Journal of neuro-AIDS最新文献

Previously, this laboratory has shown that the Maryland strain of feline immunodeficiency virus (FIV-MD) causes neurological disease in cats similar to human immunodeficiency virus type 1 (HIV-1) in people. Using morphometrical methods on neocortical histologic sections we now show a significant loss of neurons in FIV-MD infected cats compared to age-matched uninfected controls. The neuronal populations affected resembles those lost in HIV-1 infection of the brain in published reports, providing further evidence for the utility of FIV-MD infection as a model for HIV-1 infections of the brain.

The aim of this prospective study was to determine the frequency and clinical significance of detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from 120 HIV-infected individuals. Six of 8 CSF samples from patients with recent (up to 8 months previously) or concurrent cutaneous zoster contained detectable VZV DNA using the polymerase chain reaction. No detectable CSF VZV DNA was present in two patients who had an encephalopathy complicating cutaneous zoster or in 112 other patients without a history of recent of concurrent zoster. In conclusion, VZV DNA may be detected in CSF of patients with neurological disease and concurrent or recent zoster. However, the absence of detectable VZV DNA in CSF does not preclude the possibility of VZV associated neurological complications.

The pathogenesis of HIV encephalitis (HIVE) has not been determined although increased numbers of mononuclear phagocytes (macrophages and microglia), some of which are HIV-infected, and reactive astrogliosis are important pathological findings in this condition. For this experiment, fifty-one SCID mice were inoculated intracerebrally either with human cells and HIV-1, human cells only or HIV only and then sacrificed at various time points. HIV gag mRNA was detected by reverse transcriptase polymerase chain reaction (PCR) distant from the site of inoculation in 73% of mouse brains inoculated with HIV and human cells attesting to the pervasiveness of HIV infection in SCID brain. HIV mRNA was detected as long as 91 days after inoculation of human cells and virus and the presence of HIV gag, nef, and tat/rev mRNA in HIV-infected SCID brains indicates ongoing HIV mRNA synthesis. Brain tissue sections were immunostained for HIV, human macrophages, and astrocytes from a subset of mice (n = 29) from the above groups and qualitatively assessed. PCR data for HIV mRNA was correlated with staining results and these data suggested that the greatest astrogliosis was present in mice inoculated with HIV and human cells, consistent with previously reported data. The data further suggest that astrogliosis is greater when HIV is detected. Taken together the data are consistent with a synergistic effect between macrophages and HIV in the development of astrogliosis.

Goal: To determine the heterogeneity of surface marker expression of macrophages in peripheral nerve of patients who died with AIDS.

Background: Peripheral neuropathy occurs in 20%-40% of AIDS patients. There is evidence that activated macrophages may be involved in the neural damage associated with HIV-1 infection. We studied the expression of macrophage surface markers CD14, CD11c, CD68, and HLA-DR and also T cell surface markers CD3, CD4, and CD8 in peripheral nerves of AIDS patients.

Methods: Three levels of peripheral nerves (sciatic, tibial, or sural) were examined from a limited number of subjects consisting of 4 HIV-seropositive and 5 HIV-seronegative individuals. Standard immunohistochemical technique utilized alkaline phosphatase conjugate and fuchsin substrate.

Results: Surface antigen expression was significantly (p < .0025 increased in HIV-positive tissues compared with HIV-negative controls for CD14 and CD4 in sciatic nerves, CD68 and CD4 in tibial nerves, and CD68 in sural nerves. There were trends for increased expression of HLA-DR, CD3, and CD8 in sciatic nerves, CD11c and CD14 in tibial nerves, and CD14, HLA-DR, and CD4 in sural nerves in HIV-positive tissues compared with HIV-negative controls.

Conclusion: During the course of AIDS there may be an involvement of all three levels of peripheral nerves suggesting that HIV-related neuropathy is a multifocal process.

The ability of feline immunodeficiency virus (FIV) to induce neurodegenerative changes in vitro similar to those due to HIV was examined as a potential model to examine the mechanisms underlying AIDS dementia. Primary cultures of feline neural tissue (neurons, astrocytes and microglia) were established from E40-E57 fetal cat cortex and challenged by inoculation with the NCSU₁ strain of FIV. Proviral FIV was detected in the cultures and correlated with the presence of microglia. No direct toxicity of FIV was seen. Stimulation of FIV-inoculated cortical cultures with 20 uM glutamate resulted in a greatly enhanced acute swelling response in approximately 14-24% of the neurons and an increase in the number of dead cells after 24 h relative to control cultures. The enhanced responses were due to an increase in the sensitivity of the cells to glutamate and were dependent on the presence of a soluble factor in the medium. The similarity of the indirect excitoxic effects of FIV to current models of HIV-gp120 neurotoxicity and the versatility of the in vitro cultures, indicate that FIV should provide a valuable model for the investigation of the mechanisms of neurodegeneration in AIDS dementia.

Varying degrees of neurological dysfunction are observed in AIDS patients who develop AIDS dementia complex (ADC). Data from a large number of in vivo and in vitro rodent studies have suggested a role for the HIV envelope glycoprotein gp 120 in this process. These studies were initiated to clarify possible effects of recombinant gp120 on signal transduction systems and the synthesis of specific ADC-related cytokines in human neuroblastoma cells. Out results indicate that gp120 on signal transduction systems and the synthesis of specific ADC-related cytokines in human neuroblastoma cells. Our results indicate that gp120 did not induce the synthesis of cAMP, IPs or NO, nor did it alter agonist-induced synthesis of these molecules. In addition, it did not induce the synthesis of IL-6 and TNFα. However, it did activate a src-family protein tyrosine kinase which phosphorylates several substrates, including prominent proteins in the 115 and 60 kDa range. This gp120-induced tyrosine phosphorylation may contribute to neurological dysfunction since protein tyrosine kinases are known to be involved in processes important for pre- and post-synaptic neuronal function.

Unlabelled: HIV (Human Immunodeficiency Virus) infection is associated with high rates of depressive symptomatology. There is evidence that such infection is associated with damage to the basal ganglia. It has also been suggested that the basal ganglia are implicated in the aetiology of affective disorders.

Objective: This study examined the association between basal ganglia atrophy and depression in HIV seropositive men. We hypothesized that depressed HIV seropositive patients would have smaller basal ganglia compared with nondepressed HIV positive comparison subjects.

Method: Using quantitative magnetic resonance imaging (MRI) techniques we compared for the basal ganglia volumes of sixteen depressed, and sixteen group-matched nondepressed HIV seropositive homosexual men.

Results: We found no significant difference in basal ganglia volumes between the two groups.

Conclusions: We suggest that depression, at least in the early stages of HIV infection, is not associated with basal ganglia atrophy.

FIfty-six studies which used neuropsychological tests to investigate areas of function affected by central nervous system dysfunction in HIV were reviewed. Only studies which compared the performance of HIV + subjects to HIV - controls using analysis of variance techniques were included. The results are examined in terms of broad neuropsychological function domains, and are examined separately for asymptomatic and symptomatic subjects. Studies which did and did not find significant differences between HIV + and HIV - subjects were compared in terms of various confounding factors such as risk groups, number of tests, sample size and subject characteristics. There was evidence for some dysfunction among subjects who are otherwise asymptomatic in the areas of verbal memory (27% of studies), executive function (43%), motor performance (20%) and information processing (44%). Studies of subjects with more advanced HIV infection showed consistent evidence of abnormal functioning in the areas of verbal (48% of studies) and visual memory (43%), executive functioning (71%), complex attention (62%), motor performance (37%) and information processing (69%). These deficits occurred prior to the onset of clinically apparent dementia. There were no consistent significant differences between studies which did and did not find significant differences between HIV + and HIV - subjects in terms of most of the confounding variables investigated, although studies of ASX subjects were more likely to find differences between HIV + subjects and controls with larger neuropsychological test battereies. However, much of the variation in results due to the neuropsychological tests used. In many cases, tests which relied on functions with a frontal lobe component were more likely to find significant results.

The purpose of this study was to examine by proton spectroscopy for any difference in cerebral metabolites in patients taking part in the Concorde study (comparing the efficacy of immediate versus deferred treatment with zidovudine on asymptomatic HIV infected individuals). Forty seven HIV positive male patients [29 immediate, 18 deferred zidovudine] were examined in the last 9 months of the therapeutic trial. Magnetic resonance imaging and proton spectroscopy were performed at 1.5 Tesla using a single voxel placed in the parieto-occipital white matter. No significant difference was found in metabolite ratios comparing immediate versus deferred zidovudine (NA/NA+Cho+Cr 0.52 vs. 0.52). High quality spectra were acquired in relatively large numbers of patients and logistically spectroscopy may be applied to clinical therapeutic studies.

We report an unusual presentation of CNS lymphoma involving the posterior fornix in a patient with AIDS. The patient's initial symptoms included progressive cognitive impairment, consistent with AIDS dementia, as well as impotence and urinary retention suggestive of myelopathy. An MR scan with gadolinium-DTPA enhancement demonstrated enhancing lesions in the cerebellum and in the posterior fornix. At autopsy, the later lesions proved to be lymphoma. This case demonstrates the unusual clinical features that may occur with lesions in the limbic system and importance of gadolinium-enhanced MRI in the evaluation of symptoms of cognitive impairment in patients with advanced HIV infection.