DNA levels in children aged 2 to 12 years and adolescents aged 13 to 17 years with chronic HBV infection and active viral replication (chronic hepatitis B). Significantly more children and adolescents with chronic hepatitis B receiving lamivudine demonstrated a virologic response (undetectable serum hepatitis Be antigen and undetectable HBV DNA level) [23 vs 13%; p = 0.04] and/or biochemical response (55 vs 12%; p < 0.001) compared with placebo in a large, randomized, double-blind, 52-week phase III study. Despite the emergence of YMDD-variant HBV in 19% of lamivudine-treated children and adolescents, serum alanine aminotransferase and HBV DNA levels remained below baseline in these patients. Oral lamivudine is generally well tolerated by children and adolescents with chronic hepatitis B, with a similar tolerability profile to placebo at the recommended once daily dosage of 3 mg/kg up to a maximum of 100 mg/day.
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PMID:Lamivudine: in children and adolescents with chronic hepatitis B virus infection. 1226 43


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