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)

Late-stage HIV infection is characterized by profound immunodeficiency with a progressive and irreversible decline in the CD4 count, functional impairment of cellular and humoral immunity, and evidence of increased viral replication, with the appearance of p24 antigenemia and increasing levels of beta(2)-microglobulin and neopterin. These changes are associated with increased susceptibility to many infections, the emergence of malignancies, and neurological complications due to the direct infection of neural tissue with HIV. In Australia, opportunistic infections and malignancies account for 75% and 18% of AIDS diagnoses, respectively. Opportunistic infections and neurological involvement usually occur late in the illness and may be associated with disturbances of function of each part of the neuraxis. The detailed clinical nature of the involvement has been described in several recent reviews and is probably not different in the Asia-Pacific region. The most common opportunistic infections in Australia are Pneumocystis carinii pneumonia (PCP), esophageal candidiasis, toxoplasmosis, CMV infection, atypical mycobacteriosis, and cryptococcal meningitis. There are few data from Asian countries, but it seems that the most common opportunistic infections are tuberculosis, PCP, systemic Penicillium marneffei infection, and cryptococcal meningitis. There is little information from Asia on neurological conditions. Tuberculosis is probably the most significant threat to public health in Asia and the Pacific. Its management and prevention require ongoing planning and resources. To that end, a collaborative effort is called for to help resource-poor countries. Mycobacterial, fungal, viral, and protozoal infections are discussed, along with consideration of neurological complications, malignant disease, and late manifestations of HIV infection in children.
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PMID:Late manifestations of HIV in Asia and the Pacific. 785 67

Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients with acquired immunodeficiency syndrome (AIDS). Ocular microvascular changes, including cotton-wool spots, are closely associated with neuroretinal and cognitive deficits in patients infected with the human immunodeficiency virus type 1 (HIV-1). Cell adhesion has become an important pathogenetic concept in infectious diseases. We studied 39 patients with AIDS by indirect ophthalmoscopy and by slit-lamp biomicroscopy. Cotton-wool spots were counted as an indicator of retinal microvasculopathy. Conjunctival blood-flow sludging in conjunctival vessels was determined by a standardized rating scale as an indicator of blood-cell adhesion abnormalities. Parameters of immunosystemic damage were determined by fluorescein-activated cell-sorter scan, radioimmunoassay, and enzyme-linked immunosorbent assay. Conjunctival blood-flow sludging was present in 92% of our patients, and cotton-wool spots were observed in 44%. Cotton-wool spots occurred only in patients with significant blood-flow sludging, and the quantity of cotton-wool spots was closely associated with blood-flow sludging (r = 0.64, P < 0.0001). Lower correlations were found between the numbers of cotton-wool spots and the serum level of neopterin (r = 0.40, P = 0.01) or the CD4+ count (r = -0.39, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ocular microangiopathic syndrome in patients with acquired immunodeficiency syndrome and its relationship to alterations in cell adhesion and in blood flow. 786 62

Serum concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) were measured in 61 human immunodeficiency virus (HIV)-infected individuals. Thirty-five percent of these had increased serum concentrations of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrations of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4+ T-cell count. However, the increase in concentrations of sTNF-R55 in the group with a CD4+ T-cell count below the median was only moderate and did not reach statistical significance. A strong correlation was found between sTNF-R75 and the soluble immune activation markers beta 2-microglobulin (rs = 0.74, p < 0.0001) and urinary neopterin (rs = 0.67, p < 0.0001), and a less strong correlation was found with interferon-gamma (rs = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were always weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4+ T cells and sTNF-R75 (rs = -0.33, p = 0.012), but no such correlation was observed with sTNF-R55. Our findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.
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PMID:Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation. 790 82

Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor necrosis factor (TNF) alpha were measured in 42 patients with primary hypogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 congenital hypogammaglobulinemia (CH), 7 X-linked agammaglobulinemia (XLA), and in 21 healthy controls. The cytokine levels were correlated to other immunological parameters including serum levels of neopterin and soluble CD8 (sCD8) antigen. IL-6 was detectable in 48% and IL-4 in 36% of the CVI patients, but in none of the controls. Seventy-five percent of the CVI patients with elevated IL-4 levels had detectable IL-6. In contrast, no patients in the XLA group and only three CH patients had detectable IL-4 or IL-6 levels. TNF alpha and IL-1 alpha were detected in only a few serum samples with no significant differences between patients and controls. In the CVI group elevated IL-6 levels were significantly associated to reduced numbers of CD4+ and CD19+ lymphocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis. The raised IL-6 levels were confirmed in longitudinal testing, probably reflecting a characteristic immunological dysregulation in these patients. Cytokine alterations may play a role in the pathogenesis of the immunodeficiency and for the clinical manifestations in CVI patients. Alternatively, elevated cytokine levels may be only a marker of chronic immune activation, particularly in monocytes, possibly delineating a distinct subgroup of patients within the heterogeneous CVI group.
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PMID:Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. 790 14

Quantitative serum antibody to p24 was evaluated as a predictor of risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection. HIV-positive mothers, 13 with HIV-infected children and 24 with noninfected children were investigated during pregnancy and at the time of delivery. A statistically significant difference in anti-p24 titers was found between the mothers with infected and those with noninfected children independent of whether antibodies were measured during pregnancy or at the time of delivery. High anti-p24 levels correlated with a low risk of vertical transmission, whereas low anti-p24 titers were associated with an increased risk of vertical transmission. Although the number of CD4+ T-cells was lower and neopterin and beta-2 microglobulin values were higher in the group of mothers with infected children than in the noninfected group, no statistical significance was achieved due to the small sample size.
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PMID:Quantitative anti-p24 determinations can predict the risk of vertical transmission. Swiss HIV and Pregnancy Collaborative Study Group. 790 3

Vitamin D metabolites, immunologic, virologic, and clinical parameters, and survival time were determined in 22 asymptomatic human immunodeficiency virus (HIV)-infected patients (CDC stage II/III), 31 symptomatic HIV-infected patients (CDC stage IV), and 28 HIV-seronegative controls. Significantly lower serum levels of 1,25-vitamin D (1,25D) were found in symptomatic patients (median, 34 pg/mL; 25th-75th percentile, 21-45) compared with controls (49 pg/mL; 39-59) and asymptomatic patients (45 pg/mL; 42-50). In HIV-infected subjects, the serum level of 1,25D was positively correlated with CD4+ cell counts in peripheral blood (r = .35, P < .05) and negatively correlated with the level of serum neopterin (r = -.36, P < .01). HIV-infected patients with abnormally low 1,25D (< 25 pg/mL) also had shorter survival times than other HIV-infected subjects (P < .01). Low 1,25D levels did not appear to be related to vitamin D deficiency.
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PMID:Subnormal serum concentration of 1,25-vitamin D in human immunodeficiency virus infection: correlation with degree of immune deficiency and survival. 790 45

We reported recently that anti-Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus-infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the IgA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIV+ patients with ARC (p < 0.02), HIV+ patients without AIDS/ARC (p < 0.0001), HIV-negative (HIV-) patients (p < 0.001), or healthy controls (p < 0.0001). An inverse association was found between IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, p < 10(-6)). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. However, IgM-anti-Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA-anti-Fab activity and serum neopterin concentrations (r = 0.310, p < 10(-5)). IgG-anti-Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity-purified anti-Fab antibodies isolated from sera of AIDS patients bound to rgp120-preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti-Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adsorbance might be a useful approach in the treatment of AIDS.
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PMID:Isotypes and IgG subclasses of anti-Fab antibodies in human immunodeficiency virus-infected hemophilia patients. 790 73

The dementia associated with human immunodeficiency virus (HIV) is poorly understood. Dementia is accompanied by infection and activation of macrophage lineage cells in the brain and production of toxic products by these cells has been postulated to play a role in the pathogenesis of dementia. Eicosanoids are potential products of activated macrophages that can mediate cell injury. We measured the levels of prostaglandin E2 in the cerebrospinal fluid of HIV-positive individuals with dementia and/or myelopathy and compared these levels with those of HIV-negative patients with other neurological diseases and HIV-positive patients without dementia. Cerebrospinal fluid prostaglandin E2 levels were increased in dementia. This increase was associated with severity of dementia and correlated with cerebrospinal fluid levels of neopterin and beta 2-microglobulin. Prostaglandins F2 alpha and thromboxane B2, additional products of the cyclooxygenase pathway of arachidonic acid metabolism, were also elevated in dementia, but leukotriene C4, a product of the lipoxygenase pathway was not. Since synthesis of prostaglandins is regulated in part by the levels of inducible forms of cyclooxygenase, we measured the levels of cyclooxygenase-1 and 2 mRNAs in the brains of HIV-positive individuals with and without dementia by reverse transcriptase polymerase chain reaction. Levels of intact cyclooxygenase-1 mRNA were higher in the brains of demented individuals, but this did not reach statistical significance. These data demonstrate that prostaglandins are increased in the central nervous system in HIV-associated dementia and may play a role in the development of neurological dysfunction.
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PMID:Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia. 791 4

The objective of this study was to determine whether beta 2-microglobulin, neopterin, nutritional status, clinical status, immunosuppression, and hematologic status are predictors of human immunodeficiency virus (HIV)-related wasting and wasting syndrome. In addition, we aimed to determine which factors are early predictors and which are late predictors of wasting. For this cohort study of HIV-1-seropositive men seen semiannually from 1984 to 1991, a nested case-control design was used to analyze the predictive value of independent variables collected at baseline (first study visit for the seropositive cohort, first seropositive visit for seroconverters), 12 to 18 months prior, 6 to 12 months prior, and less than 6 months prior to the time at which case patients and control subjects were identified. Data on beta 2-microglobulin, neopterin, educational status, and diet were only available at baseline. A total of 41 case patients and 161 control subjects (n = 202) were identified. These were homosexual/bisexual men who were either HIV-seropositive on entering the study (n = 177) or who seroconverted during the study period (n = 25). Case patients were defined as men who had lost more than 10% of their baseline weight or who had a clinical diagnosis of wasting syndrome using the 1987 Centers for Disease Control definition. Control subjects had less than 5% weight loss from baseline or no weight loss at all. Four control subjects were matched to each case patient (where possible) by age and duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta 2-microglobulin and other early predictors of human immunodeficiency virus type 1-related wasting. 791 78

Immune activation seems to be involved in the pathogenesis of human immunodeficiency virus (HIV) infection. The immune activation markers neopterin and beta 2-microglobulin can predict the future rate of the decrease in CD4+ T cells. In a longitudinal study, we assessed whether the decline in the CD4+ T-cell count is associated with increased concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble tumor necrosis factor receptor 75 (sTNFR 75), compared to increased concentrations of beta 2-microglobulin and urinary neopterin. Forty-seven individuals representing all stages of HIV infection were followed-up for a mean of 12.7 months (range, 8 to 16 months). The percentage of the change of the CD4+ T-cell count from study entry to study end ranged from -97 to +98%; the median was -33%. Concentrations of urinary neopterin, sTNFR 75, and beta 2-microglobulin correlated with the percentage of the change of the CD4+ T-cell count from study entry to study end (r = -0.45, confidence interval (CI) -0.65 to -0.19; r = -0.42, 95% CI -0.63 to -0.15; and r = -0.416, 95% CI -0.62 to -0.15), but those of sICAM-1 did not. This difference was found despite significant correlations between sICAM-1 and sTNFR 75 and beta 2-microglobulin. Levels of sICAM-1 obtained at study entry correlated with levels of sICAM-1 obtained at study end (r = 0.46, 95% CI 0.17 to 0.68). In a multivariate linear regression analysis, urinary neopterin and sTNFR 75 were jointly significant for the percentage of the change of the CD4+ T-cell count. These results suggest that sTNFR 75 is a useful marker to estimate disease progression in HIV infection, whereas sICAM-1 does not seem to provide any information related to the decline of the CD4+ T-cell count.
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PMID:Increased concentrations of soluble tumor necrosis factor receptor 75 but not of soluble intercellular adhesion molecule-1 are associated with the decline of CD4+ lymphocytes in HIV infection. 791 41


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