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)

We measured neopterin, a biochemical indicator for the activation of cell-mediated immune reactions, in urines from 105 individuals at risk of infection with human immunodeficiency virus-1 (HIV-1), 83 of whom were seropositive for antibody to HIV-1. We compared absolute numbers of T-cell subsets (CD4+ helper/inducer T-cells, CD8+ suppressor/cytotoxic T-cells), and the ratio of CD4+ T-cells to CD8+ T-cells with the urinary neopterin concentrations. Concentrations of neopterin in urine were inversely correlated with absolute numbers of CD4+ T-cells and with CD4+/CD8+ ratios in anti-HIV-1 seropositive subjects but not in those seronegative. Various statistical comparisons of the data further demonstrated that neopterin concentrations showed larger differences between anti-HIV-1 seronegative and seropositive subjects than absolute numbers of CD4+ T-cells or CD4+/CD8+ ratios. These results seem to indicate that neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.
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PMID:Neopterin estimation compared with the ratio of T-cell subpopulations in persons infected with human immunodeficiency virus-1. 326 25

The posttrauma immunodeficiency syndrome and the related postsurgery immunodeficiency syndrome are essential for the infections often occurring after polytrauma and major surgery. Data are given here showing that after such events the levels of immunoglobulins; the complement factors C3C, C4 and C Factor B; and the numbers of circulating lymphocytes and of the subpopulations CD3, CD4, CD8 and natural killer cells as well as the stimulatory capacity of mononuclear cells to mitogen fall; while the levels of acute phase proteins, neopterin and interleukin 2 receptors and the spontaneous uptake of thymidine by mononuclear cells become augmented. Extent and duration of these changes and the rate of subsequent infections depend on the extent and kind of surgery (minor, major, clean, contaminated). However, crucial factors of the posttrauma and postsurgery immunodeficiency syndromes are not yet elucidated and relevant predictive parameters for infections are not at hand. These are essential prerequisites to initiate future immunomodulatory measures which should be added to the use of intravenous immunoglobulins yielding so far distinct but limited benefits for the prevention of infections after polytrauma and major surgery.
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PMID:Immunodeficiency after major trauma and selective surgery. 339 84

Ocular microangiopathic syndrome including retinal and conjunctival abnormalities is frequently found in patients with human immunodeficiency virus type 1 (HIV-1) disease. Kaposi's sarcoma (KS) is the most frequent neoplasia found in patients with HIV-1 disease. We have recently reported a significant association between conjunctival microvasculopathy and KS in 117 patients with HIV-1 disease. The objective of the present study was to determine whether this association is existent when matched patients with and without KS are compared. A total of 22 matched pairs were obtained under consideration of the absolute CD4+ lymphocyte count, Walter Reed (WR) classification, gender, and serum levels of beta-2-microglobulin and neopterin. Conjunctival microangiopathy was determined for each eye by a standardized rating scale ranging from 0 to 5, allowing a reliable and valid quantification of conjunctival blood-flow sludging. The mean value obtained for conjunctival sludge was 1.8 (SEM, 0.4) for patients without KS and 3.2 (SEM, 0.3) for patients with KS, demonstrating a clinically and statistically significant difference between the two groups (Student's t = 3.0; P = 0.003). This difference was higher when patients with a CD4+ lymphocyte count exceeding 200/microliters were regarded. Similar factors or mechanisms may contribute to HIV-related conjunctival microvasculopathy and KS.
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PMID:Human immunodeficiency virus-related microvasculopathy and Kaposi's sarcoma: a case-control study. 749 37

We investigated the possibility that a secreted glycoprotein of approximately 90,000 daltons, termed 90K and identified as a member of the protein superfamily characterized by the scavenger receptor cysteine-rich (SRCR) domain, might have value as a predictor of progression to acquired immunodeficiency syndrome (AIDS) in subjects infected with the human immunodeficiency virus (HIV). Among 488 HIV-seropositive intravenous drug users with a median follow-up of 32.5 months, high levels of serum 90K at baseline proved to be a significant predictor of faster progression to AIDS, either as a continuous variable (log 90K; p < 0.0001) or as a dichotomous variable with an optimized cutoff point of 30 U/ml (p < 0.00001). Analysis of 90K in relation to known prognostic factors found an association with CD4 count, beta 2-microglobulin, and p24 antigen but none with neopterin. In multivariate analysis, the baseline 90K level was an independent predictor of AIDS. As compared with subjects with low levels of 90K, the relative risk of developing AIDS was 3.5 (95% CI 1.9-6.5) among those with high levels of 90K. The predictive value of 90K was maintained after stratification by baseline CD4 count: among subjects with > or = 500 x 10(6)/L CD4 cells, the proportion in whom AIDS developed was 10.5% for those with 90K levels < or = 30 U/ml as compared with 20% for those with 90K above the cutoff point (p = 0.006). Serum 90K is an independent predictor of the risk for progression to AIDS in HIV-infected subjects, including those whose CD4 counts have not fallen.
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PMID:The 90K tumor-associated antigen and clinical progression in human immunodeficiency virus infection. 758 41

To get a measure of the extent of induction of nitric oxide synthase in infection with human immunodeficiency virus type-1 (HIV-1) in vivo, we estimated serum nitrite plus nitrate concentrations in 110 HIV-1 infected individuals compared to 76 blood donors. To monitor cytokine action and to measure induction of pteridine synthesis, we determined in parallel neopterin, biopterin, soluble tumor necrosis factor-alpha receptor 55 and 75, and beta 2-microglobulin. Serum nitrite plus nitrate concentrations were elevated in patients as compared to blood donor controls. In sera of patients, nitrite plus nitrate levels correlated significantly with neopterin, soluble tumor necrosis factor receptor 55 and 75, and beta 2-microglobulin. Nitrite plus nitrate levels were higher and correlations were stronger in groups of patients with lower CD4+ cell count. These results suggest that cytokine-mediated nitric oxide synthesis occurs in individuals with HIV-1 infection.
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PMID:Serum nitrite plus nitrate in infection with human immunodeficiency virus type-1. 759 Aug 63

alpha-Aminoadipic acid (alpha AA) is an intermediate in lysine metabolism. We report a new case with alpha AA excess in urine and plasma, without alpha-ketoadipic acid, in a full-term male child born to unrelated parents; he presented at 24h of life with seizures that failed to respond to phenobarbital, clonazepam, and Vigabatrin and death occurred on the 38th day of life. Brain imaging suggested antenatal haemorrhage. Small quantities of alpha AA were also detected in the blood and urine of both parents and a healthy brother, all three of whom exhibited the same defect in platelet aggregation as the deceased child. Both parents had decreased levels of plasma neopterin, a finding that might be related to the immunodeficiency described in other cases.
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PMID:Abnormal alpha-aminoadipic acid excretion in a newborn with a defect in platelet aggregation and antenatal cerebral haemorrhage. 762 43

Poly(I):poly(C12U) (mismatched double-stranded RNA; atvogen), an interferon inducer, is active against human immunodeficiency virus in vitro. To determine the extent and duration of the biologic effects of poly(I):poly(C12U), we administered a single dose of the drug to healthy volunteers in a randomized, double-blind, placebo-controlled 2-week crossover study. We analyzed blood for alpha and gamma interferons, neopterin, 2',5'-oligoadenylate synthetase, lymphocyte surface markers, lymphocyte proliferation after exposure to soluble antigens and mitogens, and natural killer cell activity. Minimal biologic effects were observed after administration of a single 200-mg dose to four volunteers; therefore, the dose was increased to 600 mg in 10 subjects. Only neopterin levels and symptoms were greater after administration of 600 mg of poly(I):poly(C12U) than after administration of placebo (Wilcoxon signed rank sum test, P = 0.06). A definite response in 2',5'-oligoadenylate synthetase activity, however, was seen in a few subjects. Neither alpha nor gamma interferon was detectable in serum after poly(I):poly(C12U) dosing. The neopterin changes after administration of poly(I):poly(C12U) were similar at both poly(I):poly(C12U) dose levels, with an early decrease at 6 h, a peak at 1 day, and a gradual decrease toward the baseline over the following 3 days. A mild flu-like syndrome occurred in one-half of the subjects following administration of poly(I):poly(C12U) and in only one subject following administration of placebo. This syndrome resolved within 16 h after poly(I):poly(C12U) dosing. We conclude that poly(I):poly(C12U) does not induce measurable levels of interferon and causes only minimal biologic or toxic effects among those parameters measured after administration of a single dose in the 200- to 600-mg dose range in health volunteers.
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PMID:Biologic effects after a single dose of poly(I):poly(C12U) in healthy volunteers. 768 56

To clarify useful clinical parameters for determining the need for changes in antiretroviral regimens, 586 persons who were seropositive for the human immunodeficiency virus (HIV) and who had intermediate-stage HIV disease underwent follow-up semiannually for a median of 3.1 years after zidovudine monotherapy was instituted. The strongest predictors of time to the development of AIDS and of survival were an increased CD4 lymphocyte count (> 50/microL), a decreased neopterin level (> 2.4 nmol/L), and no increase in the number of symptoms after 7-12 months of zidovudine therapy. Men who had the best quartile CD4 lymphocyte and neopterin responses and who also had no increase in the number of symptoms were 23 times less likely to die (reflecting a 96% increase in survival) than were men who had the worst responses in these variable categories. After 7-12 months of zidovudine therapy, 5-year survival rates were 63% for men with good responses in all three variable categories, 47%-49% for those with good CD4 lymphocyte responses and good responses in one other variable category, 31% for those with only a good CD4 lymphocyte response, and 0 for those with poor responses in all three variable categories.
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PMID:Prognostic value of combined response markers among human immunodeficiency virus-infected persons: possible aid in the decision to change zidovudine monotherapy. 774 42

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.
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PMID:Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study. 775 91

Patients with end-stage renal disease present an immunodeficiency that paradoxically coexists with activation of most immunocompetent cells, and the roles of chronic uremia and maintenance dialysis are poorly understood. We determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of undialyzed patients at various stages of chronic renal failure and in dialyzed patients on maintenance hemodialysis or chronic peritoneal dialysis. The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels. Although IL-1 beta could not be detected, IL-1Ra levels were significantly increased from the earliest stage of renal failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the severity of renal failure and correlated with soluble CD25, CD23, and neopterin levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels. Compared with undialyzed patients, levels of IL-1 beta were higher in patients on maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75 levels were significantly higher than in undialyzed patients and increased further at the end of dialysis sessions in the absence of an increase of TNF-alpha. Such an imbalance between cytokines and their inhibitors may play a pivotal role in the multifaceted process of immune dysfunction.
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PMID:Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes. 781 91


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