Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0085584 (encephalopathy)
18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type-1 (HIV-1) antigen was assayed in paired serum/cerebrospinal fluid (CSF) specimen from 85 adults and 58 children with acquired immunodeficiency syndrome and was compared with clinical neurological status. A quantitative comparison of HIV-1 antigen levels in matched serum and CSF specimens indicated that HIV-1 antigen expression in these compartments is independent and is correlated with acquired immunodeficiency syndrome dementia complex in adults and progressive encephalopathy in children. In a longitudinal study (n = 47), 16 patients tested positive for HIV-1 antigen in the CSF before (n = 2) or coincident (n = 14) with neurological deterioration. Six patients who tested positive for HIV-1 antigen in the CSF remained neurologically normal for a median duration of follow-up of 11 months. Six of 25 patients who tested negative for HIV-1 antigen in the CSF, subsequently showed neurological deterioration. These data indicate that HIV-1 antigen expression in the CSF is not useful in predicting neurological deterioration.
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PMID:Human immunodeficiency virus type 1 antigen in cerebrospinal fluid. Correlation with clinical neurologic status. 291 78

Human immunodeficiency virus type I (HIV-1) is associated with a spectrum of neurological disorders. At the time of primary HIV-1 infection, an acute aseptic meningitis or encephalitis indicates central nervous system invasion. Evidence of HIV-1 infection is found in the CSF of most asymptomatic seropositive individuals, suggesting viral persistence in the nervous system. After a long incubation period, viral activation is signaled by expression of HIV-1 antigen in the CSF, which correlates with a profound dementia in adults or with an analogous progressive encephalopathy in children. The neuropathological substrate of this dementing process consists of multinucleated giant cells and diffuse white matter pallor. Immunocytochemical and in situ hybridization studies demonstrate that antigen presenting cells, including blood derived macrophages and resident brain microglia, are directly infected by HIV-1, and participate in the formation of the syncytial giant cells. Astrocytes and endothelial cells may also be infected, but evidence for infection of oligodendroglia and neurons is lacking. Studies of lentiviral encephalitides in ungulates and non-human primates emphasize the importance of specific viral antigenic stimulation and the role of inflammatory cells as direct or indirect mediators of tissue damage. The disorders of the peripheral nervous system described in patients with HIV-1 infection have not been convincingly linked to direct viral infection. At least two of the neuromuscular complications, the inflammatory motor neuropathy and polymyositis are likely to have an autoimmune pathogenesis.
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PMID:Human immunodeficiency virus type 1 (HIV-1) infection of the nervous system: a review. 307 11

Human immunodeficiency virus type 1 (HIV-1) has been clearly associated with a variety of new illnesses, including profound immunodeficiency (acquired immune deficiency syndrome [AIDS]), wasting syndromes (formerly termed AIDS-related complex [ARC]) and neurologic syndromes, including neuropathy, myelopathy and encephalopathy (often termed subacute encephalitis or AIDS dementia complex). HIV-1 preferentially infects T lymphocytes by binding to a membrane receptor protein, CD4, associated with helper function. The virus can also attack macrophages and, possibly, other cells such as neuronal cells, colonic epithelial cells and B lymphocytes. Infection of macrophages or monocytes may be involved in neurologic disease. Knowledge about HIV-1 has rapidly increased, and investigators have characterized its structure, ways in which it infects cells, replicates and is cytopathic for certain cells, and how the immune system responds to it. The ideal vaccine would prevent adsorption of the virus into the cell, but it is difficult to develop stable resistance because the virus has many antigenic patterns and mutates frequently. The results of vaccine trials in animals have not been promising, but work is being done with monoclonal antibodies. Antiviral therapies being investigated include those to prevent virus binding and entry, to inhibit reverse transcription, to inhibit the virus's life cycle and to restore immune competence in immunocompromised patients.
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PMID:Vaccine and antiviral strategies against infections caused by human immunodeficiency virus. 328 28

Human immunodeficiency virus type 1 (HIV) infection of the central nervous system is characterized by neuronal loss in discrete areas of the central nervous system. We have previously demonstrated that HIV-infected monocytes in culture with astroglial cells produce high levels (> or = 200 pg/ml) of the cytokine tumor necrosis factor-alpha (TNF alpha). We now demonstrate that TNF alpha (> or = 200 pg/ml) is neurotoxic to cultured primary human fetal cortical neurons at both light and electron microscopic levels. Subtoxic doses of TNF alpha (50 pg/ml) are neurotoxic in combination with the glutamate (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) subtype receptor agonist AMPA (100 microM). The neurotoxic effects of TNF alpha (200 pg/ml) are blocked in part by the AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione (10 microM). This suggests that TNF alpha may exert neurotoxic effects on human neurons by indirect activation of AMPA receptors, which may be important in the pathogenesis and treatment of HIV-mediated encephalopathy.
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PMID:Neurotoxic effects of tumor necrosis factor alpha in primary human neuronal cultures are mediated by activation of the glutamate AMPA receptor subtype: implications for AIDS neuropathogenesis. 783 47

Human immunodeficiency virus type 1 (HIV-1) infection of the developing central nervous system results in a dementing process in children, termed HIV-1-associated encephalopathy. Infection of astroglial elements of the pediatric nervous system has been demonstrated and suggests that direct infection of some astrocytes may contribute to the neurologic deficit. In this model, HIV-1 establishes a persistent state of infection in astrocytes, which can be reactivated by the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). To better understand the natural history of viral persistence in astroglial cells, we characterized infection at the transcriptional level. The most abundant viral transcript during the establishment of persistence was the subgenomic multiply spliced 2-kb message, similar to mononuclear cell models of HIV-1 latency. Following reactivation with TNF-alpha or IL-1 beta the multiply spliced 2-kb message remained the most abundant viral transcript, in contrast to infected mononuclear cells in which reactivation leads to the reemergence of the 9- and 4-kb transcripts. Further characterization of the persistent 2-kb transcript by PCR amplification of in vitro-synthesized viral cDNA showed that, in the absence of cytokine stimulation, the most abundant multiply spliced transcripts were the Nef- and Rev-specific messages. However, following cytokine stimulation, double- and triple-spliced Tat-, Rev-, and Nef-specific messages could be identified. Immunohistochemical staining demonstrated that, during viral persistence, astrocytes expressed Nef protein but few or no viral structural proteins. These results demonstrate that viral persistence in astrocytes at the transcriptional level is fundamentally different from that seen in mononuclear cells and could account for the virtual absence of astroglial expression of viral structural antigens in vivo.
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PMID:Temporal patterns of human immunodeficiency virus type 1 transcripts in human fetal astrocytes. 825 81

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system is associated with decreased neuronal density in discrete areas of the brain. Neuronal loss may occur via apoptosis, initiated by soluble neurotoxic factors secreted from HIV-1 infected macrophages and microglia. To examine further the molecular events involved in HIV-1 neuropathogenesis, we assessed the activity of NF kappa B, an inducible transcription factor involved in the activation of multiple proinflammatory, and potentially neurotoxic, genes. NF kappa B was analysed by immunocytochemistry using specific antisera to the NF kappa B p. 50 and p. 65 subunits. Brains from children with HIV-1 encephalitis and progressive encephalopathy were found to contain increased numbers of NF kappa B immunoreactive cells, relative to control brains (HIV-1 negative, or HIV-1 positive without encephalitis). Double-labelling studies using antibodies to CD68, or RCA-1 lectin, markers for cells of monocyte/macrophage lineage, revealed an increase in the number of microglia and macrophages with nuclear immunoreactivity for NF kappa B in association with HIV-1 encephalitis. NF kappa B positive multinucleated giant cells were also detected, as were cells which contained both NF kappa B and HIV-1 antigen. In contrast, the number of neurons and GFAP-positive astrocytes that were immunoreactive for NF kappa B was approximately the same in all groups of subjects. These data are consistent with the hypothesis that persistent, high-level activation of NF kappa B may promote the sustained production of neurotoxins by microglia and macrophages during HIV-1 encephalitis.
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PMID:Activation of nuclear factor kappa B in brains from children with HIV-1 encephalitis. 874 41

Human immunodeficiency virus type 1 (HIV-1) causes infections of the central nervous system (CNS) and has been implicated as the causative agent of AIDS-associated encephalopathy and the AIDS dementia complex. The development of in vivo models of HIV-1-mediated gene expression has shown that the HIV long terminal repeat (LTR) from the viral isolate HIV(JR-CSF) specifically supports gene expression in adult and developing CNS. To determine the molecular basis for HIV-1 developmental CNS gene expression, in vivo footprinting analysis by the ligation-mediated PCR technique was performed on CNS tissue from the brain stem of a transgenic mouse. The association of cellular proteins in the CNS with sequences in the LTR was found over sequences that defined the TATA region, the Sp-1 and NF-kappaB sites, and two upstream regions (-111 to -150 and -260 to -300). A purine-rich sequence at positions -256 to -296 of the HIV(JR-CSF) LTR but not of the HIV(IIIB) LTR specifically bound protein in nuclear extracts of newborn brain tested in electrophoretic mobility shift assays. No specific protein binding was observed to this region in liver or HeLa cell nuclear extracts. This suggests the presence of a newly identified transcription factor involved in regulation of HIV-1 gene expression in the CNS.
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PMID:In vivo transcriptional regulation of the human immunodeficiency virus in the central nervous system in transgenic mice. 889 89

Human immunodeficiency virus type I (HIV-1)-derived envelope glycoprotein 120 (gp120) is proposed to play an important role in HIV-1 neuropathology. Gp120 may act through mediators including proinflammatory cytokines. Here, we investigated the regulation of the IL-1beta system [IL-1beta, IL-1 receptor type I (IL-1RI), IL-1 receptor antagonist (IL-1Ra)], TNF-alpha and TGF-alpha mRNAs in the rat central nervous system (CNS) in response to the constant intracerebroventricular (ICV) microinfusion of HIV-1 gp120 for 72 h and 144 h. The results show that gp120: (1) increased IL-1beta and IL-1Ra mRNAs levels in the same samples from the cerebellum, hypothalamus and midbrain, with the largest increase in the hypothalamus; (2) induced profiles of IL-1beta mRNA and IL-1Ra mRNA that were highly intercorrelated; (3) increased the hypothalamic TNF-alpha mRNA levels; and (4) did not affect the IL-1RI mRNA and TGF-alpha mRNA levels in any brain region. A dysregulation in the IL-1beta/IL-1Ra CNS balance and a mutual induction and synergistic activity of IL-1beta and TNF-alpha could result in a deleterious amplification cycle of cellular activation and cytotoxicity with implications to HIV-1-associated encephalitis, encephalopathy, and neurological manifestations.
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PMID:HIV-1 envelope glycoprotein 120 regulates brain IL-1beta system and TNF-alpha mRNAs in vivo. 928 32

Human immunodeficiency virus type 1 (HIV-1) infection of astrocytes has been demonstrated in the brains of patients with AIDS dementia complex (ADC) and may play an important role in neuropathological pathways of HIV-related encephalopathy. SIVmac-infected monkeys develop an acquired immunodeficiency syndrome (AIDS) with CNS involvement which is quite similar to that seen in human AIDS. We investigated the in vitro infection of primary astrocytes derived from adult macaques with SIVmac251 or an isogenic virus that expresses a non-functional Nef protein (SIVmac251-DeltaNef). In both cases we observed that viral expression was mostly limited to early regulatory genes after a transient phase of late viral gene expression (i.e. env and gag), as reported for HIV-1-infected astrocytes in vivo. Late viral gene expression could be reactivated by TNF-alpha, GM-CSF and IFN-gamma treatment of SIVmac251-infected astrocytes but not by similarly treated SIVmac251-DeltaNef-infected cells. Our findings suggest that Nef is not involved in the restricted expression of SIV in astrocytes, but may be important for astrocytes to function as a viral reservoir in the CNS. In additional experiments, we demonstrated Rev and Nef expression in 17 of 27 primary astrocyte cultures derived from macaques infected by SIVmac251. Nef was located in the cytoplasm of astrocytes infected by SIVmac251 in vivo, but displayed perinuclear localisation after infection in vitro. Attempts to activate late viral gene expression by astrocytes infected in vivo using cytokines or by coculture with human cord blood mononuclear cells were unsuccessful.
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PMID:Simian immunodeficiency virus mac251 infection of astrocytes. 1087 8

Human immunodeficiency virus type-one (HIV- 1)-associated dementia (HAD) is manifested as a spectrum of behavioral, motor and cognitive dysfunctions. The disorder commonly occurs during late stage HIV disease and remains an important complication despite highly active antiretroviral therapies. A metabolic encephalopathy, fueled by neurotoxic secretions from brain mononuclear phagocytes (MP) (macrophages and microglia) underlies HIV- I neuropathogenesis. One pivotal question, however, is how brain MP evolve from neurotrophic to neurotoxic cells. The interplay between the virus, the macrophage and the neuron has just recently begun to be unraveled. Along with a multitude of other MP secretory products, chemokines effect neuronal function by engaging neuronal receptors then activating pathways that alter synaptic transmission, cell growth, injury and protection. Both neurons and glia secrete chemokines. Interestingly, HIV-1 and its gene products can mimic chemokine neuronal signaling by binding to neuronal chemokine receptors or by other non-specific mechanisms. The elucidation of mechanisms involved in chemokine-mediated neural compromise will likely provide unique insights into the pathogenesis and treatment, not only of HAD, but of a wide range of neurodegenerative disorders.
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PMID:Macrophages, chemokines and neuronal injury in HIV-1-associated dementia. 1199 33


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