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)

Women are infected with HIV in increasing numbers; the predominant mode of spread is through heterosexual transmission. Little is known regarding the mechanism of HIV transit through the female genital tract. We investigated whether early passage cervical epithelial cells could be directly infected with HIV-1LAI. Virus production was measured using the reverse transcriptase (RT) assay and direct assay for syncytia-forming units. In-situ hybridization was performed on infected cervical cell cultures. Immunostaining was carried out using a monoclonal antibody to leukocyte common antigen (LCA). Virus was recovered in the supernatants of all infected cervical cultures. Localization of HIV infection using in-situ hybridization identified rare cells in the population which gave a strong signal. These infected cells had a lymphoid morphology and were also detected using immunostaining for LAC. Cervical epithelial cells were uninfected in this in vitro model; cells in this population which supported viral replication were most likely of the macrophage/monocyte lineage.
Int J STD AIDS
PMID:Human immunodeficiency virus infection of early passage cervical epithelial cultures. 830 76

Bronchial epithelial cells (BEC) are the progenitors of bronchogenic carcinomas and are exposed to polycyclic aromatic hydrocarbon (PAH) procarcinogens through inhalation of combustion products. PAH are converted to carcinogenic molecules through a combination of monoxygenation by cytochrome p450 (CYP) enzymes in the presence of NADPH oxidoreductase (OR) and hydrolysis by microsomal epoxide hydrolase (mEH). In artificial systems, the relative expression of these genes determines whether carcinogenic or noncarcinogenic species are generated during metabolism. This relationship was explored in humans by using quantitative competitive reverse transcriptase polymerase chain reaction amplification to determine the range of expression of CYP1A1, CYP1B1, mEH, and NADPH OR in BEC recovered from 10 nonsmokers and 9 smokers. CYP2B7 expression was evaluated because, although little is known of its substrate specificity, it is expressed at high levels in human lung tissue. CYP1A1 and CYP1B1 were expressed in BEC at significantly different levels (P < 0.05) in the 9 smokers at 1.4 +/- 2.3 x 10(4) and 2.4 +/- 3.2 x 10(3) molecules/10(6) beta-actin molecules (mean +/- STD), respectively, but each was measurable in only one of the 10 nonsmokers. There was significant inter-individual variation (P < 0.05) in both CYP1A1 and CYP1B1 expression among the subjects for whom sufficient data were obtained. The inducibility of human BEC CYP1A1 gene by PAH exposure was confirmed in vitro by incubating cultured immortalized human BEC with beta-naphthoflavone and observing a > 6-fold induction of CYP1A1 after 24 h. In contrast to BEC, alveolar macrophages expressed CYP1A1 at low (30-70 molecules/10(6) beta-actin molecules) to unmeasurable levels in both smokers and nonsmokers. There was no significant difference in expression of mEH, CYP2B7, or NADPH OR in smokers compared with nonsmokers. The inter-individual variation in absolute and relative expression of PAH metabolism enzymes in BEC reported here supports the hypothesis that inter-individual variation in ability to activate/inactivate inhaled PAH carcinogens accounts for at least some of the inter-individual variation in risk for bronchogenic carcinoma.
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PMID:Quantitative RT-PCR measurement of cytochromes p450 1A1, 1B1, and 2B7, microsomal epoxide hydrolase, and NADPH oxidoreductase expression in lung cells of smokers and nonsmokers. 922 17

Human immunodeficiency virus (HIV) infection is considered to influence the pathogenesis of human papillomavirus (HPV)-associated diseases. It is not clear whether this occurs directly through molecular interactions between viral genes and/or indirectly through effects on the immune functions. In the present study we compared molecular characteristics of penile condylomas from immunocompetent and HIV-positive individuals. Using polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR techniques we determined some characteristics of local immune responses and transcriptional activity of both viruses. Our findings revealed that HIV-seropositivity was accompanied by multiple HPV infection and a CD4-count-dependent appearance of oncogenic HPV-types. HIV infection also changed the patterns of HPV transcription favouring transcription of early genes such as E7. Apparently, HIV infection influences local immunity by altering HPV transcription and by systemic immunodeficiency.
Int J STD AIDS 1998 May
PMID:Systemic immunosuppression by HIV infection influences HPV transcription and thus local immune responses in condyloma acuminatum. 963 4

The objectives of this study were to provide individual and population-based unit cost estimates of HIV treatment and care by stage of HIV infection for adults in England and estimate the financial impact of the use of combination antiretroviral therapy. Individual unit cost estimates were calculated, based on 1997 activity data, and linked to the number of diagnosed HIV-infected individuals using statutory medical services by clinical stage of HIV infection in England during 1997 to obtain population-based cost estimates; these were compared with 1996 estimates. Most clinical guidelines now recommend the use of 3 antiretroviral agents, but cost estimates for mono and dual therapy were included as baseline estimates. Baseline costs for treating AIDS patients with zidovudine (AZT) monotherapy were estimated at pound sterling 16,830 (95% CI 14,633-18,985) per patient-year which was substantially lower than the 1996 estimate; costs for asymptomatic individuals and people with symptomatic non-AIDS were pound sterling 4450 (95% CI 3521-5612) and pound sterling 7289 (95% CI 6169-8386) per respective patient-year which did not differ substantially from 1996. The total annual population cost estimate for HIV service provision amounted to pound sterling 128 million (95% CI pound sterling 109m to pound sterling 147m), if all patients with HIV disease were treated with AZT monotherapy only. For all eligible patients to be treated with 2 nucleoside reverse transcriptase inhibitors (NRTI) (AZT and didanosine (ddI) or zalcitabine (ddC)), cost estimates amounted to pound sterling 161m (95% CI pound sterling 141m to pound sterling 181m), while for triple therapy, annual estimated expenditure amounted to pound sterling 185m (95% CI pound sterling 165m to pound sterling 206m) when a non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine) was included or pound sterling 205m (95% CI pound sterling 186m to pound sterling 235m) when a protease inhibitor was included. Compared with 1996 population-based cost estimates, the estimates for monotherapy decreased by 14%, by 11% for dual therapy, by 10% for triple therapy which included a NNRTI and by 9% if a protease inhibitor was used as part of a triple therapy regimen. Similarly, compared with 1996 estimates, the proportion of total costs attributable to treating asymptomatic individuals increased by 5% and 2-3% for people with symptomatic non-AIDS, while the proportion attributable for treating people with AIDS decreased by 8-9%.
Int J STD AIDS 1999 Jun
PMID:Changing cost of English HIV service provision 1996-1997. NPMS Steering Group. National Prospective Monitoring System. 1041 77

The aetiology of hepatic dysfunction in patients with HIV infection is multifactorial. Re-activation of hepatitis C infection, drug toxicity, and opportunistic infections are all potential causes. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy for the treatment of HIV infection. It is associated with a significant incidence of hepatotoxicity, usually occurring in the initial month of therapy. We report the case of a 49-year-old man who developed NVP-induced prolonged hepatotoxicity 5 months after commencing antiretroviral therapy.
Int J STD AIDS 2000 May
PMID:Late onset hepatitis and prolonged deterioration in hepatic function associated with nevirapine therapy. 1082 44

Given that the long-term medical management of HIV infection necessitates making best use of all available antiretrovirals, it is somewhat surprising that the nucleoside analogue reverse transcriptase inhibitor (NRTI) zalcitabine is less commonly used. This may be due to the potential for peripheral neuropathy (PN) which has been associated with the use of this drug. The perception that zalcitabine is poorly tolerated appears to have arisen largely from the results of early monotherapy trials in patients with AIDS and low CD4 cell counts. In contrast, results of more recent studies show that PN is relatively infrequent when zalcitabine is used in combination with other antiretrovirals in current treatment settings.
Int J STD AIDS 2000 Jul
PMID:Peripheral neuropathy: zalcitabine reassessed. 1091 81

Our objective was to describe clinical features and predisposing factors attributed to lactic acidosis in 4 HIV-infected patients on long-term nucleoside reverse transcriptase inhibitor (NRTI) therapy. All patients had received at least 6-20 months of NRTI-containing antiretroviral therapy: all used stavudine (d4T), in one combined with lamivudine (3TC), in the other 3 with didanosine (ddI); in one hydroxyurea was added. In all, the initial symptoms were gastrointestinal (nausea and vomiting), followed by tachypnoea preceding the lactic acidosis; death followed 6-22 days after admission (liver failure and uncontrollable arrhythmias). Treatment with riboflavin was unsuccessful in one patient. The only definite risk factor in all cases was NRTI-induced mitochondrial toxicity; one patient was concomitantly treated for Kaposi's sarcoma (with bleomycin and vinblastine) and one just recovered from pneumococcal sepsis. None of the patients had a history of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. In all patients, some sort of toxicity to other previously used NRTIs had occurred earlier. Lactic acidosis occurred after months of NRTI therapy in patients who had already suffered other forms of NRTI toxicity. Concomitant diseases or comedication might have aggravated the mitochondrial toxicity of the NRTIs. Screening methods to detect mitochondrial toxicity are necessary, since lactic acidosis occurs rather unexpectedly, with a rapid, fatal course.
Int J STD AIDS 2000 Sep
PMID:Clinical features and risk factors of lactic acidosis following long-term antiretroviral therapy: 4 fatal cases. 1099 8

Despite the success of potent combination therapy against HIV, a large proportion of patients experiences treatment failure. Due to the high degree of plasticity of the HIV genome, ongoing virus replication in the presence of drug pressure will result in the selection of virus mutants with reduced drug susceptibility. As a result, antiretroviral drug-resistance is a common denominator in treatment failure. Two methods, genotyping and phenotyping, are commercially available for measuring resistance in clinical samples. Whereas genotyping detects resistance-conferring mutations in the HIV reverse transcriptase and protease genes, the recombinant virus assay is a newly developed phenotyping technique which determines drug-susceptibility in a virus culture assay. With both methods, result interpretation remains challenging. Retrospective studies and randomized controlled clinical trials support the clinical utility of resistance testing in the setting of treatment failure. The optimal applications of resistance testing in a variety of other clinical settings remain to be defined.
Int J STD AIDS 2001 Mar
PMID:Antiretroviral resistance in clinical practice. 1123 66

Healthcare workers (HCWs) worldwide risk occupational exposure to HIV and other blood-borne pathogens. Post-exposure prophylaxis (PEP) may decrease the risk of seroconversion after occupational or sexual exposure. Current guidelines recommend immediate PEP with at least 2 drugs following HIV exposure. In high-risk exposures, the guidelines recommend the use of a protease inhibitor (PI) as well as 2 reverse transcriptase inhibitors. Protease inhibitors have been associated with dyslipidaemias, other metabolic abnormalities and lipodystrophy syndromes in AIDS patients. We report a case of new transient lipid abnormalities in a HCW receiving PEP after HIV exposure. HIV medications may produce occult metabolic abnormalities in HIV-negative individuals receiving PEP. This risk should be considered during follow-up evaluation for PEP.
Int J STD AIDS 2001 Aug
PMID:Lipid abnormalities in a healthcare worker receiving HIV prophylaxis. 1148 94

Since the adoption of highly active antiretroviral therapy (HAART) in the mid-1990s, certain metabolic toxicities have been increasingly recognized. These include a fat redistribution syndrome (lipohypertrophy, lipoatrophy), hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and osteonecrosis). Metabolic complications are principally reported with protease inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with all classes of antiretroviral therapy. In this review, we summarize the epidemiology, pathogenesis and management of these various toxicities.
Int J STD AIDS 2001 Sep
PMID:The metabolic toxicities of antiretroviral therapy. 1151 63


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