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)

Pathological evidence suggests that alterations of the blood-brain barrier (BBB) may occur in association with human immunodeficiency virus (HIV) dementia (HIVD). Increased BBB permeability could contribute to the development of dementia by facilitating the entry of activated and infected monocytes, as well as potentially toxic serum proteins, into the central nervous system. One mechanism by which BBB permeability may be altered is through increased activity of select matrix metalloproteinases (MMPs). In the present study, we examined the possibility that MMPs that target critical BBB proteins, including laminin, entactin, and collagen type IV, are elevated in the cerebrospinal fluid (CSF) of patients with HIVD. We also examined the possibility that such MMPs could be produced by brain-derived cells, and that MMP production by these cells might be increased by tumor necrosis factor-alpha, an inflammatory cytokine that is produced by HIV-infected monocytes/microglia and is elevated in HIVD. By using western blot and enzyme-linked immunosorbent assay, we observed that CSF levels of pro-MMP-2 and pro-MMP-7 were increased in association with HIVD. In addition, through the use of gelatin substrate zymography, a sensitive functional assay for MMP-2 and MMP-9, we observed that MMP-2 or pro-MMP-9 activity was more frequently detectable in the CSF of individuals with HIV dementia (9/16) than in the CSF from either nondemented seropositive (2/11) or seronegative (0/11) controls. Although the presence of MMPs in the serum could contribute to elevated levels in the CSF, we also show that brain-derived cells release MMP-2, 7, and 9, and that such release is increased after their stimulation with tumor necrosis factor-alpha. Together, these results suggest that elevated CSF levels of select MMPs may reflect immune activation within the central nervous system. They also suggest that further studies may be warranted to determine whether these proteins may play a role in the development of symptomatic neurological disease.
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PMID:Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. 1048 70

Apoptosis of neurones, macrophages, and microglia occurs in the brains of paediatric patients with human immunodeficiency virus (HIV) type 1 encephalitis, which is often associated with pre-mortem neurological disease (progressive encephalopathy). We have previously reported that TUNEL-positive neurones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic gene product Bax, in marked contrast to brain-resident macrophages and microglia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalopathy, as well as macrophages and microglia, but not astrocytes, overexpress caspase-3, a pro-apoptotic enzyme that is proteolytically activated downstream of Bax-Bcl-2 dysregulation. Co-localization of neuronal cytoplasmic caspase-3 and nuclear TUNEL staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 encephalitis and progressive encephalopathy. These findings suggest that vulnerable neurones in brain tissue from patients with HIV virus type 1 encephalitis and progressive encephalopathy undergo apoptosis by a mechanism that involves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl-2 dysregulation. Furthermore, caspase-3 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.
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PMID:Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis. 1056 27

Approximately 15-20% of individuals infected with the human immunodeficiency virus will develop severe neurological disease. This may be due in part to virus-induced release of a number of putative neurotoxins. However, there is little information to predict which individuals will progress to dementia or the precise mechanisms that drive pathogenesis. In an effort to identify early markers of neurological disease progression we used an in vitro bioassay with rat cortical neurons to test for the presence of toxins in CSF from 40 HIV-infected humans with mild, minimal or no neurological disease. A subset of HIV-infected individuals was found to have significant toxic activity in CSF indicating that toxic factors may be circulating prior to the development of dementia. The toxicity was concentration dependent and due to a factor with a molecular mass of less than 30 kDa. Only a small proportion of the cell death appeared to be due to apoptosis. Neuronal toxicity was associated with a gradual accumulation of intracellular calcium in a subset of cortical neurons over a period of 1-2 h and in the absence of a significant acute response. Individuals with both high viral burden and high CSF toxicity were significantly more likely to have neurological symptoms. These initial analyses indicate that toxic factors are present in the CSF of HIV-infected patients that could serve as useful markers of neurological disease progression and provide insights into pathogenic mechanisms in vivo.
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PMID:Neurotoxicity of CSF from HIV-infected humans. 1056 88

Plasma samples from 35 individuals with human immunodeficiency virus (HIV) infection but without peripheral neuropathy were screened by enzyme linked immunosorbent assay (ELISA) for IgM and IgG antibodies against sulphatide (GalS). Five of these were shown to contain raised anti-GalS IgM antibody titres, while six had raised IgG titres. All plasma samples screened were compared to an internal neurological disease control which contained raised anti-GalS IgM antibody titres. Anti-GalS IgM antibody titres in the HIV cohort ranged between 200 and 2000 arbitrary units/litre (AU/l), whereas, IgG titres were between 200 and 10,000 AU/l. Two of four plasma samples from HIV-infected individuals with neuropathy (HIV+PN) also showed IgM reactivity with GalS; one also binding to the gangliosides GM1, GD1a, GD1b and GT1b. The other two samples showed IgG reactivity against GalS. These data indicate that antibodies against GalS occur more frequently in HIV infection than in HIV-seronegative individuals with and without neurological disease and may participate in the pathogenesis of neuropathies associated with HIV infection.
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PMID:High titre anti-sulphatide antibodies in HIV-infected individuals. 1057 69

Two cases of cryptococcal meningitis and increased intracranial pressure in patients with acquired immunodeficiency are described. Both patients presented high intracranial pressure that persisted despite optimal antifungal treatment (amphotericin B, 5-flucytosine initially, and fluconazole posteriorly). The elevated intracranial pressure produced headache, seizures, and reduced visual and auditory acuity. CAT scan demonstrated absence of ventricular dilatation or focal lesions. Both cases were treated with adequate antifungal therapy, as well as with repeated lumbar punctures and placement of a lumboperitoneal shunt due to the persistence of elevated intracranial pressure. One patient presented with unilateral loss of vision due to optic nerve atrophy. After one year of follow-up, one patient died due to progression of his disease, while the other is still alive and without evidence of neurological disease. Intracranial hypertension is a frequent clinical manifestation of cryptococcal meningitis in patients with acquired immunodeficiency syndrome (AIDS) that requires adequate diagnosis and management. Treatment should be directed towards the reduction of intracranial pressure though repeated lumbar punctures and, in some cases, with lumboperitoneal or ventricular-peritoneal shunts.
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PMID:[Significance of intracranial hypertension management in cryptococcal meningitis in patients with acquired immunodeficiency syndrome. Report of 2 cases]. 1061 40

We investigated the epidemiology of 618 patients of mucocutaneous candidiasis who visited our outpatient clinic between 1993 and 1997. Compared with previous reports in Japan, the incidence of candida intertrigo increased and that of erythema mycoticum infantile decreased. The incidence of "others", such as nail candidiasis and candidiasis developed under plaster increased. We identified the species of Candida from patients in 496 recent cases, and these species were cultured successfully in 79.2%. As reported by previous authors, a majority or our results were Candida albicans serotype A. We also investigated the risk factors such as diseases or conditions which might be related to immunodeficiency (neoplasm, AIDS) and that might force a patient to restrict himself to bed for a long period (neurological disease). The former was found in 22.7%, and the latter in 23.3% of patients.
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PMID:[Statistical surveillance of mucocutaneous candidiasis in Showa University Fujigaoka Hospital in the past 5 years]. 1066 Jun 40

Neuromuscular disorders are the most frequent neurologic complications associated with human immunodeficiency virus (HIV) infection and AIDS. Although neurologic disorders are frequently overlooked, they add considerable morbidity and mortality to patients with HIV infection. It is critically important to properly diagnose and treat these neuromuscular complications, which leads to substantial improvement in patients' quality of life. Distal symmetric polyneuropathy is the most common form of peripheral neuropathy in HIV infection. It occurs mainly in patients with advanced immunosuppression and may also result from the neurotoxicity of several antiretroviral agents. Myopathy may occur at any stage of HIV disease and has also been described as a toxic side effect of zidovudine. Here we review the clinical features, diagnostic approach, and pathogenetic mechanisms of the neuromuscular complications of HIV infection. We also discuss management strategies and the results of clinical trials for the treatment of these disorders.
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PMID:Neuromuscular complications of the human immunodeficiency virus type 1 infection. 1071 36

We studied a cohort of children with the human immunodeficiency virus (HIV) infection in Barbados in order to determine the prevalence of HIV infection, the clinical course including morbidity and mortality and the magnitude of the health care and social problems. Forty-seven children were diagnosed with HIV infection during the study period. The number of HIV infected children increased from 5 during 1981-85, to 14 during 1986-90, and to 21 during the 1991-95 period. The majority (91.5%) of infections resulted from perinatal transmission. Six (12.8%) cases remained asymptomatic and 41 (87.2%) were symptomatic with 19(46.3%) presenting in infancy, while 22 (53.5%) presented post-infancy. The median age at diagnosis (class P-2) was 13 months. Generalized lymphadenopathy (47.5%), hepatosplenomegaly (40.0%), failure to thrive (27.5%), persistent recurrent diarrhoea (15.0%), oral candidiasis (37.5%), Pneumocystis carinii pneumonia (37.5%), lymphoid interstitial pneumonia (12.5%) and progressive neurological disease (10.0%) were common HIV related conditions. Two children developed non-hodgkin's lymphoma. The median age at death for 23 children was 12 months, whereas the median survival after diagnosis was 4 months. Mortality was higher among those diagnosed in infancy (73.7%) as compared to those diagnosed post-infancy (42.8%). Pneumocystis carinii pneumonia was the most common (65.2%) cause of death. Paediatric HIV infection is rising and contributes considerably to infant mortality. In this study, children took longer to be symptomatic when compared to other reports. However, once symptomatic, they died early.
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PMID:HIV infection among children in Barbados. 1078 51

We report on the role of vpu in the pathogenesis of a molecularly cloned simian-human immunodeficiency virus (SHIV(KU-1bMC33)), in which the tat, rev, vpu, env, and nef genes derived from the uncloned SHIV(KU-1b) virus were inserted into the genetic background of parental nonpathogenic SHIV-4. A mutant was constructed (DeltavpuSHIV(KU-1bMC33)) in which 42 of 82 amino acids of Vpu were deleted. Phase partitioning studies revealed that the truncated Vpu was not an integral membrane protein, and pulse-chase culture studies revealed that cells inoculated with DeltavpuSHIV(KU-1bMC33) released viral p27 into the culture medium with slightly reduced kinetics compared with cultures inoculated with SHIV(KU-1bMC33). Inoculation of DeltavpuSHIV(KU-1bMC33) into two pig-tailed macaques resulted in a severe decline of CD4(+) T cells and neurological disease in one macaque and a more moderate decline of CD4(+) T cells in the other macaque. These results indicate that a membrane-bound Vpu is not required for the CD4(+) T cell loss and neurological disease in SHIV-inoculated pig-tailed macaques. Furthermore, because the amino acid substitutions in the Tat and Rev were identical to those previously reported for the nonpathogenic SHIV(PPc), our results indicate that amino acid substitutions in the Env and/or Nef were responsible for the observed CD4(+) T cell loss and neurological disease after inoculation with this molecular clone.
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PMID:A molecular clone of simian-human immunodeficiency virus (DeltavpuSHIV(KU-1bMC33)) with a truncated, non-membrane-bound vpu results in rapid CD4(+) T cell loss and neuro-AIDS in pig-tailed macaques. 1087 54

The role of the viral burden in the brain for the pathogenesis of human immunodeficiency virus-associated neurological disorders is still unclear. To address this issue, we have quantified the viral load in plasma, cerebrospinal fluid (CSF) and brain tissue of macaques infected with simian immunodeficiency virus (SIV). We discovered that the viral strain used for infection determines the replicative capacity in microglial cells as well as the extent of neuropathological lesions and the occurrence of neurological symptoms. Moreover, the viral load in the brain parenchyma correlated with the development of overt neurological disease whereas the one in plasma did not. By comparing the viral load in three different compartments, we demonstrated that the viral burden in the CSF is influenced both by the viral replication in the periphery as well as in the brain parenchyma. According to these results, it is not the absolute amount of viral load in the CSF but rather the viral antigen contributed by the viral production within the brain which correlates with the development of neurological disease. In longitudinal studies, we observed that this autochthonous virus production, as evidenced by a ratio of the viral load in CSF to the one in plasma, takes place for a prolonged period of time before overt neurological signs are manifested. This finding suggests that this ratio could be used as a prognostic marker for immunodeficiency virus-induced neurological disease.
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PMID:Relationship between viral load in blood, cerebrospinal fluid, brain tissue and isolated microglia with neurological disease in macaques infected with different strains of SIV. 1087 9


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