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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Genetic evidence indicates that several mutations in tau, including G272V, are linked to frontotemporal dementia with parkinsonism. We expressed this mutation in mouse brains by combining a prion protein promoter-driven expression system with an autoregulatory transactivator loop that resulted in high expression of human G272V tau in neurons and in oligodendrocytes. We show that G272V tau can form filaments in murine oligodendrocytes. Electron microscopy established that the filaments were either straight or had a twisted structure; these were 17–20 nm wide and had a periodicity of ≈ 75 nm. Filament formation was associated with tau phosphorylation at distinct sites, including the AT8 epitope 202/205 in vivo. Immunogold electron microscopy of sarcosyl-extracted spinal cords from G272V transgenic mice using phosphorylation-dependent antibodies AT8 or AT100 identified several sparsely gold-labelled 6-nm filaments. In the spinal cord, fibrillary inclusions were also identified by thioflavin-S fluorescent microscopy in oligodendrocytes and motor neurons. These results establish that expression of the G272V mutation in mice causes oligodendroglial fibrillary lesions that are similar to those seen in human tauopathies.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Key words Argyrophilic grain disease ; Apolipoprotein E ; Dementia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apolipoprotein E (ApoE) genotypes were analyzed in 35 subjects with argyrophilic grain disases (AgD). Neuropathologically, all cases were characterized by abundant argyrophilic grains in the hippocampus and in the entorhinal or parahippocampal cortex. We found an ApoE ɛ4 allele frequency of 0.007 in AgD patients, which is significantly different from the ɛ4 allele frequencies reported in age-matched Alzheimer’s disease (AD) patients (0.24), but not from age-matched controls (0.09). We conclude that the ApoE ɛ4 allele does not constitute a risk factor for the development of AgD. Our results further suggest that AgD is a progressive disorder differentiated from AD by morphological and genetic criteria.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7373
    Keywords: medulloblastoma ; microvessel counts ; immunohistochemistry ; p53 ; bcl-2 ; Mib-1 ; factor VIII-related antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to retrospectively assess the prognostic value of p53 and bcl-2 protein expression, cell proliferation index (Mib-1 index), and tumor microvessel density (factor VIII-related antigen) in pediatric medulloblastoma patients. Tumor specimens of 55 patients (age 2–18 years) with medulloblastoma treated with a curative intent between 1972 and 1991 were studied. Slides of paraffin embedded tissue were stained with monoclonal antibodies (mAb) and examined under high power light microscopy for the presence of immunoreactivity. Microvessel density was scored both in the area of most intense staining (‘Angio-max’) and in 3 additional randomly selected areas. The sum of these 4 scores was termed ‘Angio-total’. ‘Angio-max’ and ‘Angio-total’ were evaluated separately by two independent investigators to assess reproducibility. None of the parameters studied, i.e. p53 or bcl-2 expression, Mib-1 index or microvessel density scores were associated with patient survival. Microvessel scores between observers were significantly but weakly correlated, with correlation coefficients (r)〈0.5 for both ‘Angio-max’ and ‘Angio-total’. Leptomeningeal spread at diagnosis was the only independent factor associated with a poor survival (p=0.003). There was no association of leptomeningeal metastasis with any of the biological markers tested in this study.
    Type of Medium: Electronic Resource
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