Quantification and analysis of the neuropathological features of Creutzfeldt-Jakob disease

Sutherland, K.; MacDonald, Simon T.; Ironside, James

doi:10.1016/0165-0270(95)00120-4

Cited by 10 publications

(4 citation statements)

References 9 publications

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“…Slides were coded and assessed subjectively, blind to the history and to the PCR results. For astrocyte quantification, glial fibrillary acidic protein (GFAP)‐positive cells were assessed in representative areas of identical size from separately identified grey and white matter in frontal and temporal lobes, using a highly automated, dedicated, image analysis system as described previously [ 43]. Since no equivalent computer programs exist at present for less structured immunocytochemical features, quantification of lymphocytes and microglia was undertaken by two independent observers using non‐automated screening of entire sections under a ×10 objective.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of microglia in drug users with and without pre‐symptomatic HIV infection

Tomlinson¹,

Simmonds

Busuttil³

et al. 1999

Neuropathology Appl Neurobio

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It is generally thought that infection of the central nervous system (CNS) by HIV-1 can occur early, even around the time of seroconversion, and evidence from animal studies supports this. However, the mode and timing of viral entry remain poorly understood since there have been comparatively few studies of the early neuropathology of HIV infection. In this study, samples of frontal and temporal lobes, and basal ganglia, were selected from 12 HIV-positive drug users who had been infected for 4-130 months before death, 10 HIV-negative drug users and 10 non-drug using controls, all age and sex matched. Routine and immunocytochemical staining showed that leptomeningeal and perivascular lymphocytic infiltrate was upregulated in HIV-infected cases compared with the two control groups, and choroid plexitis was confined to the HIV-positive subjects, suggesting an association with viral infection. In contrast, CD68-positive microglia were enhanced in both HIV- positive and HIV-negative drug users, considerably above the baseline seen in normal controls. However, there was no statistical difference between the three groups in relation to astrocytes. Screening and competitive polymerase chain reaction (PCR) undertaken on multiple samples including brain tissue, choroid plexus and leptomeninges from four of the HIV-positive subjects and one control case showed that the pro-viral burden was never more than 13 copies/microg DNA and was negative in multiple samples from one HIV-positive case and one control case. All the basal ganglia samples were PCR-negative. This study has not revealed any t spots' of viral load in brain tissue, choroid plexus or meninges, either early or late in the course of pre-symptomatic HIV infection. Drug use alone is associated with significant upregulation of microglia and this may predispose to HIV infection of the nervous system in drug users.

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Section: Methodsmentioning

confidence: 99%

Upregulation of microglia in drug users with and without pre‐symptomatic HIV infection

Tomlinson¹,

Simmonds

Busuttil³

et al. 1999

Neuropathology Appl Neurobio

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“…The accumulation of PrPrtS in the brain in CJD most frequently occurs in a variety of other patterns, of which the diffuse or synaptic and perivacuolar patterns are the most common (24,45) (Figure 3). PrPres accumulation in tissue sections can also be quanti- fied using computer based analysis systems, and correlated with other neuropathological abnormalities; P r P s accumulation in CJD is not confined to brain areas showing classical histopathological features of TSE as revealed by routine staining, and does not correlate with the severity of spongiform change (56,75). The interrelationship between these features has also been studied in a range of animal models of TSE, particular the murine scrapie model, where serial pathogenesis studies have allowed the temporal evolution of these structural changes to be investigated (23,65).…”

Section: Introductionmentioning

confidence: 99%

Review: Creutzfeldt‐Jakob Disease

Ironside¹

1996

Brain Pathology

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The clinicopathological spectrum of Creutzfeldt-Jakob disease has recently been extended by the identification of an apparently new variant of this disorder in the UK. The hypothesis that this new disorder is causally related to the transmissible agent responsible for bovine spongiform encephalopathy has prompted re-evaluation of the relationships between human and animal transmissible spongiform encephalopathies, and reinforced the need for adequate experimental models to investigate this field. Recent experimental transmission studies of bovine spongiform encephalopathy into primates have supported the hypothesis, and reinforced the central role of neuropathology in the investigation of this group of diseases. Whilst clearly of distinctive etiology, Creutzfeldt-Jakob disease shares both clinical and neuropathological features with other human dementias; renewed evaluation of potentially similar disease mechanisms in these devastating conditions might provide new information of both scientific and therapeutic value.

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“…GFAP‐reactive astrocytes were quantified in frontal lobe grey and white matter of each case using a computerized image analysis system based on an automated Leitz Ergolux microscope and a Sun workstation computer. This system had been validated previously for astrocyte quantification [39].…”

Section: Methodsmentioning

confidence: 99%

Relationship of Nef‐positive and GFAP‐reactive astrocytes to drug use in early and late HIV infection

Anderson¹,

Tomlinson²,

Pauly³

et al. 2003

Neuropathology Appl Neurobio

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Reactive astrocytosis is a well-documented feature of HIV encephalitis (HIVE), but it is unclear whether restricted infection of astrocytes contributes to this phenomenon. In addition, the part played by reactive and/or infected astrocytes in AIDS-related dementia is not fully understood. In this study of patients at different stages of the human immunodeficiency virus (HIV) infection, who had been treated at most with one antiretroviral drug, reactive astrocytes were identified by immunopositivity for glial fibrillary acidic protein (GFAP) and infected astrocytes by positivity for HIV Nef protein. Results were compared for drug-using AIDS patients with (n=9) and without (n=7) HIVE, for presymptomatic HIV-positive drug users (n=12) and for control HIV-negative subjects (n=20), including a group who used drugs (n=10). GFAP-reactive astrocytes in both grey and white matter were significantly more numerous in HIVE subjects than in each of the other groups but did not correlate with viral load. Nef-positive astrocytes were confined to HIVE cases and to white matter, but were numerous in only one subject who was treatment-naive. Nef-positive microglia were identified in all HIVE cases and in occasional AIDS and presymptomatic subjects who did not have HIVE. The results suggest that astrocytes may form an additional viral reservoir in late HIV infection and may contribute to HIVE. However, the number of GFAP-positive astrocytes was neither increased in pre-AIDS nor in drug abuse, in contrast with microglia which we have shown previously to be up-regulated in both states.

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Quantification and analysis of the neuropathological features of Creutzfeldt-Jakob disease

Cited by 10 publications

References 9 publications

Upregulation of microglia in drug users with and without pre‐symptomatic HIV infection

Upregulation of microglia in drug users with and without pre‐symptomatic HIV infection

Review: Creutzfeldt‐Jakob Disease

Relationship of Nef‐positive and GFAP‐reactive astrocytes to drug use in early and late HIV infection

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