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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100β is an astrocyte-derived cytokine that promotes neurite growth and induces increases in levels of intracellular calcium in neurons. In sections of neocortex of surgically resected temporal lobe tissue from patients with intractable epilepsy, we found that the number of S100β-immunoreactive astrocytes was approximately threefold higher than that found in control patients (p 〈 0.001). These astrocytes were activated, i.e., enlarged, and had prominent processes. Temporal lobe tissue levels of S100β were shown by ELISA to be fivefold higher in 21 epileptics than in 12 controls (p 〈 0.001). The expression of the astrocyte intermediate filament protein, glial fibrillary acidic protein, was not significantly elevated in epileptics, suggesting a selective up-regulation of S100β expression. Our findings, together with established functions of S100β, suggest that this neurotrophic cytokine may be involved in the pathophysiology of epilepsy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Homozygous APPV717F transgenic mice overexpress a human β-amyloid precursor protein (βAPP) minigene encoding a familial Alzheimer’s disease mutation. These mice develop Alzheimer-type neuritic β-amyloid plaques surrounded by astrocytes. S100β is an astrocyte-derived cytokine that promotes neurite growth and promotes excessive expression of βAPP. S100β overexpression in Alzheimer’s disease correlates with the proliferation of βAPP-immunoreactive neurites in β-amyloid plaques. We found age-related increases in tissue levels of both βAPP and S100β mRNA in transgenic mice. Neuronal βAPP overexpression was found in cell somas in young mice, whereas older mice showed βAPP overexpression in dystrophic neurites in plaques. These age-related changes were accompanied by progressive increases in S100β expression, as determined by S100β load (percent immunoreactive area). These increases were evident as early as 1 and 2 months of age, months before the appearance of β-amyloid deposits in these mice. Such precocious astrocyte activation and S100β overexpression are similar to our earlier findings in Down’s syndrome. Accelerated age-related overexpression of S100β may interact with age-associated overexpression of mutant βAPP in transgenic mice to promote development of Alzheimer-like neuropathological changes.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 24 (1975), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —Acid and alkaline DNase activities were determined in postnatal and adult rat cerebellum. Normal animals were compared with those injected with 10 mg/kg methylazoxymethanol acetate using varying schedules after birth in order to induce transient damage to proliferating cell populations. In all animals studied, both immature and adult, methylazoxymethanol caused an increase in acidic and decrease in alkaline DNase activity. These effects were not specific to the dividing populations and occurred in nonmitotic cells as well. When injections were given to young adults, these effects appeared irreversible and persisted up to 3 months after birth.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 28 (1977), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Rat pups were reared in litters of 20 and litters of 6 to study effects of malnutrition on cerebellar development. Cell production and cell content were determined by assaying for DNA, as a measure of cell number, and RNA and protein, as indicators of cell constituents. By comparing DNA contents at 3, 4, 8, 11, 14, 17, 21, and 28 days after birth, we concluded that (a) there is little nutritional reserve at birth since significant differences appear by day 4, (b) most relative differences between groups appeared by day 8, with absolute differences increasing to day 21, and (c) there is partial recovery of cell number and cell constituents in the malnourished rats between 21 and 28 days.Areal measurements of histological preparations showed that malnutrition resulted in less total area in cerebellar midsagittal sections at days 8, 11. and 14. In malnourished animals, the germinal matrix area of the cerebellum, the external granular layer, was smaller on the 8th postnatal day, the same on the eleventh day, and larger on the fourteenth day when compared with that of well fed animals. At all three ages alterations could be discerned in the distribution of cells between the mitotic external mantle and nonmitotic internal matrix portions of the external granular layer.Further studies involving exchanging animals between large and small litters at various ages indicated that the time around days 4 to 8 is most sensitive to malnutrition. The results suggest a process in which malnutrition exerts its maximum effect by a slowing of cell production in the external granular layer in the initial exponential growth phase. It is likely that an adaptation occurs immediately in the external granular layer which subsequently permits a partial recovery of cerebellar growth between days 21 and 28.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 275 (1978), S. 315-317 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Table 1 Effect of graft-versus-host disease on several cerebellar growth parameters Cerebellar contents (mg) Day killed Injected cells Cerebellar weight (mg) DNA RNA Protein DNAF/ASF GVHD-producing LNC injected 9 None 63.3±1.7 0.45 ±0.02 0.37±0.01 ...
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Microglia ; Interleukin-1 ; Alzheimer’s ; disease ; Aging ; Inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Microglia-mediated inflammatory responses have been implicated in the pathogenesis of neuritic plaques in Alzheimer’s disease. The strong age association of Alzheimer’s disease incidence suggests that events in normal aging may promote such responses. We used immunohistochemistry and computerized image analysis to determine the numbers, size, activation state, and immunoreactive intensity of interleukin-1α-immunoreactive (IL-1α+) microglia in mesial temporal lobe of 20 neurologically normal individuals, 2–80 years of age. We also used Northern analysis to determine tissue levels of IL-1α mRNA in an additional 11 neurologically normal individuals aged 1 day to 78 years. IL-1α+ microglia were characterized as primed, enlarged, or phagocytic (enlarged with heterogeneous cytoplasmic contents) based on morphology. These three microglial subtypes showed significant differences in size [27 ± 1 58 ± 2 114 ± 6 (mean ± SEM) μm2/cell, respectively, P 〈 0.001 for each comparison] and in immunoreactive intensity [60 ± 1 68 ± 2 79 ± 2 (arbitrary units), respectively, P 〈 0.001 or better for each comparison]. There were significant age-associated increases in the total numbers of activated IL-1α+ microglia. Among microglial subtypes, there were significant increases in the numbers of enlarged (threefold) and especially phagocytic (elevenfold), but not primed, microglia. Tissue IL-1α mRNA levels were higher in individuals over 60 than in those less than 60 (P 〈 0.05). The age-associated increases in microglial activation were independent of postmortem interval, patient sex, and the presence of Alzheimer-type ‘senile’ changes. Age-associated increases in microglial activation and IL-1 expression may contribute to the age-associated increased risk of Alzheimer’s disease.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-6830
    Keywords: head injury ; β-APP metabolism ; β-amyloid ; apolipoprotein E
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the ε4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease. 2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of β-amyloid protein (Aβ), a protein that is thought to be central to the pathogenesis of Alzheimer's disease. 3. Recent studies have revealed an over-representation of the apoE ε4 allele in those head-injured patients displaying Aβ pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE ε4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.
    Type of Medium: Electronic Resource
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