Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review aims to summarize recent work related to the pathogenesis and possible treatment of neuronal injury in the acquired immunodeficiency syndrome (AIDS), especially with reference to potential neurotoxic substances released by HIV-infected or gp120-stimulated macrophages/microglia. Approximately a third of adults and half of children with AIDS eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. Among the various pathologies reported in brains of patients with AIDS is neuronal injury and loss. A paradox arises, however, because neurons themselves are for all intents and purposes not infected by human immunodeficiency virus type 1 (HIV-1). This paper reviews recent evidence suggesting that at least part of the neuronal injury observed in the brains of AIDS patients is related to excessive influx of Ca2+ after the release of potentially noxious substances from HIV-infected or gp120-stimulated macrophages/microglia. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia or monocytes), especially after interacting with astrocytes, secrete substances that potentially contribute to neurotoxicity. Not all of these substances are yet known, but they may include eicosanoids, i.e. arachidonic acid and its metabolites, as well as platelet-activating factor. Other candidate toxins include nitric oxide (NO.), superoxide anion (O2.-), and the N-methyl-D-aspartate (NMDA) agonist, cysteine. Similarly, macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites, and cysteine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Update on current models of HIV-related neuronal injury: platelet-activating factor, arachidonic acid and nitric oxide. 787 85

Changes in mineral metabolism have recently been described in AIDS patients. To determine whether such changes affect bone turnover and bone mass, we studied 16 HIV-seropositive patients, classified according to Centers for Disease Control criteria, and 27 healthy controls. Biochemical markers of bone turnover and bone mineral density were analyzed. Serum concentrations of osteocalcin were abnormally low (0.5 +/- 1.3 ng/ml) in HIV-seropositive patients, in comparison with the control group (2.98 +/- 1.6 ng/ml) (p < 0.05). Urinary calcium/creatinine ratio was also decreased in HIV-positive patients (0.10 +/- 0.09 vs 0.14 +/- 0.09) (p < 0.05). In addition, bone mass was slightly lower in HIV-seropositive patients, although the difference was not statistically significant. The pathogenic mechanism of these alterations and their clinical relevance still remain unclear, and several factors may be implicated.
 ...
PMID:Alterations in bone turnover in HIV-positive patients. 790 Nov 71

It has previously been shown that crosslinking of the CD4 molecule, either with anti-Leu3a mAb or with gp120 (the HIV coat protein) plus anti-gp120 mAb, suppresses activation induced by wt31, a TcR/CD3-specific mAb. This suppression was associated with hindrance of the necessary association of the p56lck kinase bearing CD4 molecule with the TcR/CD3 complex. In this paper we demonstrate that this crosslinking-induced suppression can be bypassed by perturbing the microfilament system of CD4+ cells by pretreatment with 1 microM cytochalasin D. Using the fluorescence resonance energy transfer method, we have shown that the cytochalasin D-affected increase of mitogenesis is not due to changes in the TcR/CD3 to CD4 distance. Likewise, other membrane biophysical parameters, membrane potential and lateral diffusion of surface receptors, cannot be associated with these cytochalasin D-affected mitogenic changes. Cytochalasin D treatment elevates intracellular Ca2+ levels induced by wt31 mAb plus crosslinking and generates a TcR/CD3-dependent signal which is cyclosporin sensitive.
 ...
PMID:Cytochalasin D modulates CD4 crosslinking sensitive mitogenic signal in T lymphocytes. 791 66

The calcium-binding myelomonocytic protein calprotectin (L1 protein) was quantified in serum from 51 patients with HIV infection and in 20 HIV-seronegative blood donors. Significantly elevated levels were found both in asymptomatic patients and in people with AIDS compared with controls. The calprotectin level was not related to ongoing or recent opportunistic infections. For patients with CD4+ counts above 50 x 10(6)/L, a significant negative correlation was found between serum calprotectin levels and the CD4+ counts. Serial samples from 24 patients during their first year of zidovudine (ZDV) treatment showed a further elevation of serum calprotectin during the first months of ZDV treatment, with a subsequent decline to pretreatment levels. A low calprotectin response during the first 6 months, determined as area under the curve, was associated with the occurrence of at least one AIDS-defining infection during the first year of antiviral treatment. Also, a low calprotectin maximal response during ZDV therapy was associated with short survival. Similar associations were not found for neopterin, beta 2-microglobulin, HIV p24 antigen, or CD4+ or CD8+ lymphocytes in blood. Our findings in a limited number of patients suggest that calprotectin levels may reflect immune activation and other immune mechanisms correlated with enhanced antimicrobial defense induced at least transiently by antiviral treatment.
 ...
PMID:Elevated serum calprotectin levels in HIV-infected patients: the calprotectin response during ZDV treatment is associated with clinical events. 791 32

Patients with human immunodeficiency virus type 1 (HIV-1) seropositivity exhibited significantly lower intact serum parathyroid hormone (PTH) values (mean, 13.6 ng/liter; n = 44) than healthy controls (mean, 38.1 ng/liter; p < 0.001; n = 50). The reduction was greater among patients with no or mild immunodeficiency (> 400 x 10(6) CD4+ lymphocytes/ml blood; n = 22) than in those with severe immunodeficiency (< 200 x 10(6) CD4+ lymphocytes/ml blood; n 22; p = 0.03), although total serum calcium was normal in all groups. Patients with severe immunodeficiency demonstrated an inverse correlation between total serum calcium and serum PTH (r2 = 0.367; p < 0.01), which was also present in healthy controls (r2 = 0.482; p < 0.001), but not among the seropositive patients with no or mild immunodeficiency (r2 = 0.017; p = 0.58). Parathyroid cells express a protein recognized by antibodies directed against CD4, the HIV-1 receptor. This implies that these cells may be directly infected with HIV-1 and also interact with circulating autoantibodies against CD4, thus resulting in impaired PTH release.
 ...
PMID:Impaired parathyroid hormone release in human immunodeficiency virus infection. 791 22

Vaccine-induced, virus-specific CTLs may rapidly eliminate the host cells that first become infected after virus exposure, thereby preventing disseminated infection. Thus, there is much interest in the ability of candidate AIDS vaccines to elicit CTLs. All HIV-1 envelope (env) protein-based vaccines tested to date in seronegative humans induce CTLs from the CD4+ subset. Because the mechanism of cytolysis by CD4+ CTLs is controversial, a detailed study of the cytolytic reactions mediated by vaccine-induced, HIV-1-specific human CD4+ CTL clones was conducted. CD4+ CTL clones induced rapid destruction of Ag-pulsed target cells. Lysis was readily detectable within 15 min. Lysis was not a result of syncytium formation between CD4+ effector cells and env-expressing targets. Target cell destruction was not dependent upon de novo RNA or protein synthesis in either the effector or the target cell. Expression of perforin mRNA was detected by Northern blotting and reverse-transcriptase-PCR in CD4+ CTL clones but not in autologous B lymphoblastoid cell lines. Immunohistochemical studies demonstrated perforin protein in cytoplasmic granules in CD4+ CTL clones. Lysis by CD4+ CTLs was strictly dependent upon extracellular Ca2+ and was highly specific, with no lysis of innocent bystander cells. DNA fragmentation was detectable in target cells, but did not precede 51Cr release. Taken together, these results provide a dramatically different view of cytolysis by human CD4+ CTLs. Target cells are lysed by a rapid and efficient mechanism that involves a preformed mediator and that is functionally similar to the mechanism used by CD8+ CTLs.
 ...
PMID:Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL clones induced by candidate AIDS vaccines. 791 42

Rabbits were immunized with either calcium phosphate adjuvanted purified HIV-1 gp160 or a fluid preparation. Circulating antibodies were detected by ELISA, RIPA and Western Blot tests. Sera of rabbits immunized with the adjuvanted preparation contained high levels of anti-gp160 antibodies, as well as antibodies recognizing p55, p25 and p18. On the contrary, rabbits immunized with the fluid preparation contained only anti-p18 antibodies. Neutralizing antibodies were also detected. It is concluded that the calcium phosphate adjuvant could be used for preparation of candidate anti-HIV vaccines, since it permits one to induce high levels of circulating antibodies, in the absence of untoward reactions as observed when aluminium adjuvants or water in oil emulsions are used.
 ...
PMID:Humoral response in rabbits immunized with calcium phosphate adjuvanted HIV-1 gp160 antigen. 791 9

Soluble proteins of the human immunodeficiency virus (HIV) might play a significant role in the pathogenesis of HIV infection. The addition of synthetic Tat peptides, but not that of the recombinant Nef or Vif protein, inhibited proliferative responses of CD4+ tetanus antigen-specific, exogenous interleukin-2 (IL-2)-independent T-cell clones in a dose-dependent manner. In addition, Tat peptides inhibited the anti-CD3 monoclonal antibody-induced proliferative responses of both purified CD4+ and CD8+ T cells. Tat did not affect proliferative responses induced by phorbol myristate acetate plus ionomycin. The Tat peptides at the concentrations used (0.1 to 3 micrograms/ml) did not affect the viability of the cells as determined by trypan blue exclusion. Treatment of Tat peptides with polyclonal Tat antibodies abrogated the inhibitory effect of Tat. Soluble Tat proteins secreted by HeLa cells transfected with the tat gene also inhibited antigen-induced proliferation of the T-cell clones. Tat inhibited the anti-CD3 monoclonal antibody-induced IL-2 mRNA expression and IL-2 secretion but did not affect IL-2 receptor alpha-chain mRNA or protein expression on peripheral blood T cells. Finally, treatment of T-cell clones with the Tat peptide did not affect the antigen-induced increase in intracellular calcium, hydrolysis of phosphatidyl inositol to inositol trisphosphate, or translocation of protein kinase C from the cytosol to the membrane. These studies demonstrate that the mechanism of the Tat-mediated inhibition of T-cell functions involves a phospholipase C gamma 1-independent pathway.
 ...
PMID:Human immunodeficiency virus Tat induces functional unresponsiveness in T cells. 798 46

Impairment of the central nervous system (CNS) and peripheral nervous system (PNS) is common during the human immunodeficiency virus type 1 (HIV-1) infection. There are evidences of activated immune reactions in the CNS and PNS of patients with acquired immunodeficiency syndrome (AIDS). The expression of HIV-1 predominantly in monocyte/macrophage lineage cells strongly suggests immunopathogenetic mechanisms. Possible mechanisms of neuronal and glial cell damage include calcium dependent excitotoxicity by HIV-1 envelope protein, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity of quinolinic acid, injury of oligodendrocytes by tumor necrosis factor--alpha, cell injury by HIV-1-specific cytotoxic T cells, and apoptosis of oligodendrocytes or neurons. These mechanisms are not mutually exclusive. Multiple factors may be involved in the pathogenesis of HIV-1-associated neurological diseases.
 ...
PMID:[Pathogenesis of neurological disorders in AIDS]. 799 89

Interference with T cell activation signals by Human immunodeficiency virus (HIV) gene products is suggested to contribute to the impairment of immune functions observed in AIDS. Interleukin-2 (IL-2) and HIV share common stimulatory signals triggered during T cell activation. The role of HIV tat, which is the main enhancing factor for viral LTR, in the regulation of IL-2 gene transcription has been studied following transient expression of the tat gene in phorbol ester and calcium ionophore-activated Jurkat cells transfected with IL-2 promoter-chloramphenicol acetyltransferase reporter constructs. We observed that tat increased the IL-2 promoter transcriptional activity in response to phorbol ester and ionomycin. This tat-dependent synergism mapped to the (-279 to -263 bp) NFAT motif of the IL-2 enhancer, which was sufficient to be transactivated by tat. Our data suggest that tat links T cell activating signals to the shared IL-2 and HIV regulation. This may play a role in the early phase of HIV infection.
 ...
PMID:Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif. 799 66


<< Previous 1 2 3 4 5 6 7 8 9 10