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)

Event-related potentials (ERP) were determined in 138 human immunodeficiency virus (HIV)-infected outpatients and 92 healthy controls of a corresponding age. Of the HIV-infected patients, 31.8% showed an abnormal latency of the P3-component of ERPs (P3-ERP), exceeding the mean value + 2 SD of P3-ERP latencies from age-matched healthy subjects. From the untreated patients in stage Walter Reed (WR) = 6, 71.4% had abnormal P3-ERP latencies, whereas in WR = 2, only 19.6% of P3-ERPs were abnormal. Fourteen patients were observed over a period of 3-16 months. P3-ERP latencies were shortened in 7 patients under treatment with zidovudine. A marked increase in P3-ERP latencies was observed in 7 untreated HIV-infected patients. It is assumed that ERPs are a useful neurophysiological method to detect early cerebral dysfunction in HIV-infected patients.
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PMID:Event-related potentials in HIV-infected outpatients. 176 65

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.
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PMID:Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. 182 18

Infection with human immunodeficiency virus type 1 (HIV-1) is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due partially or wholly to a direct effect of the virus on the brain rather than to opportunistic infection, but its pathogenesis is not well understood. Productive HIV-1 brain infection is detected only in a subset of patients and is confined largely or exclusively to macrophages, microglia, and derivative multinucleated cells that are formed by virus-induced cell fusion. Absence of cytolytic infection of neurons, oligodentrocytes, and astrocytes has focused attention on the possible role of indirect mechanisms of brain dysfunction related to either virus or cell-coded toxins. Delayed development of the AIDS dementia complex, despite both early exposure of the nervous system to HIV-1 and chronic leptomeningeal infection, indicates that although this virus is "neurotropic," it is relatively nonpathogenic for the brain in the absence of immunosuppression. Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.
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PMID:The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. 327 72

The acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) commonly complicates the course of human immunodeficiency virus (HIV) infection and AIDS. Although many of its clinical aspects have recently been brought into clearer focus, and pathogenetic evidence has accrued implicating direct HIV brain infection, there remain a number of fundamental aspects of ADC and HIV nervous system infection that require clarification. These include clearer definition of the clinical syndrome and its variants; development of instrumentation for diagnosis and monitoring the disorder; definition of the epidemiology and natural history of both central nervous system HIV infection and ADC, which may seemingly be discordant; and understanding of both the viral pathogenesis and the biology of resultant brain dysfunction. Elucidation of these fundamental issues will enhance rational development and evaluation of therapy.
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PMID:The AIDS dementia complex: some current questions. 334 98

A small group of children with various types of immunodeficiency disorders, examined on a battery of neuropsychological and intellectual tests, was found to be impaired on perceptual speed, visuospatial sequencing, and visual attention span capacities when compared to a control group of closest aged siblings and normal children matched for age, education, and IQ. The results suggest that cerebral dysfunction may be associated with immunodeficiency disorders in children, although these findings are tentative since other factors, such as the effects of chronic illness, could not be excluded in this small cohort of patients.
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PMID:Neuropsychological functioning in children with immunodeficiency disorders. 400 61

Infection of the brain with human immunodeficiency virus 1 (HIV-1) often leads to the devastating loss of mental faculties. Surprisingly, HIV-1 elicits such brain dysfunction without significantly infecting neurons, astrocytes and oligodendroglia. The target for HIV-1 in the brain is the macrophage, which usually functions as a phagocytic, antigen-presenting and immune-regulatory cell. How can these cells produce such serious cognitive and motor brain impairments? Here, Hans Nottet and Howard Gendelman propose that HIV-1 penetrates the blood-brain barrier inside differentiating macrophages, which become immune activated once inside the brain, and secrete high levels of neurotoxins. Chronic, subclinical disease results by astrocyte regulation of macrophage effector functions. Ultimately, endogenous control mechanisms break down, leading to motor and mental impairments in some affected subjects.
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PMID:Unraveling the neuroimmune mechanisms for the HIV-1-associated cognitive/motor complex. 754 9

The pathological correlates of dementia due to human immunodeficiency virus (HIV) infection are glial cell activation and cytokine dysregulation. These findings occur in the setting of small numbers of productively infected cells within the brain. We determined whether exposure of susceptible cells to Tat protein of HIV could result in the production of select proinflammatory cytokines. In a dose-responsive manner, Tat induced interleukin (IL)-1beta production in monocytic cells, while astrocytic cells showed an increase in mRNA for IL-1beta, but had a translation block for IL-1beta protein production. Conversely, IL-6 protein and mRNA productions were strongly induced in astrocytic cells and minimally in monocytic cells. IL-1beta and IL-6 production were independent of tumor necrosis factor-alpha production. An exposure to Tat for a few minutes was sufficient for sustained releases of cytokines for several hours. This prolonged cytokine production is likely maintained by a positive feed back loop of Tat-induced nuclear factor kappaB activation and cytokine production that is independent of extracellular calcium. Thus a transient exposure may be sufficient to initiate a cascade of events resulting in cerebral dysfunction and a "hit and run" approach may be in effect. Hence cross-sectional measurement of viral load in the brain may not be a useful indicator of the role of viral products in the neuropathogenesis of HIV dementia.
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PMID:Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes. A hit and run phenomenon. 1035 63

Although our understanding of how human immunodeficiency virus (HIV)-related neurobehavioural deficits develop is nascent and preliminary, some clues have emerged which may clarify lingering uncertainties. In particular, HIV seems to yield brain dysfunction by mediating pathological changes upon neuronal function. HIV also compromises immunological integrity, thereby resulting in secondary infections that may further increase brain dysfunction. Notably, many individuals with HIV tend to be current or past abusers of drugs, and, in some cases, their drug use may have actually presented a pathway for initial HIV infection. Similar to HIV, many drugs tend to yield pathological changes upon neuronal function. Further paralleling HIV, some drugs seem to compromise immune function, which in turn may yield secondary detrimental effects upon the brain. Yet, despite the relatively high comorbidity rates of HIV infection and substance abuse, few investigations have addressed the potential interaction between these two factors upon neurobehavioural status. Towards this end, the present paper reviews the existing literature concerning neuropsychological effects of HIV and substance use, and suggests potential mechanisms whereby substance use may potentiate and exacerbate the onset and severity of neurobehavioural abnormalities in HIV infection.
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PMID:Neurobehavioural consequences of substance abuse and HIV infection. 1110 1

Blood-borne human immunodeficiency virus type 1 (HIV-1) crosses the blood-brain barrier (BBB) to induce brain dysfunction. How HIV-1 crosses the BBB is unclear. Most work has focused on the ability of infected immune cells to cross the BBB, with less attention devoted to the study of free virus. Since the HIV-1 coat glycoprotein gp120 can cross the BBB, we postulated that gp120 might be key in determining whether free virus can cross the BBB. We used radioactive virions which do (Env+) or do not (Env-) bear the envelope proteins to characterize the ability of HIV-1 to be taken up by the murine BBB. In vivo and in vitro studies showed that the envelope proteins are key to the uptake of free virus and that uptake was enhanced by wheat germ agglutinin, strongly suggesting that the envelope proteins induce viral adsorptive endocytosis and transcytosis in brain endothelia. Capillary depletion showed that Env+ virus completely crossed the vascular BBB to enter the parenchyma of the brain. Virus also entered the cerebrospinal fluid, suggesting passage across the choroid plexus as well. About 0.22% of the intravenously injected dose was taken up per g of brain. In vitro studies showed that postinternalization membrane cohesion (membrane binding not reversed with acid wash or cell lysis) was a regulated event. Intact virus was recovered from the brain endothelial cytosol and was effluxed from the endothelial cells. These results show that free HIV-1 can cross the BBB by an event related to adsorptive endocytosis and mediated by the envelope proteins.
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PMID:Transport of human immunodeficiency virus type 1 pseudoviruses across the blood-brain barrier: role of envelope proteins and adsorptive endocytosis. 1131 39

Neurodegeneration, synaptic alterations, and gliosis are prominent features of human immunodeficiency virus (HIV) encephalitis, but HIV encephalitis is distinct from other viral encephalitides because neurodegeneration occurs in uninfected neurons at anatomical sites that are often distant from the site of viral replication. The HIV protein Tat is both neurotoxic and proinflammatory; however, its contribution to HIV-related synaptic dysfunction remains unknown. To determine the consequences of continuous Tat production in brain, we genetically engineered rat C6 glioma cells to stably produce Tat and stereotaxically infused these cells into the rat striatum or hippocampus. We discovered that HIV-Tat protein could be transported along anatomical pathways from the dentate gyrus to the CA3/4 region and from the striatum to the substantia nigra, resulting in behavioral abnormalities, neurotoxicity, and reactive gliosis. This demonstrates a unique neuronal transport property of a viral protein and establishes a mechanism for neuroglial dysfunction at sites distant from that of viral replication. Tat may thus be an important participant in brain dysfunction in HIV dementia.
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PMID:Synaptic transport of human immunodeficiency virus-Tat protein causes neurotoxicity and gliosis in rat brain. 1296 4


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