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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the origin of viruses has not yet been clarified, definite differences in evolutionary patterns have been found among RNA. Retro and DNA viruses. These differences are reflected in infectious diseases. RNA viruses, which have RNA in their genome, replicate many times over in cells within a short period of time, destroying the host cells and causing an acute infection. As the error frequency of RNA replicase enzymes is high, the rate of evolution of RNA viruses is very rapid. Retroviruses also contain RNA as their genome, but the genome RNA is reversely transcribed to the DNA in nuclei and then incorporated into the host chromosome to replicate. The error frequency of reverse transcriptase is also high, and therefore mutations easily occur as well. The transcribed DNA is integrated into host DNA in the nucleus, and it remains in the integrated state for human entire life time, causing chronic disease or developing malignant tumors. As DNA viruses except poxviruses replicate inside the cell nucleus and the error frequency of DNA polymerase is low, the speed of mutation and the degree of resulting diversity are lower than those in the case of the RNA virus. DNA viruses tend to stay inside the body for long periods of time and easily become latent. In this paper, I shall discuss 1) the nature of viruses, 2) the origin of viruses, 3) mutation and recombination, 4) diversity of RNA viruses, 5) quickly changing viral diseases, 6) eradicated viral diseases, 7) chronic and malignant diseases, and 8) control of viral diseases.
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PMID:[Evolution and ecological changes of animal viruses]. 140 23

Recently, a newly discovered lentivirus--Feline Immunodeficiency Virus (FIV)--was identified as the cause of an AIDS-like syndrome in the cat. For the detection of FIV antigen in cell culture, an antigen capture ELISA was developed. In this assay FIV specific IgG was used as a capture antibody and the same preparation coupled to biotine as a conjugate. With this test viral antigen could be demonstrated in FIV infected cell cultures within four days after infection and the assay proved to be at least as sensitive as a reverse transcriptase test in demonstrating virus infected cultures. A modification of this assay in which a titrated amount of FIV antigen was incubated with dilutions of serum samples of naturally or experimentally infected cats, allowed the detection of FIV specific antibodies. In a serological survey, conducted among cats with different clinical histories in The Netherlands and The Federal Republic of Germany, the antibody inhibition ELISA was compared with a commercially (IDEXX) available indirect ELISA system. It was shown that both assays identified nine seropositive cats among 200 animals with a history of undefined chronic disease, whereas no positive reactions were obtained with 65 serum samples from apparently healthy animals. Both assays also gave positive results with serum samples from experimentally infected cats, within five weeks after infection. Of an additional panel of eight serum samples which had been found positive in the IDEXX indirect ELISA system, only five were found positive in the antibody inhibition ELISA and western blotting assay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An enzyme linked immunosorbent assay (ELISA) for the detection of feline immunodeficiency virus (FIV) antigen in cell culture and FIV specific antibodies in feline serum. 217 15

A combination treatment has recently become available for HIV-infected patients; it consists of two reverse transcriptase inhibitors and one protease inhibitor. This combination therapy has consequences for primary medical care as regards diagnostics, treatment, follow-up and counselling of patients with HIV and AIDS, education of patients requiring the HIV test, information of seropositive patients not yet being treated and the cooperation and task distribution between GPs and AIDS specialists. The new combination method creates new problems for patients, such as medicalization of their lives, side effects and compliance; it also affects their prospects (social reintegration, resumed occupational activity). In the medical management, the focus shifts to early start of treatment, stimulating compliance, monitoring of effect and side effects, if any, of the treatment and coping with the patients' uncertainty about durability of the effect. If the new treatment proves to be successful in the long run as well, HIV infection/AIDS will become a chronic disease, so that the needs of care and the care methods will increasingly resemble those of other chronic diseases. There will be a growing need of extramural care, leading to new requirements regarding the study of medicine and postgraduate instruction of GPs.
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PMID:[AIDS; new developments. IV. Changes in primary medical care due to new possibilities of treating HIV-infected patients]. 934 May 62

Human immunodeficiency virus type 1 (HIV-1) RNA was measured in lymph node (LN) mononuclear cells of 50 patients with sustained plasma RNA of <200 copies/mL with therapy. Six patients had received a combination of three reverse transcriptase inhibitors (RTIs) since primary infection, 11 received this same combination during chronic disease, 21 received a combination of two RTIs plus a protease inhibitor (PI), and 12 received three RTIs plus a PI. The mean overall duration of therapy was 8.9 +/- 0.5 months (range, 5-24), with no significant difference between groups. LN HIV-1 RNA levels varied from undetectable to 1.7 million copies/10(6) cells according to cases. The mean LN HIV-1 RNA level was 2.99 +/- 0.42 log10 copies/10(6) cells in the 17 patients receiving three RTIs compared with 1.93 +/- 0.25 log10 copies/10(6) cells in the 33 patients receiving a PI (t test, P = .02). These data demonstrate that highly active antiretroviral regimens have unequivalent effects on LNs and invite redefinition of suboptimal therapy at this level.
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PMID:Residual human immunodeficiency virus type 1 RNA in lymphoid tissue of patients with sustained plasma RNA of <200 copies/mL. 941 97

HIV-related lipodystrophy has emerged as one of the most prevalent problems for patients with HIV, since this infection can now be seen as a chronic disease. Despite its growing importance, crucial issues such as aetiopathogenesis, diagnosis, prevention and therapy remain largely unknown and unexplored. Current evidence suggests that aetiology is multifactorial. HIV infection, antiretroviral therapy and patient-related factors probably all contribute to the development of lipodystrophy. The lack of a formal definition and the nature of wasting syndromes that affect HIV-infected patients can hinder the diagnosis and treatment of lipodystrophy. Body fat changes have a major negative impact on the quality of life of patients. Metabolic abnormalities are also well known cardiovascular risk factors that can increase the morbidity and mortality due to cardiovascular disorders in a relatively young population. As yet, we do not know whether lipodystrophy is preventable or reversible. Several therapeutic approaches have been tested with limited success, however potential complications must be considered. These therapeutic approaches include general health measures (diet, exercise and discontinuation of smoking), switching antiretrovirals (from protease inhibitors to non-nucleoside reverse transcriptase inhibitors or abacavir, or from stavudine to other nucleoside reverse transcriptase inhibitors) and use of drugs with metabolic effects (metformin, thiazolidinediones, recombinant growth hormone and anabolic steroids). A judicious use of available data, and opting for an individualised approach seems the best option for management of this problem at present.
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PMID:Strategies for treating HIV-related lipodystrophy. 1177 61

Chlamydia pneumoniae is associated with several chronic human diseases, including chronic obstructive pulmonary disease and atherosclerotic cardiovascular disease. During chronic disease, organisms are believed to exist in a persistent phase that is not well understood at the genetic level. Long-term in vitro continuous infections are spontaneously persistent and are less susceptible than in vitro acute infections to treatment with antibiotics, and are therefore particularly relevant as an in vitro model of in vivo chronic disease. Real-time reverse transcriptase-PCR (r-t RT-PCR) was used to quantitate transcript copy numbers of 13 genes in continuous and acute infections with C. pneumoniae. The set of genes studied encodes proteins with known or predicted functions in the cell membrane, the inclusion membrane, cell division, metabolism, and immunopathology. Significant upregulation was seen for five genes (CPn0483, nlpD, ompA, pmp1 and porB) in continuous cultures. The genes omcB, pmp1, and porB, all of which encode membrane proteins, shared similar patterns of expression over both acute and continuous profiles. These results show that Chlamydia in the long-term continuous model of persistence have a unique transcription profile, adding to our knowledge of regulation of this important stage of chlamydial growth.
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PMID:Differential expression of genes encoding membrane proteins between acute and continuous Chlamydia pneumoniae infections. 1262 Mar 80

The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. The causes of these diseases remain unknown; however, prevailing theories suggest that chronic intestinal inflammation results from a dysregulated immune response to ubiquitous bacterial antigens. While a substantial body of data has been amassed describing the role of the adaptive immune system in perpetuating and sustaining inflammation, very little is known about the early signals, prior to the development of inflammation, that initiate and direct the abnormal immune response. To this end, we characterized the gene expression profile of A/JCr mice with Helicobacter hepaticus-induced typhlitis at month 1 of infection, prior to the onset of histologic disease, and month 3 of infection, after chronic inflammation is fully established. Analysis of the gene expression in ceca of H. hepaticus infected mice revealed 25 up-regulated and 3 down-regulated genes in the month-1 postinoculation group and 31 up-regulated and 2 down-regulated genes in the month-3 postinoculation group. Among these was a subset of immune-related genes, including interferon-inducible protein 10, monokine induced by gamma interferon, macrophage-induced protein 1 alpha, and serum amyloid A1. Semiquantitative real-time reverse transcriptase PCR confirmed the increased expression levels of these genes, as well as elevated expression of gamma interferon. To our knowledge, this is the first report profiling cecal gene expression in H. hepaticus-infected A/JCr mice. The findings of altered gene expression prior to the development of any features of pathology and the ensuing chronic disease course make this an attractive model for studying early host response to microbe-induced inflammatory bowel disease.
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PMID:Analysis of gene expression in ceca of Helicobacter hepaticus-infected A/JCr mice before and after development of typhlitis. 1281 73

The persistence of herpes simplex virus (HSV) and the diseases that it causes in the human population can be attributed to the maintenance of a latent infection within neurons in sensory ganglia. Little is known about the effects of latent infection on the host neuron. We have addressed the question of whether latent HSV infection affects neuronal gene expression by using microarray transcript profiling of host gene expression in ganglia from latently infected versus mock-infected mouse trigeminal ganglia. (33)P-labeled cDNA probes from pooled ganglia harvested at 30 days postinfection or post-mock infection were hybridized to nylon arrays printed with 2,556 mouse genes. Signal intensities were acquired by phosphorimager. Mean intensities (n = 4 replicates in each of three independent experiments) of signals from mock-infected versus latently infected ganglia were compared by using a variant of Student's t test. We identified significant changes in the expression of mouse neuronal genes, including several with roles in gene expression, such as the Clk2 gene, and neurotransmission, such as genes encoding potassium voltage-gated channels and a muscarinic acetylcholine receptor. We confirmed the neuronal localization of some of these transcripts by using in situ hybridization. To validate the microarray results, we performed real-time reverse transcriptase PCR analyses for a selection of the genes. These studies demonstrate that latent HSV infection can alter neuronal gene expression and might provide a new mechanism for how persistent viral infection can cause chronic disease.
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PMID:Latent herpes simplex virus infection of sensory neurons alters neuronal gene expression. 1291 67

With the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection has become a chronic disease with more frequent end-stage organ failures. As a result, the question of transplantation in HIV patients is raised more often. However, some of the HAART regimen medications require elimination or metabolism via the P-glycoprotein (P-gp) and multidrug-resistant protein (MRP) transporters or via the cytochrome P450 enzyme system. Since these transporters and enzymes are also responsible for the clearance of immunosuppressive drugs, drug-drug interactions are likely to occur. Indeed, profound drug-drug interactions between protease inhibitors and immunosuppressive drugs have been observed and they required reductions in drug dosage. In contrast, HAART using nucleoside or nonnucleoside reverse transcriptase inhibitors without the use of protease inhibitors has been shown to produce less significant drug-drug interactions. It is thus crucial to take into account those potential pharmacokinetic and/or pharmacodynamic drug-drug interactions in order to avoid drug toxicity or a lack of efficacy. The aim of this work was to review and synthesize the international literature on this field in order to give practical recommendations on how to manage immunosuppressive drugs in HIV patients who get transplanted and on how to handle HAART therapy in transplant-recipient patients who get infected with HIV.
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PMID:Antiretroviral and immunosuppressive drug-drug interactions: an update. 1556 42

Usually thyroid cells isolated from tissue obtained by surgery or thyroid cell lines are used to investigate the pathogenesis of autoimmune thyroid diseases. Isolation and cultivation of thyrocytes from fine-needle aspiration biopsy (FNAB) has not yet been published. The aim of this study was to isolate and cultivate thyrocytes from samples of FNAB. FNAB samples were obtained from nine adults and nine children with Hashimoto's thyroiditis (HT). The aspiration material was filtered resulting in small samples of tissue on the surface of the filter membrane. These tissue fragments were digested by collagenase I and dispase II. The yielding cells were cultivated for 3 weeks in Ham's F12 Kaighn's Modification medium in presence of 1 mU/mL bovine thyrotropin (TSH), 10 microg/mL human insulin, 6 microg/mL transferrin, and 10(-8) M hydrocortisone. Finally, isolated thyroid cells were characterized by determination of gene expression of thyrotropin receptor (TSHR), thyroperoxidase (TPO), and thyroglobulin (Tg) using a nested reverse transcriptase-polymerase chain reaction (RT-PCR). Thyroid cells obtained by FNAB can be maintained over a time period of approximately 3 weeks. Depending on the sample size a final number of 1000-14,000 cells was gained per FNAB. In addition, all cells isolated by the described method expressed TPO mRNA. TSHR mRNA was found in 4 samples, whereas 15 samples were Tg mRNA-positive. There were no differences with respect to the expression TSHR and TPO mRNA between samples from adults and children. The isolation and cultivation of thyroid cells obtained by FNAB has been established. In contrast to surgical specimen, this technique provides an easy access to thyrocytes derived from individual patients allowing repeated sampling to investigate the time progression of the chronic disease or the effect of treatment over time.
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PMID:Isolation of thyroid cells obtained by fine-needle aspiration biopsy. 1618 6


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