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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report for the first time the concentrations of free amino acids in human intestinal biopsies obtained by routinely performed endoscopy. We studied 15 medical patients with no changes of the mucosa and six HIV-infected persons with duodenitis. The mean (and SD) sum of all amino acids, taurine excepted, was 61.9 (5.4) mmol/kg dry weight in duodenal biopsies of HIV-negative subjects (n = 11) and 82.9 (0.6) mmol/kg in colonic specimens: 50% (44%) of the total (minus taurine) consisted of aspartate and glutamate and 14% (12%), of the essential amino acids. The relative amino acid pattern in duodenum and colon differed completely from that for muscle: aspartate was fourfold higher; glutamate, phenylalanine, glycine, valine, leucine, and isoleucine were about twofold higher. In contrast, glutamine amounted only to 4% (duodenum) to 14% (colon) of muscle glutamine. In duodenal biopsies of the HIV-infected persons, we found significantly (P less than 0.01, except glutamine: P less than 0.025) increased concentrations of glutamate (24.1 vs 17 mmol/kg dry weight), ornithine (1.4 vs 0.4), valine (2.2 vs 1.7), and glutamine.
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PMID:Intracellular free amino acid patterns in duodenal and colonic mucosa. 230 84

We tested the hypothesis that the loss of immunological reactivity in HIV-1-infected persons may result partly from a virus-induced metabolic disorder. Patients who are infected with the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus 1 were found to have, on average, markedly elevated and highly variable plasma glutamate concentrations. A similar elevation of the extracellular glutamate concentration was found to inhibit DNA synthesis in cultures of mitogenically stimulated lymphocytes. An even stronger inhibition was seen with the structural analogue quisqualate, and a moderate inhibition was seen with N-methyl-D-aspartate and kainate, i.e. with well established pharmacological probes for the excitatory glutamate receptors in the vertebrate central nervous system. The inhibitory effect of glutamate was compensated by adding cysteine or relatively large numbers of 'splenic adherent cells' to the culture. Elevated extracellular glutamate levels were also found to reduce the capacity of murine macrophages, human blood monocytes, and murine fibroblastoid cells (L929 cells) to release acid-soluble thiol (cysteine) into the extracellular space. The three cell types differed, however, with respect to their sensitivity against the three structural analogues of glutamate. The elevated glutamate concentration was not non-specifically toxic for cultured macrophages, since glycolytic activity and arginase activity were not inhibited. Implications of these observations for the pathogenetic mechanism of AIDS are discussed.
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PMID:Elevated plasma glutamate concentrations in HIV-1-infected patients may contribute to loss of macrophage and lymphocyte functions. 257 75

Blood plasma samples from HIV-1-infected persons contain elevated glutamate concentrations up to 6-fold the normal level and relatively low concentrations of acid-soluble thiol (i.e. decreased cysteine concentrations). The intracellular glutathione concentration in peripheral blood-mononuclear cells (PBMC) and monocytes from HIV antibody-positive persons are also significantly decreased. Therapy with azidothymidine (AZT) causes a substantial recovery of the plasma thiol levels; but glutamate levels remain significantly elevated and intracellular glutathione levels remain low. Cell culture experiments with approximately physiological amino-acid concentrations revealed that variations of the extracellular cysteine concentration have a strong influence on the intracellular glutathione level and the rate of DNA synthesis [( 3H]thymidine incorporation) in T cell clones and human and murine lymphocyte preparations even in the presence of several-fold higher cystine and methionine concentrations. Cysteine cannot be replaced by a corresponding increase of the extracellular cystine or methionine concentration. These experiments suggest strongly that the low cysteine concentration in the plasma of HIV-infected persons may play a role in the pathogenetic mechanism of the acquired immunodeficiency syndrome.
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PMID:Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients. 278 73

The acquired immunodeficiency syndrome (AIDS) is accompanied by a metabolic disturbance. Serum samples from persons with antibodies against the AIDS associated human immunodeficiency virus (HIV/LAV/HTLV III) including persons without overt symptoms, patients with lymphadenopathy syndrome (LAS) and patients with AIDS or AIDS-related complex (ARC) contain on the average significantly elevated concentrations of arginine and glutamate. The serum from patients with overt AIDS contains also, on the average, significantly reduced concentrations of methionine and cystine. In vitro experiments revealed that the [3H]thymidine incorporation by mitogenically stimulated murine lymphocytes and cloned T cells is inhibited by an elevation of the extracellular glutamate concentration and augmented by the addition of cysteine. This suggests the possibility that the abnormal concentrations of glutamate and cystine in the blood of HIV-infected persons may contribute to the defect in the lymphoid system.
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PMID:Abnormal amino-acid concentrations in the blood of patients with acquired immunodeficiency syndrome (AIDS) may contribute to the immunological defect. 289 98

We measured the free amino acids in plasma of 58 patients with HIV infection and in six persons in the risk group. The HIV+ patients had significantly increased concentrations of arginine, phenylalanine, and glutamate in comparison with both age- and sex-matched controls and the members of the risk group. Glutamate concentrations increased only in an advanced stage of the disease (WR 5 and 6 of the Walter Reed staging classification), whereas arginine and phenylalanine increased independently of the stage. There was no correlation between the amino acid concentrations and the number of T4 and T8 lymphocytes, the sedimentation rate, and the existence or absence of Kaposi's sarcoma. The amino acid pattern of HIV-infected persons is similar to that of cancer patients or those with other immune deficiencies.
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PMID:Plasma amino acid pattern of patients with HIV infection. 290

Amino acid concentrations were analyzed in the sera of HIV (LAV/HTLV-III) positive persons and in the plasma of colorectal carcinoma patients. Both groups of persons showed significantly elevated glutamate concentrations when compared with healthy control persons. Glutamate concentrations were found to be strongly elevated in all groups of HIV-positive persons including patients with acquired immunodeficiency syndrome (AIDS) or lymphadenopathy as well as HIV-positive persons without overt symptoms, indicating that increased plasma glutamate levels may be among the earliest consequences of the HIV infection. Moreover, the increased plasma glutamate concentrations in the colorectal carcinoma patients were correlated with a decreased immunological reactivity (mitogenic responses against concanavalin A). This suggests the possibility that the increased plasma glutamate concentrations may be causally responsible for the decreased immunological reactivity in colorectal carcinoma patients as well as in patients with AIDS.
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PMID:Elevated plasma glutamate levels in colorectal carcinoma patients and in patients with acquired immunodeficiency syndrome (AIDS). 367 79

AIDS dementia complex (ADC) is a complex, progressive neuropsychiatric syndrome seen in 60-70% of the patients with AIDS. The structural and functional changes associated with ADC may be the result of a variety of indirect mechanisms mediated via activated brain cells or/and virus that produce neurotoxins including N-methyl-D-aspartate receptor agonist (eg, quinolinic acid, glutamate), cytokines, gp 120 and nitric oxide. The level of the neurotoxin and kynurenine pathway metabolite, quinolinic acid, is increased in the brain and CSF of HIV-1-infected patients, and is correlated with quantitative measures of neurologic impairment. Importantly, increased CSF and brain levels of QUIN also occur in other inflammatory neurologic diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicemia), independent of HIV-1 infection. Therefore, QUIN and other neuroactive kynurenine pathway metabolites may be final common mediators of neurologic dysfunction in a broad spectrum of inflammatory neurologic diseases. Conversion of L-tryptophan to QUIN has also been demonstrated in vitro in both brain tissue following macrophage infiltration, and in macrophages stimulated by interferon-gamma or HIV infection. Macrophages in vitro have a high capacity to synthesize QUIN following exposure to interferon-gamma, tumor necrosis factor-alpha, IL-1 beta and IL-6, compared to cells derived from other tissues. Notably, the concentrations achieved in the macrophage incubates exceeded the levels found in the CNS of HIV-1-infected patients, and exceeded the concentrations shown to be neurotoxic in vitro. We hypothesize that increased kynurenine pathway metabolism following inflammation reflects the presence of macrophages and other reactive cell populations at the site of brain infection. Strategies to attenuate the neurotoxic effects of kynurenines, such as inhibitors of kynurenine pathway metabolism and cytokine antibodies may offer new approaches to therapy.
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PMID:[Biochemical studies on AIDS dementia complex--possible contribution of quinolinic acid during brain damage]. 747 52

S-2720 and other members of the quinoline/quinoxaline class of HIV-1-specific nonnucleoside reverse transcriptase inhibitors (NNRTIs) select for a glycine to glutamate substitution at residue 190 (Gly 190 Glu) of the reverse transcriptase (RT), when drug-resistant viruses are generated in cell culture. This mutation has not been described to appear upon selection for resistant viral variants using derivatives of any other class of NNRTIs. Notably, the RNA-dependent DNA polymerase activity of the Gly 190 Glu mutant enzyme is drastically diminished with respect to the wild-type RT. We describe here the effects of other amino acid substitutions at position 190 of the RT that were introduced by using site-directed mutagenesis. Polymerase activities and sensitivities to inhibition by a number of NNRTIs were determined for the different RT mutants. In general, an inverse correlation was found between the enzymatic activity and increasing length of the side chain, whereas the size of the residue and the level of resistance to NNRTIs appeared to be positively related. Double mutants, which contain the Gly 190 Glu mutation together with substitutions that confer resistance to other RT inhibitors, were all shown to possess severely diminished polymerase activity.
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PMID:Mutational analysis of residue 190 of human immunodeficiency virus type 1 reverse transcriptase. 751 21

HIV infection can cause extensive neuronal loss and clinically a severe dementia. The cause of the neurotoxicity remains unclear as neurons are not infected, but disturbance of glutamate-linked calcium entry has been implicated. In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA and protein of the GluR-A flop subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor in cerebellar Purkinje cells. Although Purkinje cells are relatively resistant to loss, the observed disturbance of AMPA receptors may contribute to the neurotoxic process in other vulnerable brain regions and clinically to the development of dementia.
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PMID:Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model for HIV-associated neurotoxicity. 758 90

The effects of human immunodeficiency virus type-1 (HIV-1) coat protein gp120 on levels of intrasynaptosomal calcium ([Ca2+]i) were determined in rat cortical synaptosomes. gp120 at concentrations of > or = 400 pM, significantly (P < 0.05) increased levels of [Ca2+]i. Treatment with 20 mM KCl, reduced the concentrations of gp120 necessary to produce significant (P < 0.001) increases in [Ca2+]i. gp120-evoked increases in [Ca2+]i were prevented either by treatment with dantrolene or by removal of extracellular calcium with BAPTA. The peak levels of gp120-induced increases in [Ca2+]i were not affected by calcium channel blockers lanthanum and nicardipine, by glutamate receptor antagonists MK-801 and NBQX, or by removal of endogenous glutamate with glutamate dehydrogenase. gp120-induced [Ca2+]i increases in presynaptic terminals may play a role in HIV-mediated effects in the central nervous system.
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PMID:HIV-1 coat protein gp120-induced increases in levels of intrasynaptosomal calcium. 762 Aug 88


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