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)

Treatment of chronic hepatitis B (CHB) with human leukocyte interferon (IFN-alpha) was studied in terms of increase of 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral blood lymphocytes (PBL) after IFN-alpha administration. The 2-5A synthetase activity in PBL increased to a maximum 16-24 h after IFN-alpha injection and then gradually decreased, while serum HB virus DNA polymerase (HBV-DNAP) activity, which corresponds to the amount of HBV virions in the serum, decreased to a minimum after about 48 h. Increase in 2-5A synthetase activity was followed about 1 day later by decrease in DNAP activity. Furthermore, of 9 patients treated with IFN for at least 22 weeks and observed for over 1 year after IFN treatment, the effective 5 cases in which HBeAg disappeared during IFN therapy and did not reappear showed rather high increases in 2-5A synthetase activity, whereas the ineffective 4 cases in which HBeAg remained positive at the end of IFN therapy showed little increases in enzyme activity. The present study suggests that prescreening by 2-5A synthetase assay before IFN therapy should be useful for obtaining better results in IFN treatment of CHB patients.
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PMID:2',5'-Oligoadenylate synthetase activity in peripheral blood lymphocytes as a clinical marker in interferon therapy for chronic hepatitis B. 358 79

Seven children with chronic active hepatitis (CAH) and one child with persistently abnormal results of liver function test due to hepatitis B virus (HBV) infection were treated with human leukocyte interferon (Hu-alpha-IFN). Five of them were positive for eAg and two of the three who were measured for DNA polymerase (DNAP) activity in sera showed moderate elevations of its levels. Hu-alpha-IFN was injected intramuscularly daily or once weekly at doses of 0.05-1 X 10(6) IU. The total dose per patient varied from 10.5-54 X 10(6) IU. After administration of Hu-alpha-IFN, rapid loss of eAg was observed in two of the five eAg patients, and DNAP activity reverted to normal ranges in the two patients with moderate elevations of its levels. One of the patients who lost eAg has retained normal serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels for more than 2 years after therapy with Hu-alpha-IFN. Serial hepatic biopsies were performed in only one patient. In the second biopsy, 3 months after therapy with Hu-alpha-IFN, infiltration of inflammatory cells in the portal region was improved compared with earlier findings. Immediate and/or prolonged adverse side effects were not observed during or after administration of Hu-alpha-IFN. For the present, we propose these six conditions for use of Hu-alpha-IFN in children with HBV infection. Children should: (a) be more than 1 year old; (b) have abnormal liver function for more than 6 months; (c) have a liver biopsy demonstrating CAH; (d) have moderate elevation of DNAP activity; (e) be eAg positive; and (f) be unresponsive to other treatments.
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PMID:Therapeutic effects of human leukocyte interferon on chronic active hepatitis B in children. 398 64

Ten young adult patients with chronic hepatitis B virus infection and positive hepatitis B e antigen and DNA polymerase (DNAP) levels were treated with alternating courses of seven to 28 days of 5 to 7.5 mg/kg of vidarabine monophosphate (adenine arabinoside monophosphate) and 28 days of human leukocyte interferon (IFN-alpha); three different regimens were given on an outpatient basis. All patients with a fall in their DNAP level, and the DNAP remained undetectable six months after treatment was stopped in one patient. The major side effect, which most often occurred in those patients receiving 7.5 mg/kg of vidarabine monophosphate, was severe muscular pains. This study demonstrated the feasibility of administering vidarabine monophosphate and interferon to outpatients. Based on data from this and other studies, it is now possible to use a relatively nontoxic regimen that includes 28 days of 5 mg/kg of vidarabine monophosphate in a larger controlled study to answer the question of efficacy.
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PMID:Vidarabine monophosphate and human leukocyte interferon in chronic hepatitis B infection. 617 74

We have developed an in vitro assay to assess and predict the potential efficacy of in vivo interferon-alpha (IFN-alpha) treatment (5 x 10(6) units/m2 per day) for patients with chronic myelogenous leukemia (CML). Although determining the numbers and affinities of IFN-alpha receptors on CML cells has been developed as a method for predicting treatment response to IFN-alpha, it fails to predict response in CML. Previously, we and others observed that mitogens, toxins and lectins that bind to cell-surface receptors are endocytosed, escaping endosomes in order to act directly on cellular targets. Therefore, we tested the ability of low concentrations of IFN-alpha (5-10 units) to act directly on DNA polymerase (Pol) in purified chromatin nucleoprotein complexes (NPC). NPC were prepared by a methodology that uses direct treatment of leukocyte nuclei with MspI to generate six NPC-containing fractions (S1, M1, S2, M2, 0.1K and R). We found three general categories of in vitro DNA synthesis response for the six different NPC fractions isolated from the white blood cells of patients with CML (n = 19) before their treatment with IFN-alpha. IFN-alpha induced either stimulation, inhibition or had no apparent effect on Pol activity in the six different NPC fractions in a blind assay. In most of the NPC fractions isolated from the leukocytes of patients with progressive CML and in those from CML patients who failed to show a clinical response to IFN-alpha, this cytokine stimulated or had no effect on Pol activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-alpha directly inhibits DNA polymerase activity in isolated chromatin nucleoprotein complexes: correlation with IFN-alpha treatment outcome in patients with chronic myelogenous leukemia. 754 66

The effect of interferon alfa (IFN-alpha) therapy on the expression of transforming growth factor alpha (TGF-alpha) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-alpha for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-alpha in an avidin-biotin-peroxidase-complex system. The expression of TGF-alpha in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-alpha expression before or after therapy between 13 patients receiving daily IFN-alpha, 13 receiving alternate-day IFN-alpha, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients ("responders"); the 18 other patients were "nonresponders." Expression of TGF-alpha before IFN-alpha therapy was significantly higher in responders than in nonresponders; after IFN-alpha therapy, TGF-alpha expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-alpha in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-alpha therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond.
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PMID:Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B. 755 46

Intensive multidrug chemotherapy with concomitant IFN was performed in three hepatitis B virus (HBV) carriers with malignant lymphomas. All of the patients were HBsAg+, HBsAb-, HBcAb+, HBeAg- and HBeAb+ (mutant strain+). HBV-DNA polymerase (DNA-P) was normal at the beginning of chemotherapy, and complete response was achieved with CO-BLAM chemotherapy (without PDN) in all cases. In case 1, a slight elevation of DNA-P and normal GOT and GPT was observed after IFN-alpha was started during the third course. IFN-alpha was administered twice a week. In case 2, elevation of DNA-P and normal GOT and GTP were noted at the end of the 5th course, then daily IFN-alpha was started. In case 3, daily IFN-alpha was started during the 3rd course because of elevation of DNA-P. It was possible to prevent severe liver damage by administering IFN immediately after the elevation of DNA-P, since DNA-P elevation is noted before GOT and GPT elevation. The detection of the HBV mutant strain could be helpful in the treatment of HBsAg+ and HBeAb+ patients. In all of three patients, DNA-P, serum GOT and GPT normalized quickly after the administration of IFN-alpha. Severe hepatitis did not develop.
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PMID:[Chemotherapy with concomitant IFN treatment in three HBV carriers (mutant strain) with malignant lymphoma]. 756 13

Among the six species of hepatitis viruses, HBV (hepatitis B virus) and HCV (hepatitis C virus) can induce persistent infection. HBV and HCV are transmitted parenterally, of which maternal transmission and transfusion-associated infection is a major route respectively. We opened the special clinic for carriers detected through blood donation, and followed them at regular intervals for their health care. The prevalence rate of HBV carriers decreased from 3.0% to 1.2% in these 10 years, and that of HCV decreased from 0.9 to 0.4% in these 4 years. Prevalence rate of HBV peaks at 50s and that of HCV peaks at 60s. Due to nearly complete screening of donated blood, post-transfusion hepatitis almost disappeared. HBV vaccine for neonates born from infected mothers reduced the new incidence of HBV carriers. In HBV carriers seroconversion of HBeAg to HBeAb occurs at teens with transient hepatitis and appearance of mutant virus. Ninety percent of the carriers remains healthy for the lifetime but some of them aggravate into chronic hepatitis leading to HCC (hepatocellular carcinoma). In HCV acute infection at adult age succeeds to chronic infection and eventually to liver cirrhosis with sporadic appearance of HCC. On the other hand, less than 50% of HCV carriers seem to be asymptomatic and do not lead to grave disease. In HBV carriers tendency to reject the virus occurs and eventually HBV is cleared in some percentage of the population. In contrast HCV does not tend to be cleared. HBsAb is a defensive antibody. In contrast HCVAb is not a defensive antibody but an infective antibody like HBcAb. DNA polymerase is a good marker of disease state in HBV, and HCV RNA is a good marker of HCV proliferation. Treatment with IFN is sometimes effective for seroconversion in HBV, and for eradication of virus in HCV.
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PMID:[Basic and clinical aspects of hepatitis virus carriers]. 880 69

Extensive diagnostic and scientific investigations are often restricted by limited availability of material. Therefore, methods like multiplex PCR strategies are needed to conserve as much sample as possible. Unfortunately, the establishment of such procedures poses several difficulties. Here we describe the advantages of a new enzyme, AmpliTaq Gold DNA Polymerase, in multiplex and time-release PCR. The application of this thermostable recombinant Taq DNA polymerase allows the specific amplification of DNA/cDNA targets with very high sensitivity. With our protocol, the specific amplification of 13 different cDNAs of cytokines and cytokine receptors can be realized in three multiplex PCRs (IL-2R alpha, IL-2/15R beta, gamma c-chain, IL-4 and IL-4R alpha; IL-10, IL-15 and IL-15R alpha; and IL-2, IFN gamma, IL-7, IL-7R alpha and IL-9R alpha). The novel application of AmpliTaq Gold DNA Polymerase in a time-release PCR protocol allows specific amplification of target DNA/cDNA when only limited amounts of material are available or only low-copy-number DNA/cDNA is suspected. No IL-9 cDNA can be detected in peripheral blood mononuclear cells (PBMC) in the absence of any stimulation, thus it was difficult to amplify this target with routine PCR protocols. Here we demonstrate the reliable and reproducible amplification of IL-9 cDNA in the Hodgkin's lymphoma cell line KM-H2, in PBMC and in stimulated PBMC. Results with AmpliTaq Gold DNA Polymerase were more sensitive and specific compared with AmpliTaq DNA Polymerase, with and without manual hot-start procedure.
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PMID:Advantages of a new Taq DNA polymerase in multiplex PCR and time-release PCR. 945 68

In order to facilitate cytokine mRNA detection in blood cells, we have developed a highly reproducible and easily performed RNA isolation method for use with whole blood. Previously frozen human whole blood samples were lysed in guanidine thiocyanate solution to isolate total RNA. After reverse transcription a PCR method was applied to detect beta-actin and cytokine mRNA expression (interleukin-(IL)2, IL4, IL10, tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma)). The presence of cDNA was confirmed by agarose gel electrophoresis and quantitated on-line using sequence-specific fluorochrome labeled internal oligonucleotide probes. This quantitative method is based on the cleavage of fluorescent dye labeled probes by the 5' --> 3' endonuclease activity of the Taq DNA polymerase during PCR and measurement of fluorescence intensity by a Sequence Detector System. The signal generated was directly proportional to the starting copy number of target molecules in the sample over 6 log concentrations and quantitative analysis of cDNA concentrations was performed in comparison to beta-actin or cytokine cDNA standards. mRNAs coding for beta-actin and TNF alpha were readily detectable in cDNAs prepared from the whole blood of eight healthy donors, while the other cytokines were expressed in lower amounts (IFN gamma, IL10) or were undetectable (IL2, IL4). The assay described is highly reproducible, requires no post PCR manipulation of the amplicons and permits the analysis of several hundred PCR reactions per day. Using this method it is possible to detect and quantify cytokine mRNA expression reliably in small amounts of previously frozen blood even after storage of samples for at least several months.
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PMID:Quantification of cytokine mRNA expression by RT PCR in samples of previously frozen blood. 952 Mar 2

Treatment of cells with combinations of human interferon-alpha (IFN-alpha) and the nucleoside analog, acyclovir (ACV), leads to the synergistic inhibition of herpes simplex virus type 1 (HSV-1) replication. We have examined the effect of these agents on the replication of HSV-1 DNA and the synthesis of early viral enzymes to understand the mechanism(s) responsible for this synergistic activity. Combination treatment with 100 IU/ml IFN-alpha and 5 microM ACV led to HSV-1 DNA levels more than 8-fold lower than in cells treated with ACV alone, while IFN-alpha treatment alone had no detectable effect on viral DNA synthesis. Steady state levels of DNA polymerase were reduced approximately 50% by IFN-alpha and 25% by ACV, but combination treatment did not decrease enzyme levels to an extent greater than the sum of these effects. In contrast, the activity of another early viral enzyme, alkaline DNase, was reduced less than 20% by IFN-alpha alone or combination treatment and was unaffected by ACV treatment. No decrease in the level of mRNA encoding either enzyme was detected in IFN-alpha-treated cells although ACV treatment reduced polymerase mRNA levels. These studies suggest that the synergistic anti-HSV activities of IFN-alpha with ACV could be mediated, in part, through some post-transcriptional mechanism induced by IFN-alpha treatment, leading to the reduction in production of viral early enzymes, especially DNA polymerase.
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PMID:Combined effects of interferon-alpha and acyclovir on herpes simplex virus type 1 DNA polymerase and alkaline DNase. 970 72


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