Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1983 Luc Montagnier and his colleagues claimed to have discovered a novel retrovirus presently known as human immunodeficiency virus (HIV). By 1984 HIV was almost universally accepted to be the cause of AIDS. However, 20 years later, HIV cannot account for the phenomena for which the retroviral hypothesis was proposed, namely, Kaposi's sarcoma, decrease in T4 lymphocytes and thus the opportunistic infections in AIDS patients which were assumed to be the direct results of this decrease. Agents other than HIV to which patients belonging to the AIDS risk groups are exposed cause decrease in T4 cells. Neither have the main predictions of the HIV hypothesis been fulfilled. HIV seropositivity in the developed countries still remains restricted to the original high risk groups, no HIV vaccine exists, and no successful animal model has been developed. In this communication, we critically analyse the evidence which in 1983 was claimed to prove the existence of HIV. The phenomena which Montagnier and his colleagues considered proof for the existence of HIV are detection of reverse transcriptase activity; the presence of retrovirus-like particles in the culture; immunological reactivity between proteins from the culture supernatant which, in sucrose density gradients, banded at the density of 1.16 g/ml ("purified virus") and antibodies in a patient's (BRU) serum. Reverse transcriptase activity can be found in viruses other than retroviruses and in all normal cells. Reverse transcription can be brought about not only by the enzyme reverse transcriptase but also by normal, cellular DNA polymerases. Retrovirus-like particles are ubiquitous in cultures not infected with retroviruses, especially in conditions employed by Montagnier et al. From the reaction between proteins in the "purified virus" and antibodies in the patient serum Montagnier concluded that the proteins were HIV proteins and the antibodies were HIV antibodies. Since all antibodies are polyspecific, from such a reaction it is not possible to define the origin of even one reactant let alone both. Even if this were possible, since Montagnier's "purified virus" did not contain particles with the "morphology typical of retroviruses", the proteins cannot be retroviral. We conclude that, these phenomena are non-specific to retroviruses and thus cannot be considered proof for the existence of a unique retrovirus HIV.
 ...
PMID:A critique of the Montagnier evidence for the HIV/AIDS hypothesis. 1532 2

The aim of the present study was to evaluate the impact of highly active antiretroviral therapy (HAART) on HIV viral load of plasma and intraocular fluids in AIDS patients with ophthalmic opportunistic infections. We further compared the treatment effect of HAART on these patients. From June 1997 to July 2003, we examined and followed up the ophthalmic conditions of 49 patients receiving HAART with ophthalmic diseases during this period. The method of reverse-transcriptase polymerase chain reaction was used to detect and monitor HIV load in plasma and/or aqueous humor of AIDS patients. Before HAART, the HIV levels in the plasma and aqueous humor in 8 AIDS patients with ophthalmic opportunistic infections were significantly higher than those in 6 patients with HIV-related retinopathy (p < 0.05). Compared to the eye findings and clinical improvement, HIV loads of aqueous humor in 10 of 14 AIDS patients (6 with HIV-related retinopathy, 5 with cytomegalovirus retinitis, 2 with toxoplasmic retinitis and 1 with cryptococcal chorioretinitis) declined to undetectable levels (< 400 copies/ml) after 4-8 months of HAART. HIV virus levels in the plasma of AIDS patients were significantly decreased, and the CD4 counts of these patients were significantly increased (Wilcoxon test) after initiation of HAART.
 ...
PMID:The HIV RNA Levels of Plasma and Ocular Fluids in AIDS Patients with Ophthalmic Infections. 1533 14

HIV-seropositive individuals are at an increased risk for an accelerated form of emphysema. The purpose of this study was to determine the distribution of HIV-1 RNA in lung tissues and correlate this with the histologic findings and expression of matrix metalloproteases (MMPs). Reverse transcriptase (RT) in situ PCR analysis was performed on 11 AIDS lung autopsy specimens which showed varying degrees of emphysematous changes. In each lung, HIV-1 RNA was detected. In areas of histologically normal lung, very rare HIV-1-infected cells were evident. In contrast, many HIV-1-infected cells were noted in areas of emphysema. HIV-1 gag RNA was evident primarily in macrophages; infected pneumocytes were also seen. Similarly, MMP mRNA and protein, primarily MMP-9, localized to the areas of emphysema. Colabeling experiments documented that MMP expression was found primarily in cells that were HIV-1 negative and adjacent to HIV-1-infected macrophages. These results suggest that AIDS-related emphysema may be due, in part, to direct infection by HIV-1 of, primarily, alveolar macrophages, and concomitant up-regulation of MMP expression in the neighboring, noninfected cells.
 ...
PMID:Correlation of HIV-1 detection and histology in AIDS-associated emphysema. 1571 64

The increasing incidence of tuberculosis and other mycobacterial infections due to AIDS epidemic resulted in the need of rapid and accurate identification of isolated mycobacteria. The correct identification result leads to the selection of an appropriate therapeutic regimen. Polymerase chain reaction and restriction enzyme analysis (PCR-REA) has been developed since 1992 and used as the rapid method for identifying mycobacteria. Several genes or sequences have been used as an amplified target for PCR-REA. The present study aims to evaluate the potential use of PCR-REA of gene-encoding heat shock protein 65 kDa (hsp65) and beta-subunit RNA polymerase (rpoB) for the identification of mycobacteria compared with conventional biochemical identification. Two hundreds clinical isolates, consisting of 50 isolates of Mycobacterium tuberculosis and 150 isolates of nontuberculous mycobacteria (NTM), were submitted for identification using PCR-REA and biochemical method. The results demonstrated that PCR-REA identified 188 isolates of both M. tuberculosis and NTM concordantly with biochemical identification. Discordant identification results obtained from 12 isolates, comprised of 8 M. scrofulaceum, 1 M. avium complex, 1 M. malmoense, 1 M. terrae complex, and 1 M. chelonae/abscessus. Overall, the concordant percentage of results obtained from PCR-REA compared with biochemical method was 100%, 98.8%, and 83.3% for M. tuberculosis complex, rapidly growing, and slowly growing mycobacteria, respectively, and the results of hsp65 PCR-REA was in agreement with those obtained from rpoB PCR-REA. From this study, PCR-REA appears to be a simple, rapid, and reliable method for identifying mycobacteria in a routine microbiology laboratory.
 ...
PMID:Comparative evaluation of polymerase chain reaction and restriction enzyme analysis: two amplified targets, hsp65 and rpoB, for identification of cultured mycobacteria. 1576 1

One of the major challenges raised by HIV chemotherapy is the insurgence of viral resistance to drugs. Resistance to antiviral therapy has been observed for each of the different classes of anti-viral drugs: nucleoside reverse-transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. The crucial question for AIDS drug research community is: Should we continue the search of new anti-HIV drugs which can overcome HIV resistance insurgence or should we consider resistance to anti-HIV drugs as a futile challenge? This review, focussed specifically on HIV antiprotease drugs, highlights the different strategies which have been developed to design new anti-protease drugs which could overcome HIV resistance, and also reviews the different classes of compounds (peptidomimetic or non-peptidomimetic) actually under investigation in order to face the problem of HIV resistance to drug.
 ...
PMID:Prospects for the resistance to HIV protease inhibitors: current drug design approaches and perspectives. 1617 46

To assess the prevalence of mutations associated with drug resistance in antiretroviral-naive patients in Kuala Lumpur, Malaysia, genotypic resistance testing was conducted among drug-naive HIV-1 patients attending the University Malaya Medical Center (UMMC) between July 2003 and June 2004. Reverse transcriptase (RT) and protease genes of plasma virions were sequenced from 100 individuals. The majority of the patients were recently diagnosed. Codons 20-255 of the RT and 1-96 of the protease gene were examined for major and minor mutations associated with antiretroviral resistance reported by the International AIDS Society- USA (IAS-USA) Drug Resistance Mutations Group. The prevalence of patients with at least one major mutation conferring drug resistance was 1%, with only one patient having a Y181C amino acid substitution in the RT gene that confers high-level resistance to nevirapine and delavirdine. Minor mutations were detected in high prevalence in the protease gene. Amino acid substitutions I13V, E35D, and M36I were associated with CRF01_AE while L63P, V77I, and I93L were associated with subtype B. Baseline prevalence of major mutations associated with resistance to antiretroviral drugs was low among antiretroviral-naive HIV-1 patients, suggesting that routine drug resistance testing may be unnecessary for all individuals newly diagnosed with HIV or all patients beginning antiretroviral therapy.
AIDS Res Hum Retroviruses 2006 Feb
PMID:Short communication: low prevalence of genotypic drug resistance mutations among antiretroviral-naive HIV type 1 patients in Malaysia. 1647 92

Patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome have high rates of psychiatric illness. The effective management of these psychiatric conditions can improve a patient's quality of life and may improve antiretroviral adherence. Care providers for patients with HIV infection frequently encounter clinical situations in which psychotropic medications are needed or are being used. Those clinical situations require familiarity with the broad category of medications termed "psychotropic." That familiarity should include a basic understanding of indications, adverse effects, and drug interactions. In particular, it is very important to recognize the many potential interactions based on cytochrome P450 metabolism, which is common to many psychotropics, the protease inhibitors, and the nonnucleoside reverse-transcriptase inhibitors. In a brief review of the use of psychotropic medications in patients with HIV infection, we discuss indications, adverse effects, and drug interactions for commonly used antidepressants, mood stabilizers, anxiolytics, antipsychotics, psychostimulants, and drugs of abuse.
 ...
PMID:Psychotropic medications and HIV. 1658 91

We describe the use of the l1 norm for selection of a sparse set of model parameters that are used in the prediction of viral drug response, based on genetic sequence data of the Human Immunodeficiency Virus (HIV) reverse-transcriptase enzyme. We discuss the use of the l1 norm in the Least Absolute Selection and Shrinkage Operator (LASSO) regression model and the Support Vector Machine model. When tested by cross-validation with laboratory measurements, these models predict viral phenotype, or resistance, in response to Reverse-Transcriptase Inhibitors (RTIs) more accurately than other known models. The l1 norm is the most selective convex function, which sets a large proportion of the parameters to zero and also assures that a single optimal solution will be found, given a particular model formulation and training data set. A statistical model that reliably predicts viral drug response is an important tool in the selection of Anti-Retroviral Therapy. These techniques have general application to modeling phenotype from complex genetic data.
 ...
PMID:Use of the l1 norm for selection of sparse parameter sets that accurately predict drug response phenotype from viral genetic sequences. 1677 91

Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the anti-viral effects of PCIs have also been observed against various viruses, including human immunodeficiency virus (HIV), herpes simplex virus, and murine leukemia virus. Through the inhibition of CDK2 and 9, the cellular co-factors for HIV-1 Tat transactivation, HIV-1 replication is blocked by two specific PCIs, CYC202 and flavopiridol, respectively. In this article, we will review the inhibitory mechanisms of flavopiridol and CYC202 and discuss their possible usage in AIDS treatment.
 ...
PMID:Potential use of pharmacological cyclin-dependent kinase inhibitors as anti-HIV therapeutics. 1678 40

Until today, the susceptibility of human immunodeficiency virus type 2 (HIV-2) to protease and nucleosidic reverse-transcriptase inhibitors (PI and NRTI, respectively) has not been clearly documented. In this report we studied HIV-2 proviral sequences (n = 30) from drug-naive patients. Our results revealed that several amino acid positions in the protease and reverse transcriptase coding sequence harbored residues that have been associated with drug resistance in HIV-1-infected patients. In particular, the M46I substitution in the protease was detected in 90% of the sequences analyzed, which, together with the other substitutions identified, may indicate a reduced susceptibility of HIV-2-infected drug-naive patients to PI. Furthermore, interpretation of genotypic data with four available algorithms, developed for interpretation of HIV-1 sequence data, suggested nonoverlapping profiles of drug resistance.
AIDS Res Hum Retroviruses 2006 Nov
PMID:Natural polymorphisms of HIV type 2 pol sequences from drug-naive individuals. 1714 7


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