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)

Telomerase is a multi-subunit ribonucleoprotein holoenzyme that stabilizes telomere length through the addition of new repeat sequence to the ends of chromosomes. Telomerase reverse transcriptase is the subunit of this complex responsible for the enzymatic activity of telomerase. Expression of the reverse transcriptase is regulated at the level of transcription through the action of transcription factors that target its promoter. Most Kaposi's sarcoma tumor cells are latently infected with the Kaposi's sarcoma-associated herpesvirus, and the constitutive expression of a viral-encoded latency-associated nuclear antigen has been shown to be important for the maintenance of the viral episome. The proliferative nature of Kaposi's sarcoma suggests that this antigen may also play a critical role in viral-mediated oncogenesis. In this study telomerase reverse transcriptase promoter elements cloned into a luciferase reporter plasmid were analyzed to determine the ability of the latency-associated nuclear antigen to regulate transcription. The latency-associated nuclear antigen transactivated the full-length promoter in 293T, 293, and BJAB cell lines. Furthermore, truncation promoter studies implicated sequence from -130 to +5 in viral-mediated activation. This region contains five Sp1 transcription factor-binding sites. Electrophoretic mobility shift assays indicated that the latency-associated nuclear antigen targets and affects the Sp1-DNA complex in the context of BJAB nuclear extracts.
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PMID:The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus transactivates the telomerase reverse transcriptase promoter. 1131 52

At the 36th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC), updates on research on non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and newer treatments were presented. Among the research topics reviewed are results from the CAESAR study, guidelines for use of antiretrovirals, and the efficacy of new antiretroviral combinations. Also included are data tables showing the impact of viral load and CD4 count on risk of progression among 2,008 persons in trials of delavirdine; the detection of HIV RNA after 40 to 52 weeks in a trial of nevirapine/ZDV/ddI; viral load and CD4 changes in a phase I/II study of 141W94; viral load changes, principal side effects, and dropouts in a trial of ritonavir plus saquinavir; clinical endpoint results of the CAESAR trial; viral load and CD4 changes after 50 weeks of IL-2 plus indinavir; comparison of regimens for treating CMV retinitis; prevalence of Kaposi's sarcoma-associated herpesvirus antigen in HIV-positive and -negative groups; and rates of MAC bacteremia in ACTG 196/CPCRA 009, a trial comparing clarithromycin, rifabutin, and the combination for prophylaxis.
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PMID:Piloting the meanders of AIDS research. 1136 56

We investigated, in a prospective cohort follow-up study, whether substituting efavirenz (EFV) for protease inhibitors (PIs) could be safe in HIV-infected patients with optimal viral suppression achieved on PI-containing regimens. In patients with undetectable plasma viral load (pVL) <50 copies/ml who were naive to therapy with nonnucleoside reverse transcriptase inhibitors (NNRTIs), PIs were replaced by EFV whereas associated nucleoside analogs (NAs) were retained. 62 patients were enrolled. Median follow-up on EFV was 64 weeks (2-88 weeks). Side effects due to EFV occurred in 48 patients. Two patients experienced a high level viral rebound due to diminished compliance; 55 (88.7%) maintained a pVL <50 copies/ml; 3 showed one episode of viremia (52-89 copies/ml); 2 stopped EFV before any VL control. Mean CD4 cell count did not change significantly. One AIDS patient experienced a single cutaneous recurrence of Kaposi's sarcoma after 40 weeks on EFV. Replacing PI with EFV in patients with optimal pVL suppression appears to be safe both virologically and immunologically.
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PMID:Efavirenz as a substitute for protease inhibitors in HIV-1-infected patients with undetectable plasma viral load on HAART: a median follow-up of 64 weeks. 1151 22

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.
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PMID:Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy. 1167 23

Therapy of HIV infection has undergone significant changes since the introduction of highly-active antiretroviral therapy (HAART). Mortality and the appearance of opportunistic infections have significantly been reduced. Diseases of the skin and adjacent mucous membranes often provide the first signs for HIV infection. The spectrum of dermatologic findings related to HIV includes a variety of cutaneous and mucocutaneous disorders. The most frequent diagnoses are oral candidiasis, mollusca contagiosa, oral hairy leuokoplakia, herpes zoster and herpes simplex, seborrheic dermatitis, and Kaposi's sarcoma. Incompatibility reactions to drugs are observed on a strikingly frequent basis in HIV infection. Such severe incompatibility reactions are much more frequent in HIV patients than in the normal population. Inducers often include sulfonamides, cotrimoxazole, tuberculostatics as well as nucleoside-type reverse transcriptase inhibitors.
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PMID:Dermatological diseases and signs of HIV infection. 1189 Nov 45

Zidovudine (AZT) is a thymidine analogue which inhibits retroviral reverse transcriptase, terminates DNA chain synthesis, and thus inhibits viral replication. The clinical benefit of AZT patients with advanced HIV disease was established in a phase II placebo-controlled study. Administered at dosages of 500 mg per day, AZT benefits asymptomatic patients with CD4 counts below 500, slows progression to AIDS, and increases survival. It has therefore become the major antiviral drug for treating HIV infection. Psoriasis is a common papulosquamous disease affecting 1-2% of the general population. It may also be the initial symptom of HIV infection, potentially very severe and difficult to treat with conventional therapy in such patients. The presence of psoriasis contributes significantly to AIDS morbidity and may be even more disabling than Kaposi's sarcoma. Researchers have, however, reported in the Archives of Dermatology the complete clearing of psoriasis in two patients several weeks after they began AZT therapy for AIDS. 33% of patients had a complete clearing of disease symptoms, while 90% had a partial improvement. A more than 75% reduction in body surface involvement was observed in 47% of patients. Improvement during AZT therapy was correlated with the presence of antigenemia and an increase in mean white blood cell count. While other forms of therapy for severe psoriasis have resulted in profound immunosuppression in some patients with AIDS, may activate HIV, or may be poorly tolerated in patients, AZT therapy seems safe and effective for ameliorating or clearing psoriasis in HIV-infected individuals at dosages of 1200 mg per day. The effectiveness of the drug at lower doses has not been established. Information is also lacking on what effect the early administration of AZT in asymptomatic HIV patients may have on the eventual expression of psoriasis.
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PMID:Zidovudine improves psoriasis in HIV-positive males. 1217 18

Primary effusion lymphoma is a form of diffuse large B-cell lymphoma with neoplastic cells largely limited to proliferation within major body cavities. Human herpes virus-8 is both integral to and required for an unequivocal diagnosis of primary effusion lymphoma. Prior methods for virus identification include DNA extraction with Southern blot analysis or in situ hybridization from paraffin-embedded samples. Our aim is to examine the utility of human herpesvirus-8 identification performed directly on smears from effusion samples by reverse transcriptase in situ polymerase chain reaction in patients with primary effusion lymphoma. Smears and cell block of body cavity fluids from five patients with effusions (three pleural, one peritoneal, and one both pleural and peritoneal) were examined microscopically by conventional Papanicolaou and Romanowsky (Diff-Quik) staining, and by reverse transcriptase in situ polymerase chain reaction for human herpesvirus-8 detection. In situ hybridization was performed also for Epstein-Barr virus (EBER-1, -2), T-cell receptor-beta, and kappa (kappa) and lambda (lambda) mRNA in all cases. Five adults ranged from 40-81 years of age. Three adults were HIV positive, one was a renal transplant recipient, and the oldest patient (Case 3) had the unusual distinction of a normal immune status. Two of three HIV-seropositive patients had concurrent Kaposi sarcoma. All samples were cytologically similar with lymphocytes having large-cell, plasmablastic, and immunoblastic morphology. Malignant cells from effusions were as follows: human herpesvirus-8 positive (all five cases), exhibited kappa monoclonal light chain (five cases), Epstein-Barr virus positive (three cases), and T-cell beta-gene receptor positive (two cases). Diffuse large B-cell lymphoma was evident in one peritoneal nodule (< 10% human herpesvirus-8 positive cells in contrast to > 90% positive in effusions, all kappa positive). Six other tissue specimens (lung, bone marrow, spleen, lymph node) were human herpesvirus-8 negative, and showed no evidence of lymphoma. Reverse transcriptase in situ polymerase chain reaction demonstrated near-complete restriction of human herpesvirus-8-infected malignant lymphoid cells to those in body cavities. Definitive diagnosis of primary effusion lymphoma is possible directly from cytologic smears/cell block by combining cytologic morphology with reverse transcriptase in situ polymerase chain reaction detection of human herpesvirus-8.
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PMID:Primary effusion lymphoma: cytopathologic diagnosis using in situ molecular genetic analysis for human herpesvirus 8. 1221 12

Almost all of the approved antiviral drugs have become available during the past two decades. Approximately one half of these agents are for the treatment of human immunodeficiency virus (HIV) infections and comprise five classes. The first three classes all act to inhibit reverse transcriptase: nucleoside analogs; nonnucleoside analogs; and nucleotide analogs. The fourth class, protease inhibitors, prevent viral packaging; the fifth class, fusion inhibitors, prevent fusion between HIV and the target cell. Four nucleoside analogs, acyclovir, valacyclovir, famciclovir and penciclovir, are approved for the therapy of herpes simplex and varicella zoster infections. Interferon alpha is approved in the injectable form for condyloma acuminatum and Kaposi's sarcoma, but the more efficient method of delivering this agent is via interferon induction following topical use of imiquimod cream. Antiviral agents are also approved for infections with cytomegalovirus, hepatitis B and C, respiratory syncytial virus, and influenza viruses. Most of these antiviral drugs are virastatic and not viracidal. Vaccines and public health measures are much more effective and cost effective than antiviral drugs and must be promoted accordingly in the defense against viral infections.
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PMID:Changing paradigms in dermatology: antivirals in dermatology. 1467 23

Angiogenesis is thought to play a major role in the development of Kaposi's sarcoma (KS), considered by many to be a hyperplastic disorder caused in part by local production of inflammatory cytokines. The antiangiogenic effects of protease inhibitors, in particular ritonavir, have been suggested in laboratory work to lead to regression of KS, and recent data have shown the importance of ritonavir as a model of pharmaceutical development. As our clinical cohort data has shown that non-nucleoside reverse transcriptase inhibitor-based regimens are not inferior to protease inhibitor-based therapy in the prevention of KS, we investigated the specific contribution of ritonavir to chemoprevention of this AIDS-defining illness. In a logistic regression analysis, we found that ritonavir-based therapy confers no advantages compared to other regimens in the prevention of KS. This is consistent with data suggesting that regression of KS is mediated by an overall improvement in immune function and not by the effects of specific antiretrovirals.
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PMID:The efficacy of ritonavir in the prevention of AIDS-related Kaposi's sarcoma. 1469 32

Human herpes virus type 8 (HHV8) has been strongly associated with Kaposi sarcoma, primary effusion lymphoma (PEL), and Castleman's disease. To our knowledge, infection by this virus has not been strongly associated with other hematopathologic malignancies. We examined five oral cavity lymphomas from men with AIDS for HHV8 and HIV-1 by reverse transcriptase in situ polymerase chain reaction, as well as for Epstein-Barr virus (EBV) (EBER-1, -2) using in situ hybridization and HHV8 protein with immunohistochemistry. Four of these tumors were plasmablastic lymphomas; the final case was diffuse large B-cell lymphoma. Most of the neoplastic cells in these five lymphomas contained HHV8 RNA and protein. Further, the four plasmablastic lymphoma cases had tumor cells that contained EBV. HIV-1 RNA was not detected in the tumor cells but was noted in surrounding benign T cells. In comparison, HHV8 RNA was not detected in any of the five oral cavity lymphomas from people who did not have acquired immunosuppression nor in five lymphomas from AIDS patients that were located at a site other than the oral cavity. It is concluded that oral cavity lymphomas from people with AIDS are strongly associated with infection by HHV8 and EBV. Given the poor prognosis of oral cavity lymphomas in immunocompromised patients, therapy directed against the HHV8 and EBV infection may be of therapeutic value.
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PMID:Oral plasmablastic lymphomas in AIDS patients are associated with human herpesvirus 8. 1548 61


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