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  • 1
    Electronic Resource
    Electronic Resource
    Mechanism of Agonist-Induced Down-Regulation and Subsequent Recovery of Muscarinic Acetylcholine Receptors in a Clonal Neuroblastoma X Glioma Hybrid Cell Line (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 52 (1989), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The mechanisms of carbachol-induced muscarinic acetylcholine receptor (mAChR) down-regulation, and recovery following carbachol withdrawal, were studied in the neuroblastoma X glioma hybrid NG108-15 cell line by specific ligand binding assays. N-[3H]Methylscopolamine ([3H]NMS) and [3H]quinuclidinyl benzilate ([3H]QNB) were used as the ligands for the cell surface and total cellular mAChRs, respectively. Exposure of cells to 1 mM carbachol for 16 h decreased the specific binding of [3H]NMS and [3H]QNB by ∼80%. Bacitracin (1–4 mg/ml) and methyl-amine (1–15 mM), inhibitors of transglutaminase and of endocytosis, prevented agonist-induced loss of surface mAChRs. Pretreatment of cells with the antimicrotubular agents nocodazole (0.1–10 μM) and colchicine (1–10 μM) prevented carbachol-induced loss of [3H]QNB binding, but not that of [3H]NMS binding. These results indicate that agonist-induced mAChR down-regulation occurs by endocytosis, followed by microtubular transport of receptors to their intracellular degradation sites. When carbachol was withdrawn from the culture medium following treatment of cells for 16 h, receptors recovered and were incorporated to the surface membrane. This recovery process was antagonized by monovalent ionophores monensin (0.1 μM) and nigericin (40 nM), which interfere with Golgi complex function. Receptor recovery was also prevented by the antimicrotubular agent nocodazole. Thus, recovery of receptors appears to be mediated via Golgi complex and microtubular transport to the surface membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1989.tb09135.x
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  • 2
    Electronic Resource
    Electronic Resource
    Implementing A Research Agenda for Complementary and Alternative Medicine* (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 55 (2004), S. 239-254 
    Details
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Complementary and alternative medicine (CAM) consists of diverse clinical interventions that are practiced because of their popularity rather than the prior demonstration of safety and efficacy required for conventional agents. CAM therapies can be grouped into five categories: biologically based therapies, manipulative and body-based interventions, mind-body interventions, "energy" therapies, and alternative medical systems. The present evidence that individual CAM interventions are efficacious is largely anecdotal, but hundreds of small trials have yielded positive results. For a few modalities, existing data are either very encouraging or else sufficient to conclude that they are ineffective. CAM interventions are presumed to be safe, yet they may not be, particularly in the case of botanical agents with inherent toxicities, significant drug interactions, or potent adulterants. The public health questions regarding CAM can only be addressed through a research agenda that defines which interventions have favorable therapeutic indices. Implementation of this agenda involves adequate characterization and standardization of the product or practice, with rigorous investigation to demonstrate its safety, mechanism of action, and efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.med.55.091902.103657
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  • 3
    Electronic Resource
    Electronic Resource
    Fine-structural Alterations in Leishmania tropica within Human Macrophages Exposed to Antileishmanial Drugs in Vitro (1983)
    Oxford, UK : Blackwell Publishing Ltd
    The @journal of eukaryotic microbiology 30 (1983), S. 0 
    Details
    ISSN: 1550-7408
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The mechanism of action of antileishmanial compounds is poorly understood. Ultrastructural changes in Leishmania tropica within human macrophages exposed in vitro to Pentostam, pentamidine, amphotericin B, WR 6026, ketoconazole, and Formycin B were examined in these experiments. In Pentostam-treated cultures, some organisms exhibited diminished definition of mitochondrial and other membranes, while other organisms had completely disintegrated. Pentostam-exposed macrophages demonstrated loss of membrane definition in the absence of further alterations; it is therefore hypothesized that impaired macrophage membrane function may contribute towards the effect of this drug against macrophage-contained organisms. Leishmania parasites in pentamidine-treated cultures initially demonstrated swollen kinetoplasts and fragmentation of the kinetoplast DNA core. The initial observed effect of the other four drugs on the parasites was cytoplasmic condensation. These ultrastructural studies suggest that all five non-antimonial drugs may have different mechanisms of action than antimony (Pentostam) against Leishmania.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1550-7408.1983.tb01421.x
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  • 4
    Electronic Resource
    Electronic Resource
    In Vivo and In Vitro Localization of Leishmania within Macrophage Phagolysosomes: Use of Colloidal Gold as a Lysosomal Label (1981)
    Oxford, UK : Blackwell Publishing Ltd
    The @journal of eukaryotic microbiology 28 (1981), S. 0 
    Details
    ISSN: 1550-7408
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The interaction of Leishmania with lysosomes within macrophages in vivo has been investigated. Lysosomes labeled with colloidal gold in vivo fused with phagocytic vacuoles containing Leishmania amastigotes within the macrophages of infected footpad tissue of BALB/c mice. This localization of Leishmania within macrophage phagolysosomes in vivo is the first confirmation for any obligate intracellulaire protozoon that parasite-lysosome interactions in vitro occur in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1550-7408.1981.tb02839.x
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  • 5
    Electronic Resource
    Electronic Resource
    Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line (1991)
    Springer
    Neurochemical research 16 (1991), S. 1121-1124 
    Details
    ISSN: 1573-6903
    Keywords: NG108-15 cells ; cyanide ; 2-deoxy glucose ; ATP depletion ; metabolic inhibition ; cyanide antidote
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG): cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased, to about 40% of control due to treatment with 0.5 mM NaCN+0.05 mM IA and 0.1 mM NaCN+20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN+20 mM 2-DG was reduced 75% and 100%, respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06–0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN+20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00966589
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  • 6
    Electronic Resource
    Electronic Resource
    Inhibition of bioenergetics alters intracellular calcium, membrane composition, and fluidity in a neuronal cell line (1994)
    Springer
    Neurochemical research 19 (1994), S. 57-63 
    Details
    ISSN: 1573-6903
    Keywords: NG108-15 cells ; ATP ; calcium ; arachidonic acid ; spin label ; membrane fluidity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of inhibited bioenergetics and ATP depletion on membrane composition and fluidity was examined in cultured neuroblastoma-glioma hybrid NG108-15 cells. Sodium cyanide (CN) and 2-deoxyglucose (2-DG) were used to block oxidative phosphorylation and anaerobic glycolysis, respectively. Endoplasmic reticulum (ER) Ca2+-pump activity measured by45Ca2+ uptake was 〉92% inhibited in intact cells incubated with CN (1 mM) and 2-DG (20 mM) for 30 min. In addition, exposure of cells to CN and 2-DG caused a 134% increased release of isotopically labeled arachidonic acid (3H-AA) or arachidonate-derived metabolites from membranes. Removal of Ca2+ from the incubation medium ablated the CN/2-DG induced release of3H-AA or its metabolites. Membrane fluidity of intact cells was measured by electron spin resonance spectroscopy using the spin label 12-doxyl stearic acid. The mean rotational correlation time (τc) of the spin label increased 49% in CN/2-DG exposed cells compared to controls, indicating a decrease in membrane fluidity. These results show that depletion of cellular ATP results in inhibition of the ER Ca2+-pump, loss of AA from membranes, and decreased membrane fluidity. We propose that impaired bioenergetics can increase intracellular Ca2+ as a result of Ca2+-pump inhibition and thereby activate Ca2+-dependent phospholipases causing membrane effects. Since neurons derive energy predominantly from oxidative metabolism, ATP depletion during brain hypoxia may initiate a similar cytotoxic mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00966729
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  • 7
    Electronic Resource
    Electronic Resource
    Prevention of muscarinic acetylcholine receptor down-regulation by chloroquine: Antilysosomal or antimuscarinic mechanisms (1989)
    Springer
    Neurochemical research 14 (1989), S. 533-535 
    Details
    ISSN: 1573-6903
    Keywords: Muscarinic receptor ; chloroquine ; antilysosomal mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the antimalarial drug chloroquine on the carbachol-induced down-regulation of muscarinic acetylcholine receptors (mAChRs) was studied in the neuroblastoma-glioma hybrid NG108-15 cells. Chloroquine, which is proposed to have both antilysosomal and antimuscarinic effects (4,11), blocked the loss of both cell surface and total mAChRs as monitored by [3H]N-methyl-scopolamine (NMS) and [3H] quinuclidinyl benzilate (QNB) bindings respectively. To the contrary, NH4Cl, only an antilysosomal agent, had no effect on the loss of surface receptors, but blocked degradation of internalized receptors following the effect of carbachol. These findings demonstrate that chloroquine prevents the agonist-induced mAChR down-regulation in NG 108-15 cells by both its antilysosomal and antimuscarinic effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00964914
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  • 8
    Electronic Resource
    Electronic Resource
    Can community mental health centers meet the challenge of HIV? a response to Knox, Davis, and Friedrich (1994)
    Springer
    Community mental health journal 30 (1994), S. 91-94 
    Details
    ISSN: 1573-2789
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02188879
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  • 9
    Electronic Resource
    Electronic Resource
    Book reviews (1993)
    Springer
    Community mental health journal 29 (1993), S. 85-88 
    Details
    ISSN: 1573-2789
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00760636
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