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  • Articles: DFG German National Licenses  (3)
  • 1985-1989  (2)
  • 1975-1979  (1)
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  • Articles: DFG German National Licenses  (3)
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  • 1
    Electronic Resource
    Electronic Resource
    CYCLIC NUCLEOTIDE PHOSPHODIESTERASE OF HUMAN CEREBROSPINAL FLUID (1975)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 25 (1975), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Cyclic 3′,5′-AMP (cAMP) and cyclic 3′,5′–GMP (cGMP) phosphodiesterase activities were found in human cerebrospinal fluid (CSF) using low substrate concentration (0.4μM). More rapid hydrolysis of cGMP than that of cAMP was observed in human CSF. However, cGMP hydrolytic activity of CSF was very much lower (0.3 pmol/min/ml CSF) than that of human cerebral cortex (33.7 nmol/min/g wet cortex). The pH optimum was found to be 8.0 (cGMP phosphodiesterase) and 7.5 (cAMP phosphodiesterase). The maximum stimulation of both cAMP and cGMP phosphodiesterase was achieved at 4 mM-MgCl2. Cyclic AMP had relatively little effect on the hydrolysis of cGMP in CSF and the cortex, while cGMP inhibited hydrolysis of cAMP in both tissues. Snake venom was found to stimulate cAMP and cGMP phosphodiesterase activity of CSF, by 60% and 110% respectively. This stimulation by snake venom was also observed in the cortex phosphodiesterase, but was not observed in human plasma or thyroid phosphodiesterase. When CSF was applied to Sepharose 6B column, cGMP phosphodiesterase was separated into three different molecular forms. A plot of activity against substrate concentration using peak I (largest molecular size) revealed a high affinity (Km= 2.6μM) and a low affinity (Km= 100μM) for cAMP suggesting the existence of at least two molecular forms of the enzyme. On the other hand, using a cGMP as substrate the only one Km value (1.90 μm) was obtained. These Km values of CSF enzymes described above were close to those obtained from human cerebral cortex preparations. The enzyme under peak I corresponded to the cortex enzyme when judged from its molecular size and stimulation by snake venom. It seems likely from our results that at least a part of CSF phosphodiesterase originates from the central nervous system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1975.tb07692.x
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs (1988)
    Springer
    Acta neurochirurgica 90 (1988), S. 53-59 
    Details
    ISSN: 0942-0940
    Keywords: Calcium antagonist ; chronic cerebral vasospasm ; HA 1077 ; subarachnoid haemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nefedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10−6 M HA 1077 for the “intracranial” basilar and middle cerebral arteries, while a 10−5 M was needed to obtain the same effect for the “extracranial” common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the “two haemorrhage” model of Varsoset al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5–3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20–30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time. Such spasmolytic effects by intravenous administration could not have been obtained with the usual calcium channel blockers. HA 1077 may be suitable for the treatment of a vasospasm in humans as well.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01541267
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Quantitative radioautographic study of intracellular localization of calmodulin antagonist, W-7, in Chinese-hamster ovary cells (1985)
    Springer
    Histochemistry and cell biology 82 (1985), S. 75-80 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The purpose of the present study was to analyse quantitatively the localization of calmodulin antagonist, n-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) in CHO-Kl cells. The cultured CHO-Kl cells were labelled with 1 (16.7 μM), 2 (33.4 μM), 5 (83.5 μM) and 10 μCi/ml (167 μM) tritiated W-7. Some cells were preincubated in 10, 50 and 100 μM unlabelled W-7 for 30 min and then labelled with 2 or 5 μCi/ml tritiated W-7 for 1 h. The cells were doubly fixed in glutaraldehyde and osmium-tetroxide solution, and embedded in Epon. For light-microscopic radioautography, 2 μm-thick sections were wet mounted with radioautographic emulsion and exposed for 1 month. The radioautograms showed that large numbers of silver grains were mainly localized in the cytoplasm as well as in the nucleus. Quantitative analysis demonstrated that, in both the cytoplasm and nucleus, the number of silver grains was dependent on the concentration of the administered tritiated W-7 and the number was dramatically decreased by the pretreatment of unlabelled W-7. These results show that, in CHO-Kl cells, the W-7 binding sites are saturable. It is concluded that W-7 may get into CHO-Kl cells and be bound to a specific protein that may be calmodulin protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00502093
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    Paper (German National Licenses)
    Fulltext
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