Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 mg and 800 mg) and placebo was conducted at six medical centers. Two hundred fifteen adults were enrolled over a 5-month period and randomized to receive ribavirin 800 mg daily (74 subjects), ribavirin 600 mg (71 subjects), or placebo (70 subjects). Active treatment was administered for 24 weeks followed by a 4-week wash-out period. Fifteen patients receiving placebo, 10 receiving ribavirin 600 mg, and 18 receiving ribavirin 800 mg developed AIDS during the 28-week study period. Ribavirin at daily doses of 600 mg or 800 mg for 24 weeks did not significantly affect the rate of progression to AIDS as defined by the Centers for Disease Control, in univariate analysis, Kaplan-Meier survival analysis, or Cox proportional hazards modeling. Although in the proportional hazards analysis, the dose-response regression coefficients indicated a reduction of 43% in the hazard of progression to AIDS among patients on active treatment, it was not statistically significant (p = 0.19). Furthermore, there was no evidence that ribavirin had a significant effect upon any immunologic or virologic parameter measured, including CD4 count, CD4:CD8 ratio, lymphocyte proliferative response, skin test reactivity, interferon-gamma production, peripheral blood mononuclear cell culture for human immunodeficiency virus (HIV), or level of HIV p24 antigen in serum. The most prominent adverse effect of ribavirin was induction of a mild reversible hemolytic anemia (mean fall in hematocrit, 5%). No severe or unremitting drug reaction was documented.
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PMID:Multicenter clinical trial of oral ribavirin in symptomatic HIV-infected patients. The Ribavirin ARC Study Group. 841 72

Mononuclear cells of the lamina propria (LpMNC), isolated from endoscopically taken biopsies of the large bowel from AIDS patients, were analysed for their ability to secrete tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6. Stimulation of LpMNC from normal controls with pokeweed mitogen (PWM) led to a time- and dose-dependent enhancement of TNF-alpha, IL-1 beta and IL-6 secretion. In contrast, PWM stimulation of LpMNC from AIDS patients resulted in only a small increase in TNF-alpha release. Constitutive secretion of IL-1 beta and IL-6 in these patients was already increased to the concentration range of stimulated cells from normal controls and could not be further increased, probably due to maximal in vivo stimulation. Secretion of TNF-alpha, IL-1 beta and IL-6 by peripheral blood monocytes (PBM) and alveolar macrophages from AIDS patients was elevated with or without stimulation compared with normal controls. Obviously, the regulation of TNF-alpha secretion is dependent on the microenvironment. Since it is known that interferon-gamma (IFN-gamma) may induce the production of TNF-alpha, the secretion of this cytokine was examined. Release of IFN-gamma was constitutively and under stimulation lowered in LpMNC from AIDS patients compared with normal controls. Addition of IFN-gamma to LpMNC did not result in enhanced TNF-alpha secretion. Our data indicate a defective function of intestinal mononuclear cells in AIDS patients as shown by the diminished TNF-alpha secretion.
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PMID:Differences in cytokine secretion by intestinal mononuclear cells, peripheral blood monocytes and alveolar macrophages from HIV-infected patients. 841 83

Mononuclear phagocytes generate microbicidal oxygen metabolites spontaneously and after phagocytic stimulation by a NADPH-dependent enzymatic reaction called the oxidative burst. The spontaneous release of reactive oxygen radicals and intermediates (ROI) increases five- to eightfold after treatment of monocytes with the lymphokine interferon-gamma (IFN-gamma). The effect of the IFN-gamma-activated release of ROI by human monocytes on the infectivity of free human immunodeficiency virus (HIV) in the supernatant was investigated with the following results. First, IFN-gamma-activated, but neither control monocytes nor lipopolysaccharide-stimulated monocytes effectively decreased the infectivity of cell-free HIV-1 in culture medium supernatant. Second, the mechanism of inactivation was dependent on the enhanced spontaneous release of ROI by IFN-gamma-activated mononuclear phagocytes, since either the enzyme catalase or the free radical scavenger butylated hydroxyanisole (BHA) could block this activity. Third, soluble and solid-phase HIV-1 outer envelope glycoprotein (gp120) failed to trigger the oxidative burst activity after specific gp120-monocytic CD4 receptor interaction. These results indicate an anti-viral effect of IFN-gamma-activated monocytes/macrophages on HIV-1 which may have important implications for our understanding of spread of the virus in the body and the development of full-blown AIDS after a long period of latency.
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PMID:Interferon-gamma-activated monocytes impair infectivity of HIV particles by an oxygen metabolite-dependent reaction. 847 9

The pathogenesis of the dementia associated with human immunodeficiency virus (HIV) infection is unclear, but has been postulated to be due to indirect effects of HIV infection including the local production of cytokines. To determine which cytokines are produced in the nervous system and to identify any correlations with dementia, cytokine and HIV messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction in the brains from 24 HIV-infected patients with and without dementia and 9 HIV-uninfected control subjects. Levels of tumor necrosis factor-alpha messenger RNA were significantly higher and levels of interleukin (IL)-4 messenger RNA were significantly lower in demented compared to nondemented HIV-infected patients. Demented patients also had lower IL-1 beta levels than did nondemented patients. No significant differences were detected in the amounts of leukemia inhibitory factor, IL-6, transforming growth factor-beta 1 and -beta 2, monokine induced by gamma interferon-2 (MIG-2), or interferon-gamma messenger RNAs. IL-10 and IL-2 messenger RNAs were undetectable in all brains examined. Cytokine messenger RNA levels in nondemented HIV-positive patients were similar to those in HIV-negative control subjects. HIV transcripts were more abundant in subcortical white matter than in the basal ganglia, cortex, or deep white matter. Our findings suggest a possible role for tumor necrosis factor-alpha in the development of neurological dysfunction. Increased levels of tumor necrosis factor-alpha messenger RNA were not associated with increased levels of IL-1 beta messenger RNA, suggesting differential regulation of these monokines in acquired immunodeficiency syndrome dementia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. 849 37

Rhodococcus equi is a facultative, intracellular, gram-positive coccobacillus increasingly reported as an opportunistic pathogen in AIDS patients. In vitro, splenic cells of noninfected euthymic mice produced tumor necrosis factor-alpha (TNF alpha) in greater amounts when incubated with live R. equi rather than with killed bacteria. In vivo, interferon-gamma (IFN-gamma) and TNF alpha serum levels of infected euthymic mice remained below the level of detectability. Treatment of infected nude mice, which developed chronic infection, with discontinuous injections of IFN-gamma, TNF alpha, or both did not decrease bacterial colony-forming units in liver, spleen, or lungs. However, treatment of infected euthymic mice, which cured a R. equi inoculum within 3 weeks, with anti-IFN-gamma or anti-TNF alpha antibodies (or both) significantly increased tissue colony counts. These data argue that, in this murine model, endogenous IFN-gamma and TNF alpha are involved in the cell-mediated immunologic response against R. equi infection.
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PMID:Involvement of interferon-gamma and tumor necrosis factor-alpha in host defense against Rhodococcus equi. 850 39

At an outpatient AIDS research clinic in Kinshasa, Zaire, physicians conducted a medical examination and took blood samples from 48 women with AIDS, 51 women with asymptomatic HIV-1 infection, and 11 healthy HIV-1 seronegative women to study the relationship of circulating cytokines and cytokine antagonists to the progression of HIV-1 infection. Asymptomatic HIV-1-infected women had higher levels of the cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) than AIDS cases and controls (320 vs. 156 pg/ml, p 0.001, and 210 vs. 78 pg/ml, p 0.001, respectively) and even higher levels of interleukin-1Ra and TNFsRp55 (both natural cytokine antagonists) (4300 vs. 100 pg/ml, p 0.001; and 12,500 vs. 1450 for the AIDS group [p 0.0001] and 950 for controls [p 0.001]). The high levels of the two proinflammatory cytokines in asymptomatic HIV-1 infected women suggests that the high levels of antagonist cytokines blocked the clinical effects of interleukin-1beta and TNF-alpha. 46 AIDS patients had no detectable interleukin-1beta. 42 AIDS patients had no detectable TNF-alpha. The lack of cytokines in most AIDS patients suggests that persons in end-stage HIV-1 disease have a limited capacity to synthesize cytokines, perhaps depleting the remaining cytokine-producing central and peripheral lymphoid tissues. Asymptomatic HIV-1-infected women also had higher levels of interleukin-8 than AIDS cases and controls (750 vs. 40 pg/ml; p 0.001). 11 of the 13 highest values of interferon-gamma (11 pg/ml) belonged to AIDS patients rather than asymptomatic HIV-1-infected cases (p = 0.005). In the last 2 months, AIDS patients with detectable interferon-gamma had fever of longer duration than those with no interferon-gamma (17 vs. 9 days, p = 0.05), indicating that AIDS cases with interferon-gamma were still capable of responding to inflammatory stimuli. These findings suggest that cytokine antagonists may modulate cytokine-associated symptoms in the early phases of HIV-1 infection.
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PMID:Plasma cytokines, cytokine antagonists, and disease progression in African women infected with HIV-1. 863 37

C57BL/6 mice were injected with different doses of human T-cell receptor (TCR) V beta 8.1 CDR1 peptide at different times after murine retrovirus (LP-BM5) infection. Injection with TCR V beta 8.1 CDR1 peptide largely prevented the retrovirus-induced reduction in B- and T-cell proliferation, and T-helper 1 (Th1) cytokines [interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)] secretion. It also suppressed T-helper 2 (Th2) cytokines (IL-6 and IL-10) production, which was stimulated by retrovirus infection. These effects were accomplished using at least 100 micrograms of peptide per mouse and the most effective dose of peptide had to be given within 4 weeks after retrovirus infection. Immunization with doses above 100 micrograms/mouse as long as 4 weeks postinfection maintained natural killer (NK) cell activity during retrovirus infection. Reducing the dose of peptide or delaying it until the disease progressed towards early murine acquired immune deficiency syndrome (AIDS) allowed development of immune dysfunction. These studies provide data suggesting that immune dysfunction, induced by murine retrovirus infection, was largely prevented by TCR V beta CDR1 peptide injection.
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PMID:T-cell-receptor dose and the time of treatment during murine retrovirus infection for maintenance of immune function. 869 80

In severe HIV infection, the majority of patients exhibit signs of hematopoietic deficiency including anemia, leukopenia, and thrombocytopenia. Besides other pathophysiological mechanisms, the disturbed helper/suppressor ratio of T-lymphocytes suggests that alterations within T cell subpopulations may have a suppressive effect on HIV-associated hematopoiesis. Since a delta TCS-1- and mostly CD-8-positive subpopulation of cytotoxic T-lymphocytes expressing the gamma delta-receptor is increased in peripheral blood and bone marrow of HIV-infected persons, it was the aim of this study to investigate the role of gamma delta-positive cells in HIV-associated bone marrow deficiency. The number of bone marrow-derived pluripotent colony-forming units (CFU-GEMM), burstforming units-erythrocyte (BFU-E), and colony-forming units-granulocyte-monocyte (CFU-GM) of HIV-1-positive patients was significantly (p < 0.05) increased after depletion of CD-8-positive, gamma delta-positive, and delta TCS-1-positive T-lymphocytes. In contrast, the depletion of these subpopulations had no stimulatory effect in healthy controls. Further experiments identified direct cellular contact between effector and hematopoietic progenitor cells and the production of interferon-gamma and tumor necrosis factor-alpha as the mechanisms mediating the suppressive effect of the delta TCS-1-positive cells in HIV-positive patients.
AIDS Res Hum Retroviruses 1996 May 01
PMID:Gamma delta-T cell-receptor-positive lymphocytes inhibit human hematopoietic progenitor cell growth in HIV type 1-infected patients. 874 83

Spleen cells from mice resistant or sensitive to mouse acquired immune deficiency syndrome (MAIDS) were examined for cytokine mRNA. In MAIDS-resistant BALB/c mice, cytokine transcripts peaked at 1 week after infection with Type 1 cytokines [interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-12], dominating over Type 2 cytokines (IL-4, IL-10). Expression of cytokines other than IL-2 later declined to levels seen in uninfected mice. In MAIDS-sensitive B6 mice, transcripts for all cytokines were increased at 1 week and, except for IL-2, increased progressively. Spontaneous production of IFN-gamma protein was associated with enhanced mRNA expression at 1 week after infection of either strain, but none was detectable in association with even higher levels of transcripts at later times after infection of B6 mice. Spleen cells from longer-term-infected B6 mice, however, produced substantial amounts of IFN-gamma following treatment with lipopolysaccharide (LPS) or IL-12. Inclusion of anti-IL-12 or anti-TNF-alpha antibodies blocked induction of IFN-gamma by LPS. Induction of IFN-gamma by IL-12 was potentiated by TNF-alpha following stimulation of intact spleen cells and purified CD4+ or CD8+ T cells, as well as negatively selected CD4-8- cells from infected B6 mice. Further studies showed that IFN-gamma knockout mice on a B6 background developed MAIDS with a prolonged time-course, whereas BALB/c knockout mice were unchanged in their resistance to MAIDS. These studies suggest that continuing low-level expression of IFN-gamma, stimulated by IL-12 and TNF-alpha, contributes to the susceptibility of B6 mice to MAIDS but is not required for the resistance of BALB/c mice to disease.
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PMID:Retrovirus-elicited interleukin-12 and tumour necrosis factor-alpha as inducers of interferon-gamma-mediated pathology in mouse AIDS. 877 35

We studied lumbosacral dorsal root ganglia (DRGs) from 10 patients with acquired immunodeficiency syndrome (AIDS) and five controls using immunocytochemistry, in situ hybridization and NADPH-diaphorase (NADPHd) histochemistry. Human immunodeficiency virus (HIV)-1 RNA was detected in five AIDS cases, and HIV-1 p24 antigen was found in four of these patients. The densities of nodules of Nageotte (nN), macrophages and major histocompatibility complex-class II-positive cells were significantly increased in the DRGs of AIDS patients compared to controls. Cytomegalovirus antigen was observed in the DRGs of four AIDS cases and one control, but without its presence being related to neuronal degeneration. Furthermore, we detected tumor necrosis factor, interferon-gamma, interleukin (IL)-1 beta, and IL-6 in the DRGs from AIDS patients. Using NADPHd histochemistry, we showed that the number of NADPHd-positive neurons was significantly increased in the DRGs of AIDS patients compared to controls, implying upregulation of nitric-oxide (NO) production in AIDS DRGs. Generally, there were increased numbers of nN in DRGs which contained more NADPHd-positive neurons. Additionally, immunoreactivity for an inducible form of NO synthase was detected in interstitial cells in AIDS DRGs. These results suggest that reactive inflammation, including the production of cytokines, occurs in the DRGs of AIDS patients and that excessive production of NO may be related to neuronal degeneration in AIDS DRGs.
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PMID:Increased NADPH-diaphorase reactivity and cytokine expression in dorsal root ganglia in acquired immunodeficiency syndrome. 881 58


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