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)

We investigated the pharmacokinetics of antipyrine and the endogenous plasma levels of interferon alpha (IFN alpha), interferon beta (IFN beta) and interferon gamma (IFN gamma) in 10 otherwise healthy volunteers before outbreak (baseline) and in the symptomatic interval of an acute viral respiratory infection, and also in HIV-1 infected homosexual patients in stadium WR 2-3 (n = 11) and WR 5-6 (n = 11) before and one day after application of the antiretroviral agent zidovudine 800 mg day-1 for 14 days. Interferons were measured by RIA or ELISA, respectively. The concentrations of antipyrine and its metabolites in serum and urine were measured by HPLC. Antipyrine is a pharmacokinetic model substance to estimate the cytochrome P 450 enzyme activity. The plasma levels of IFN alpha and IFN gamma in the symptomatic interval of an acute viral respiratory infection were elevated from 4.7 U ml-1 to 12.6 U ml-1 and from 0.3 U ml-1 to 3.4 U ml-1, respectively. The antipyrine clearance showed a significant decrease from 57.9 ml min-1 to 45.0 ml min-1. In the HIV-1 infected patients in stadium WR 2-3 no alterations in plasma levels of interferons or in the pharmacokinetics of antipyrine were observed after treatment with zidovudine. In contrast to these results, in patients in stadium WR 5-6 we found a significant decrease of IFN alpha and an elevation of the clearance and the clearances to metabolite of antipyrine by about 20 percent.
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PMID:Endogenous interferon plasma levels and antipyrine pharmacokinetics in patients with viral infections. 128 84

1. Toxoplasma gondii is a ubiquitous, obligate intracellular parasite of worldwide distribution. In humans, the parasite exists in two forms: the tachyzoite is the rapidly multiplying stage of the parasite which actively invades host cells and represents the principal pathogenic form at the acute phase of the disease; the bradyzoite is the form which multiplies slowly in host cells, resulting in the formation of cysts which persist in tissues. Several antigenic components have been identified, some of which are characteristic for each parasitic stage; particularly, in tachyzoites, the 30 kDa membrane protein represents up to 5% of the total protein content. 2. Toxoplasma infection in humans is usually asymptomatic because of effective immunity involving antibodies, T cells and cytokines. Activated macrophages, CD4 and CD8 lymphocytes and cytokines, such IFN gamma, play a major role in the control of acute infection and the maintenance of infection at the chronic stage. The alteration of immune functions, as observed in congenitally infected children and in HIV-infected patients, may induce the recrudescence of previously latent toxoplasmosis, in relation to disruption of the cyst form of the parasite. The resulting reactivation is responsible for life-threatening infections which are frequently manifested as toxoplasmic encephalitis. 3. In this review, the parasite and immunological factors participating in the pathogenesis of the lesions associated with acute, chronic and reactivated toxoplasmosis are presented.
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PMID:Pathogeny and immunological control of toxoplasmosis. 134 11

Brucella abortus has been characterized as a T-independent type 1 antigen/carrier in human and murine antibody responses. In this report it is shown that BA can activate human CD3+ T cells to secrete interferon-gamma (IFN gamma). Unlike mitogens, such as phytohemagglutinin, this stimulation was associated with minimal T-cell proliferation or upregulation of interleukin-2 (IL-2) receptor. Monocytes inhibited BA-mediated IFN gamma secretion since their removal resulted in increased responses, whereas adding monocytes back to cultures caused inhibition. BA elicited IFN gamma from CD4+ and CD8+ T cells, although CD4+ T cells secrete significantly more (p less than 0.05) IFN gamma than CD8+ T cells. The ability of BA to elicit IFN gamma from human T cells was inhibited in the presence of anti-Tac, suggesting that BA also induces IL-2 secretion and that IL-2 is involved in BA-mediated IFN gamma secretion. Detectable IL-2 secretion was induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically with BA to enhance IFN gamma secretion, suggesting that the amount of IL-2 released by BA alone was insufficient for optimal IFN gamma release. Furthermore, addition of IL-2 to T cells from individuals with poor or absent responses to BA, including individuals infected with HIV-1, restored their ability to secrete IFN gamma in response to BA. These data indicate that BA is capable not only of activating human B cells but can also induce T cells, probably of the TH1 phenotype, to secrete IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brucella abortus stimulates human T cells from uninfected and HIV-infected individuals to secrete IFN gamma: implications for use of Brucella abortus as a carrier in development of human vaccines. 135 Sep 16

A newly developed method for assaying 2', 5'-oligoadenylate (2, 5A) synthetase activity by polyacrylamide gel electrophoresis was applied to peripheral blood mononuclear cells (PBMC) from normal subjects, HIV-positive subjects, and renal cell carcinoma (RCC) patients. Sex differences were observed in 2, 5A synthetase activity of PBMC from normal young adults, males having eightfold higher activities of this enzyme than females. Moreover, compared to values for postmenopausal (PM) females receiving estrogen replacement, untreated PM females had higher activities. Collectively, these results suggest that estrogen downregulates 2, 5A synthetase activity. Activities of 2, 5A synthetase were investigated in two disease states associated with altered immune function. In one patient with AIDS-related Kaposi's sarcoma, interferon-alpha (IFN-alpha) therapy increased 2, 5A synthetase activity twofold. In addition, combined therapy with interleukin-2 (IL-2) and IFN-alpha increased 2, 5A synthetase activities in eight of nine patients with RCC. Therefore, in patients receiving immunotherapy with IL-2 and IFN-alpha, our new assay could contribute to evaluation of immune stimulation. In general, studies in vitro confirmed these observations; however, exposure of PBMC from RCC patients revealed that in vitro IL-2 failed to induce this enzyme activity as it did in PBMC from normal volunteers.
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PMID:Hormonal and immunological regulation of 2', 5'-oligoadenylate synthetase activity in human peripheral blood mononuclear cells. 135 75

To improve evaluation of new antiretroviral drugs in the acquired immunodeficiency syndrome (AIDS), sensitive biological markers that accurately predict response to treatment are needed. Two possible markers are endogenous interferon (E-IFN), which is a cytokine involved in the pathophysiology of AIDS, and serum triglycerides (TG), which are raised in patients with AIDS, possibly reflecting enhanced cytokine activity. E-IFN, TG, body-mass index, CD4 count, and HIV p24 were measured in 19 patients (15 with AIDS, 4 with AIDS-related complex), who were part of the phase II licensing trial of zidovudine (ZDV). 10 received ZDV and 9 received placebo. Rapid, significant, and sustained declines from initial values in E-IFN and TG concentrations were observed in ZDV patients but not in placebo patients. Baseline values of E-IFN and TG concentrations after 4 months on ZDV treatment were both important contributors to long-term survival. The findings suggest that these indicators of abnormal cytokine expression may be useful measures of not only disease severity but also efficacy of antiretroviral therapy in AIDS.
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PMID:Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. 134 48

Infection causes disturbances in lipid metabolism that may be mediated by cytokines. Therefore we studied plasma lipids, lipoproteins, triglyceride (TG) metabolism, and serum cytokines in three groups: patients with the acquired immunodeficiency syndrome (AIDS) without active secondary infection, patients with evidence of human immunodeficiency virus infection but without clinical AIDS (HIV+), and controls. Plasma TGs and FFA were increased in AIDS, while plasma cholesterol, high density lipoprotein (HDL) cholesterol, apolipoprotein-A-1 (Apo-A-1), low density lipoprotein (LDL) cholesterol, and Apo-B-100 levels were decreased. Increased TG levels in AIDS were primarily due to increases in very low density lipoprotein of normal composition; in addition, LDL and HDL were TG enriched. In HIV+, TGs and FFA were not increased, but total cholesterol, HDL cholesterol, Apo-A-1, and Apo-B-100 were significantly decreased. Interferon-alpha (IFN alpha) and C-reactive protein levels were increased in AIDS, but tumor necrosis factor and haptoglobin levels were not. There was a significant correlation between plasma TGs and IFN alpha levels (r = 0.477; P less than 0.01), but not between TGs and tumor necrosis factor, C-reactive protein, haptoglobin, or P-24 antigen. In addition, there was no relationship between circulating IFN alpha levels and plasma cholesterol, HDL cholesterol, Apo-A-1, LDL cholesterol, Apo-B-100, or FFA. TG clearance time and postheparin lipase were significantly decreased in AIDS and HIV+. There was a strong correlation between serum IFN alpha levels and TG clearance time in AIDS and HIV+ (r = 0.783; P less than 0.001). In summary, decreases in cholesterol and cholesterol containing lipoproteins (including HDL) in both AIDS and HIV+ precede the appearance of hypertriglyceridemia and are not related to IFN alpha or TG levels. Our data raise the possibility that with development of AIDS, subsequent increases in IFN alpha may contribute to increases in plasma TG levels in part by decreasing the clearance of TG.
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PMID:Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. 137 35

Cells infected with human immunodeficiency virus (HIV) induce antiviral activity in peripheral blood mononuclear cells (PBMC) from healthy donors. This activity is neutralized by anti-interferon-alpha antibody and partially destroyed at pH 2. Previous studies with enriched cell populations and monoclonal antibodies suggest that B lymphocytes are the main IFN-producing cells, and that both CD4 and HLA class II antigens are essential for IFN induction. Since the initial event of HIV infection of CD4+ cells is the interaction of the virus coat glycoprotein gp120 with CD4 molecule, we investigated whether gp120 is responsible for IFN induction. Using PBMC and recombinant gp120 obtained from a baculovirus expression system, dose-dependent induction of antiviral activity was observed with titers approaching 10(3) IU/ml. This induction was blocked in the presence of antibody to gp120. The antiviral activity was characterized as IFN-alpha by neutralization with IFN alpha-specific antibody. Preincubation of PBMC with anti-CD4 or the presence of soluble CD4 during incubation inhibited IFN induction, indicating that interaction of gp120 with cell-associated CD4 is responsible for this induction. Neither lymphoproliferation nor interleukin-2 (IL-2) production was observed during IFN induction. However, class G immunoglobulin secretion was enhanced by gp120, indicating that B cells are direct or indirect targets of gp120 stimulation in this experimental system. Since gp120 is shed from HIV-infected cells and occurs in the serum of acquired immunodeficiency syndrome (AIDS) patients, our data suggest that this glycoprotein is responsible for the induction of endogenous IFN and the polyclonal activation of B cells both of which are observed in AIDS patients.
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PMID:Recombinant glycoprotein 120 of human immunodeficiency virus is a potent interferon inducer. 138 Dec 3

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05 micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found at concentrations at least 2,000-fold greater than the 50% HIV inhibitory concentration in M/M. Molecular analysis by polymerase chain reaction (PCR) suggests that ADR substantially affects virus DNA production at concentrations that inhibit viral replication. Finally, late stages of HIV replication were not affected by ADR. At least additive effects of the association ADR + AZT and ADR + IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes. 138 99

Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.
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PMID:Absence of circulating interferon in patients with inflammatory bowel disease. Suggestion against an autoimmune etiology. 138 5

Two acute phase reactants, four cytokines, five soluble factors and lymphocyte subpopulations have been simultaneously evaluated in 16 subjects before and closely after the HIV-Ab seroconversion time. The same variables have also been determined in 50 HIV-Ab-negative high risk subjects, in 36 CDC II-III and in 30 CDC IV patients, utilizing a mixed longitudinal epidemiological model. The results show significant variations of few parameters in the early phases (increase: sCD8, beta-2-Microglobulin, sIL-2R, sCD23, Neopterin, IFN-alpha; decrease: CD4+ lymphocytes). In the course of the disease, many others parameters progressively increase (IFN-tau, IL-4, IL-6, acid-alpha 1-glycoprotein, alpha 1-antitrypsin) or decrease (B- and T-lymphocytes). Ferritin, in particular, highly increases only in CDC IV stage. These data may be useful to monitor patients during the entire course of their disease and to suggest the time elapsed from seroconversion.
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PMID:Behaviour of several 'progression markers' during the HIV-Ab seroconversion period. Comparison with later stages. 138 75


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