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  • 1
    Electronic Resource
    Electronic Resource
    Critical reevaluation of proximity effects in the barton oxidation and related intramolecular reactionsTaken from S. Vijayakumar, PhD Thesis, University of Toledo, Toledo, Oh, 1992. (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 14 (1993), S. 1313-1319 
    Details
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: The limiting factor to account for the increased rate of intramolecular reactions between functional groups as opposed to their intermolecular counterparts can and has been explained both by proximity effects and by activation energy. Neither explanation has emerged as the single most important reason in all or even the majority of cases studied. We have therefore reexamined the spatiotemporal hypothesis of Menger and the transition-state energy approach of Houk on a consistent set of compounds subjected to the Barton oxidation or related reactions in an effort to more clearly define the reasons for the proximity effect. For the 26 structures studied, neither hypothesis provides a consistent, quantitative explanation although the transitionstate energy hypothesis offered the most promise. © John Wiley & Sons, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcc.540141107
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  • 2
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    Teaching psychology : a step by step guide (2000)
    Mahwah, N.J
    Details
    Keywords: Psychology, Study and teaching.
    ISBN: 1-410-61163-9
    URL: http://www.netLibrary.com/urlapi.asp?action=summary&v=1&bookid=124575
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    E-Book (German National Licenses)
  • 3
    Electronic Resource
    Electronic Resource
    Chronic subdural haematoma following epidural anaesthesia, presenting as puerperal psychosis (1993)
    Oxford, UK : Blackwell Publishing Ltd
    BJOG 100 (1993), S. 0 
    Details
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-0528.1993.tb14276.x
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  • 4
    Electronic Resource
    Electronic Resource
    Staurosporine Induces Programmed Cell Death in Embryonic Neurons and Activation of the Ceramide Pathway (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We activated the death pathway in embryonic chick cerebral hemisphere neuron (E7CH) cultures with staurosporine (0.1–1.0 µM) and observed the morphological changes, DNA laddering patterns, and DNA fragmentation (determined by Hoechst 33258 dye) associated with apoptosis. N-Acylsphingosine (C2-ceramide), a soluble ceramide analogue, was also able to induce apoptosis in these cells with the same characteristics and in the same time frame. We then observed that staurosporine was effective in inducing hydrolysis of sphingomyelin to ceramide as measured by a threefold increase in ceramide mass and increased incorporation of [3H]-palmitate into ceramide, concurrent with activating the cell death program. Furthermore, the coaddition of a specific ceramidase inhibitor, oleoylethanolamine (15 µM), enhanced the formation of ceramide as well as the degree of DNA fragmentation and cell death. Exogenous addition of sphingomyelinase activated the death pathway whereas ceramide glycanase did not, and inhibitors of sphingomyelin or protein synthesis failed to block this type of killing. Our data suggest that the formation of ceramide from sphingomyelin is a key event in staurosporine-induced and potentially all programmed cell death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.66041418.x
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  • 5
    Electronic Resource
    Electronic Resource
    Selective Inhibition of Cholesterol Biosynthesis in Brain Cells by Squalestatin 1 (1995)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 65 (1995), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of squalestatin 1 (SQ) on squalene synthase and other enzymes utilizing farnesyl pyrophosphate (F-P-P) as substrate was evaluated by in vitro enzymological and in vivo metabolic labeling experiments to determine if the drug selectively inhibited cholesterol biosynthesis in brain cells. Direct in vitro enzyme studies with membrane fractions from primary cultures of embryonic rat brain (IC50 = 37 nM), pig brain (IC50 = 21 nM), and C6 glioma cells (IC50 = 35 nM) demonstrated that SQ potently inhibited squalene synthase activity but had no effect on the long-chain cis-isoprenyltransferase catalyzing the conversion of F-P-P to polyprenyl pyrophosphate (Poly-P-P), the precursor of dolichyl phosphate (Dol-P). SQ also had no effect on F-P-P synthase; the conversion of [3H]F-P-P to geranylgeranyl pyrophosphate (GG-P-P) catalyzed by partially purified GG-P-P synthase from bovine brain; the enzymatic farnesylation of recombinant H-p21ras by rat brain farnesyltransferase; or the enzymatic geranylgeranylation of recombinant Rab1A, catalyzed by rat brain geranylgeranyltransferase. Consistent with SQ selectively blocking the synthesis of squalene, when C6 glial cells were metabolically labeled with [3H]mevalonolactone, the drug inhibited the incorporation of the labeled precursor into squalene and cholesterol (IC50 = 3–5 µM) but either had no effect or slightly stimulated the labeling of Dol-P, ubiquinone (CoQ), and isoprenylated proteins. These results indicate that SQ blocks cholesterol biosynthesis in brain cells by selectively inhibiting squalene synthase. Thus, SQ provides a useful tool for evaluating the obligatory requirement for de novo cholesterol biosynthesis in neurobiological processes without interfering with other critical reactions involving F-P-P.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.65031365.x
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  • 6
    Electronic Resource
    Electronic Resource
    Regulation of Tyrosine Hydroxylase Gene Expression in the Rat Carotid Body by Hypoxia (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 58 (1992), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The activity (Vmax) of tyrosine hydroxylase (TH; EC 1.14.16.2), the rate limiting enzyme in the synthesis of catecholamines, is increased in carotid body, superior cervical ganglion, and the adrenal medulla during hypoxia (i.e., reduced Pao2). The present study was undertaken to determine if the increase in TH activity in these tissues during hypoxia is regulated at the level of TH mRNA. Adult rats were exposed to hypoxia (10% O2) or room air for periods lasting from 1 to 48 h. The carotid bodies, superior cervical ganglia, and adrenals were removed and processed for in situ hybridization using 35S-labeled oligonucleotide probes. The concentration of TH mRNA was increased by hypoxia at all time points in carotid body type I cells, but not in cells of either superior cervical ganglion or adrenal medulla. The increase in TH mRNA in carotid body during hypoxia did not require innervation of the carotid body or intact adrenal glands. In addition, hypercapnia, another physiological stimulus of carotid body activity, failed to induce an increase in TH mRNA in type I cells. Our findings suggest that hypoxia stimulates TH gene expression in the carotid body by a mechanism that is intrinsic to type I cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb11376.x
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  • 7
    Electronic Resource
    Electronic Resource
    Extracellular N-Acetylaspartate in the Rat Brain: In Vivo Determination of Basal Levels and Changes Evoked by High K+ (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 62 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The purpose of this study was to determine the extracellular concentrations of N-acetylaspartate (NAA) in the rat cerebral cortex, striatum, and hippocampus of halo-thane-anaesthetised rats by intracerebral microdialysis, and to examine the effects of high K+-induced local depolarisation, which provokes synchronous neurotransmitter release, cell swelling, and acid-base changes. Basal levels of NAA in the extracellular fluid (EOF) were determined by the zero net flux method. Tissue levels of NAA in the cortex, striatum, and hippocampus were 8.4, 5.7, and 7.2 mmol/kg, respectively. The corresponding extracellular concentrations of NAA were much lower (35.1, 83.7, and 23.0 tiM). High tissue/ECF concentration ratios may suggest little release or leakage of NAA under basal conditions, and potent reuptake mechanisms for NAA in the cellular membrane of CNS cells. There was no change in ECF NAA during K+-induced local depolarising stimuli produced in the striatum, but NAA levels consistently increased after the K+ stimuli, irrespective of whether or not Ca2+ was present in the perfusion medium. These data confirm that NAA is not a neurotransmitter and suggest strongly that NAA is not directly involved in the release and reuptake or metabolism of neuroactive compounds. The increase of NAA in the ECF immediately after K+ stimulation may reflect an involvement in brain osmoregulation and/or acid-base homeostasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.62062349.x
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  • 8
    Electronic Resource
    Electronic Resource
    Receptor-Coupled Phosphoinositide Hydrolysis in Human Retinal Pigment Epithelium (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 56 (1991), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of 3H-inositol phosphates in the presence of 10 mM Li+. Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC50 of 60 μM; stimulation was linear up to 60 min. This activation likely occurred via the M3 muscarinic cholinergic receptor based on the IC50 values for 4-diphenylacetoxy-N-methylpiperidine methiodide (0.47 nM), pirenzepine (280 nM), and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (1.4 μM). Carbachol-mediated PPI hydrolysis was decreased by 80% in the absence of extracellular Ca2+. Histamine stimulated PPI turnover in a linear manner by 180% with an EC50 of 20 μM by the H1 histaminergic receptor. Serotonin, glutamate, norepinephrine, and dopamine were inactive. In human RPE, the resting cytoplasmic Ca2+ concentration, as determined by fura-2 fluorescence, was 138 ± 24 nM. On the addition of carbachol, there was a 180% increase in peak intracellular Ca2+; addition of histamine increased intracellular Ca2+ by 187%. These results suggest receptor-mediated, inositol lipid hydrolysis is coupled to intracellular Ca2+ flux in human RPE.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1991.tb03471.x
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  • 9
    Electronic Resource
    Electronic Resource
    Comparison of (R)-[3H] Tomoxetine and (R/S)-[3H] Nisoxetine Binding in Rat Brain (1995)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 64 (1995), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: (R)-[3H]Tomoxetine is a radioligand that binds to the norepinephrine (NE) uptake site with high affinity but also binds to a second, lower-affinity site. The goal of the present study was to identify the nature of this low-affinity site by comparing the binding properties of (R)-[3H]tomoxetine with those of (R/S)-[3H]nisoxetine, a highly selective ligand for the NE uptake site. In homogenate binding studies, both radioligands bound to the NE uptake site with high affinity, whereas (R)-[3H]tomoxetine also bound to a second, lower-affinity site. The autoradiographic distribution of binding sites for both radioligands is consistent with the known distribution of NE-containing neurons. However, low levels of (R)-[3H]-tomoxetine binding were seen in the caudate-putamen, globus pallidus, olfactory tubercle, and zona reticulata of the substantia nigra, where (R/S)-[3H]nisoxetine binding was almost absent. In homogenates of the caudate-putamen, the NE uptake inhibitors desipramine and (R)-nisoxetine and the serotonin (5-HT) uptake inhibitor citalopram produced biphasic displacement curves. Autoradiographic studies using 10 nM (R)-nisoxetine to mask the binding of (R)-[3H]tomoxetine to the NE uptake site produced autoradiograms that were similar to those produced by [3H]citalopram. Therefore, (R)-[3H]tomoxetine binds to the NE uptake site with high affinity and the 5-HT uptake site with somewhat lower affinity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.64062792.x
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  • 10
    Electronic Resource
    Electronic Resource
    Carcinostatic activity of thiosemicarbazones of formyl heteroaromatic compounds. VI. 1-Formylisoquinoline derivatives bearing additional ring substituents, with notes on mechanism of action (1970)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 13 (1970), S. 1117-1124 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00300a024
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