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

Assays were developed to assess a variety of conditions and presentations of infectious HIV to potential inactivating sources. A range of commercially available disinfectants with active constituents including glutaraldehyde, chlorine, phenolics, alcohol, iodine and quaternary ammonium compounds was tested. In addition, u.v. light was investigated as a potential inactivating source. All products were assessed against cell-free HIV in culture medium and cell-associated HIV suspended in medium or whole human blood. All products completely inactivated cell-free HIV following a 1 min exposure. However, cell-associated HIV was more resilient, requiring exposure of 5 min or more for some disinfectants. The effectiveness of the disinfectants was further compromised in the presence of blood.
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PMID:Susceptibility of HIV to inactivation by disinfectants and ultraviolet light. 852 73

Halogenated gomisin J (a derivative of lignan compound), represented by the bromine derivative 1506 [(6R, 7S, S-biar)-4,9-dibromo-3,10-dihydroxy-1,2,11,12-tetramethoxy-6, 7-dimethyl-5,6,7,8- tetrahydrodibenzo[a,c]cyclo-octene], was found to be a potent inhibitor of the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) on MT-4 human T cells (50% effective dose, 0.1 to 0.5 microM). Gomisin J derivatives were active in preventing p24 production from acutely HIV-1-infected H9 cells. The selective indices (toxic dose/effective dose) of these compounds were as high as > 300 in some systems. 1506 was active against 3'-azido-3'-deoxythymidine-resistant HIV-1 and acted synergistically with AZT and 2',3'-ddC. 1506 inhibited HIV-1 reverse transcriptase (RT) in vitro but not HIV-1 protease. From the time-of-addition experiment, 1506 was found to inhibit the early phase of the HIV life cycle. A 1506-resistant HIV mutant was selected and shown to possess a mutation within the RT-coding region (at position 188 [Tyr to Leu]). The mutant RT expressed in Escherichia coli was resistant to 1506 in the in vitro RT assay. Some of the HIV strains resistant to other nonnucleoside HIV-1 RT inhibitors were also resistant to 1506. Comparison of various gomisin J derivatives with gomisin J showed that iodine, bromine, and chlorine in the fourth and ninth positions increased RT inhibitory activity as well as cytoprotective activity.
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PMID:Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase. 854 Jul 6

A series of novel 3'-C-branched 2',3'-dideoxynucleosides have been synthesized and evaluated as anti-HIV agents. Hydroboration of 2',3'-dideoxy-3'-C-methylene nucleoside proceeded regio- and stereoselectively to give 1-(2,3-dideoxy-3-C-hydroxy methyl-5-O-trityl-beta-D-threo-pentofuranosyl)thymine (5) after oxidation. 3'-C-Chloromethyl and 3'-C-iodomethyl 5'-O-protected 2',3'-dideoxynucleosides 9 and 12 were obtained from 5 by reaction with carbon tetrachloride/triphenylphosphine and methyltriphenoxyphosphonium iodide, respectively. Arbuzov reaction of 12 with triethyl phosphite afforded 3'-C-(diethyl-phosphono)methyl 5'-O-protected 2',3'-dideoxynucleoside 14. Compounds 5, 9, 12 and 14 were detritylated to give 1-(3-C-chloromethyl-2,3-dideoxy-beta-D-threo-pentofuranosyl)thymine (10), 1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)-thymine (11), 1-(2,3-dideoxy-3-C-iodomethyl-beta-D-threo-pentofuranosyl)thymine (13) and 1-(2,3-dideoxy-3-C-(O,O'-diethylphosphono)methyl-beta-D-threo- pentofuranosyl)thymine (15), respectively. These nucleoside analogues were evaluated for antiviral activity against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro. Compound 5 demonstrated selective antiviral activity against HIV-1 but not HSV-1.
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PMID:Stereoselective synthesis, chemistry and antiviral evaluation of 1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)thymine derivatives. 856 13

We have recently shown that lymphocyte apoptosis induced by dexamethasone or superantigens is accompanied by reduction of mitochondrial transmembrane potential (delta psi m) which precedes nuclear DNA fragmentation. Here, we demonstrate that fluorochromes such as 3,3' dihexyloxacarbocyanine iodide [DiOC6(3)] which measure delta psi m, or fluorochromes such as hydroethidine (HE) which measure mitochondrial superoxide anion production allow the identification of thymocytes or peripheral T lymphocytes which are eliminated by apoptosis in vivo. In mice bearing transgenic alpha/beta T cell receptor (TCR) specific for a class I-restricted male-specific peptide, the superoxide-mediated oxidation of HE into ethidium (Eth) is enhanced among thymocytes which are being deleted due to negative selection (CD4+ CD8+ cells expressing the transgenic TCR in male mice) or lack of positive selection (CD4+ CD8- thymocytes from female mice). delta psi m reduction and/or enhanced HE oxidation are also found when apoptosis is induced by a series of pathogenic agents. Thus, lethal irradiation provokes mitochondrial and nuclear signs of apoptosis, and both these alterations are absent in mice bearing a p53 null mutation, underlying the correlation between mitochondrial perturbation and nuclear apoptosis. Similarly, superantigen-triggered deletion of peripheral T cells in vivo is accompanied by enhanced HE-->Eth conversion and reduced DiOC6(3) uptake. More importantly, as compared to normal controls, CD4+ or CD8+ cells from clinically asymptomatic human immunodeficiency virus-1 (HIV-1) carriers also contain a significantly elevated percentage of cells endowed with reduced DiOC6(3) uptake. In superantigen- and HIV-induced apoptosis, the percentage of T lymphocytes with a subnormal DiOC6(3) uptake is more important than that of cells marked by enhanced HE-->Eth conversion. In conclusion, mitochondrial alterations precede and/or accompany nuclear signs of apoptosis induced by physiological and a variety of different pathogenic agents in vivo.
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PMID:Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in vivo. 856 12

Glycoproteic (GP) IIb/IIIa+ megakaryocytic cells were purified from the bone marrow (BM) of 15 HIV-1 seropositive thrombocytopenic patients, eight HIV-1 seronegative patients affected by immune thrombocytopenic purpura (ITP) and 14 HIV-1 seronegative normal donors. The presence of apoptosis was evaluated in freshly isolated GPIIb/IIIa+ cells by flow cytometry after propidium iodide staining and electron microscopy. GPIIb/IIIa+ cells from HIV-1 seropositive thrombocytopenic patients showed a significant (P < 0.0001) increase of apoptosis with respect to both HIV-1 seronegative ITP patients and normal donors. Moreover, the degree of apoptosis in bone marrow GPIIb/IIIa+ cells purified from HIV-1 seropositive thrombocytopenic patients was inversely (P < 0.01) related to the count of circulating platelets, whereas it did not show any significant correlation with the absolute number of circulating CD4 T cells, the CD4/CD8 ratio or the presence of proviral gag DNA sequences. Therefore neither an advanced stage of HIV-1 disease nor a direct infection with HIV-1 seems to play a primary role in the impaired survival of BMGPIIb/IIIa+ megakaryocytic cells. These findings strengthen the notation that, besides the immune targeting of peripheral platelets, an impairment of the bone marrow megakaryocyte compartment may also contribute to the pathogenesis of HIV-1 related thrombocytopenia.
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PMID:Impaired survival of bone marrow GPIIb/IIa+ megakaryocytic cells as an additional pathogenetic mechanism of HIV-1-related thrombocytopenia. 861 42

We found that TGF-beta1, a cytokine that previously has been reported to have neuroprotective effects, was able to prevent the toxicity induced by the HIV-1 coat protein gp120 in hippocampal pyramidal neuron cultures. In the presence of glia, gp120 induced time- and dose-dependent cell death, which was more pronounced in mature (7-19 d in culture) than in young neurons (2-7 d in culture). Staining with nuclear dyes (propidium iodide and Hoechst 33342), in situ detection of DNA fragments, and DNA analysis on agarose gels indicated that apoptosis was mainly responsible for the death caused by the viral protein. However, after several days of treatment, death-displaying necrotic features also occurred. Neurotoxicity induced by gp120 was dependent on the activation of NMDA receptors and required the presence of glia as well as new protein synthesis. Thus, the effect of gp120 was abolished by the NMDA receptor antagonist APV and partially reduced by cycloheximide. Only modest neurotoxicity was observed in pure neuronal cultures deprived of the glia feeder layer. Fura-2-based videoimaging showed that treatment with gp120 enhanced the ability of NMDA to increase neuronal [Ca2+]i. The impairment of neuronal Ca2+ homeostasis was prevented completely by TGF-beta1. Therefore, it is likely that the neuroprotective action of the cytokine is attributable to its ability to stabilize neuronal [Ca2+]i.
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PMID:gp120-induced neurotoxicity in hippocampal pyramidal neuron cultures: protective action of TGF-beta1. 875 70

We investigated cytokine production and accessory cell function in human macrophage hybridoma cell lines and primary monocytes after infection with HIV-1. HIV-1 infection induced IL-10 production in the macrophage hybridoma cell line with loss of IL-12 1 wk after infection. There were also significant increases in production of IL-10 (537 +/- 521 vs 687 +/- 625 pg/ml) while there was a reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary monocytes 5 days after HIV-1 infection. In addition, the hybridoma cell lines and primary monocytes failed to support PHA, Con A, PWM, or anti-CD3- induced T cell proliferation 1 wk after infection. The viability of the T cells cocultured with the HIV-1-infected macrophage cell lines or the primary monocytes as determined by propidium iodide staining was unaltered and there was no increase in apoptosis-specific DNA strand breaks or increased expression of Bcl-2 in the T cells. No soluble suppressor factor was present, since UV-inactivated supernatants from the hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3-induced T cell proliferation. Early events in T cell activation, including calcium flux and phosphotyrosine kinase activity, were intact in the T cells cocultured with the HIV-1- infected hybridomas and monocytes but there was reduced IL-2 production. Addition of exogenous IL-2 restored the proliferative responses. Taken together, these data suggest that alteration of cytokine production and accessory cell function for mitogens and anti-CD3-induced T cell proliferation independent of induction of apoptosis, suppressor factor production, or inhibition of T cell signaling occurs very early after HIV-1 infection and may contribute to the global immunosuppression observed in AIDS.
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PMID:Altered cytokine production and accessory cell function after HIV-1 infection. 875 40

Eosinophils, when stimulated, release a variety of agents that can be toxic to ingested or extracellular targets. Among these systems is one that consists of eosinophil peroxidase (EPO), H2O2, and a halide. We report here that phorbol myristate acetate (PMA)-stimulated human eosinophils are virucidal to HIV-1 in a chloride-containing medium. When the eosinophil concentration is decreased to a level at which the virucidal effect is incomplete, the addition of bromide or iodide restored complete virucidal activity. The virucidal effect of eosinophils, PMA, and bromide under these conditions is inhibited by the peroxidase inhibitor azide and catalase, but not heated catalase or superoxide dismutase, implicating the EPO-H2O2-halide system. Purified EPO when combined with H2O2 in a chloride-containing medium is virucidal to HIV-1. When the EPO concentration is suboptimal, virucidal activity is increased by bromide, iodide, and, in this instance, thiocyanate and the virucidal activity of the bromide-supplemented system is inhibited by azide and catalase. Our findings, together with the demonstration that eosinophils express CD4 on their surface and, under some circumstances, can be productively infected with HIV-1, raise the possibility that biological oxidants formed by eosinophils can influence the pathogenesis of HIV-1 infection by their toxicity to eosinophil-associated or extracellular virus.
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PMID:Virucidal effect of stimulated eosinophils on human immunodeficiency virus type 1. 882 15

Apoptosis plays a role in AIDS pathogenesis in the immune system, but its role in HIV-1-induced neurological disease is unknown. In this study, we examine apoptosis induced by HIV-1 infection of the central nervous system (CNS) in an in vitro model and in brain tissue from AIDS patients. HIV-1 infection of primary brain cultures induced apoptosis in neurons and astrocytes in vitro as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and propidium iodide staining and by electron microscopy. Apoptosis was not significantly induced until 1-2 wk after the time of peak virus production, suggesting induction by soluble factors rather than by direct viral infection. Apoptosis of neurons and astrocytes was also detected in brain tissue from 10/11 AIDS patients, including 5/5 patients with HIV-1 dementia and 4/5 nondemented patients. In addition, endothelial cell apoptosis was frequently detected in the brain of AIDS patients and was confirmed by electron microscopy. Most of the apoptotic cells were not localized adjacent to HIV-1-infected cells, providing further evidence for induction by soluble factors. In six non-AIDS control patients with normal brain, apoptotic cells were absent or limited to rare astrocytes. However, TUNEL-positive neurons and astrocytes were frequently detected in seven patients with Alzheimer's disease or abundant senile plaques. These studies suggest that apoptosis is a mechanism of CNS injury in AIDS which is likely to be induced by soluble factors. The apoptosis of endothelial cells in the CNS raises the possibility that some of these factors may be blood-derived.
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PMID:Apoptosis induced by HIV-1 infection of the central nervous system. 890 16

Removal of Acm-protecting group from thiol functional groups of Cys residues with simultaneous disulfide bridge formation by iodine in acetic acid was studied in the course of the synthesis of a peptide fragment corresponding to 593-603 sequence of HIV-2 gp41 glycoprotein. The excess iodine influence on the cyclization process was investigated. By-products of the oxidative disulfide formation were isolated, and their structures were elucidated by means of amino acid and elemental analyses, mass spectrometry, NMR, and UV-spectroscopy.
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PMID:[Direct transition of S-acetamidomethyl-protected peptide 593-603 of HIV-2 gp41 into a cyclic disulfide using iodine. Study of side reactions]. 892 23


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