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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract We recently presented evidence that the reversible opening of the blood-brain barrier (BBB) by the infusion of 1.6 M mannitol into the rat internal carotid artery is mediated by a rapid stimulation of ornithine decarboxylase (ODC) activity and putrescine synthesis in cerebral capillaries. We have now investigated this hypothesis further, using isolated rat cerebral capillaries as an in vitro model of the BBB. The ODC activity of cerebral capillary preparations was enriched up to 15-fold over that of the cerebral homogenate. Hyperosmolal mannitol in physiological buffer evoked a rapid (〈15 s), concentration- and time-dependent increase in capillary ODC activity and an accumulation of putrescine and spermidine which was blocked by the specific ODC inhibitor, α- difluoromethylornithine (DFMO, 10 m M). Mannitol (1 M), as well as 2 M urea, evoked a two- to fivefold increase in the temperature-sensitive influx of 45Ca2+ and uptake of horseradish peroxidase (HRP) and 2-deoxy-D-[1-3H]glucose (DG), but not α-[1-14C]aminoisobutyrate, during a 2-min incubation. DFMO (10 mM) abolished 1 M mannitol-mediated stimulation of 45Ca2+ influx and uptake of HRP and DG, whereas 1 mM putrescine replenished capillary polyamines and reversed the DFMO effects. Mannitol (1 M)-induced stimulation of ODC activity and membrane transport processes was Ca2+-dependent and verapamil- and nisoldipine-sensitive. Phorbol myristate acetate (PMA, 10 nM), a protein kinase C activator, also evoked a two- to threefold stimulation of 45Ca2+ transport and HRP and DG uptake. This PMA effect was abolished by DFMO, suggesting involvement of rapid, ODC-controlled polyamine synthesis. The effects of 10 nM PMA and 1 M mannitol were additive, suggesting that hyperosmolal stimulation of ODC-activated polyamine synthesis does not involve protein kinase C. These data support the hypothesis that ODC-activated polyamine synthesis and Ca2+ influx (via Ca2+ channels) play a key role in mediating the effects of hyperosmolality on BBB permeability.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We investigated the role of polyamines and their regulatory enzyme ornithine decarboxylase in N-Methyl-D-aspartate-induced excitotoxicity in embryonic chick retina. N-Methyl-D-aspartate (200 μM) produced an early increase in ornithine decarboxylase activity, putrescine concentration, and Ca2+ entry, leading to selective neuronal death by 30 min. This response was attenuated by the ornithine decarboxylase inhibitor α-difluoromethylornithine and the N-methyl-D-aspartate receptor antagonist 5-aminophosphonovaleric acid. Exogenous putrescine increased intracellular putrescine and spermine levels and reversed neuroprotection by α-difluoromethylornithine, but not by 5-aminophosphonovaleric acid. N-Methyl-D-aspartate-receptor stimulation of putrescine/polyamine synthesis mediates abnormal Ca2+ entry and acute excitotoxic neuronal death. Postreceptor inhibition of the ornithine decar-boxylase/polyamine cascade by α-difluoromethylornithine may provide neuroprotection against N-methyl-D-aspartate-induced excitotoxicity.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular histology 13 (1981), S. 445-452 
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Whith the unique observation, using conventional cytochemistry, of acid phosphatase reaction production in the T-tubules of the posterior latissimus dorsi muscle of the chicken, the possibility of andocytosis of lysosomal enzymes by muscle cells came into question. After testing the substrate specificity of this T-tubular phosphatase, it was clear that the enzyme was not 5′-nucleotidase for a typical lysosomal acid phosphatase. The T-tubular enzyme hydrolysed glucose 6-phosphate and β-glycerophosphate at pH 5.0 but not cytidine-5′-monophosphate which was hydrolysed by dense bodies and autophagic vacuoles. The cytochemical evidence points to a mique phosphatase present on mucle cell membranes which apparently does not belong to the vacuolar apparatus of skeletal muscle and is not 5′-nucleotidase.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four hours following cryo-injury rat cerebral pericapillary astrocytes from the perilesional area were markedly swollen occupying 17% of the pericapillary space as compared to 11% in sham operated controls. Ornithine decarboxylase activity and polyamine levels were increased over sham controls. The astrocytic swelling, the percentage of the pericapillary space occupied by astrocytic processes, and polyamine levels were reduced to near control levels by the following: (1) α-difluoromethylornithine; (2) Ifenprodil; and (3) MK-801. α-Difluoromethylornithine is a specific inhibitor of ornithine decarboxylase, Ifenprodil is an inhibitor of the polyamine binding site on the n-methyl-d-aspartate receptor, and MK-801 is an antagonist to n-methyl-d-aspartate binding to the n-methyl-d-aspartate receptor. Addition of putrescine, the product of ornithine decarboxylase activity, reversed the effect of α-difluoromethylornithine and restored the pericapillary swelling. Putrescine did not affect the MK-801-induced reduction in pericapillary astrocytic swelling. Therefore, polyamines and the n-methyl-d-aspartate receptor modulate excitotoxic responses to cryo-injury in pericapillary cerebral astrocytes.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 204 (1982), S. 307-314 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The cells of the intervertebral disc exist in a unique environment; not only are discs subject to large mechanical loads, they are the largest avascular structures in the body. To describe the ultrastructure and age changes in cells from human nucleus pulposus, we studied these cells in individuals ranging in age from the 26th week of fetal life to 91 years. Viable chondrocyte-like cells existed in specimens from all ages. The presence of Golgi cisternae and well-developed endoplasmic reticulum in these cells suggests that they are capable of producing and maintaining the extracellular matrix. Necrotic cells were also present in all samples, and many cells which appeared viable when examined by light microscopy proved to be necrotic when examined by electron microscopy. The percentage of necrotic cells increased with age from 2% or less in fetal specimens to over 50% in adults. In addition, with age, a distinct pericellular matrix or “nest,” consisting of collagen fibrils, fine filaments, dense particles, and banded structures, formed around most cells with no apparent preference for viable or necrotic cells. Nest formation and increasing density of the cell nests may reflect accumulation of cell products.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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