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)

The epidemiology of cocaine abuse and potential relationships of cocaine withdrawal to human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are discussed. Neuroendocrinological changes in HIV-1 infection of the central nervous system (CNS) are discussed with the relevant impact of cocaine abuse. HIV-1 load in the brain tissue of infected substance users is described along with possible associations with neuropathology and HAD. Finally, the molecular epidemiology and sequence heterogeneity of HIV-1 and their implications for neuropathogenesis are summarized. The complex context of addressing cocaine abuse in the setting of HIV-1 infection appears more tractable when decomposed into its components.
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PMID:Cocaine abuse and HIV-1 infection: epidemiology and neuropathogenesis. 961 Jun 77

We examined the neurological differences between human immunodeficiency virus (HIV)-infected men (n = 193) and women (n = 41) receiving primary medical care. There was no difference between men and women in the rate of HIV-related neurological syndromes (i.e. polyneuropathy, myelopathy, myopathy, HIV- dementia [HAD]). A logistic regression analysis indicated that low CD4+ cell count predicted all neurological syndromes. In addition, HAD was predicted by intravenous-drug use and lower education level, while neuropathy was associated with older age and with race. These findings indicate that there are no differences in the rate of neuropsychiatric disorders attributable to gender. The presence of other factors (e.g. drug abuse) could explain previously reported gender differences in neurological manifestations of HIV infection.
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PMID:Neurological characteristics of HIV-infected men and women seeking primary medical care. 1005 33

The numbers of immune-activated brain mononuclear phagocytes (MPs) affect the progression of human immunodeficiency virus (HIV)-1-associated dementia (HAD). Such MPs originate, in measure, from a pool of circulating monocytes. To address the mechanism(s) for monocyte penetration across the blood-brain barrier (BBB), we performed cross-validating laboratory, animal model, and human brain tissue investigations into HAD pathogenesis. First, an artificial BBB was constructed in which human brain microvascular endothelial and glial cells-astrocytes, microglia, and/or monocyte-derived macrophages (MDM)-were placed on opposite sides of a matrix-coated porous membrane. Second, a SCID mouse model of HIV-1 encephalitis (HIVE) was used to determine in vivo monocyte blood-to-brain migration. Third, immunohistochemical analyses of human HIVE tissue defined the relationships between astrogliosis, activation of microglia, virus infection, monocyte brain infiltration, and beta-chemokine expression. The results, taken together, showed that HIV-1-infected microglia increased monocyte migration through an artificial BBB 2 to 3.5 times more than replicate numbers of MDM. In the HIVE SCID mice, a marked accumulation of murine MDM was found in areas surrounding virus-infected human microglia but not MDM. For human HIVE, microglial activation and virus infection correlated with astrogliosis, monocyte transendothelial migration, and beta-chemokine expression. Pure cultures of virus-infected and activated microglia or astrocytes exposed to microglial conditioned media produced significant quantities of beta-chemokines. We conclude that microglial activation alone and/or through its interactions with astrocytes induces beta-chemokine-mediated monocyte migration in HAD.
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PMID:Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis. 1055 Mar 17

In human immunodeficiency virus (HIV)-1-associated dementia (HAD), consequences of interactions between infiltrating monocytes and brain endothelial cells are not yet fully understood. This study investigated whether the blood-brain barrier is affected in brain tissue of patients suffering from HAD and whether it was possible to find a correlation with the presence or absence of monocytic cells, which have been suggested to play a major role in HAD. Immunohistochemical analysis for zonula occludens 1, a tight junction protein, and CD68, a macrophage marker, revealed that loss of tight junction immunoreactivity was highly correlated with monocyte infiltration and with HAD. This suggests that the presence of perivascular macrophages cells is associated with breakdown of the blood-brain barrier thereby facilitating infiltration of more monocytic cells hence enhancing disease progression.
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PMID:Monocyte infiltration is highly associated with loss of the tight junction protein zonula occludens in HIV-1-associated dementia. 1093 69

Human immunodeficiency virus (HIV)-associated dementia (HAD) has been detected in 20-30% of patients suffering AIDS. The envelope glycoprotein 120 (gp120) derived from HIV seems to play a critical role in the pathophysiology of this dementia. Likewise, the feline immunodeficiency virus (FIV)-derived gp120 causes neurological and electrophysiological abnormalitites in cats. We have studied the effects of gp120 derived from HIV or FIV on learning and memory processing, hippocampal long-term potentiation (LTP), hippocampal neuronal cAMP production, the sleep-waking cycle, and locomotor activity and equilibrium in rats. Results showed that while both HIV- and FIV-gp120 impaired the rat's performance in the Barnes maze task, only HIVgp120 impaired the induction and maintenance of LTP. However, both glycoproteins induced a significant decrease in the posttetanic potentiation. HIVgp120 also caused a significant reduction in cAMP production in the hippocampus. Regarding the sleep-waking cycle, HIV- and FIV-gp120 increased the waking state and slow-wave sleep 1 (SWS1), while decreasing both SWS2 and REM sleep. Locomotor activity and equilibrium were significantly altered by these glycoproteins. These results suggest that HIVgp120 causes neurophysiological abnormalities and therefore may facilitate HAD development in AIDS patients.
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PMID:HIV- and FIV-derived gp120 alter spatial memory, LTP, and sleep in rats. 1096 9

The pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is mediated mainly by mononuclear phagocyte (MP) secretory products and their interactions with neural cells. Viral infection and MP immune activation may affect leukocyte entry into the brain. One factor that influences central nervous system (CNS) monocyte migration is matrix metalloproteinases (MMPs). In the CNS, MMPs are synthesized by resident glial cells and affect the integrity of the neuropil extracellular matrix (ECM). To ascertain how MMPs influence HAD pathogenesis, we studied their secretion following MP differentiation, viral infection, and cellular activation. HIV-1-infected and/or immune-activated monocyte-derived macrophages (MDM) and human fetal microglia were examined for production of MMP-1, -2, -3, and -9. MMP expression increased significantly with MP differentiation. Microglia secreted high levels of MMPs de novo that were further elevated following CD40 ligand-mediated cell activation. Surprisingly, HIV-1 infection of MDM led to the down-regulation of MMP-9. In encephalitic brain tissue, MMPs were expressed within perivascular and parenchymal MP, multinucleated giant cells, and microglial nodules. These data suggest that MMP production in MP is dependent on cell type, differentiation, activation, and/or viral infection. Regulation of MMP expression by these factors may contribute to neuropil ECM degradation and leukocyte migration during HAD.
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PMID:Mononuclear phagocyte differentiation, activation, and viral infection regulate matrix metalloproteinase expression: implications for human immunodeficiency virus type 1-associated dementia. 1141 25

Leukocyte migration and activation play an important role in immune surveillance and the pathogenesis of a variety of neurodegenerative disorders, including human immunodeficiency virus (HIV)-1-associated dementia (HAD). A novel chemokine named fractalkine (FKN, CX3CL1), which exists in both membrane-anchored and soluble isoforms, has been proposed to participate in the generation and progression of inflammatory brain disorders. Upon binding to the CX3C receptor one (CX3CR1), FKN induces adhesion, chemoattraction, and activation of leukocytes, including brain macrophages and microglia (MP). Constitutively expressed in the central nervous system (CNS), mainly by neurons, FKN is up-regulated and released in response to proinflammatory stimuli. Importantly, FKN is up-regulated in the brain tissue and cerebrospinal fluid (CSF) of HAD patients. Together, these observations suggest that FKN and its receptor have a unique role in regulating the neuroinflammatory events underlying disease. This review will examine how FKN contributes to the recruitment and activation of CX3CR1-expressing MP, which are critical events in the neuropathogenesis of HAD.
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PMID:Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia. 1247 52

The neuroimmune events leading to human immunodeficiency virus (HIV)-1-associated dementia (HAD) are linked to macrophage secretory neurotoxins (cellular and viral toxins). To study such events, we developed a murine model of HIV-1 encephalitis (HIVE), the pathological equivalent of HAD. Severe combined immunodeficient (SCID) mice injected with HIV-1-infected monocyte-derived macrophages (MDMs) into basal ganglia exhibited many of the pathological features of human HIVE. Moreover, behavioral and cognitive abnormalities in the HIVE mice were associated with neuronal dysfunction and decreased synaptic density. Thus, the rationale for testing novel therapeutic approaches (anti-inflammatory, antiretroviral, or neuroprotective) in the HIVE SCID mice is clear. Animals treated with anti-inflammatory compounds (platelet-activating factor [PAF] antagonist and tumor necrosis factor [TNF]-alpha release inhibitor) showed a marked reduction in brain inflammation and a reduction in neuronal injury. Comparative analyses of highly active antiretroviral therapy (HAART) regimens provided direction for which one might be most efficient for reduction of viral load in infected brain tissue. Moreover, modifications of the HIVE model might serve as a vehicle for testing vaccine approaches. Reconstitution of immunodeficient animals with syngeneic T lymphocytes followed by injection of HIV-1-infected MDMs in the brain resulted in cytotoxic antivirus T lymphocyte (CTL) response. CD8-positive T cells migrated to the sites of human MDMs, leading to the cell-mediated destruction of HIV-1 infected MDMs. These results, taken together, strongly support the use of HIVE SCID mouse model as a novel system for studies of the neuropathogenesis of HIV-1 infection, as well as for testing novel therapeutic and vaccine interventions for human disease.
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PMID:Murine models for human immunodeficiency virus type 1-associated dementia: the development of new treatment testing paradigms. 1249 Nov 51

Several patients with acquired immunodeficiency syndrome (AIDS) develop neurological complications, which are referred to as human immunodeficiency virus (HIV)-associated dementia (HAD). The HIV-1 coat glycoprotein gp-120 has been proposed as the major etiologic agent for neuronal loss reported postmortem in the brain of AIDS patients. Chemokine receptors may play a role in gp-120-triggered neurotoxicity, both in vitro and in vivo, thus being an intriguing target for developing therapeutic strategies aimed to prevent or reduce neuronal damage occurring during HIV infection. We have previously shown that human CHP100 neuroblastoma cells express CXCR4 and CCR5 chemokine receptors and that interaction between gp-120 and these receptors contributes to cytotoxicity elicited by the protein. Here, we examined the neuroprotective potential of neomycin B hexa-arginine conjugate (NeoR), a recently synthesized compound with anti-HIV activity. We found that gp-120-triggered death is significantly reduced by NeoR, and this protective effect seems related to the ability of NeoR to interact with CXCR4 receptors. The ability of NeoR to cross the blood-brain barrier, as demonstrated in mice by systemic administration of the fluorescein conjugate drug, makes this compound a powerful and attractive therapeutic agent.
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PMID:The Tat antagonist neomycin B hexa-arginine conjugate inhibits gp-120-induced death of human neuroblastoma cells. 1261 24

The final pathways for neuronal injury in human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) were investigated in Xenopus oocytes expressing recombinant NR1a/NR2B N-methyl-D-aspartate (NMDA) receptors exposed to secretory products from HIV-infected macrophages. Pressure ejection of HIV-1-infected and CD40 ligand-stimulated human monocyte-derived macrophage (MDM) fluids produced inward currents in oocytes expressing NR1a/NR2B (30.2+/-5.1 nA, n=42, mean+/-SE), but not in uninjected cells. In contrast, control (uninfected MDM) fluids induced currents of 4.5+/-0.5 nA (n=17). Infected or stimulated MDM without virus showed intermediate responses. The induced currents were MDM fluid dose-dependent and blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (50 microM), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). Although low levels of glutamate were detected in the culture fluids, the addition of L-glutamate decarboxylase to the MDM did not significantly change the level of induced inward currents. Our experiments demonstrate that secretory factors from HIV-1-infected MDM activate NMDA receptors NR1a/NR2B and may contribute to neuronal demise during HAD.
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PMID:Activation of NR1a/NR2B receptors by monocyte-derived macrophage secretory products: implications for human immunodeficiency virus type one-associated dementia. 1269 94


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