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

---

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

The virological, clinical and electrophysiological manifestations of acute and experimentally reactivated infections of the rabbit central nervous system (CNS) and trigeminal ganglia have been studied after intranasal infection with herpes simplex virus type 1 (strain KOS-63). All animals shed virus in nasal secretions during the acute phase of infection. Although no rabbits developed clinical signs during the acute phase of infection, mild electroencephalographic (EEG) abnormalities consistent with viral invasion of the CNS were seen. KOS-63 produced only occasional gross and histopathologic herpetic lesions of the CNS and was very rarely recovered from the brain. These results indicate that KOS-63 was poorly neuroinvasive and only mildly neurovirulent during the acute phase of infection. However, KOS-63 did establish latency within the CNS and trigeminal ganglia of infected rabbits as demonstrated by in situ hybridization and by recovery of virus from co-cultivation cultures, but not from cell-free homogenates of nervous tissue. Cyclophosphamide and dexamethasone injections were used to reactivate latent CNS and trigeminal ganglionic infections. Following injection of the drugs, no animal shed virus in nasal secretions or developed obvious clinical or EEG changes. However, KOS-63 was recovered from co-cultivation cultures of brain and trigeminal ganglia at greater frequency following drug injection than during latency. These results indicate that KOS-63 was only poorly susceptible to drug-induced reactivation. In vivo experiments confirmed that the apparent poor neuroinvasiveness and weak neurovirulence of KOS-63 was not due to viral temperature-sensitive defects, deficient production of viral thymidine kinase, or abnormal defects in viral DNA polymerase function.
...
PMID:The weakly virulent herpes simplex virus type 1 strain KOS-63 establishes peripheral and central nervous system latency following intranasal infection of rabbits, but poorly reactivates in vivo. 132 37

Inhibitory effects of snuff extract and the tobacco chemicals nicotine, anabasine, diethyl-N-nitrosamine (DEN), and the tobacco-specific nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on herpes simplex virus type 1 (HSV-1) replication in vitro and on HSV-1 protein synthesis in infected cells were analysed. Snuff extract and nicotine caused a significant reduction of HSV-1 attachment to cell membranes whereas anabasine, DEN, NNN and NNK did not affect adsorption of HSV-1. Virus production assays in the presence of snuff added after virus adsorption resulted in a significantly reduced production of virus at low multiplicities of infection (MOI), but at high MOI the inhibitory effect of snuff extract was less pronounced. DEN, NNN and NNK only affected virus production at toxic concentrations. Nicotine and anabasine reduced virus production in non-toxic doses but not at the concentrations present in snuff extract. In HSV-infected cells exposed to snuff extract, the immediate early (alpha-) infected cell proteins (ICPs) 4 and 27 (as well as the early (beta-) ICPs 6 and 8) were markedly increased, whereas the late (gamma-) ICPs 5, 11 and 29 were reduced. Nicotine had a less pronounced stimulating effect on the production of alpha-proteins but no detectable effect on production of beta- or gamma-proteins. Anabasine, DEN, NNN and NNK did not affect HSV protein synthesis at non-toxic concentrations. Synthesis of thymidine kinase and DNA polymerase was significantly reduced by snuff extract. Also nicotine and anabasine affected thymidine kinase and DNA polymerase but only at toxic concentrations. The production of the cellular protein actin, which almost disappears a few hours after HSV-1 infection, remained at a significant level in HSV-infected cells exposed to snuff. Thus snuff extract blocks the replicative cycle of HSV at an early stage, which results in an increased production of alpha-proteins in the infected cells and in prolonged maintenance of cellular functions. This may be of importance for HSV-induced transformation and the development of HSV-associated tumours.
...
PMID:Inhibition of herpes simplex virus replication and protein synthesis by non-smoked tobacco, tobacco alkaloids and nitrosamines. 133 51

The activity of nuclear DNA polymerases alpha, beta and delta/epsilon, uracil-DNA glycosylase, thymidine kinase and the presence of Proliferating Cell Nuclear Antigen (PCNA) have been examined in developing rat glial cells, in rat and human glioma, in human neuroblastoma and in differentiated neuroblastoma cell lines in vitro. During glial development the activity of all enzymes tested, except DNA polymerase beta, markedly decreased, suggesting their coordinate regulation in respect to the proliferative state of the cells. Glioma and neuroblastoma cell lines restore the enzymatic activities that were no longer expressed in normal adult cells. Neuroblastoma cell lines induced to differentiate in vitro by retinoic acid showed a decline of the activities of DNA polymerase alpha, DNA polymerase delta/epsilon, uracil-DNA glycosylase and thymidine kinase similar to that observed during in vivo differentiation. We also demonstrate that PCNA is not detectable in glial and neuronal cells at all developmental stages, but can be found in tumor nerve cells. A possible use of enzymatic assays or anti-PCNA antibodies to detect brain tumors is discussed.
...
PMID:DNA synthesis enzymes and proliferating cell nuclear antigen in normal and neoplastic nerve cells. 135 31

The outcome of virus-host interaction after peripheral inoculation of herpes simplex virus (HSV) depends on virus replication at the portal of entry, the ability of the virus to invade nerve endings and capillary endothelium cells and, the rate of virus replication in neurons and nonneural cells of the nervous system. Functions involved are the activity of viral thymidine kinase, DNA polymerase, immediate early transactivator proteins, the transcription initiation protein, the envelope protein(s) governing virus penetration, syncytium formation and natural killing of infected cells as well as some other regulatory DNA sequences.
...
PMID:DNA regions and genes determining the virulence of herpes simplex virus. 135 74

G1-specific temperature-sensitive (ts) mutants of the cell cycle arrest in G1 after serum stimulation at the restrictive temperature. Under these conditions, the RNA levels of late growth-regulated genes (such as DNA polymerase alpha, PCNA, thymidine kinase, and core histones) are markedly decreased or even undetectable, while early growth-regulated genes (for instance, c-myc) are normally expressed, and certain promoters are actually super-induced. We have used the human PCNA gene transfected into TK-ts13 cells (a G1-specific ts mutant) to investigate whether the inhibition of gene expression caused by this type of growth inhibition occurs at a transcriptional or post-transcriptional level. Constructs were made in which the 5' and 3' flanking sequences of the human PCNA gene were replaced by the corresponding elements of the SV40 T antigen coding gene. Using these constructs and data from run-on assays and RT-PCR, we conclude that the failure of expression of the PCNA gene in G1-arrested TK-ts13 cells occurs at the transcriptional level.
...
PMID:The role of the promoter in the expression of the PCNA gene. 136 Feb 87

Topoisomerases are essential enzymes for DNA metabolism in prokaryotes and eukaryotes. In human cells, DNA topoisomerase II enzyme activity can be modulated by both viral transformation and changes in proliferation status. To identify elements important for regulation of topoisomerase II alpha gene expression, genomic DNA clones covering the 5'-end of the gene were isolated. The intron/exon structure of a 2.5-kilobase region encompassing the translation start site was determined. Transcription was found to initiate at multiple sites clustered around 90 base pairs 5' to the ATG initiation codon. Transient expression of chimeric topoisomerase II-reporter gene constructs in HeLa cells revealed that the 5'-flanking region exhibited promoter activity. The region -90 to -1 upstream of the major transcription start site was shown by deletion analysis to include a promoter. This minimal promoter lacks a TATA box, is moderately GC-rich, and contains a high frequency of CpG dinucleotides; characteristic of a "housekeeping" gene promoter. Maximal promoter activity was observed using a fragment extending to position -562. Putative regulatory elements are contained within and immediately upstream of the minimal promoter region. The regulatory region of the topoisomerase II alpha gene identified here is similar in basic structure to those of the human thymidine kinase and DNA polymerase alpha genes, which are also controlled by proliferation-specific factors.
...
PMID:Cloning and characterization of the 5'-flanking region of the human topoisomerase II alpha gene. 138 64

The involvement of calmodulin in the proliferation of Chinese hamster embryo fibroblast cells has been studied with a specific monoclonal antibody to calmodulin. We observed that calmodulin levels increase 2-fold in the late G1 period in these cells, and this coincides with the increase in DNA polymerase alpha activity as the cells progress synchronously from a quiescent state in the G1 to the S phase. However, there is a concurrent 10-fold enhancement of thymidine kinase activity, which is tightly coupled to the entry of cells into the S phase. Incubation of permeabilized S-phase cells with calmodulin-specific murine monoclonal antibody resulted in a dose-dependent inhibition of DNA replication. This inhibitory effect of anti-calmodulin antibodies on DNA replication is completely reversed by the addition of exogenously purified calmodulin. These observations provide evidence for the involvement of calmodulin in DNA replication and, therefore, in cell proliferation during the S phase.
...
PMID:Calmodulin-specific monoclonal antibodies inhibit DNA replication in mammalian cells. 142 Jan 60

Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy.
...
PMID:DNA synthesis and related enzymes altered in compensatory lung growth in rats. 145 64

Herpes simplex virus (HSV) resistant to acyclovir can produce persistent mucocutaneous ulcerative disease in patients with the acquired immunodeficiency syndrome (AIDS). The incidence of clinically significant acyclovir-resistant HSV disease has dramatically increased since the advent of the AIDS epidemic. The primary mechanism of acyclovir resistance is induction of viral mutants defective or deficient in thymidine kinase, the viral-encoded enzyme, which catalyzes the rate-limiting step in the triphosphorylation of acyclovir to its active form (acyclovir triphosphate). Foscarnet, a potent inhibitor of HSV DNA polymerase, does not require phosphorylation for its antiviral activity. This compound has been found to be effective in the treatment of acyclovir-resistant HSV infection by several investigators. A recently completed dose-comparative trial of foscarnet in AIDS patients with acyclovir-resistant HSV has confirmed the safety and efficacy of two doses of foscarnet (40 mg/kg every 8 or 12 hours) in the treatment of this disease, as well as providing preliminary evidence supporting the utility of foscarnet maintenance therapy in delaying recurrence of HSV lesions. Analysis of data from this trial has been complicated by the tremendous variability in lesion size at initiation of therapy, making any statistically valid comparison of treatment regimens almost impossible. A further trial in AIDS patients with acyclovir-resistant HSV infection has been designed to define better the role of foscarnet maintenance and, in light of evidence that a significant proportion of initial recurrences are due to acyclovir-sensitive HSV, to examine the potential utility of acyclovir maintenance following foscarnet induction therapy.
...
PMID:Foscarnet treatment of acyclovir-resistant herpes simplex virus infection in patients with acquired immunodeficiency syndrome: preliminary results of a controlled, randomized, regimen-comparative trial. 153 Dec 85

Combination therapy with A1110U, an inactivator of the herpes simplex virus (HSV) and the varicella zoster virus ribonucleotide reductase, and acyclovir (ACV) was evaluated for treatment of cutaneous herpetic disease in athymic mice infected on the dorsum. In this model, infection with HSV produces a 'zosteriform-like' rash that is first visible on day 3 or 4 post-infection (p.i.) and eventually extends from the anterior mid-line to the dorsal mid-line of the affected flank. In untreated mice, the infection is fatal at about day 7 p.i. presumably due to central nervous system involvement. Topical treatment of infections induced by either wild-type (wt) HSV-1 or wt HSV-2 with 3% A1110U in combination with 5% ACV resulted in synergistic (P less than 0.01) reductions in lesion scores. Therapy was also synergistic in mice infected with an ACV-resistant thymidine kinase-deficient mutant and an ACV-resistant TK-altered mutant HSV-1 isolated. Combination therapy was very effective in reducing lesion scores of mice infected with an ACV-resistant HSV-1 DNA polymerase mutant, but did not result in statistically significant synergy (P = 0.07) because of the enhanced efficacy of A1110U alone against this virus. These results provide encouragement that the combination of A1110U and ACV may offer an effective therapy for topical treatment of cutaneous HSV infections in humans.
...
PMID:Synergistic topical therapy by acyclovir and A1110U for herpes simplex virus induced zosteriform rash in mice. 165 Jan 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---