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 pattern of expression of GFAP immunoreactivity in astrocytes of the juvenile rhesus monkey cortex was examined following infection with simian immunodeficiency virus (SIV). Blocks of cerebral cortex plus subjacent white matter from saline- and formalin-perfused brain were examined by peroxidase-linked immunochemical and immunofluorescence staining of deparaffinized sections. Strong GFAP immunoreactivity was found in astrocytic cells in both uninfected and SIV-infected juvenile macaque in the subpial cerebral cortex and in subcortical white matter, where GFAP-positive cells were abundant. GFAP staining of cortical layers 2-6 on the other hand was weak or absent in three uninfected controls and one infected animal without cognitive impairment, but moderate to strong in animals productively infected with SIV that demonstrated cognitive and/or motor impairment. These data demonstrate a cortical locus of astrocytic activation in rhesus monkeys infected with primate immunodeficiency virus isolate SIVB670 which, like HIV-1 in man, causes motor/cognitive impairment as well as immunodeficiency disease.
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PMID:Cortical astrocytosis in juvenile rhesus monkeys infected with simian immunodeficiency virus. 847 48

The cause of cerebral atrophy in patients with acquired immunodeficiency syndrome (AIDS) is obscure because human immunodeficiency virus type 1 (HIV-1)-related histopathological changes hardly correlate with cerebral atrophy. In this study, brain ventricular expansion was compared to the frontal lobe density of mononuclear and astroglial cells at autopsy. Twenty-eight male patients with AIDS displaying varying degrees of atrophy were compared to 17 age-matched male control subjects without AIDS or atrophy. An index of ventricular expansion was measured in uniformly sliced, formalin-fixed brain specimens, and immunochemically marked cells in coronal sections of the left superior frontal gyrus (Brodmann area 8) were quantified by field counting and planimetry. In the cortex, diffuse ferritin-stained microglia and glial fibrillary acidic protein-positive astrocytes were about twice as numerous in the patients with AIDS. Sixty-five percent (18/28) of the patients with AIDS had a microglial cell density greater than 2 standard deviations above the control mean. Microglial cell density was correlated positively with the severity of ventricular expansion (r = 0.71, p < 0.0001), while hypertrophied astroglial cells were very weakly related. In white matter, Ham-56-positive macrophages and glial fibrillary acidic protein-positive astrocytes were not meaningfully correlated with the index of ventricular expansion. Brain ventricular expansion and diffuse cortical microgliosis are highly prevalent anomalies in patients with AIDS, and their interrelationship may be more important than previously recognized.
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PMID:Diffuse microgliosis associated with cerebral atrophy in the acquired immunodeficiency syndrome. 851 82

Neuropathological examination of the central nervous system of 13 naturally and 13 experimentally feline immunodeficiency virus (FIV)-infected cats revealed diffuse gliosis of gray and white matter and vacuolar myelinopathy in a large proportion of infected animals, sometimes associated with lymphocytic meningitis. Multinucleated giant cell formation, the hallmark of multifocal giant cell encephalitis in HIV infection, was never observed. Morphometric analysis confirmed a marked increase of GFAP reactivity in infected cats. Gliosis was mainly present in cortical structures of frontal, parietal, and occipital lobes. Only one naturally infected animal evidenced clinical symptoms of neurological damage. This study confirms that FIV provides an interesting model for studying HIV-induced cortical and subcortical brain pathology believed to be the cause of the neurological manifestations frequently observed in AIDS patients.
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PMID:Regional distribution of lesions in the central nervous system of cats infected with feline immunodeficiency virus. 857 82

The human immunodeficiency virus (HIV) is neuroinvasive and commonly causes cognitive and motor deficits during the later stages of viral infection. (referred to as HIV dementia). The mechanism(s) for disease revolves around secretory products produced from immune-activated brain macrophages/microglia. Recently, we developed an animal model system for HIV dementia that contains xenografts of HIV-1-infected cells inoculated into brains of mice with severe combined immunodeficiency (SCID). This animal system was used to quantitatively evaluate HIV-induced neuropathology. Xenografts of HIV-1-infected human monocytes (placed into the putamen and cortex of SCID mice) remained viable for 5 weeks. HIV-1 p24 antigen expression in mouse brain was persistent. Progressive inflammatory responses (including astrogliosis and cytokine production), which began at 3 days, peaked at day 12. The range of astrocyte proliferative reactions exceeded the inoculation site by > 1000 microns. Brains with virus-infected monocytes showed a > or = 1.6-fold increase in glial fibrillary acidic protein (staining distribution and intensity) as compared with similarly inoculated brains with uninfected control monocytes. These findings paralleled the accumulation and activation of murine microglia (increased branching of cell processes, formation of microglial nodules, interleukin (IL)-1 beta and IL-6 expression). An inflammatory reaction of human monocytes (as defined by HLA-DR, IL-1 beta, IL-6, and tumor necrosis factor-alpha expression) and neuronal injury (apoptosis) also developed after virus-infected monocyte xenograft placement into mouse brain tissue. These data, taken together, demonstrate that this SCID mouse model of HIV-1 neuropathogenesis can reproduce key aspects of disease (virus-infected macrophages, astrocytosis, microglial activation, and neuronal damage). This model may serve as an important means for therapeutic development directed toward improving mental function in HIV-infected subjects with cognitive and motor dysfunction.
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PMID:Human immunodeficiency virus encephalitis in SCID mice. 878 Mar 78

Astrocytes respond vigorously to diverse neurological insults. It is still not clear, however, whether this response is stereotypic following different insults or varies according to the injury. We have used a novel immunocytochemical marker of reactive astrocytes, termed M22, together with antibodies to glial fibrillary acidic protein (GFAP), to analyze region- and insult-specific differences in reactive astrocytosis in the murine central nervous system (CNS). Pathology was variously induced by (1) infectious agents, (2) transgenic overexpression of a viral glycoprotein or cytokine, or (3) focal trauma. Scrapie infection induced high levels of both GFAP and M22 epitope expression by hippocampal reactive astrocytes, but neither scrapie nor wild mouse retrovirus infection induced detectable M22 staining in reactive astrocytes of the caudal brain. Focal trauma and human immunodeficiency virus gp120 overexpression induced M22 expression only in the hippocampus, while interleukin-6 overexpression induced it in cerebellar astrocytes. Although M22 expression was limited to areas with extensive damage, GFAP expression was induced in every region of the mouse brain displaying pathology. Staining of routinely fixed human brain tissue demonstrated that M22 also labeled reactive astrocytes in chronic human CNS disease. The restriction of M22 expression to areas of strongly GFAP-positive astrocytosis suggests that the M22 antibody identified highly activated reactive astrocytes. Because of this selective staining of activated astrocytes, the M22 antibody may provide neuropathologists with a good marker for qualitative analysis of the astrocytic response to different injuries.
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PMID:The M22 antibody identifies highly activated reactive astrocytes responding to central nervous system disease. 883 43

In vitro neurovirological studies of viral infectivity or viral gene expression may be confounded by the multiple neural cell types and/or fibroblast contamination present in early passage cultures prepared from dissociated human central nervous system (CNS) tissue. We have developed highly enriched astrocyte cultures for neurovirological study by culturing in a serum-free defined medium, B16, supplemented with basic fibroblast growth factor (FGF-2). Subculture in this medium selects against fibroblast proliferation and favors sustained proliferation of a highly enriched glial fibrillary acidic protein (GFAP)-positive cell population. These astrocytes support productive replication of cytomegalovirus (CMV) and transient expression of transfected CMV and human immunodeficiency virus type 1 (HIV-1) viral promoters. By comparison, CNS cultures developed in standard serum-containing medium initially contain predominantly astrocytes, but show increasing contamination with fibroblasts with sequential passage. These cultures support CMV viral synthesis in both fibroblasts and astrocytes, cell types distinguishable only by immunostaining for cell specific antigen. CMV or HIV-1 promoter activities, quantitated by transient gene expression assays, are distinctly lower in CNS cultures maintained in serum-containing medium.
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PMID:Media components influence viral gene expression assays in human fetal astrocyte cultures. 922 66

Neuropathological changes have been described associated with feline immunodeficiency virus (FIV) infection. The objective of our study was to characterize the lesions found in the brain and spinal cord of experimentally FIV-infected cats and to quantify, by morphometric analysis, the intensity of gliosis found in these subjects at different time post infection (pi). The brains and spinal cords appeared grossly normal. Gray matter of cortical and subcortical structures showed a moderate to pronounced gliosis particularly in all cerebral cortex and hippocampus. Morphometric analysis demonstrated that GFAP immunoreactivity was markedly higher in infected animals. Gliosis was present 15 days pi and did not appear to progress during the infection, whereas neuronal changes when present were observed only in long-term infected animals (15-23 months pi). In a large proportion of infected cats a diffuse gliosis of white matter and vacuolar myelinopathy was also present. Despite some discrepancies observed between neuropathological changes in FIV-infected animals and HIV-infected individuals, the presence in the cerebral cortex of cats with FIV infection of alterations similar to those observed in AIDS patients demonstrates that FIV is an interesting animal model particularly that may be useful for clarifying the pathogenesis of neuropathological changes associated with HIV infection.
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PMID:Neuropathology in cats experimentally infected with feline immunodeficiency virus: a morphological, immunocytochemical and morphometric study. 937 57

Polyomaviruses have proven oncogenicity in nonhost experimental animals; however, studies concerning the association between human brain tumors and simian and human polyomaviruses have yielded inconclusive results. We examined the relationship of SV40 to a malignant astrocytoma found in the right frontal lobe of a pigtail macaque (Macaca nemestrina) infected with simian immunodeficiency virus (SIV). Consistent with the histologic diagnosis, the tumor was immunoreactive with antibodies to S-100 protein, vimentin, and glial fibrillary acidic protein, but negative for neurofilament protein, synaptophysin, neuron-specific enolase, and chromogranin A. At the time of SIV inoculation, the animal was seropositive for SV40. Polymerase chain reaction assay of tumor DNA, but not normal brain DNA, yielded a 300 base-pair fragment corresponding to the carboxy-terminal coding region (C-terminus) of the large T antigen gene of SV40, suggesting an association with the tumor.
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PMID:A malignant astrocytoma containing simian virus 40 DNA in a macaque infected with simian immunodeficiency virus. 937 84

The human immunodeficiency virus type-1 envelope glycoprotein gp120 is shed from the virus and from infected cells and thus can diffuse and interact with a variety of central nervous system cells. Transgenic mice constitutively expressing glial fibrillary acidic protein-driven gp120 from brain astrocytes display neuronal and glial changes resembling abnormalities in human immunodeficiency virus type-1-infected human brains. To assess the neurophysiology of these transgenic mice and determine whether gp120 expression impairs synaptic plasticity, we examined CA1 population excitatory postsynaptic potentials in hippocampal slices from transgenic mice and from non-transgenic controls, using a double-blind protocol. Compared with slices from non-transgenic littermate controls, slices from gp120 transgenic mice showed four significant alterations: (i) increased mean slopes of normalized population excitatory postsynaptic potentials; (ii) larger paired-pulse facilitation after induction of long-term potentiation at 50 ms interpulse intervals; (iii) markedly elevated short-term potentiation after 10 and 20 shocks at 100 Hz; and (iv) a significant reduction in the magnitude of CA1 long-term potentiation. In slices from transgenic mice expressing Escherichia coli beta-galactosidase from the same promoter, paired-pulse facilitation and long-term potentiation were normal. These results indicate that brain slice preparations from gp120 transgenic mice can be used to assess pathophysiological effects of gp120 on neuronal networks. Because short-term potentiation involves presynaptic mechanisms, our results suggest that gp120 expression in these mice enhances either presynaptic glutamate release or postsynaptic glutamate receptor function, or both. These changes could lead to increased Ca2+ influx, thereby contributing to neuronal dysfunction and injury. As long-term potentiation is a cellular model of learning and memory, our results may be relevant to memory (cognitive) impairments seen in patients with AIDS.
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PMID:Transgenic mice with cerebral expression of human immunodeficiency virus type-1 coat protein gp120 show divergent changes in short- and long-term potentiation in CA1 hippocampus. 948 53

Astrocyte activation has been postulated to be a major contributor to functional changes in the brain of AIDS patients. We assessed astrocyte activation in the simian immunodeficiency virus (SIV) model. Four groups of macaque brains were examined: uninoculated controls, animals inoculated with virus that did not cause disease, animals inoculated with virus that caused AIDS but did not cause encephalitis, and animals with SIV encephalitis. We examined expression of calbindin-D-28K, a calcium binding protein that is upregulated in astrocytes during excitotoxic events, as well as glial fibrillary acidic protein (GFAP). The presence of calbindin in astrocytes was confirmed by double-labeling using confocal microscopy. Increases in calbindin staining were most apparent in the white matter, but increases in GFAP staining were most apparent in middle layers of the cerebral cortex. Six of the seven animals with SIV encephalitis had calbindin immunoreactive astrocytes in the subcortical white matter, corpus callosum, internal capsule, cerebral peduncle, pontine white matter, and cerebellar white matter. Very rarely, a few, very lightly calbindin-immunoreactive astrocytes were present in the uninoculated control brains. The increase in calbindin expression by astrocytes in SIV encephalitis suggests that these cells are subject to calcium toxicity. In uninoculated control macaques, and in macaques inoculated with virus that did not cause disease, GFAP-immunoreactive astrocytes were present throughout the subcortical white matter and in layer I, but very few were found in layers III-V of the cerebral cortex. Two animals that died of AIDS without encephalitis had somewhat higher numbers of GFAP immunoreactive astrocytes in middle cortical layers. In seven animals that received passaged neurovirulent virus and developed both AIDS and encephalitis, the number of GFAP-immunoreactive astrocytes in middle cortical layers was high, indicating widespread astrocyte activation.
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PMID:Neurovirulent simian immunodeficiency virus induces calbindin-D-28K in astrocytes. 977 44


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