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)

While many of the molecular events in viral replication are well studied, the molecular mechanisms by which viral infections trigger such constitutional symptoms as fever and 'malaise' are unknown. The hypothesis that these viral constitutional symptoms can be triggered by the toxic action of dsRNA associated with viral replication was investigated. Total lung RNA from mice acutely infected with PR8 influenza virus, but not from sham-infected mice, was shown to induce fever and altered sleep (excess slow-wave sleep, enhanced amplitudes of electroencephalographic slow waves, and reduced rapid eye movement sleep) when injected into the rabbit brain. Viral-associated dsRNA was shown to be responsible for the rabbit responses by differential nuclease digestion. Influenza viral dsRNA was directly demonstrated in the active lung RNA preparations by reverse transcriptase-polymerase chain reaction techniques. The time course of the responses paralleled those seen in the same model inoculated with nanogram quantities of the synthetic dsRNA polyriboinosinic-polyribocytidylic acid and suggested that they were mediated by induced cytokines. A model for the role of viral-associated dsRNA in eliciting both local cytotoxicity and viral constitutional symptoms is presented.
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PMID:Detection of toxic viral-associated double-stranded RNA (dsRNA) in influenza-infected lung. 189 Sep 49

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.
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PMID:Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results. 242 53

We compared an antigen capture assay (Abbott Laboratories, North Chicago, Ill.) with a reverse transcriptase assay to identify and quantify human immunodeficiency virus (HIV) in culture. In direct comparisons of serial dilutions of lymphadenopathy-associated virus type 1, the antigen assay was 100-fold more sensitive than the reverse transcriptase assay in detecting the virus. The antigen assay reacted strongly with 60 different HIV isolates but did not cross-react with human T-cell lymphotropic virus type I, human T-cell lymphotropic virus type II, cytomegalovirus, varicella-zoster virus, herpes simplex virus type 1, Epstein-Barr virus, adenovirus type 5, or poliovirus type 1 or with extracts from four different control human cell lines and eight different phytohemagglutinin-stimulated normal human lymphocytes. Peripheral blood lymphocyte samples from 50 individuals were evaluated by both the antigen assay and the reverse transcriptase assay. The cells from the 34 seropositive individuals were all positive by the antigen assay (range, 3 to 9 days; average time, 5.9 days) and the reverse transcriptase assay (range, 7 to 16 days; average time, 9.6 days). Cells from the 16 seronegative individuals were negative by both assays. These results indicate that the antigen assay is an important addition to the monitoring of HIV production in the lymphocytes of infected patients.
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PMID:Comparison of antigen assay and reverse transcriptase assay for detecting human immunodeficiency virus in culture. 244 34

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.
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PMID:Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. 365 Mar 39

Forty-five subjects with symptomatic human immunodeficiency virus type 1 (HIV-1) infection, CD4+ lymphocyte counts of > or = 150 x 10(6)/L, and Karnofsky scores > or = 60 were enrolled in a multicenter, randomized, controlled trial that compared zidovudine monotherapy and combination therapy for 48 weeks with zidovudine and interferon-alpha (IFN-alpha). Zidovudine with IFN-alpha (n = 25) had a favorable effect on CD4+ cell counts compared with zidovudine alone (n = 20). At all time points analyzed, the mean change from baseline was higher, reaching significance at week 24 (+10% versus -21%; P = .029). At week 48 the difference was -12% versus -45% (P = .07). Anti-CD3 monoclonal antibody-induced T cell reactivity improved temporarily in both groups. Serum HIV p24 antigen levels decreased maximally during the first 12 weeks of treatment. At weeks 0 and 48, polymerase chain reaction analysis for mutations at codons 67 and 215 of the HIV-1 reverse transcriptase gene conferring zidovudine resistance was conducted in 10 subjects receiving zidovudine and in 8 subjects receiving combination therapy. At week 48, 1 of 8 and 4 of 6 samples from the groups receiving zidovudine only or combination therapy, respectively, contained wild type virus at codon 215. Grade 3 or 4 toxicity was uncommon. Drug-related malaise and anorexia were observed more frequently in patients receiving both zidovudine and IFN-alpha.
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PMID:Zidovudine and interferon-alpha combination therapy versus zidovudine monotherapy in subjects with symptomatic human immunodeficiency virus type 1 infection. 791 Aug 38

Abacavir is a nucleoside analogue reverse transcriptase inhibitor that inhibits clinical isolates of HIV in vitro with a potency similar to that of zidovudine. Resistance to abacavir develops relatively slowly. Cross-resistance between abacavir and didanosine, zalcitabine or lamivudine, but not zidovudine or stavudine, has been reported in vitro. Abacavir has good oral bioavailability, as demonstrated in animals, and penetrates the CNS. Treatment with abacavir, alone or in combination with other anti-HIV agents (zidovudine, lamivudine, nevirapine, amprenavir and/or other protease inhibitors), decreased viral load and increased CD4+ cell count in patients with HIV infection. Effectiveness was maintained for at least 48 weeks. In early phase I/II trials, headache, gastrointestinal disturbances, rash, malaise, fatigue and/or asthenia were the most common adverse events reported with abacavir alone or in combination with other anti-HIV agents. Hypersensitivity reactions lead to discontinuation of therapy in 2 to 3% of patients.
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PMID:Abacavir. 958 69

The Hexaplex assay (Prodesse, Inc., Milwaukee, Wis.) is a multiplex reverse transcriptase (RT)-PCR assay for the detection of parainfluenza virus types 1, 2, and 3, respiratory syncytial virus (RSV) types A and B, and influenza virus types A and B. We evaluated the Hexaplex assay in comparison with conventional viral cell cultures and rapid enzyme immunoassays (EIAs) for RSV (Directigen; Becton Dickinson Inc., Cockeysville, Md.) and influenza A virus (Abbott Test Pack; Abbott Laboratories, Abbott Park, Ill.) for the detection of respiratory viruses from pediatric respiratory specimens obtained from children seen at Children's Hospital of Wisconsin from December 1997 through May 1998. A total of 363 respiratory specimens were evaluated. The tissue culture prevalence of parainfluenza virus during this period of time was low (1.1%). The sensitivity, specificity, and positive and negative predictive value of Hexaplex compared to tissue culture for the detection of parainfluenza virus were 100, 95.8, 19.0, and 100%, respectively. Only one specimen was determined to contain influenza B virus by Hexaplex; it was tissue culture negative. A specimen was considered to contain RSV or influenza A virus when it was either culture positive or culture negative but Hexaplex and EIA positive. Prior to the analysis of discrepant results, the sensitivity, specificity, and positive and negative predictive value for the detection of RSV were 91.2, 100, 100, and 98.0%, respectively, for tissue culture; 84.5, 100, 100, and 96.6% for EIA; and 98.5, 91.5, 72.8, and 99.6% for Hexaplex, respectively. The sensitivity, specificity, and positive and negative predictive value for the detection of influenza A virus prior to the analysis of discrepant results were 100, 100, 100, and 100%, respectively, for culture, 78.0, 100, 100, and 89.4% for EIA, respectively, and 95.1, 94.1, 67.2, and 99.3% for Hexaplex, respectively. Culture- and/or EIA-negative, Hexaplex-positive specimens were analyzed by a second RT-PCR assay which used primers specific for a different genomic region than that used in the Hexaplex assay. After analysis of these discrepant results, the sensitivity, specificity, and positive and negative predictive value for the detection of RSV were 74.3, 100, 100, and 93.5%, respectively, for tissue culture; 70.3, 100, 100, and 92.5% for EIA; and 98.6, 97.4, 91.2, and 99.6% for Hexaplex. The sensitivity, specificity, and positive and negative predictive value for the detection of influenza A virus were 83.3, 100, 100, and 97.4%, respectively, for tissue culture; 69.4, 100, 100, and 83.3% for EIA; and 95.8, 98.7, 92.0, and 99.3% for Hexaplex. Hexaplex is a rapid, sensitive, and specific method for the detection of the seven most common respiratory viruses in children.
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PMID:Evaluation of the Hexaplex assay for detection of respiratory viruses in children. 1132 76

The triple combination tablet containing lamivudine (150 mg), zidovudine (300 mg) and abacavir (300 mg, as abacavir sulfate) is a new formulation of three nucleoside analogue reverse transcriptase inhibitors. Two studies in treatment-naive patients (one double-blind, one nonblind) have reported that lamivudine/zidovudine (dual combination tablet) plus abacavir showed efficacy similar to that of lamivudine/zidovudine plus indinavir. In both studies, similar numbers of patients in each treatment group had plasma HIV RNA levels </=400 copies/mL at week 48 (51% vs 51% and 64% vs 50%). In treatment-experienced patients with baseline plasma HIV RNA levels <50 copies/mL, switching to lamivudine/zidovudine/abacavir (triple combination tablet) was as effective as remaining on highly active antiretroviral treatment (mainly protease inhibitor [PI]-based). Virological failure, the primary endpoint, defined as two consecutive plasma HIV RNA values >400 copies/mL, was reported in 22% of patients in both treatment groups at week 48. Treatment-naive patients receiving lamivudine/zidovudine/abacavir combination therapy experienced several adverse events, including nausea, malaise/fatigue and vomiting.
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PMID:Lamivudine/zidovudine/abacavir: triple combination tablet. 1274 41

Much of the success attributed to HIV therapy in the last few years has resulted from improved ways of using existing drugs in combination therapy regimens. The availability of new, more potent drugs such as protease inhibitors and more accurate viral load tests to aid decisions to start or change treatment has also contributed to the success. Published recommendations for pediatric HIV therapy, generated by a panel of experts and specialists, are readily available and regularly updated. Preferred regimens of 'potent' therapy (referred to as highly active antiretroviral therapy, or HAART) currently consist of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor. More intense four-drug regimens using an NNRTI or a second protease inhibitor as a fourth drug are being evaluated. Problems with HAART include: unpalatable drug formulations and adverse effects, coupled with lack of data on the pharmacokinetics, efficacy, and safety of various drug combinations. Adherence is a major factor influencing the efficacy and outcome of antiretroviral therapy. Many children cannot adhere to complex multidrug regimens, which cause virologic failure, despite excellent CD4+ cell count responses. This means a rapid progression through the limited number of treatment regimens available. Simpler regimens such as those containing three NRTIs have been proposed as a method of treatment that will allow suppression of the virus, yet circumvent many of the problems previously mentioned. An additional benefit would be the preservation of antiretroviral drugs from other classes for future treatment options if required. The major advantages of triple NRTI regimens are the simplicity of the regimen, good tolerability, few drug-drug interactions, and infrequent adverse effects coupled with a low pill burden. However, abacavir hypersensitivity remains a major problem. Up to 3% of patients may develop an early idiosyncratic hypersensitivity reaction - fever, malaise, and mucositis with or without rash, which can progress to more advanced stages of shock and death. A major concern is the apparently inferior virologic control of triple NRTI therapy as demonstrated in the AIDS Clinical Trials Group A5095 study with zidovudine/lamivudine/abacavir (Trizivir) combination in adults. Such a combination should only be considered in special situations. Examples cited include informed patient choice based on anticipated poor adherence on other treatment regimens, or if concomitant drugs such as tuberculosis medication are prescribed. The low pill burden of triple NRTI regimens (especially if combined in a single pill such as Trizivir), offers hope that regimen simplification may still be possible in the future.
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PMID:Triple nucleoside reverse transcriptase inhibitor therapy in children. 1517 Mar 62

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%-80% in the first week of the illness.
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PMID:Severe acute respiratory syndrome (SARS): epidemiology and clinical features. 1525


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