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)

In a previous study, we revealed that tumor necrosis factor (TNF) was secreted in mouse liver at an early phase of liver regeneration after partial hepatectomy. Here, we investigated direct actions of TNF on the in vitro DNA synthesis of adult mouse hepatocytes in primary culture. TNF enhanced both 3H-TdR uptake and the number of 3H-TdR-labeled nuclei of hepatocytes. Their time courses were similar to those by epidermal growth factor (EGF) with about a 15 h lag period and a peak period of 24-48 h. This action of TNF was abrogated by DNA polymerase alpha inhibitor, aphidicolin and blocked specifically by anti-TNF antibody. The actions of rmTNF and rhTNF were not distinguishable; ED50 was about 7.5U/ml (5ng/ml) and 30U/ml (20ng/ml) for maximal response (about 2-fold or more of control). Other inflammatory monokines showed differential effects on in vitro DNA synthesis of hepatocyte. Neither type of interleukin 1 affected hepatocyte DNA synthesis in the range examined (up to 50 ng/ml). IL-6 markedly inhibited the hepatocyte DNA synthesis stimulated by TNF and EGF. The action of TNF was completely suppressed by transforming growth factor beta, which is known as a potent inhibitor of hepatocyte growth. Interferon gamma also blocked this TNF action when added simultaneously. These results indicate that the activation of tissue macrophages and local secretion of TNF in liver after partial hepatectomy is of physiological importance in liver regeneration, in part by a direct stimulation of hepatocyte DNA synthesis. Cytokines induced by TNF may also participate in the later termination of liver regeneration.
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PMID:Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is suppressed by transforming growth factor beta and interleukin 6. 173 Jul 79

We previously purified a potent serum suppressor factor from malignant ascites fluid and showed that it had serologic cross-reactivity with E receptor of human T lymphocytes. We termed this factor "suppressive E receptor factor" (SER). Subsequent studies on SER showed that SER interfered with the production of interleukin 1 and 2 as well as interfering with their activities on target cells. However, SER was not directly cytotoxic to lymphocytes. In this study, we compared the inhibitor of DNA-polymerase (IDP) activity with the suppressive activity on phytohemagglutinin-induced DNA synthesis on intact cells. These two activities were closely correlated (with a linear correlation coefficient of 0.988) even with the whole plasmas derived from cancer patients. Fractionation and purification of IDP activity identified it with SER of a similar potency. Therefore, SER appeared to exhibit its potent immunosuppressive effect via its direct interference on DNA-polymerase activity. Furthermore, the DNA-polymerase inhibitory activity of SER appeared to be specific to DNA and it did not affect the RNA-polymerase activity. SER inhibition of DNA polymerase activity with respect to DNA primer as well as with the nucleotide substrate. Direct inhibition on DNA-polymerase-alpha activity may be one of the possible mechanisms of action of SER on lymphocyte proliferation.
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PMID:E receptor-related immunosuppressive factor in malignant pleural fluid and plasma: molecular mechanism of action on DNA-polymerase-alpha. 399 67

It is well known that EBV has developed strategies to evade immune surveillance. Previously, EBV was shown to bind specifically to monocytes and regulate expression of proinflammatory mediators such as IL-1, IL-6, TNF-alpha, and leukotrienes. EBV was also found to affect phagocytosis of monocytes. In this study, we show that in addition to these effects, EBV suppresses the biosynthesis of PGE2, a pleiotropic immunomodulatory molecule that is synthesized by the dioxygenation of arachidonic acid via the cyclooxygenase (COX) pathway. This down-regulation of PGE2 formation involved the inhibition of the inducible COX-2 isoform expression both at the transcriptional and translational levels, whereas expression of the constitutive COX-1 isoform was unaltered. Furthermore, exposure of monocytes to EBV was found to impact on the NF-kappaB activation pathway, which plays an essential role in the induction of COX-2 in monocytes. The inhibition of PGE2 biosynthesis was relieved when the experiments were conducted in presence of phosphonoacetic acid, an inhibitor of herpesviruses DNA polymerase, indicating that viral replication and/or neosynthesized viral proteins were involved in this process. Thus, inhibition of PGE2 biosynthesis in monocytes may represent an additional mechanism underlying EBV pathogenicity.
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PMID:EBV suppresses prostaglandin E2 biosynthesis in human monocytes. 1084 3

Venous blood is currently the most common source of DNA for gene polymorphism screening; however, blood sampling is invasive and difficult to perform in general dental treatment. Buccal mucosa samples provide an alternative source of DNA, but it is frequently difficult to effectively amplify the DNA owing to the small amounts of sample material obtained. This study was performed to establish a method for performing total genomic DNA amplification from buccal mucosa samples using phi29 DNA polymerase. Total genomic DNA was isolated from buccal mucosa samples obtained from healthy subjects and was amplified using phi29 DNA polymerase. To determine the suitability of the extracted DNA for genotyping, polymerase chain reaction and restriction fragment length polymorphism analyses were performed for the IL-1 gene polymorphism. Genotyping of the IL-1 polymorphism was successful using the amplified DNA from a buccal mucosa, but genotyping was unsuccessful using the unamplified control because of low DNA purity. The method of extracting DNA from a buccal mucosa is painless, simple, minimally invasive, and rapid. Genomic DNA from a buccal mucosa can be amplified by phi29 DNA polymerase in sufficient quantity and quality to conduct gene polymorphism analyses.
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PMID:DNA amplification using phi29 DNA polymerase validates gene polymorphism analysis from buccal mucosa samples. 2129 40