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

N-acetyl-L-cysteine (NAC) is known to antagonize the PMA- or cytokine-stimulated HIV-1 replication in latently and acutely infected monocytic and lymphocytic cell lines, and to reduce the virus multiplication in acutely infected, PHA-stimulated PBMC. We here report on the modulatory effects of NAC on the HIV-1 multiplication in both chronically and acutely infected lymphocytes that produce high virus levels independently from cytokine activation. In both cases, NAC doses of 0.12 and 0.25 mM decreased, whereas doses of 0.5-2 mM increased the infectious HIV-1 yield. At these concentrations, the modulatory effect of NAC on the HIV-1 multiplication paralleled that on cell proliferation, suggesting a close correlation between the two phenomena; in fact, under conditions where NAC could not modulate the cell growth, the drug also failed to modulate the HIV-1 multiplication. High NAC concentrations (4-16 mM), which were able to increase the proliferative rate of both chronically infected H9/IIIB and normal T lymphocytes, increased up to 6-fold the virus multiplication in H9/IIIB cells but were inhibitory to HIV-1 in acutely infected cells. This inhibition was due to the fact that, like dextran sulfate, NAC interfered with an early event in the virus growth cycle. The finding that high NAC doses were also capable of preventing syncytium formation in H9/IIIB and C8166 (or MT-4) cocultures further indicated an interference of the drug with receptor-binding-related events.
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PMID:Modulatory effect of N-acetyl-L-cysteine on the HIV-1 multiplication in chronically and acutely infected cell lines. 825 May 42

The prevalence of H. pylori associated gastritis seems to be different in HIV positive and HIV negative patients. Therefore a correlation to immunodeficiency can be postulated. The histology of gastritis, status of H. pylori infection and parameters of humoral and cellular immune response were investigated in 41 HIV positive and 47 HIV negative patients, who were subjected to upper endoscopy for the evaluation of gastrointestinal symptoms. In HIV positive patients 37% had active chronic gastritis against 62% of the HIV negative patients. In 73% of HIV positive cases of active chronic gastritis H. pylori was detected by bacteriological culture and/or Warthin-Starry stain. In HIV negative patients active chronic gastritis was always associated to H. pylori infection. Production of antibodies as measured by two commercially available ELISA tests was significant in HIV positive and HIV negative patients; both tests correlated well with H. pylori detection by culture or direct microscopy. Immunoglobulin class specific immunoblots corresponded to the ELISA results in HIV negative patients but to a lesser extent in the HIV positive group which was assumed to be related to unspecific polyclonal activation in these patients. Systemic cellular immunity was investigated by proliferation assays of peripheral blood mononuclear cells (PBMC). Proliferative response to the unspecific mitogen PHA was reduced in HIV positive patients. A sonicated H. pylori antigen failed to induce lymphocyte proliferation. The antimitogenic effect was also seen in case of coincubation with PHA. This observation was independent of H. pylori and HIV infection status. We conclude that in HIV positive as in HIV negative patients active chronic gastritis is predominantly related to H. pylori infection. The prevalence of H. pylori associated gastritis in HIV positive patients is significantly reduced (p < 0.025) compared to HIV negative controls. Decreased susceptibility to H. pylori infection in HIV positive patients may not be explained by the abnormal reactivity of their humoral or cellular immune response.
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PMID:Humoral and cellular immunity in HIV positive and HIV negative Helicobacter pylori infected patients. 828 Sep 41

The ability of activated T lymphocytes to extravasate and reach inflammatory and malignant foci in the tissues is a basic function of cellular immunity. Recent evidence strongly suggests that the urokinase receptor (uPAR) holds a central position in the development of human two-chain urokinase-mediated pericellular proteolysis and matrix degradation, an important element in cell migration. In this report we establish uPAR as a pan T cell activation Ag. As determined by FACS analysis, CD3+ lymphocytes from healthy donors exhibited no significant uPAR expression. In contrast, patients (e.g., HIV-positive donors) showed distinct uPAR expression, confined to HLA-DR+ cells, in up to 80% of all T cells. In vitro activation by PMA caused a rapid up-regulation of membrane uPAR in all healthy donor T cells and was accompanied by enhanced receptor synthesis and elevated uPAR mRNA levels. A similar induction resulted from activation via the TCR/CD3 complex using mitogens (PHA, and Con A), anti-CD3 antibodies, and alloantigen. Receptor expression at single cell level was also modulated by a number of cytokines. IL-2, IL-4 and IL-7 increased uPAR presentation on 20 to 50% of the T cell population, and combined stimulation of bulk cultures demonstrated an additive effect of IL-2 and IL-7, whereas the response to each of the two was inhibited by IL-4. In addition, TGF-beta 1 substantially reduced the uPAR expression in T cell cultures responding to PHA, IL-2, and IL-7. Irrespective of the activating reagent, the T cells appeared to produce the same molecular uPAR species, but the affinity of uPAR expressed in PMA blasts was decreased, presumably because of a differential location at the cell surface. All activated cultures showed co-expression of uPAR and CD25. The finding that the urokinase receptor is an activation Ag may suggest that cell-associated plasminogen activation is involved in extravasation and migration of activated T cells.
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PMID:Urokinase receptor. An activation antigen in human T lymphocytes. 828 34

A family of transcriptional activating proteins, the GATA factors, has been shown to bind to a consensus motif through a highly conserved C4 zinc finger DNA binding domain. One member of this multigene family, GATA-3, is most abundantly expressed in T lymphocytes, a cellular target for human immunodeficiency virus type 1 (HIV-1) infection and replication. In vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region (the transcriptional regulatory domain) of the HIV-1 LTR. Cotransfection of an hGATA-3 expression plasmid with a reporter plasmid whose transcription is directed by the HIV-1 LTR resulted in 6- to 10-fold stimulation of LTR-mediated transcription, whereas site specific mutation of these GATA sites resulted in virtual abrogation of the activation by hGATA-3. Further, deletion of the hGATA-3 transcriptional activation domain abolished GATA-dependent HIV-1 trans-activation, showing that the stimulation of viral transcription observed is a direct effect of cotransfected hGATA-3. Introduction of the HIV-1 plasmids in which the GATA sites have been mutated into human T lymphocytes also caused a significant reduction in LTR-mediated transcription at both the basal level and in (PHA- plus PMA-) stimulated T cells. These observations suggest that in addition to its normal role in T lymphocyte gene regulation, hGATA-3 may also play a significant role in HIV-1 transcriptional activation.
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PMID:Human T cell transcription factor GATA-3 stimulates HIV-1 expression. 833 92

Data from cross-sectional studies suggest that periodontitis in HIV-infected patients is a more destructive form of disease in contrast to the slowly progressing form of adult periodontitis in the general population. We studied prospectively over an 18-month period 30 HIV infected, but asymptomatic, patients and compared the rate of periodontal attachment loss with that of a healthy control group (n = 10) matched for age and plaque index. Every 6 months, each subject was assessed for their clinical status by a physician and CD4+ cell count determined. The proliferative response of peripheral blood lymphocytes was determined by in vitro cultures with PHA and Con A. The periodontal health status was assessed by scoring with plaque index (PI), gingival index (GI), and periodontal disease index (PDI). The control subjects were assessed for periodontal status only. Of the 30 HIV-positive patients whose data were analyzed 14 received Zidovudine (AZT) while the remaining 16 did not. There was no correlation between any clinical parameter measured and periodontal status as determined by PI or GI. However, a significant difference in the change of periodontal disease index (PDI) was observed between the HIV-infected and control groups (P = 0.005). We concluded that HIV-infected patients with pre-existing periodontitis tend to experience a greater rate of attachment loss over time compared with controls.
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PMID:Progression of periodontal disease in HIV seropositive patients. 836 14

The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti-CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL-4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism. 836 71

The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI) against HIV-1 was comparatively evaluated in PHA-stimulated PBM. The mean drug concentration which yielded 50% p24 Gag negative cultures were substantially different: 0.06, 0.2, and 6 microM for AZT, ddC, and ddI, respectively. We found that AZT was preferentially phosphorylated to its triphosphate (TP) form in PHA-PBM rather than unstimulated, resting PBM (R-PBM), producing 10- to 17-fold higher ratios of AZTTP/dTTP in PHA-PBM than in R-PBM. The phosphorylation of ddC and ddI to their TP forms was, however, much less efficient in PHA-PBM, resulting in approximately 5-fold and approximately 15-fold lower ratios of ddCTP/dCTP and ddATP/dATP, respectively, in PHA-PBM than in R-PBM. The comparative order of PHA-induced increase in cellular enzyme activities examined was: thymidine kinase > uridine kinase > deoxycytidine kinase > adenosine kinase > 5'-nucleotidase. We conclude that AZT, ddC, and ddI exert disproportionate antiviral effects depending on the activation state of the target cells, i.e., ddI and ddC exert antiviral activity more favorably in resting cells than in activated cells, while AZT preferentially protects activated cells against HIV infection. Considering that HIV-1 proviral DNA synthesis in resting lymphocytes is reportedly initiated at levels comparable with those of activated lymphocytes, the current data should have practical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy.
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PMID:Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. 838 46

Recently, as a new type of anti-AIDS drug, an HIV-1 protease inhibitor, KNI-174, has been synthesized; it shows a potent and selective HIV-1 protease inhibitory activity in vitro. In this study, we developed an HPLC assay system for KNI-174 in rat plasma and examined the pharmacokinetics of KNI-174 in rats using this assay method after both intravenous (i.v.) and intraduodenal (i.d.) administrations to obtain the disposition characteristics and bioavailability of this new anti-AIDS drug. This HPLC assay method is specific to KNI-174 and the standard curve was linear from 0.02 to 30 micrograms ml-1 plasma. After i.v. administration, 10.0 mg kg-1, KNI-174 disappeared from the rats' plasma in a three-exponential decay. The mean terminal elimination half-life, t1/2 lambda z, was 3.97 +/- 0.19 (S.E.) h, the total body clearance, CLtot, was 9.53 +/- 1.08 ml min-1 and the distribution volume at steady state, Vd,ss, was 7070 +/- 960 ml kg-1. In the case of the i.d. administration, 10.0 mg kg-1, the mean peak plasma concentration, Cmax, and the peak time, tmax, were 0.196 +/- 0.076 micrograms ml-1 and 0.444 +/- 0.193 h, respectively. The bioavailability of KNI-174 till infinity, BA(0-infinity), was 5.37 per cent. Because the IC50 of KNI-174 against HIV-1 in PHA-PBM was 138 ng ml-1, the time needed for maintaining the concentrations above IC50 after a single i.d. administration of KNI-174 is estimated to be 0.350 +/- 0.184 h.
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PMID:Pharmacokinetic study of a tripeptide HIV-1 protease inhibitor, KNI-174, in rats after intravenous and intraduodenal administrations. 849 Jan 8

The development of effective therapies for the treatment of AIDS would be facilitated by a better understanding of HIV pathogenesis in vivo. While some aspects of pathogenesis may be assessed by standard tissue culture assays, in vivo animal models may provide clues to other aspects of HIV-mediated progression toward AIDS. Current animal models include primate models for the study of simian immunodeficiency virus (SIV) and HIV, SCID-hu and hu-PBL SCID mouse models for the study of HIV, and feline models for the study of feline immunodeficiency virus (FIV). In general these models are costly and labor intensive. We have developed a simple human fetal thymic organ culture (TOC) system that is permissive for HIV infection and that exhibits pathology similar to that observed in vivo. A key feature of this system is the time-dependent destruction of thymocytes typified by the preferential loss of CD4-expressing cells. HIV-mediated thymocyte destruction occurs by a process involving programmed cell death. We have infected TOC with a panel of HIV isolates and found that the resulting viral replicative and pathogenic profiles are similar to those seen in the SCID-hu Thy/Liv mouse, yet different from profiles observed in standard PHA-blast tissue culture assays. In addition, we find that TOC may be used to assess efficacy of antiviral agents such as AZT (3'-azido-3'-deoxythymidine) and ddI (2',3'-dideoxyinosine) in blocking both viral replication and virus-induced pathology. These results indicate that this model is amenable to the systematic manipulation, analysis, and characterization of a variety of HIV virus isolates and antiviral therapies.
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PMID:Development of a human thymic organ culture model for the study of HIV pathogenesis. 855 4

The effect of isoniazid on proliferative response, natural killer (NK) cell activity and lymphocyte subset distribution of blood mononuclear cells (BMNC) was investigated. To evaluate the effect of treatment with isoniazid in pharmacologic concentrations, twenty healthy HIV-seronegative volunteers were randomized into two groups: one group received isoniazid tablets plus pyridoxin tablets once a day for 30 days, the other group received pyridoxin only. Blood samples were collected on day 0 and day 30. Inhibition of the PHA-induced proliferative response was demonstrated in lymphocyte cultures from isoniazid-treated volunteers (p < 0.001). However, no effect was seen on the IL-2- or antigen (PPD)-induced proliferative response or the NK cell activity of isolated BMNC. Inhibition of the PHA-induced proliferative response could not be related to changes in the distribution of CD3+, CD4+, CD8+, CD14, or CD19+ lymphocyte subsets. The effects, in vitro, were investigated by addition of isoniazid to cultures of BMNC isolated from either HIV-seroposive or HIV-seronegative donors who did not receive any treatment. We found that isoniazid did not influence the mitogen- or antigen-stimulated proliferative response or the NK cell activity.
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PMID:Effects of isoniazid treatment on human lymphocyte proliferative response, lymphocyte subsets and natural killer cell activity. 855 25


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