Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing evidence that cytokines contribute to the immunopathogenesis of human immunodeficiency virus (HIV) infection. It may be, therefore, that compensatory rises in circulating cytokine antagonists also occur in HIV infection and that such changes mark disease progression. To test this idea, plasma concentrations of the cytokine antagonists alpha-melanocyte-stimulating hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor (sTNFr) were measured in patients of different Centers for Disease Control (CDC) categories of HIV infection and in seronegative controls. Plasma levels of all these cytokine antagonists were higher in HIV-infected patients. IL-1ra and sTNFr concentrations were correlated with indicators of disease activity: positively with plasma neopterin and negatively with CD4+ T lymphocyte counts. alpha-MSH and sTNF r were greater in CDC groups III and IV, whereas IL-1ra was elevated only in the latter group. Because cytokines activate the hypothalamic-pituitary-adrenal axis and adrenal steroids inhibit cytokine production, we measured circulating adrenocorticotropic hormone (ACTH) and cortisol in HIV-infected patients and investigated relations among these hormones, cytokine antagonists, and markers of disease progression. It appears that these physiological modulators of cytokine activity are not closely linked to sTNFr, IL-1ra and alpha-MSH: there were no significant correlations between plasma concentrations of ACTH or cortisol and those of cytokine antagonists, nor were there correlations between hormones and markers of disease progression such as neopterin or CD4+ T cell counts. It is notable that severe adrenal insufficiency was extremely rare (3%) in HIV-infected patients; it was confined to the AIDS group and was consistently secondary to ACTH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma concentration of cytokine antagonists in patients with HIV infection. 852 84

We evaluated the clinical significance of measurement of urinary neopterin levels in primary immunodeficiencies and persistent infections exclusively at afebrile or asymptomatic periods. Despite the examinations at afebrile or asymptomatic periods, urinary neopterin levels were elevated in some patients with primary immunodeficiencies and in patients with persistent infections of human immunodeficiency virus (HIV) or Epstein-Barr virus (EBV). Therefore, urinary neopterin measurement at afebrile periods will be useful as one of the screening tests in the detection of such disorders among children with occasional episodes of infections.
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PMID:Detection of immunodeficiencies and persistent infections by urinary neopterin measurement. 853 81

In untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1) infection, elevated serum concentrations of soluble receptors for tumor necrosis factor (sTNFR) types I and II are associated with progression to AIDS. To assess the utility of sTNFRs as markers for the assessment of antiretroviral treatment, sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who participated in a double-blind, randomized, placebo-controlled study. Progression to AIDS or severe AIDS-related complex occurred in six zidovudine (ZDV)- and six placebo-treated subjects. During ZDV treatment (n = 28) both types of sTNFRs declined compared with baseline and placebo, whereas they increased during placebo treatment (n = 19). A sustained decline of sTNFRs occurred only in subjects who experienced no disease progression. During the first 3 months of ZDV treatment, the hazard ratio for disease progression when sTNFR type II rose above the baseline value plus 5% was significantly increased (hazard ratio: approximately 25; 95% confidence interval: approximately 1.5-400; p < 0.03). Simultaneously determined CD4+ counts and serum neopterin levels showed a similar pattern in progressors and nonprogressors. Thus, in contrast to CD4+ counts and neopterin levels, sTNFR concentrations, especially those of the type II STNFR, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection.
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PMID:Soluble tumor necrosis factor receptors as surrogate markers for the assessment of zidovudine treatment in asymptomatic HIV-1 infection. 854 32

The purpose of this study was to evaluate the use of the biologic immune activation markers neopterin and beta 2-microglobulin in monitoring human immunodeficiency virus (HIV)-positive patients without acquired immunodeficiency syndrome (AIDS) treated with isoprinosine and placebo. Serum samples obtained at the commencement of study and samples obtained after 24 weeks were available from 277 HIV-positive patients in the Scandinavian multicentre isoprinosine trial. After 24 weeks' treatment, the concentrations of beta 2-microglobulin and neopterin had increased both in the isoprinosine group and the placebo group. However, in the isoprinosine group the relative increase within beta 2-microglobulin was significantly smaller. Within neopterin, the increase from baseline level was small and not significantly different from the change in the placebo group. The beta 2-microglobulin data might reflect a suppressive effect of isoprinosine on the HIV-induced activation of the cellular immune system. Because of the minor changes, there is no real evidence of neopterin and beta 2-microglobulin being valuable as surrogate markers in monitoring therapy effects of isoprinosine.
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PMID:Neopterin and beta 2-microglobulin as serum markers in a placebo-controlled anti-HIV therapy trial. 861 64

The proportion of T-cell receptor gamma/delta+ cells and the CD4/CD8 ratio relative to all CD3+ intraepithelial lymphocytes (IEL) were determined by immunofluorescence in duodenal mucosa of late-stage (mostly CDC IVC1/D) subjects (n = 21) infected with human immunodeficiency virus type 1 (HIV-1). The gamma/delta fraction (median, 14.2%; range, 1.7 to 59.8%) was increased (P < 0.03) compared with that in HIV- controls (n = 11; median 2.8%; range, 0.3 to 38%). Also, the number of gamma/delta+ IEL per mucosal unit was increased (P < 0.05) in the HIV+ subjects (median, 11.1/U) compared with the controls (3.2/U). Approximately 100% of the gamma/delta+ IEL were CD8-, and most expressed the Vdelta1vJdelta1-encoded epitope (median, 90.9%). The total number of CD3+ IEL tended to be lower than in the controls (67.4 versus 72.9/U). Both the epithelium and the lamina propria contained mainly CD8+ T cells, the median ratios of CD4+ T cells being 1 and 7.6%, respectively. This result accorded with the reduced CD4 cell number in blood (median, 18 X 10(6)/liter). The HIV+ subjects had increased serum levels of neopterin and beta2-microglobulin (both P < 0.0001), probably reflecting immunostimulation. Serum neopterin and beta2-microglobulin were inversely related to duodenal gamma/delta IEL, particularly in the premortal group (r = -0.97 and r = -0.58, respectively). The increased gamma/delta IEL might reflect enhanced intestinal protection in late-phase HIV infection. Short survival expectancy (<7 months) was associated not only with high levels of neopterin and beta2-microglobulin but also with a reduced number of duodenal gamma/delta+ cells (P < 0.03).
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PMID:Intraepithelial gamma/delta T cells in duodenal mucosa are related to the immune state and survival time in AIDS. 864 88

Mannose binding protein (MBP) is a serum lectin which, upon binding to a carbohydrate extremity, acquires the ability to activate the classical complement pathway. MBP binds human immunodeficiency virus (HIV) in vitro via glycans on gp120 and thus, it may play a defensive role in HIV infection and contribute to virus clearance through the activation of complement associated with this condition. We measured serum MBP and activation indices of the classical complement pathway (plasma C4d and C3d) in HIV-seropositive patients at different stages of disease severity, and in normal subjects. MBP was higher in HIV patients as a whole and in each Centers for Disease Control (CDC) group than controls (P<0.01). MBP was not significantly different between CDC groups and and did not significantly correlate either with CD4-positive lymphocytes, neopterin or beta2-microglobulin or with C4d and C3d. The possibility that MBP plays a defensive role in HIV infection cannot be excluded, but, it it is, it does not appear to act by recruiting complement for vital elimination.
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PMID:Circulating levels of mannose binding protein in human immunodeficiency virus infection. 866 45

It is widely assumed that the time since human immunodeficiency virus (HIV) infection is an important indicator of HIV disease stage, yet for most infected individuals the date of infection is unknown. We consider whether marker values, such as CD4 lymphocyte number or percent and levels of serum beta2 microglobulin or serum neopterin, render time since infection unimportant for predicting the residual time to acquired immunodeficiency syndrome (AIDS) diagnosis. The Multicenter AIDS Cohort Study (MACS) contains a subsample of homosexual men whose date of HIV seroconversion is known within +/-6 months and who provide data for this analysis. From this subsample, we extract two overlapping data subsets. The first subset consists of 370 persons whose 3,723 study visits include complete data on the cellular markers CD4 lymphocyte number and percent for a period of 9 years. The second consists of 272 persons whose 1,593 visits include complete information on cellular markers and on the serological markers beta2-microglobulin and neopterin for a period of 5 1/2 years. We model the residual time to AIDS diagnosis with a regression model, in which cellular and serologic markers are the explanatory covariates (independent variables) and the residual time to AIDS is the responses variable (dependent variable). A robust estimate of the variance-covariance matrix corrects for the dependence of repeated measurements in the same individual. In the case of CD4 number and percent, the results indicate that time since infection is of none or at most little importance if the marker value is known, suggesting that time since infection can be adequately replaced by the combination of marker values. However, the serological markers alone do not eliminate the importance of the time since infection.
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PMID:Replacing time since human immunodeficiency virus infection by marker values in predicting residual time to acquired immunodeficiency syndrome diagnosis. Multicenter AIDS Cohort Study. 867 37

A predictive marker for AIDS dementia complex (ADC) in a cohort of neurologically asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected patients with < 200 CD4 cells/microL was sought. Patients were assessed neurologically and neuropsychologically at entry. Blood and cerebrospinal fluid (CSF) were taken for assay of beta 2-microglobulin (beta 2M), and neopterin and T cell subsets were assessed from blood. Patients were evaluated every 4 months. Of 37 patients recruited, 35 had sufficient follow-up data. Seventeen patients progressed to ADC stage > or = 1. In univariate analyses, concentrations of CSF beta 2M and neopterin and CD4 cell count were each significantly associated with ADC development. In a multivariate analysis, concentrations of CSF beta 2M remained significant, with levels > 5 mg/L carrying approximately 17 times the risk of ADC. CSF beta 2M and neopterin levels and CD4 cell count are useful in identifying patients at risk of ADC and as such can be used to target high-risk patients so therapy can be optimized.
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PMID:Predictive markers of AIDS dementia complex: CD4 cell count and cerebrospinal fluid concentrations of beta 2-microglobulin and neopterin. 869 58

Previous studies of asymptomatic human immunodeficiency virus (HIV) infection have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR) are good predictors of disease progression and clinical outcome during zidovudine (ZDV) therapy. The present study of symptomatic HIV infection was designed to evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are predictors of death < or = 3 years after the start of ZDV 1,000 mg alone or combined with low-dose interferon-alpha (ZDV 500 mg + IFN-alpha 3 MIU three times weekly). CD4+ T-cell numbers and serum neopterin were analyzed in a similar way. Forty previously untreated symptomatic HIV-infected persons with CD4+ T-cell numbers > or = 150 x 10(6)/L were included. At baseline, in the nonsurvivor group, mean age (42.1 vs. 34.4 years, p = 0.002) and neopterin (24.7 vs. 18.0 nmol/L, p = 0.02) were higher, whereas mean CD4+ T-cell counts (202 vs. 295 x 10(6)/L, p = 0.02) were lower than in the survivors. All analyses were adjusted for age. For the pretreatment marker values, a significant relative risk (RR) for death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR 3.1; 95% confidence interval (CI) 1.1-8.8; p = 0.04]. During therapy, CD4+ counts < 200 x 10(6)/L at week 24 and 48 and neopterin > 20 nmol/ml at week 48 were independent predictors of survival in the uni- and multivariate analysis. Marker values relative to baseline were not predictive. sTNFR-p55 and p75 were of little use as surrogate markers for clinical efficacy during ZDV-containing drug regimens in symptomatic HIV-infected patients with CD4+ counts 150 x 10(6)/L.
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PMID:Predictive value for survival of soluble tumor necrosis factor receptors p55 and p75 during zidovudine-containing treatment in symptomatic human immunodeficiency virus type 1 infection. 875 25

Human immunodeficiency virus (HIV) infection is associated with increased concentrations of neopterin derivatives, released in large quantities by human macrophages on stimulation with interferon-gamma (INF-gamma). Neopterin concentrations thus inversely correlate with absolute CD4+ T-cell numbers and strongly predict progression of disease from latency to AIDS. Investigations of hydrogen peroxide-induced chemiluminescence indicated a potential role of neopterin and 7,8-dihydroneopterin in oxygen free radical-mediated processes. Indeed, 7,8-dihydroneopterin is able to enhance tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, accompanied by an increased production of reactive oxygen intermediates (ROIs). In line with this finding, the same combination appears to contribute to the upregulation of HIV replication due to activation of nuclear factor-kappa B (NF-kappa B), a central enhancer element of the HIV LTR promoter. Thus, besides the role of neopterin as sensitive indicator of disease activity in HIV infection, neopterin derivatives apparently are associated with the cascade of events that regulate the HIV production in infected individuals.
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PMID:Role of neopterin and 7,8-dihydroneopterin in human immunodeficiency virus infection: marker for disease progression and pathogenic link. 886 84


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