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

HIV produces a chronic viral infection of the central nervous system that elicits chronic glial activation and overexpression of glial cytokines that are also implicated in Alzheimer disease (AD) pathogenesis. A genetic risk factor for AD is the E4 isoform for apolipoprotein E (APOE). Here we compare the frequency of neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(-), respectively) in an HIV cohort. Compared with E4(-) subjects, twice as many E4(+) subjects were demented (30% compared with 15%) or had peripheral neuropathy (70% compared with 39%) at least once, and they had threefold more symptomatic examinations (13% compared with 3% and 42% compared with 14%, respectively)(P < 0.0001). Thus, neurologic symptoms for HIV-infection and AD are linked through an etiologic risk factor. Long-term survivors of HIV infection with E4 may be at high risk for AD; conversely, gene-viral interactions may speed AD pathogenesis.
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PMID:HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy. 984 54

Microglia are the resident macrophages of the brain. They are the central cellular element to initiate defense mechanisms against destructive environmental influences and to facilitate regenerative processes. No other cell type of the brain is endowed with a comparably comprehensive, immunocompetent machinery like microglia. It encompasses cell proliferation, migration and differentiation into full-blown macrophages able to present antigen and to phagocytose cell debris. Relatively little is known about these stages of microglia activation on the cellular and molecular level, although microglia have been described as a separate cell type of the brain as early as in the 30ies of this century by P.del Rio Hortega. This review summarizes the data that have accumulated until now in this respect and tries to embed them into a clinical framework. Special focus has been given to the role of this cell type in the development and progression of Multiple Sclerosis, HIV-associated dementia and Alzheimer's disease.
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PMID:[Microglia: mechanisms of activation and significance in pathogenesis of neuropsychiatric illnesses]. 978 66

Antisense oligonucleotides (ODNs) and peptide nucleic acids (PNAs) are potential therapeutics for eradication of malignancies, viral infections, and other pathologies. However, ODNs and PNAs in general are unable to cross cellular membranes and blood-tissue barriers, such as the blood-brain barrier (BBB), which is only permeable to lipophilic molecules of molecular weight <600 Da. Cellular delivery systems based on conjugates of streptavidin (SA) and the OX26 monoclonal antibody directed to the transferrin receptor may be employed as a universal carrier for the transport of mono-biotinylated peptides, ODNs, or PNAs. 3'-Biotinylation of phosphodiester (PO)-ODN produces complete protection of ODN against serum and cellular 3'-exonucleases, facilitating the conjugation to avidin-based delivery systems and maintaining the activation of RNase H. These delivery systems markedly increased the cellular uptake and antisense efficacy of 3'-biotinylated ODNs in models of Alzheimer's disease and HIV-AIDS. In vivo brain delivery studies demonstrated that 3'-protected PO-ODNs and PO-phosphorothioate(PS)-ODN hybrids containing a single PO linkage are subjected to endonuclease degradation in vivo. On the contrary PS-ODNs, which were also protected at 3'-terminus by biotinylation, are metabolically stable in vivo and resistant to exo/endonuclease degradation. However, because of the strong binding of these oligomers to plasma protein, PS-ODNs are poorly transported into the brain through the BBB by the OX26-SA delivery vector following intravenous administration. PNAs are also resistant to exo/endonuclease and protease degradation, and these molecules biotinylated at the amino terminal group were transported into the brain by the OX26-SA delivery system with brain uptake levels comparable to that of morphine. Using the rev gene of HIV as a model target, RNase protection assays and cell-free translation arrest showed that the PNA-OX26-SA conjugate maintained active recognition and inactivation of target mRNA, respectively. The overall experimental evidence suggests that PNA-OX26-SA conjugates represent optimal antisense molecules for drug delivery to the brain.
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PMID:Drug delivery of antisense molecules to the brain for treatment of Alzheimer's disease and cerebral AIDS. 981 82

The levels of several low-molecular-weight metabolites were measured in 1H nuclear magnetic resonance (NMR) spectra of extracts of Syrian hamster brain infected with Creutzfeldt-Jakob disease (CJD). Metabolite levels were determined in cerebral cortex in CJD-infected and age-matched controls at defined times (40, 65, 85, 105, and 135 days) during the 130- to 135-day incubation period to terminal disease. At 135 days, CJD-infected hamsters showed a significant decrease in N-acetylaspartate of 32% (p < 0.05) and an increase in myo-inositol of 67% (p < 0.001) from age-matched controls. At earlier times (40 to 110 days) levels of N-acetylaspartate and myo-inositol were not significantly different from controls. No significant changes were detected in the cortical levels of glutamate, aspartate, or GABA between 40 and 135 days. The late changes in N-acetylaspartate and myo-inositol in CJD-infected hamsters are similar to those observed in magnetic resonance spectroscopy studies of human CJD. Because they also correspond to the changes found in other dementias, including Alzheimer's disease and HIV dementia, these changes indicate converging pathogenetic pathways involved in many neurodegenerative diseases.
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PMID:Changes in N-acetylaspartate and myo-inositol detected in the cerebral cortex of hamsters with Creutzfeldt-Jakob disease. 981 79

Laboratory services of the early 21st century will be heavily influenced by significant demographic redistributions and shifts in the incidence and prevalence of disease. A persistent influx of immigrants literally will change the face of the U.S. population. Persons born between 1946 and 1964 will reach middle and old age and will require testing for arthritis, diabetes, cardiac dysfunction, Alzheimer's disease, and stroke. Efforts to combat infertility will expand. Tuberculosis, wrongly assumed to be under control, will continue to proliferate. Testing will be needed for the millions of people living with AIDS and for the millions more infected or suspected to be infected with HIV. Cancer screening and information from genetic markers will widen. Public screenings will be routinely offered in assorted sites. As the national focus shifts from curing illness to promoting health, laboratory tests will assess healthy persons to a greater degree than ever.
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PMID:Changing disease patterns, shifting demographics: effects on laboratory services. 1017 18

Evolutionary conservation of homologous genes that cause related phenotypes in humans and Drosophila help to unravel genes implicated in polygenic human diseases. Among them are neurodegenerative disorders, such as Huntington, Parkinson, Alzheimer and HIV-induced diseases. They are characterized by a late onset disturbances of memory, changes in volumetric indices of the brain structures involved in memory formation, synaptic and glial pathology, and altered content of the intermediates of the kynurenine pathway, the endogenous modulators of the NMDA receptors. This pathway in conserved in insects, rodents and humans. We, therefore, studied the effects of aberrant tryptophan metabolism on memory, brain plasticity, synaptic and glial immunoreactivity in the Drosophila mutants vermilion (no kynurenines) and cinnabar (excess of neuroprotective kynurenic acid) over the life time. The mutant vermilion demonstrated gradual decline of 3-th memory performance and complete memory failure on the 28th day of life in a paradigm of conditioned courtship suppression. A drastic increase in the volume of the calyces of the mushroom bodies, and a decay in immunochemical staining of this brain structure with antibodies to synaptic protein csp and glia, precede the age-dependent memory defect and develop from the 12th day of adult life.
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PMID:Age-dependent changes in memory and mushroom bodies in the Drosophila mutant vermilion deficient in the kynurenine pathway of tryptophan metabolism. 1038 74

Progressive neuronal degeneration in brain regions involved in learning and memory processes is a common occurrence in patients infected with human immunodeficiency virus type 1 (HIV-1). We now report that levels of Par-4, a protein recently linked to neuronal apoptosis in Alzheimer's disease, are increased in neurons in hippocampus of human patients with HIV encephalitis and in monkeys infected with a chimeric strain of HIV-1 and simian immunodeficiency virus. Par-4 levels increased rapidly in cultured hippocampal neurons following exposure to the neurotoxic HIV-1 protein Tat, and treatment of the cultures with a Par-4 antisense oligonucleotide protected the neurons against Tat-induced apoptosis. Additional findings show that Par-4 participates at an early stage of Tat-induced neuronal apoptosis before caspase activation, oxidative stress, and mitochondrial dysfunction. Our data suggest that Par-4 may be a mediator of neuronal apoptosis in HIV encephalitis and that therapeutic approaches targeting the Par-4 apoptotic cascade may prove beneficial in preventing neuronal degeneration and associated dementia in patients infected with HIV-1.
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PMID:Evidence that Par-4 participates in the pathogenesis of HIV encephalitis. 1039 34

Alterations in the neuronal expression of some neurotrophins have been shown in various neurodegenerative processes, particularly Alzheimer's disease (AD). Glia may up-regulate neurotrophins and their high-affinity tyrosine kinase (trk) receptors in response to neural injury. In human immunodeficiency virus type 1 (HIV-1) encephalitis, activated microglia were shown to express brain-derived neurotrophic factor (BDNF), while reactive astrocytes expressed trkB receptor. This observation has suggested the existence of local neurotrophic regulation between different glial populations. To characterize the glial cellular distribution of BDNF and trkB receptor proteins in AD, we studied selected regions of postmortem brains from four AD and three age-matched control patients by double-immunofluorescence confocal microscopy. In both groups, BDNF immunoreactivity was distributed in neuronal perikarya and neuritic processes in the neocortex and hippocampus. No BDNF immunoreactivity was observed in microglia or astrocytes within and between senile plaques of AD. Catalytic trkB receptor immunoreactivity was present in neuronal perikarya in the neocortex and hippocampus. Reactive astrocytes and microglia were not immunoreactive for catalytic trkB. The absence of BDNF and trkB proteins in glia in AD patients is in contrast to the finding in patients with HIV-1 encephalitis. This difference suggests that glial expression of BDNF and trkB proteins may be characteristic of particular disease processes, rather than merely representing a stereotyped response to any type of neural injury.
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PMID:Absence of brain-derived neurotrophic factor and trkB receptor immunoreactivity in glia of Alzheimer's disease. 1050 38

Carnitine is a well-known cofactor for the beta-oxidation of long-chain fatty acid. It also plays a role in transport of acetyl moity for fatty acid and cholesterol synthesis, excretion of organic acid and xenobiotic acid as carnitine ester, and control of ratio of acetylCoA to CoA. Therapeutic effect of acetylcarnitine on Alzheimer disease and HIV-infection, and aberrant incorporation acetylcarnitine into brain under chronic fatigue syndrome have been reported. Carnitine deficiency causes hyperammonemia through suppression of gene expression of urea cycle enzymes. On the other hand, a large amount of carnitine has a therapeutic effect on hyperammonemia by still unclear mechanism. These suggest carnitine as a multifunctional biofactor.
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PMID:[Carnitine as a vitamin-like biofactor]. 1054 Aug 73

Acetyl-L-carnitine (ALC) is an ester of the trimethylated amino acid, L-carnitine, and is synthesized in the human brain, liver, and kidney by the enzyme ALC-transferase. Acetyl-L-carnitine facilitates the uptake of acetyl CoA into the mitochondria during fatty acid oxidation, enhances acetylcholine production, and stimulates protein and membrane phospholipid synthesis. ALC, similar in structure to acetylcholine, also exerts a cholinomimetic effect. Studies have shown that ALC may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, diabetic neuropathies, ischemia and reperfusion of the brain, and cognitive impairment of alcoholism.
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PMID:Acetyl-L-carnitine. 1060 18


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