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)

Plasma membrane fluidity of intact peripheral blood lymphocytes (PBL) of phenytoin-treated nonepileptic patients and phenytoin-treated CD4+ lymphoid cells H9 and K37 was determined by fluorescence anisotropy measurements. Anisotropy values of the membrane probe 6-(9-anthroyloxy) stearic acid were decreased in all cell types as compared with controls, indicating increased plasma membrane fluidity of phenytoin-treated cells. Specific binding of 125I-labeled vasoactive intestinal peptide (VIP) to its cellular receptor CD4 on PBL was decreased in PBL of phenytoin-treated patients as compared with untreated, healthy subjects. Adsorption of a different ligand to the CD4 receptor on PBL, the human immunodeficiency virus type 1 (HIV-1), was likewise abolished to PBL of phenytoin-treated patients and phenytoin-treated CD4+ H9 and K37 cells, as assessed by indirect immunofluorescence. Subsequent HIV-1 infection of phenytoin-treated H9 and K37 cells was reduced as measured by indirect immunofluorescence and p24 antigen production. These data indicate that CD4 receptor availability for VIP and HIV-1 was reduced in phenytoin-treated cells. Using the DNA-specific dye Hoechst 33258, we examined cell cycle phase distributions of HIV-1 adsorbing and nonadsorbing H9 cells, as separated by flow cytometry. The majority of HIV-1 adsorbing cells were found to be in the G2/M phase, while nonadsorbing cells were mainly in the G0/G1 phase, during which plasma membrane fluidity is supposed to be increased. This study indicates that plasma membrane fluidization by phenytoin may serve to disrupt CD4 receptor function and emphasizes the impact of plasma membrane properties on HIV-1 adsorption and infection.
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PMID:Decreased binding of HIV-1 and vasoactive intestinal peptide following plasma membrane fluidization of CD4+ cells by phenytoin. 197 37

The CD4 molecule was originally described as a marker for a subset of lymphocytes; however, recent work has shown that a similar, if not identical, molecule is present on human brain. We have realized that this cell-surface recognition molecule is normally modulated by vasoactive intestinal peptide (VIP), one of the 50 or more neuropeptides that compose a shared intercellular network joining the brain, glands, and immune system. Human immunodeficiency virus (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), has been found to mimic VIP binding via peptide T (4-8), a pentapeptide sequence present in approximately the same region of all 20 HIV isolates whose sequences are currently known. AIDS dementia results from interference of gp120, present on the HIV envelope protein, with normal VIP-ergic neurotrophic effects, and effects on cerebral blood flow.
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PMID:AIDS and its dementia as a neuropeptide disorder: role of VIP receptor blockade by human immunodeficiency virus envelope. 283 5

The clinical manifestations of AIDS (acquired immune deficiency syndrome) often include neuropsychiatric and neurological deficits, including early memory loss and progressive dementia. HIV (human immunodeficiency virus), the aetiological agent of AIDS, is probably carried by infected macrophages in the central nervous system. The virus enters cells by binding its envelope glycoprotein gp120 to the CD4 antigen present on brain and immune cells. From the data reported in this paper, we now suggest that the neuronal deficits associated with HIV may not be entirely a result of infectivity, but that gp120 shed from HIV could directly produce the neuropathology as a result of its interference with endogenous neurotrophic substances. It is known that an analogue of a sequence contained in vasoactive intestinal peptide (VIP) occurs in all known sequenced gp120 isolates and that VIP is important for neuronal survival in cell culture. Here we show that purified gp120 from two diverse HIV isolates and a recombinant gp120 from a third isolate were all potent in specifically producing significant neuronal cell death in dissociated hippocampal cultures derived from fetal mice, and that this could be reduced by monoclonal antibodies against the murine CD4 antigen and completely antagonized by VIP.
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PMID:Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. 284 76

Cognitive and motor impairment are common symptoms among patients infected with the human immunodeficiency virus (HIV), including children who suffer neurological deficits and are frequently developmentally impaired. The HIV envelope protein, gp120, which has been shown to be toxic to neurons in culture, is shed in abundance by infected cells, and thus may play a significant role in the neuropathology of AIDS. To test this possible mechanism, neonatal rats were injected systemically with purified gp120 and the following consequences were observed: (1) radiolabeled gp120 and toxic fragments thereof were recovered in brain homogenates; (2) dystrophic changes were produced in pyramidal neurons of cerebral cortex; (3) retardation was evident in developmental milestones associated with complex motor behaviors. In parallel studies, co-treatment with peptide T, a gp120-derived peptide having a pentapeptide sequence homologous with vasoactive intestinal peptide, prevented or attenuated the morphological damage and behavioral delays associated with gp120 treatment. These studies suggest that gp120 and gp120-derived toxic fragments may contribute to the neurological and neuropsychiatric impairment related to HIV infection, and that peptide T appears to be effective in preventing gp120-associated neurotoxicity in developing rodents.
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PMID:HIV envelope protein-induced neuronal damage and retardation of behavioral development in rat neonates. 846 78

The ability of the human immunodeficiency virus type 1 (HIV-1) to persist and replicate in human CD4+ cells is under the control of both virally encoded proteins and a variety of host-related factors. Transcription of human immunodeficienty virus type 1 (HIV-1) is regulated by multiple cis-acting regulatory elements located in the viral long terminal repeats (LTRs). Here we report that the human vasoactive intestinal peptide (VIP) can activate the HIV-1-LTR. The activity of VIP is dose-dependent and specific. The effective concentration of VIP is within the physiological range suggesting that VIP release may modulate the activity of HIV-1 in vivo. A sequence in U3 region could be involved in VIP and in various VIP-related peptides' activation of HIV-1-LTR. This cis-acting element conferring VIP responsiveness is indistinguishable from HIV NF-kappa B tandem repeat binding sites (HIV-1 kappa B).
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PMID:Activation of transcription from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat by the vasoactive intestinal peptide (VIP). 974 Oct 48

The vulnerability of neurons and the irreversibility of loss make discoveries of neuroprotective compounds fundamentally important. Here, the complete coding sequence of a novel protein (828 amino acids, pI 5.99), derived from mouse neuroglial cells, is revealed. The sequence contained (1) a neuroprotective peptide, NAPVSIPQ, sharing structural and immunological homologies with the previously reported, activity-dependent neurotrophic factor; (2) a glutaredoxin active site; and (3) a zinc binding domain. Gene expression was enriched in the mouse hippocampus and cerebellum and augmented in the presence of the neuropeptide vasoactive intestinal peptide, in cerebral cortical astrocytes. In mixed neuron-astrocyte cultures, NAPVSIPQ provided neuroprotection at subfemtomolar concentrations against toxicity associated with tetrodotoxin (electrical blockade), the beta-amyloid peptide (the Alzheimer's disease neurotoxin), N-methyl-D-aspartate (excitotoxicity), and the human immunodeficiency virus envelope protein. Daily NAPVSIPQ injections to newborn apolipoprotein E-deficient mice accelerated the acquisition of developmental reflexes and prevented short-term memory deficits. Comparative studies suggested that NAPVSIPQ was more efficacious than other neuroprotective peptides in the apolipoprotein E-deficiency model. A potential basis for rational drug design against neurodegeneration is suggested with NAPVSIPQ as a lead compound. The relative enrichment of the novel mRNA transcripts in the brain and the increases found in the presence of vasoactive intestinal peptide, an established neuroprotective substance, imply a role for the cloned protein in neuronal function.
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PMID:Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. 1003 2

Severe xerosis occurs in approximately 20% of human immunodeficiency virus seropositive patients. Changes in cutaneous innervation have been found in various inflammatory skin diseases and in xerotic skin in familial amyloid. We have therefore carried out a quantitative examination of the cutaneous peptidergic innervation in human immunodeficiency virus-associated xerosis. Immunohistochemistry and image analysis quantitation were used to compare total cutaneous innervation (protein gene product 9.5), calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide peptidergic fibers, at two sites in the skin of human immunodeficiency virus-associated xerosis patients (upper arm, n = 12; upper leg, n = 11) and site-matched seronegative controls (upper arm, n = 10; upper leg, n = 10). Measurement of lengths of fibers of each type was carried out for each subject in the epidermis and papillary dermis, and around the sweat glands. Immunostained mast cells in these areas were counted. Epidermal integrity and maturation were assessed by immunostaining for involucrin. There were significant (Mann-Whitney U test; p < 0.02) decreases in total lengths of protein gene product 9.5 fibers in both epidermis/papillary dermis and sweat gland fields; of calcitonin gene-related peptide innervation in the epidermis/papillary dermis; and of substance P innervation of the sweat glands. There were no differences in the distribution of mast cells, or in the epidermal expression of involucrin. Depletion of the calcitonin gene-related peptide innervation may affect the nutrient blood supply of the upper dermis, and the integrity and function of basal epidermis and Langerhans cells. Diminished substance P innervation of the sweat glands may affect their secretory activity. Both of these changes may be implicated in the development of xerosis.
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PMID:Depletion of cutaneous peptidergic innervation in HIV-associated xerosis. 1008 3

Natural killer (NK) cell dysfunction is common in human immunodeficiency virus (HIV)-infected subjects, although its mechanisms are poorly understood. A direct effect of HIV envelope glycoprotein gp120 may be involved. We investigated the in vitro effects of gp120 on the major NK cell effector functions, natural cytotoxicity and cytokine production. In addition, the ability of the vasoactive intestinal peptide (VIP) to modulate these effects was investigated. Our results indicated that gp120 inhibits NK natural cytotoxicity and showed, for the first time, that the inhibition affects also the production of the proinflammatory cytokine interferon-gamma (IFN-gamma). Interestingly, the inhibitory effect on NK cell functions was obtained with gp120 at concentrations within the range measured in the serum of HIV-infected subjects. Furthermore, we showed that the inhibitory activity of gp120 can be prevented by coincubation with VIP, even if VIP has no stimulatory activity by itself. Taken together these data suggest that (1) an inhibitory effect of gp120 may account for the NK cell dysfunction in HIV-infected subjects; (2) the gp120-mediated decrease in IFN-gamma production by NK cells may contribute to the cytokine imbalance observed in HIV infection; and (3) VIP counteracts the inhibitory effect of gp120 on NK cell functions.
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PMID:Inhibition of natural killer cell cytotoxicity and interferon gamma production by the envelope protein of HIV and prevention by vasoactive intestinal peptide. 1093 22

The envelope protein (gp120) of the human immunodeficiency virus produces neuronal cell death in cultures that can be prevented by co-treatment with pituitary adenylate activating peptide-38 (PACAP-38) or chemokines. To investigate the hypothesis that a functional relationship exists between these two protectants, the release of chemokines was measured in rat astrocyte cultures after PACAP-38 treatment. Chemokine analyses were performed by immunoaffinity capillary electrophoresis. Bell-shaped dose-responses for PACAP-mediated release of chemokines into the culture medium were observed with EC(50)'s of 3 x 10(15) M (RANTES: regulated upon activation normal T cell expressed and secreted), 3 x 10(-11) M (MIP-1 beta) and 10(-7)M (MIP-1 alpha). In addition, PACAP-mediated depletion of chemokines from cultured astrocytes exhibited inverted bell-shaped curves, with similar EC(50)'s to those observed for chemokine measurements of the medium. Comparative studies with structurally related peptides (vasoactive intestinal peptide [VIP] and secretin) revealed that PACAP was the most potent secretagogue for RANTES on astrocyte cultures. Gp120-mediated neuronal cell death was prevented by co-treatment with PACAP-38, although the efficacy of protection varied significantly among the gp120 isolates. A bi-model dose-response was observed with EC(50)'s of 3 x 10(-15) and 3 x 10(-11) M. Co-treatment with neutralizing antiserum to RANTES attenuated PACAP-mediated protection from toxicity associated with gp120. In contrast to previous studies with VIP and gp120 toxicity, co-treatment with anti-MIP-1 alpha did not affect PACAP-induced protection. These studies support the hypothesis that PACAP produces neuroprotection from gp120 toxicity, in part, through the release of RANTES and this mechanism is distinct from that observed with VIP.
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PMID:Chemokine release is associated with the protective action of PACAP-38 against HIV envelope protein neurotoxicity. 1237 1

It has been reported that the C-terminus of the second conserved region (C2) of the envelope glycoprotein gp120, encompassing peptide RSANFTDNAKTIIVQLNESVEIN (NTM), is important for infectivity and neutralization of the human immunodeficiency virus type 1 (HIV-1). It was also demonstrated that human natural anti-vasoactive intestinal peptide (VIP) antibodies reactive with this gp120 region play an important role in control of HIV disease progression. The bioinformatic analysis based on the time-frequency signal processing revealed non-obvious similarities between NTM and VIP. When tested against a battery of sera from 46 AIDS patients, these peptides, in spite of a significant difference in their primary structures, showed a similar reactivity profiles (r = 0.83). Presented results point out that similarity in the periodical pattern of some physicochemical properties in primary structures of peptides plays a significant role in determination of their immunological crossreactivity. Based on these findings, we propose this bioinformatic criterion be used for design of VIP/NTM peptide mimetics for prevention and treatment of HIV disease.
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PMID:Design of peptide mimetics of HIV-1 gp120 for prevention and therapy of HIV disease. 1296 95


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