Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS. Following entry into the host cell, the viral RNA is reverse transcribed into DNA and subsequently integrated into the host genome as a chromatin template. Chromatin structure may be responsible for silencing retroviral gene expression. Transcriptional activation occurs after ATP-dependent chromatin remodeling complexes alter chromatin structure and positioning of nucleosomes. Histone acetyltransferases (HATs), histone deacetylases (HDACs), kinases, and methyltransferases (HMTs), covalently modify nucleosomes by adding or removing chemical moieties in the N-terminal tails of histones. Recent advances have indicated that HIV-1 encoded proteins interact with chromatin remodeling complexes and histone modifying enzymes, implying that chromatin remodeling plays an important role in the HIV-1 life cycle. Nucleosomes are positioned on the HIV-1 LTR and are barriers to transcription. Following cellular activation, these nucleosomes are modified and repositioned allowing for activation of viral gene expression. Tat recruits various HATs to the HIV-1 promoter region and can also be acetylated by some of these enzymes. Unmodified Tat is involved in binding to the CBP/p300 and cdk9/cyclin T complexes and facilitates transcription initiation. Acetylated Tat dissociates from the TAR RNA structure and recruits bromodomain-containing chromatin modifying complexes such as p/CAF and SWI/SNF to facilitate transcription elongation. This review summarizes our current knowledge and understanding of chromatin remodeling complexes and their regulation of HIV-1 replication, and highlights the important contributions HIV-1 research has made to further our understanding of the transcription process.
Curr HIV Res 2003 Jul
PMID:Chromatin remodeling and modification during HIV-1 Tat-activated transcription. 1504 58

HIV-infected individuals are at risk for developing certain types of cancers. While there are data to show that non-random HIV integration may occur, our goal was to identify preferential genomic sites where HIV integration might be targeted leading to oncogenesis. Initially, a linker-primer PCR strategy was used to identify HIV integration in isolated macrophages. Inverse-PCR was then used to analyze specimens from patients diagnosed with HIV-associated malignancies. From isolated macrophages, integration near a toll-like receptor on chromosome 4 was found. Necropsy tissues from 11 cases were analyzed with 1 tumor specimen found to have HIV integrated in chromosome 22q13.2 and within 300 kb of HSCBCIP1 (CAP-binding protein complex interacting homologue). Tumor-specific primers were then used to screen uninvolved tissue from the same patient, which did not amplify the site-specific region. This report demonstrates that in both an in vitro system and human malignant tissue, specific viral integration can be identified.
 ...
PMID:Preferential HIV-1 integration sites in macrophages and HIV-associated malignancies. 1555 24

The sexual transmission of human immunodeficiency virus type 1 (HIV-1) is facilitated by inflammation and related epithelial barrier perturbation. Microbicides for vaginal applications are currently being developed to reduce the risk of HIV-1 transmission. However, little is known about their interference with epithelial immune function. In recent clinical trials, nonoxynol-9 (N-9), a virucide with a long history of intravaginal use as a contraceptive, failed to protect against HIV-1 possibly due to mucosal inflammatory damage. Cellulose acetate 1,2-benzenedicarboxylate, also named CAP (for "controls AIDS pandemic"), is an anti-HIV-1 microbicide selected from pharmaceutical excipients that are regarded as safe for oral administration but have not been assessed for potential effects on inflammatory factors in the vaginal environment. Here we use a sensitive human cell culture system to evaluate proinflammatory profiles of soluble CAP in reference to N-9 and known epithelial activators such as tumor necrosis factor alpha (TNF-alpha) and bacterial lysates. Within 6 h of exposure, TNF-alpha and N-9 triggered NF-kappaB and AP-1/cFos activation and upregulated interleukins and an array of chemokines by vaginal and polarized cervical epithelial cells. The induced proinflammatory status continued after removal of stimuli and was confirmed by enhanced transepithelial neutrophil migration. While sustaining stability and anti-HIV-1 activity in the epithelial environment, CAP did not increase the production of proinflammatory mediators during or after exposure, nor did it modify the epithelial resistance to leukocyte traffic. CAP attenuated some TNF-alpha-induced responses but did not interfere with epithelial cytokine responsiveness to gonococcal determinants. The described system may be useful for predicting proinflammatory side effects of other microbicide candidates for vaginal application.
 ...
PMID:Anti-human immunodeficiency virus type 1 microbicide cellulose acetate 1,2-benzenedicarboxylate in a human in vitro model of vaginal inflammation. 1561 12

The combination of two candidate microbicides, cellulose acetate 1,2-benzenedicarboxylate (CAP), a polymer that blocks human immunodeficiency virus type 1 (HIV-1) entry by targeting gp120 and gp41, and UC781, a tight-binding HIV-1 reverse transcriptase inhibitor (RTI), resulted in effective synergy for inhibition of MT-2 cell infection by HIV-1(IIIB), a laboratory-adapted virus strain. The 95% effective concentration values for the combination were reduced about 15- to 20-fold compared with those corresponding to the single compounds. The combination of CAP and UC781 is also synergistic in inhibiting infection of peripheral blood mononuclear cells by a primary HIV-1 isolate, 92US657. Combinations of CAP with other RTIs, such as efavirenz or zidovudine, also had significant synergistic effects on the inhibition of HIV-1 infection. In addition, CAP and UC781 had complementary effects against HIV-1 infection since (i) CAP inhibited infection by the UC781-resistant strain HIV-1(IIIB) A17 and (ii) pretreatment of MT-2 cells with UC781, but not CAP, abolished subsequent infection after removal of the compound. This suggests that the combination of CAP and UC781 represents a promising candidate microbicide for prevention of sexual transmission of HIV-1.
 ...
PMID:Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic and complementary effects against human immunodeficiency virus type 1 infection. 1585 3

A human colorectal explant culture was developed to assess the safety and efficacy of topical microbicides proposed for use in humans. Because any product marketed for vaginal application will likely be used for anal intercourse, it is important to evaluate these products in colorectal explant tissue. Microbicides tested included cellulose acetate 1,2-benzenedicarboxylate (CAP), PRO 2000, SPL7013, Vena Gel, and UC781, along with their accompanying placebos. Colorectal tissues were exposed to microbicides overnight and either fixed in formalin to evaluate toxicity by histological analysis or placed in 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) to quantitatively determine tissue viability. Histological analysis showed minimal toxicity for CAP, UC781, and Vena Gel. Shedding of epithelium with intact lamina propria occurred for the PRO 2000 and SPL7013 products, and shedding of epithelium and necrosis of the lamina propria occurred in explants cultured with nonoxynol-9. The MTT assay confirmed these results for PRO 2000 (4% and 0.5%), SPL7013 (and placebo), and nonoxynol-9 but also demonstrated reduced viability for CAP. However, viability of tissues treated with all products was not significantly different from that of the medium control. Efficacy of the microbicides was evaluated by measuring human immunodeficiency virus type 1 (HIV-1) infection of explants in the absence or presence of products. All microbicide formulations tested were highly effective in preventing HIV infection. However, explants treated with some of the placebo formulations also exhibited a lower level of infection. Most of the products developed for vaginal application showed minimal toxicity and were effective in reducing HIV-1 infection in colorectal tissues. These results suggest that this model is useful for evaluating the safety and efficacy of topical microbicides when used rectally.
 ...
PMID:A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection. 1620 69

Traditional, complementary and alternative medicine (TM/CAM) is globally increasing in popularity. The World Health Organization (WHO) has advocated for the integration of TM/CAM in national public health policies to enhance health care resources. Interest in collaboration between traditional and biomedical health sectors has been renewed in attempts to strengthen control of the AIDS epidemic. However, studies exploring communities' views on the prerequisites for such collaboration are inexistent. We conducted 21 focus group discussions with community members in two Zambian urban centres (Ndola and Kabwe) to explore their perspectives on preconditions for useful collaboration between traditional and modern health workers in the management of STIs and HIV/AIDS. This study shows that laypersons' perspectives can be rich and inform complex policy issues. Five categories indicating key areas of actions were identified, including protection of traditional medicine and of compensation of healers, education of both groups of providers and adequate community involvement. The respect for some degree of secrecy in traditional medicine was also called for. As part of efforts to strengthen available resources for better care of STI/HIV/AIDS, this study provides policymakers, researchers and practitioners with an outline of fundamentals in terms of needed crucial changes at health policy level, among providers and in the community for sustainable collaboration between modern and traditional health practitioners.
 ...
PMID:Communities' views on prerequisites for collaboration between modern and traditional health sectors in relation to STI/HIV/AIDS care in Zambia. 1629 Jan 28

To determine the impact of initial antimicrobial choice on 30-day mortality rate in patients with community-acquired pneumonia due to Streptococcus pneumoniae (CAP-SP), a prospective, observational study was conducted in 35 Spanish hospitals. A total of 638 patients with CAP-SP were identified. Antimicrobials were chosen by the attending physician. Patients were grouped into the following categories: beta-lactam monotherapy (n = 251), macrolide monotherapy (n = 37), beta-lactam plus macrolide (n = 198), levofloxacin alone/combination (n = 48), and other combinations (n = 104). The reference category was beta-lactam+macrolide. The 30-day survival probability was 84.9%. Using multivariate survival analysis, factors related to mortality in the entire population were: bilateral disease, suspected aspiration, shock, HIV infection, renal failure and pneumonia severity index (PSI) score Class IV versus I-III and categories V versus I-III. The association of beta-lactams+macrolides was not better than the use of beta-lactams alone. The current authors analysed the different groups of patients with significant mortality/morbidity: intensive care unit, PSI Class >III, renal failure, chronic lung disease and bacteraemia. Only in patients with PSI Class >III, who had undergone initial antimicrobial choice classified as other combinations, were associated with higher mortality. In conclusion, the current authors have not demonstrated an independent association between initial antimicrobial regimen and 30-day mortality in community-acquired pneumococcal pneumonia patients, except for those with a higher pneumonia severity index score.
 ...
PMID:Impact of initial antibiotic choice on mortality from pneumococcal pneumonia. 1645 24

The non-tuberculous mycobacteriosis (NTM) is not a unitary disease. It is a general term for the bronchopulmonary diseases caused by any mycobacterium other than M. tuberculosis. We don't call the pulmonary "pseudomoniosis" for the diffuse bronchiectasis caused by Pseudomonas aeruginosa, though conditions of the disease looks like NTM. The name of NTM represents that the causativebacteria belong to the same species with M. tuberculosis which causes serious pulmonary infectious disease. The pulmonary diseases caused by M. kansasii or M. szulgai are usually treated by RFP, EB and INH, the same regimens with tuberculosis, which generally lead to sufficient results for patients. But for MAC diseases, the number of patients is top of NTM in Japan, recent treatment with new-macrolides and some anti-tuberculous drugs generally does not bring about the desired effect. The plenty clinical experiences for NTM in HIV positive patients have lead to such new regemens in the USA. For NTM caused by rare Mycobacterium detectedvery seldom, clinical experiences and knowledge are definitely insufficient. (1) Present state of therapy for pulmonary MAC disease (drug therapy): Yoshihiro KOBASHI (Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama Prefecture) Co-operative study of Research Committee of Mycobacterium in the Chugoku and Shikoku areas revealed that the combined therapy according to the guidline is clinically appropriate for pulmonary Mycobacterium avium complex (MAC) disease. (2) Relapse and chemotherapy duration of pulmonary Mycobacterium avium complex infection: Atsuyuki KURASHIMA (Division of Clinical Research, National Organization Tokyo National Hospital, Kiyose, Tokyo) Reviewing the 71 relapses out of 1170 pulmonary MAC infection cases, he indicated that 11.3% relapsed during the chemotherapy continuation, 23.9% after the reduction of chemotherapy, 64.8% after the termination of chemotherapy. In the last group, there is no correlation to the relapse period after the end of treatment with the preceding chemotherapy duration. It is supposed that the main cause of these relapses are enviromental re-infection. (3) Chemotherapy for pulmonary M. kansasii disease: Katsuhiro SUZUKI (Clinical Research Center, Nationl Organization Kinki-chuo Chest Medical Center, Sakai, Osaka) Analysis of 938 pulmonary mycobacteriosis in 2003 revealed that 244 (26%) patients suffered from NTM, in which 66 (27% of NTM) were M. kansasii disease. The 48 (73%) patients were male. From 2001 to 2004, in the 190 M. kansasii patients treated by anti-tuberculous drugs, H/R/E prescribed for 84 cases (44%), other 41% of prescriptions included CAM and (or) LVFX. Almost all patients were converted into bacilli negative in about 30 days with any prescription. (4) Treatment and management for NTM patients in aprivate clinic: Seiji MIZUTANI (Mizutani Respiratory Clinic, Nerima ward, Tokyo) Analysing clinical experiences, he emphasized that most NTM patients with some symptoms visits private clinics in the first place. In Japan, diagnosis of NTM with radiological and bacteriological examinations is not difficult, and most NTM patients can be controlled as the outpatients of the clinics. (5) Surgical Treatment for non-tuberculous mycobacteriosis: Kouji KIKUCHI (Division of Chest Surgery, Medical Center, Saitama Medical School, Iruma county, Saitama Prefecture) The 9 NTM cases surgically treated were analysed, 8 were MAC cases and 1 was M. kansasii case. The main reasons for sugical resection were, continuous hemoptisis, continuous productive cough, or exacerbation on chest X-ray features. The NTM bacilli were positive in 8 cases, another one was bacilli negative, though X-ray shadows increased. After the surgery, expectoration of bacilli converted to negative in 5 SPECIAL COMMENTARIES: Can pneumonectomy be an acceptable procedure for non-tuberculous mycobacterial infection?: Yuji SHIRAISHI (Division of Chest Surgery, Fukujuji Hospital, Kiyose, Tokyo) The 11 NTM patients were analysed, who underewent pneumonectomy. The median blood loss was 555 ml and there was no operative mortality. Bronchpleural fistula or empyema occured in 4 patients. The bacilli negative conditions were achieved in all patients after surgery. The NTM is not a legal epidemic disease and Japanese Tuberculosis Prevention Act doesn't cover this disease. The medical treatment insurance system doesn't contain the NTM in the list of applicable diseases in Japan. Though these some problems with increasing numbers of patients remain in clinical practice, chairpersons hope that this symposium will be a milestone for the generalized progress of treatment and management of NTM in Japan.
 ...
PMID:[Treatment of non-tuberculous pulmonary mycobacteriosis]. 1647 99

The lymphocyte profile of 521 HIV-infected subjects hospitalized at Jackson Memorial (2001-2002) was compared across main respiratory diseases. Study data included medical history and all laboratory evaluations performed during hospitalization. Community-acquired pneumonias (CAP, 52%), Pneumocystis jiroveci pneumonia (PCP, 24%), tuberculosis (TB, 9%) and non-tuberculous mycobacterial diseases (NTM, 12%) were the most frequent causes of admission. Patients hospitalized with PCP and NTM exhibited the lowest CD4 counts (P=0.003). PCP patients had the highest B-cell percentages (P=0.04). CAP patients had the highest CD8 and CD4 percentages and the lowest percentage of Natural Killer (NK) cells and viral burdens. TB patients exhibited the lowest NK-cell (11.4+/-6.3) and B-cell percentages (13.6+/-12) and the highest CD8 (59+/-14) percentage. NTM patients, in contrast, had the highest NK-cell percentages of the groups (19.1+/-11.6, P=0.01). Additionally, immune responses associated with respiratory pathogens differed in HIV-infected patients with CD4(+) cells above and below 200 counts.
 ...
PMID:Cellular immune response to pulmonary infections in HIV-infected individuals hospitalized with diverse grades of immunosuppression. 1649 Jan 30

Cellulose acetate 1,2-benzenedicarboxylate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was previously shown to have potent inhibitory activity against infection by human immunodeficiency virus type 1 (HIV-1) T cell line-adapted (TCLA) strains. In the present study, we determined the inhibitory activity of CAP against infection by cell-free and cell-associated primary HIV-1 isolates with distinct genotypes and biotypes in cervical explants, peripheral blood mononuclear cells (PBMCs), monocytederived macrophages (MDMs), and CEMx174 5.25M7 cells. CAP blocked infection by cell-free and cell-associated HIV-1 in cervical explants. It inhibited infection by cell-free primary HIV-1 isolates (clades A to G and group O) in PBMCs, MDMs, and CEMx174 5.25M7 cells and blocked transmissions of the cell-associated primary HIV-1 isolates from dendritic cells (DCs) to PBMCs, from MDMs to PBMCs, and from PBMCs to CEMx174 5.25M7 cells. The inhibitory activity of CAP on infection by the cell-free and cell-associated primary HIV-1 isolates is independent of viral subtypes and coreceptor usage. These data suggest that CAP is a good microbicide candidate that can be further developed for preventing sexual transmission of HIV-1.
 ...
PMID:Cellulose acetate 1,2-benzenedicarboxylate inhibits infection by cell-free and cell-associated primary HIV-1 isolates. 1670 17


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