UMLS:C0019693 - FACTA Search

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Query: UMLS:C0019693 (HIV)
170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increased incidence of HIV/AIDS disease in women aged 15 - 49 years has identified the urgent need for a female-controlled, efficacious and safe vaginal topical microbicide. To meet this challenge, new topical microbicide candidates consisting of molecules or formulations that modify the genital environment (BufferGel, engineered Lactobacillus, over-the-counter lubricants), surfactants (C31D/Savvy, sodium dodecyl sulfate, sodium lauryl sulfate), polyanionic polymers (PRO 2000, beta-cyclodextrin, Carraguard, CAP, D2S, SPL-7013), proteins (cyanovirin-N, monoclonal antibodies, thromspondin-1 peptides, Pokeweed antiviral protein and others), reverse transcription inhibitors (PMPA [Tenofovir ]), UC-781, SJ-3366, DABO and thiourea) and other molecules (NCp7-specific virucides, chemokine receptor agonists/antagonists, WHI-05 and WHI-07) are currently being investigated for activity, safety and efficacy. This review will assess the development of these molecules in the context of cervicovaginal defences and the clinical failure of nonoxynol-9.
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PMID:Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. 1215 Jul 3

CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8(+) T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.
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PMID:Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor. 1219 9

The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a promiscuous activator of viral and cellular promoters. We report that Vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to p/CAF or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting protein 1. Vpr forms a stable complex with p300 and also interacts with the ligand-bound glucocorticoid receptor in vivo. Mutation analysis showed that the C-terminal part of Vpr binds to the C-terminal portion of p300/CBP within amino acids 2045 to 2191. The same p300 region interacts with the p160 coactivators and with the adenovirus E1A protein. Accordingly, E1A competed for binding to p300 in vitro. Coexpression of E1A or of small fragments of p300 containing the Vpr binding site resulted in inhibition of Vpr's transcriptional effects. The C-terminal part of p300 containing the transactivating region is required for Vpr transactivation, whereas the histone acetyltransferase enzymatic region is dispensable. Vpr mutants that bind p300 but not the GR did not activate expression of the MMTV promoter and had dominant-negative effects. These results indicate that Vpr activates transcription by acting as an adapter linking transcription components and coactivators.
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PMID:Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators. 1220 51

It has been known since 1986 that CD8 T lymphocytes from certain HIV-1-infected individuals who are immunologically stable secrete a soluble factor, termed CAF, that suppresses HIV-1 replication. However, the identity of CAF remained elusive despite an extensive search. By means of a protein-chip technology, we identified a cluster of proteins that were secreted when CD8 T cells from long-term nonprogressors with HIV-1 infection were stimulated. These proteins were identified as alpha-defensin 1, 2, and 3 on the basis of specific antibody recognition and amino acid sequencing. CAF activity was eliminated or neutralized by an antibody specific for human alpha-defensins. Synthetic and purified preparations of alpha-defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that alpha-defensin 1, 2, and 3 collectively account for much of the anti-HIV-1 activity of CAF that is not attributable to beta-chemokines.
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PMID:Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. 1473 39

Outcome studies examining the efficacy of CAM among people living with HIV-AIDS are often conducted among small sample sizes with very little follow-up data or time points. Generalizability of many of the study findings is further limited by participant attrition. It is difficult to conduct clinical studies on chronically ill patients without participants dropping out, typically because the study demands coupled with their illness become too burdensome. Several studies have been conducted that include control groups, double-blind designs, and randomization. These scientifically sound studies have demonstrated promising results that strongly indicate a need for further research with larger samples in a prospective research design so that safety and efficacy can be determined over time. Many of the studies with small sample sizes reported trends, but did not find statistical significance. Increasing sample sizes in future studies is necessary to evaluate the scientific merit of these trends. Moreover, researchers need to evaluate the clinical and statistical significance in CAM use. The psychologic benefits of taking CAM should not be underestimated. For the purposes of this article, the authors did not include psychologic outcomes; however, there is evidence suggesting that decreasing depression can decrease HIV-related somatic complaints [69]. Studies need also to examine the effectiveness of CAM on psychologic outcomes and physical outcomes. This article and the authors' own research (Gore-Felton C et al, unpublished data) have revealed a high prevalence of alternative supplement use in conjunction with HIV medication, indicating an urgent need to understand the health benefits and the health risks of alternative supplements among patients with HIV and AIDS. Patients and physicians need more empirically based research to examine the toxicities, interactions, and health benefits of CAM. Many patients do not report the use of CAM to their physicians and very few physicians record treatments in the clinical record [70]. This will likely change as CAM becomes more widely recognized as a legitimate medical intervention; however, controlled outcome studies among large, diverse samples of people living with HIV-AIDS are needed. Health care providers need to assess the use of herbal and alternative therapy practices by their patients. Some patients may not be aware that they are taking a supplement or plant-based herb. Furthermore, some patients may believe that they are using something innocuous and even healthy simply because it came from a health food store. Understanding the contraindications of alternative therapies is necessary to prevent deleterious outcomes and to facilitate the safe and efficacious use of CAM in the management of HIV disease and related symptoms. As the epidemic in the United States continues to rise among women and minority populations, clinical research trials must include ethnically diverse patient populations that are gender balanced. Current available studies indicate that many CAM interventions may improve the quality of life of people living with HIV-AIDS; however, further studies using longitudinal, controlled designs are needed to accurately assess the safety of such interventions.
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PMID:HIV: effectiveness of complementary and alternative medicine. 1239 16

In this preliminary study, we evaluated the performance of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test (CAP; Roche Molecular Systems, Branchburg, NJ) for automated specimen preparation and quantitative detection of human immunodeficiency virus type 1 (HIV-1) RNA and compared it to the Cobas Amplicor HIV-1 Monitor Ultrasensitive Test (MCA; Roche), which includes a manual sample preparation protocol. A dilution panel of a patient sample was prepared. Additionally, 584 EDTA plasma samples were collected from HIV-1 infected patients. Reproducibility was estimated with six assay runs using the dilution panel. The inter-assay coefficient of variation ranged from 39.4 to 48.4% (CAP assay) and from 34.3 to 45.6% (MCA assay), whereas the intra-assay coefficient of variation ranged from 6.2 to 58.0% (CAP assay) and from 4.4 to 57.3% (MCA assay). Comparison of CAP assay results with the HIV-1 copy number of the dilution panel determined by the MCA assay resulted in a good agreement, although the CAP results were found to be slightly lower. A significant correlation between both test systems was found when clinical samples were analyzed. The mean viral load of 152 samples, which were within the linear range of both tests, was 3.70 log(10) HIV-1 copies/ml by the CAP assay compared to 3.73 by the MCA assay. In conclusion, we could demonstrate that the new Cobas AmpliPrep/Cobas Amplicor HIV Monitor Ultrasensitive Test is reproducible and sensitive. In comparison to the assay with manual extraction, no significant difference in HIV-1 RNA copy numbers was observed.
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PMID:Evaluation of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test: comparison with the Cobas Amplicor HIV-1 Monitor test (manual specimen preparation). 1246 84

We recently demonstrated that a unique HIV-1-infected nonprogressor was infected with a nonevolving replication-incompetent HIV-1 strain, showing a total absence of viral evolution in vivo. Potent immune responses against HIV-1 were observed in his PBMC, despite an apparent lack of viral replication for at least 8 years. His PBMC resisted superinfection with CCR5, CXCR4, and dual-tropic HIV-1 strains, although highly purified CD4+ T cells supported infection, but without any visible cytopathic effect. Potent noncytolytic CD8+ T cell antiviral activity was shown to protect his PBMC from productive infection. This activity was not mediated by several known chemokines or IFN-gamma, which were produced at high levels after PHA activation of his CD8+ T cells, indicating the action of other CAF-like CD8 factors. This antiviral activity was a memory response, induced by HIV-specific stimulation to similar levels observed by PHA stimulation, but absent in ex vivo resting T cells. Immunological mechanisms associated with this antiviral suppressive activity included vigorous Gag-specific helper T cell proliferative responses and high-level IFN-gamma release by both CD4 and CD8 T cells. These responses were broadly directed against multiple Gag epitopes, both previously reported and some novel epitopes. Strong HIV-specific helper T cell function was also associated with strong neutralizing antibodies. Understanding how to induce these protective immune responses in other individuals could provide a major step forward in the design of effective immunotherapies or vaccines against HIV infection.
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PMID:Comprehensive analyses of a unique HIV-1-infected nonprogressor reveal a complex association of immunobiological mechanisms in the context of replication-incompetent infection. 1250 66

Interleukin-2 (IL-2) is a cytokine produced by lymphocytes T CD4+, T CD8+ and NK cells. IL-2 increases the number of lymphocytes T and prolongs their survival and has extensive immunomodulatory effect. High levels of IL-2 are observed during asymptomatic phase of HIV infection (TH-1 dependent cytokine) and low levels are observed during progression of immunodeficiency. IL-2 inhibits apoptosis of CD4+ T cells, improves NK cells activity, has influence on production of soluble antiviral factor (CAF) which inhibits viral activity etc. That is why IL-2 has been introduced to the treatment of HIV infection along with highly active antiretroviral therapy (HAART). High T CD4+ cells count predicts long survival of HIV infected individual. Phase III clinical trials concerning IL-2 are now performed and the preliminary results are promising. Polish centers also take part in the ESPRIT study. Adverse events of various severity are seen in patients under treatment (anti inflammatory drugs are required). The symptoms usually resolve within a few days after IL-2 therapy is stopped.
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PMID:[The role of therapeutic use of interleukin-2 in HIV infection]. 1266 84

CD8(+) T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that alpha-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether alpha-defensins, particularly alpha-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant alpha-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8(+) cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with alpha-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, alpha-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, alpha-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8(+) cells with potent HIV-1 inhibitory activity and a neutralizing antibody against alpha-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that alpha-defensin-1 inhibits HIV-1 infection following viral entry but that alpha-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.
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PMID:CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from alpha-defensin-1 HIV inhibition. 1276 98

A multicenter study of 638 cases of community-acquired pneumonia due to Streptococcus pneumoniae (SP-CAP) was performed to assess current levels of resistance. Of the pneumococcal strains, 35.7% had an minimum inhibitory concentration (MIC) of penicillin of > or =0.12 microg/mL (3 isolates had an MIC of 4 microg/mL), 23.8% had an MIC of erythromycin of 128 microg/mL, and 22.2% were multidrug resistant. Logistic regression determined that chronic pulmonary disease (odds ratio [OR], 1.44], human immunodeficiency virus infection (OR, 1.98), clinically suspected aspiration (OR, 2.12), and previous hospital admission (OR, 1.69) were related to decreased susceptibility to penicillin, and previous admission (OR, 1.89) and an MIC of penicillin of MIC > or =0.12 microg/mL (OR, 15.85) were related to erythromycin resistance (MIC, > or =1 microg/mL). The overall mortality rate was 14.4%. Disseminated intravascular coagulation, empyema, and bacteremia were significantly more frequent among patients with penicillin-susceptible SP-CAP. Among isolates with MICs of penicillin of > or =0.12 microg/mL, serotype 19 was predominant and was associated with a higher mortality rate. In summary, the rate of resistance to beta -lactams and macrolides among S. pneumoniae that cause CAP remains high, but such resistance does not result in increased morbidity.
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PMID:Drug-resistant pneumococcal pneumonia: clinical relevance and related factors. 1547 72

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