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)

Hepatitis B virus DNA polymerase is a viral enzyme that can use viral DNA as well as viral RNA as a template for DNA synthesis. Since both activities are essential for the production of new virus particles, blocking of this enzyme should reduce viral replication. In the present study the in vitro effect of zidovudine triphosphate on hepatitis B virus DNA polymerase activity and the in vivo effect of zidovudine on viral replication in chronic HBsAg-positive patients are investigated. Zidovudine triphosphate inhibited in vitro DNA polymerase activity by 50% at a concentration of 0.3 microM. Serum DNA polymerase activity was significantly reduced in 7 patients who received zidovudine (200 mg orally 4 times daily) for one week. A dose-response effect was suggested by the results found for 6 patients who received 100 mg, 200 mg and 300 mg orally 4 times daily for one week with 2 drug-free weeks between each course. We conclude that zidovudine may be of value for non-responders to alpha-interferon therapy or patients with high initial levels of viral replication prior to the start of interferon treatment.
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PMID:Zidovudine inhibits hepatitis B virus replication. 144 23

A multiparametric analysis of the effects of human recombinant interferon alpha type A on Daudi cells involving flow cytometry and in vitro analysis of alpha and beta DNA polymerase activities has been performed. Results have disclosed (within 60 min of interferon treatment) a decrease of alpha polymerase driven DNA synthesis persisting to at least 24 h, while beta polymerase was poorly affected. Moreover, after 24 h of interferon treatment, a reduction of BrdUrd incorporation per cell, assessed by flow cytometry, was observed suggesting that DNA synthesis in S phase cells is almost completely abolished. The analysis of the effect of interferon on the distribution of cell cycle phases indicated that the G1/S transition is not inhibited by the treatment. These results support the hypothesis that interferon generates a transient initiating signal which quickly reaches the nucleus and produces a rapid inhibition of alpha polymerase activity, leading finally to the slowing of cell cycle progression.
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PMID:Interferon affects cell growth progression by modulating DNA polymerases activity. 159 35

The effect of human recombinant DNA interferon alpha type A on nuclear inositol lipids, diacylglycerol (DAG) and DNA metabolism has been investigated in Friend erythroleukemia cells. A transient enhancement of phosphatidylinositol (4,5) - bisphosphate (PIP2) phosphorylation together with an increase of diacylglycerol mass were observed in nuclei isolated from cells treated with interferon alpha for 90 min. At the same time, a marked reduction of DNA polymerase alpha activity was observed, suggesting a possible involvement of nuclear inositol fraction in the response of the cell nucleus to interferon treatment.
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PMID:Interferon transiently modulates intranuclear signalling system in erythroleukemia Friend cells. 165 86

We have evaluated the problem of autoantibodies such as antinuclear antibodies (ANA), smooth muscle antibody (SMA) and antibodies to thyroid microsomal (TMA) and to thyroglobulin (TGA) related to interferon therapy in 27 patients with chronic hepatitis B. Anti-interferon antibody was also studied by Western blot method. Eight patients had ANA and 2 had SMA during interferon therapy. However, 6 of the 8 patients were ANA positive and one of the 2 was SMA positive prior to interferon treatment. No patients developed TMA, TGA or anti-interferon antibody. Eight (29.6%) of the 27 patients had clearance of both DNA polymerase and HBeAg and persistent normalization in alanine aminotransferase levels with interferon therapy. Seven of the 8 responders developed none of the autoantibodies related to interferon therapy. These results suggest that the presence of ANA or SMA during treatment may affect the therapeutic response to interferon.
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PMID:[Autoantibodies related to interferon therapy in chronic hepatitis B may affect the therapeutic response to interferon]. 172 18

Seventeen patients with chronic hepatitis B were treated with a 4-week administration of glycyrrhizin followed by a 4-week treatment with human lymphoblastoid interferon, then followed for 6 months after the end of treatment. All were positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B virus-associated DNA polymerase (DNA-p) for at least 6 months before entry. All patients were Japanese and none of them were homosexuals. Eleven patients lost DNA-p activity and 10 of them lost HBeAg. Three of these 10 patients had antibody to HBeAg. In 10 patients who became HBeAg-negative, alanine aminotransferase levels after glycyrrhizin administration were higher and initial DNA-p activities relatively lower than the levels found in seven patients who remained HBeAg-positive. The immunomodulator provided by a short course of glycyrrhizin before administration of human lymphoblastoid interferon may be an effective treatment for patients with chronic hepatitis B.
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PMID:Glycyrrhizin withdrawal followed by human lymphoblastoid interferon in the treatment of chronic hepatitis B. 176 47

The biological significance of antibody reactivities towards the preS2 gene encoded proteins of HBV is not yet well known. We investigated the pretreatment IgM anti-preS2 (1-55) ad reactivity in 22 Chinese and 11 Swedish patients with active HBV disease. Significantly enhanced IgM anti-preS2 levels (titers greater than 1/1000) were observed in 48% (16/33) of these patients. The OD405 values for sera from patients with indolent HBsAg carriership were within the range of that obtained for "normal" control-sera when tested at dilutions from 1/1000 to 1/128,000. Five Chinese patients were treated with a short course of corticosteroids, followed by alpha-interferon 2b (IFN-alpha 2b) treatment for 16 weeks. The IgM anti-preS2 response was consecutively monitored during treatment. A beneficial effect on the outcome of the combined treatment was associated with rising titers of IgM anti-preS2 during the prednisolone cycle. The IgM anti-preS2 levels fell dramatically upon steroid withdrawal and were followed by a second peak response of IgM anti-preS2 reactivity during the IFN-alpha 2b treatment. No sustained loss of HBV-DNA or DNA polymerase with concomitant HBe/anti-HBe seroconversion was observed in treated patients, who lacked detectable pretreatment levels of IgM anti-preS2 in circulation.
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PMID:IgM anti-preS2 monitoring during combined corticosteroid/interferon-alpha 2b therapy in chronic hepatitis B. 177 15

A pilot study was designed to determine the tolerance and effectiveness of natural or recombinant gamma interferon in patients with chronic hepatitis B. Sixteen patients received 0.5 to 3.0 million units (MU) per day of gamma interferon (IFN-gamma) for 7 days. Nineteen chronic hepatitis B patients who were treated with 5-6 MU leukocyte-derived alpha interferon (IFN-alpha) daily served as controls. All completed the treatment schedule. IFN-gamma exerted mild, but significant inhibitory effects (P less than .05) on serum DNA polymerase levels. However, the changes were significantly less (P less than .001) than those seen with IFN-alpha therapy when compared with percent change from basal values. In contrast, serum 2', 5'-oligoadenylate synthetase (2-5 AS) activities were markedly enhanced to a similar extent during therapy with both IFNs. Serum beta 2-microglobulin values were significantly increased by administration with both IFNs, although higher values were seen with IFN-gamma. Five patients received 1 MU IFN-gamma for 28 consecutive days and their HBeAg levels similarly decreased as those seen in patients treated with IFN-alpha. Side effects seemed to be greater during IFN-gamma therapy than IFN-alpha despite the lower doses used. The antiviral effect on serum HBV levels appeared less with IFN-gamma than with IFN-alpha. Alternatively immunomodulatory functions may have been enhanced with IFN-gamma in patients with chronic HBV infection.
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PMID:Treatment with human gamma interferon of chronic hepatitis B: comparative study with alpha interferon. 194 Aug 81

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by positivity for hepatitis B e antigen and hepatitis B virus DNA, with increased DNA polymerase levels for more than 6 months, were entered into a prospective trial of low-dose recombinant human alpha-interferon therapy. All patients were treated with 5 million units of recombinant interferon alfa-2b given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNA polymerase levels (p less than or equal to 0.001), which reached normal values in ten (48%). After 10 months' mean follow up, seven patients (33%) were hepatitis B e antigen negative and five (24%) subsequently became positive for antibodies to e antigen. By 27 months, nine patients (43%) were both hepatitis B e antigen negative and e antibody positive. Only one patient became permanently negative for hepatitis B surface antigen. One patient relapsed during the second year of follow up. Side effects necessitated withdrawal of therapy in two patients: one due to worsening thrombocytopenia after two doses of interferon (data omitted from the study results) and one due to a local reaction at the injection sites. Our data indicate that small doses of recombinant interferon alfa-2b given during a 12-week period induce a significant reduction in viral replication and approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.
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PMID:Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a long-term follow-up study. 207 69

Eight patients with chronic hepatitis B entered a pilot study of gamma interferon and alpha interferon in combination. Gamma interferon alone had minimal inhibitory effects on serum levels of hepatitis B virus as monitored by serum HBV DNA and DNA-polymerase activity. The drug also gave troublesome side effects. In contrast, alpha interferon had more potent inhibitory effects on serum HBV levels and fewer side effects. When combined, the two interferons showed no additive or synergistic effects in inhibiting serum levels of HBV DNA or DNA polymerase. These findings indicate that the addition of gamma interferon to alpha interferon provides no additional antiviral effects but contributes significantly to side effects.
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PMID:Therapy of chronic hepatitis B with recombinant human alpha and gamma interferon. 210 74

To determine whether natural human interferon administered under the usual therapeutic dosing scheme would inhibit the hepatic drug metabolism, we performed an antipyrine test in eight patients with chronic B or non-A, non-B hepatitis before and after a subchronic interferon therapy (6 megaunits/day for 17 +/- 4 days, mean +/- SD). Six patients received interferon-beta and 2 received interferon-alpha. To circumvent a possible influence of interferon-induced fever on the hepatic drug metabolism, the antipyrine test during the interferon therapy was performed at least 14 days after the interferon-induced fever disappeared. The kinetic parameters of antipyrine were obtained from seven saliva samples over 32 hours postdose. There were no significant differences in any kinetic parameters of antipyrine observed before and during the interferon therapy. With the sample size of the study, there was only a 20% chance (i.e., beta-power = 0.8 at alpha = 0.05) that we might have missed a 17% reduction in antipyrine clearance by the interferon therapy (type II error). On the other hand, the subchronic interferon therapy lowered serum aminotransferases and DNA polymerase activity significantly (P less than .05) compared with the respective baseline values. Our results suggest that the subchronic therapeutic dosing scheme of interferon as conducted in the present study does not cause the inhibitory effect on the oxidative drug metabolism to a statistically significant or clinically relevant degree in patients with chronic hepatitis, while it improves their liver function. Further studies are required for determining if different types of interferons administered under the different dosing schemes would alter the hepatic drug metabolism and the inhibitory effect would be time-dependent.
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PMID:Effects of subchronic treatment with natural human interferons on antipyrine clearance and liver function in patients with chronic hepatitis. 211 64


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