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

Recent studies have shown that progesterone, a sex steroid hormone, enhances the sexual transmission of various pathogens, including SIV. The goal of this study was to determine whether progesterone affects mechanisms underlying the sexual transmission of HIV-1. We first studied the effects of various physiologic concentrations of progesterone on the expression of chemokines and chemokine receptors by T cells and macrophages. Chemokines are involved in leukocyte recruitment to peripheral sites; in addition, the chemokine receptors CCR5 and CXCR4 are HIV-1 coreceptors, and their ligands can block HIV-1 infection. Progesterone treatment had no effect on constitutive expression of CCR5 and CXCR4 by nonactivated T cells and macrophages, but significantly inhibited IL-2-induced up-regulation of CCR5 and CXCR4 on activated T cells (p < 0.05). Progesterone also inhibited both mitogen-induced proliferation and chemokine secretion (macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, RANTES) by CD8+ T lymphocytes. Control and progesterone-treated PBMC cultures were also tested for susceptibility to infection by T cell-tropic (HIV-1MN) and macrophage-tropic (HIV-1JR-CSF) viral strains in vitro. Infection with low titers of HIV-1MN was consistently inhibited in progesterone-treated cultures; progesterone effects on infection with the HIV-1JR-CSF strain were more variable, but correlated with progesterone-induced reductions in CCR5 levels. These results indicate that progesterone treatment can inhibit mechanisms underlying HIV-1 transmission, including infection of CD4+ target cells via CXCR4/CCR5 coreceptors and effects on chemokine-mediated recruitment of lymphocytes and monocytes to mucosal epithelia.
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PMID:Progesterone-induced inhibition of chemokine receptor expression on peripheral blood mononuclear cells correlates with reduced HIV-1 infectability in vitro. 1035 6

Over the past decade, the involvement of tyrosine kinases in signal transduction pathways evoked by cytokines has been intensively investigated. Only relatively recently have the roles of serine/threonine kinases in cytokine-induced signal transduction and anti-apoptotic pathways been examined. Cytokine receptors without intrinsic kinase activity such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and the interferons were thought to transmit their regulatory signals primarily by the receptor-associated Jak family of tyrosine kinases. This family of tyrosine kinases activates STAT transcription factors, which subsequently transduced their signals into the nucleus to modulate gene expression. Cytokine receptors with intrinsic tyrosine kinase activity such as c-Kit were initially thought to transduce their signals independently of serine/threonine kinase cascades. Recently, both of these types of receptor signaling pathways have been shown to interact with serine/threonine kinase pathways as maximal activation of these tyrosine kinase regulated cascades involve serine/threonine phosphorylation modulated by, for example MAP kinases. A common intermediate pathway initiating from cytokine receptors is the Ras/Raf/MEK/ERK (MAPK) cascade, which can result in the phosphorylation and activation of additional downstream kinases and transcription factors such as p90Rsk, CREB, Elk and Egr-1. Serine/threonine phosphorylation is also involved in the regulation of the apoptosis-controlling Bcl-2 protein, as certain phosphorylation events induced by cytokines such as IL-3 are anti-apoptotic, whereas other phosphorylation events triggered by chemotherapeutic drugs such as Paclitaxel are associated with cell death. Serine/threonine phosphorylation is implicated in the etiology of certain human cancers as constitutive serine phosphorylation of STATs 1 and 3 is observed in chronic lymphocytic leukemia and can be inhibited by the chemotherapeutic drug fludarabine. Serine/threonine phosphorylation also plays a role in the etiology of immunodeficiencies. Activated STAT5 proteins are detected in reduced levels in lymphocytes recovered from HIV-infected individuals and immunocompromised mice. Serine/threonine phosphorylation may be an important target of certain chemotherapeutic drugs which recognize the activated proteins. This meeting report and mini-review will discuss the interactions of serine/threonine kinases with signal transduction and apoptotic molecules and how some of these pathways can be controlled by chemotherapeutic drugs. Leukemia (2000) 14, 9-21.
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PMID:Serine/threonine phosphorylation in cytokine signal transduction. 1063 71

Human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins interact with CD4 and chemokine receptors on T cells to deliver signals that trigger either activation, anergy, or apoptosis. However, the molecular mechanisms driving these responses remain poorly understood. In this study we demonstrate that apoptosis is induced upon HIV-1 envelope binding to the chemokine receptor CXCR4. Cells expressing a mutant form of CXCR4 with a C-terminal deletion were also sensitive to HIV-1 envelope-mediated apoptosis, indicating that the cytoplasmic tail of CXCR4 is not required to induce the apoptotic pathway. The specificity of this process was analyzed using several inhibitors of gp120-CD4-CXCR4 interaction. Monoclonal antibodies directed against the gp120-binding site on CD4 (ST4) and against CXCR4 (MAB173) prevented the apoptotic signal in a dose-dependent manner. The cell death program was also inhibited by SDF-1alpha, the natural ligand of CXCR4, and by suramin, a G protein inhibitor that binds with a high affinity to the V3 loop of HIV-1 gp120 envelope protein. These results highlight the role played by gp120-binding on CXCR4 to trigger programmed cell death. Next, we investigated the intracellular signal involved in gp120-induced apoptosis. This cell death program was insensitive to pertussis toxin and did not involve activation of the stress- and apoptosis-related MAP kinases p38(MAPK) and SAPK/JNK but was inhibited by a broad spectrum caspase inhibitor (z-VAD.fmk) and a relatively selective inhibitor of caspase 3 (z-DEVD.fmk). Altogether, our results demonstrate that HIV induces a caspase-dependent apoptotic signaling pathway through CXCR4.
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PMID:Caspase-dependent apoptosis of cells expressing the chemokine receptor CXCR4 is induced by cell membrane-associated human immunodeficiency virus type 1 envelope glycoprotein (gp120). 1070 41

There is a paucity of normative data on hormonal levels among HIV-infected women. Hormonal levels may influence fertility and HIV-related immunological and virological factors. The objective of this study was to determine progesterone and estradiol levels during the menstrual cycle in HIV-seropositive women compared with high-risk seronegative women. The study enrolled 55 HIV-infected and 10 high-risk uninfected women with self-reported regular menstrual cycles (25-30-day cycles). Progesterone and estradiol levels were determined on a weekly basis for 8 weeks. The analysis included evaluations from the first complete menstrual cycle for the 54 HIV-infected and 9 uninfected women who had at least one complete cycle. The median age was 35 years for HIV-infected women and 36 years for uninfected women. The median CD4+ count for HIV-seropositive women was 210 cells/mm3. The median menstrual cycle length was 28 days (range 22-49 days) for HIV-infected women and 25 days (range 24-44 days) for uninfected women. The maximum progesterone level during the luteal phase was normal (>3.0 ng/ml) for 52 (96%) of 54 HIV-seropositive women and 7 (78%) of 9 HIV-seronegative women (p = 0.09, Fisher's exact test). The median maximum progesterone level was 12.2 ng/ml in HIV-seropositive women and 7.2 ng/ml in HIV-seronegative women (p = 0.07, Wilcoxon test). The median maximum estradiol value during the follicular phase was 148 pg/ml for HIV-seropositive women and 111 pg/ml for HIV-seronegative women (p = 0.04, Wilcoxon test). Among HIV-infected women, there were no significant differences in progesterone and estradiol levels by antiretroviral therapy, baseline plasma viral load, or median CD4+ cell count. We conclude that HIV-infected women with self-reported normal menstrual cycles have normal levels of progesterone and estradiol during the menstrual cycle.
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PMID:Hormonal levels among HIV-1-seropositive women compared with high-risk HIV-seronegative women during the menstrual cycle. Women's Health Study (WHS) 001 and WHS 001a Study Team. 1107 51

The female condom is the latest in a series of sexual and reproductive technologies to be imported into the third world, following the contraceptive pill, the Depo-Provera injection, the latex male condom, and others. It is an example of "traveling technology", which accrues different meanings and connotations in the different settings into which it is introduced in its journey through the circuits of international technological diffusion, from the headquarters of international NGOs and bilateral aid programs, through the bureaucracies of national ministries of health to the communities in urban and rural settings where the condoms are distributed. The female condom almost always carries connotations of women's empowerment, and the possibility of greater sexual autonomy for women. This association is a result of the female condom being the first new "post-Cairo" technology, the diffusion of which was spurred by the consensus reached at the 1994 International Conference on Population and Development in Cairo, at which the need to promote women's empowerment was moved to the center of international family planning and population movements. However, I demonstrate that "empowerment" is an ambiguous term, interpreted in different ways in different contexts. I illustrate this through interviews conducted in 1998 and 1999 with stakeholders in the female condom in Cape Town, Nairobi, and in rural western Kenya. These stakeholders range from directors of US-based development programs to heads of national AIDS-prevention efforts to community-based distributors and primary health care nurses at the village level. I argue that three different notions of empowerment are being articulated with respect to the female condom--two which correspond to Maxine Molyneux's typology of strategic and practical gender interests, and a third in which women's empowerment is conceived of as something which diminished the power of men. I argue further that the disjunctures between these three different notions of what "empowerment" means will pose a challenge for people at all levels which are seeking to make the female condom more widely accessible to women at risk of HIV/AIDS.
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PMID:"It's some kind of women's empowerment": the ambiguity of the female condom as a marker of female empowerment. 1121 80

The National Institute of Child Health and Human Development (NICHD) in Bethesda, MD, is conducting a study on how various contraceptives affect HIV transmission. Diaphragms and cervical caps are effective contraceptive shields, but are less reliable against pregnancy and sexually transmitted diseases than the male condom. NICHD is evaluating a new customized cervical cap that would be fitted in one visit by a health care provider. Other contraceptives, including a modified diaphragm, a vaginal sponge, and vaginal ring that would release a contraceptive hormone, are also in development. Only three new contraceptives have been approved this decade: the female condom; Norplant, a hormonal implant; and Depo-Provera, an injectable hormone. The NICHD is also investigating whether the use of hormonal contraceptives increases HIV risk. The agency recently reported that the physiologic effects of hormonal contraceptives may affect HIV transmission.
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PMID:Contraceptives' role in HIV transmission is examined. 1136 41

Several small studies conducted by the Centers for Disease Control and Prevention (CDC) have shown that although progesterone appears to increase the likelihood of simian immunodeficiency virus (SIV) transmission in exposed monkeys, women using hormone contraceptives do not appear to have the same increased risk for HIV. The results, published in the May issue of Science, show little, if any, increase in the rate of HIV infection in women on Depo-Provera, an injectable contraception containing progestin, compared to those who were not taking it. Another study, conducted in Thailand, found similar results. However, this contrasts sharply with the results of a monkey study that found that rhesus monkeys given progesterone experienced significant thinning of the vaginal wall. Researchers are examining the effects of progesterone on the lining of the vagina. Researchers are finding some thinning, but not to a significant degree. The CDC continues to stress that only abstinence or the use of latex condoms can prevent the spread of AIDS.
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PMID:Progesterone-HIV link questioned by new studies. 1136 49

After a recent study showing that monkeys given progesterone are more likely to acquire simian immunodeficiency virus (SIV), women's reproductive health experts are advising clinicians to stress the importance of condom use and calm worried women by pointing out that other studies are needed to understand the relationship between hormones and HIV risk. Researchers have learned that progestin causes a thinning of the vaginal wall--possibly an explanation for the increase in SIV infection in the monkey study. Because Depo-Provera and Norplant are long-acting progestin-based contraceptives, women using them to prevent pregnancy may be especially alarmed by reports of the monkey study. Women should be advised that using these contraceptives do protect them from pregnancy; women should assess the risk of contracting HIV or other sexually transmitted diseases; and women should modify their behavior to lower their risk.
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PMID:Advice for women seeking progesterone counseling. 1136 50

An animal study with rhesus macaque monkeys showed that those who received subcutaneous progesterone implants were 7.7 times more likely to become infected with SIV. The findings raised strong concerns about two contraceptives on the market that contain progesterone, Depo-Provera and Norplant. The findings are not necessarily applicable to humans, and further research is needed to learn how hormones affect HIV transmission in women. Researchers caution that the findings do not merit a woman changing her birth control method.
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PMID:The influence of hormones and HIV genital transmission in women. 1136 34

Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S(169)-Q(170)-K(171)-E(172)-G(173) of CCR5 and E(179)-A(180)-D(181)-D(182)-R(183) of CXCR4) which are components of the undecapeptidyl arch (UPA: from R(168) to C(178) in CCR5, from N(176) to C(186) in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4). Of the antibodies raised, one monoclonal antibody, CPMAb-I (IgMkappa), reacted with cCD-MAP, but not with the linear chimeric dodecapeptide-MAP. The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors. Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4(+) cell clone 1-10 (MAGIC-5). Moreover, CPMAb-I interfered with LAV-1(BRU) infection (m.o.i. = 0.01) of Molt4#8 cells cocultured with CPMAb-I-producing hybridoma in the transwell, and significantly interfered with neither chemotaxis nor calcium influx induced with stromal cell-derived factor 1 alpha (SDF-1alpha). Thus, the antibody raised against the cCD-MAP provides powerful protection or defense against HIV-1 infection. We therefore propose the cCD-MAP or its derivative immunogen as a novel candidate for an HIV-1 coreceptor-based self-defense vaccine.
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PMID:Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4. 1147


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