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  • 1
    Electronic Resource
    Electronic Resource
    Attenuation of channel kinetics and conductance by cholesterol: An interpretation using structural stress as a unifying concept (1995)
    Springer
    The journal of membrane biology 143 (1995), S. 51-63 
    Details
    ISSN: 1432-1424
    Keywords: Calcium-activated potassium channel ; Cholesterol ; Conductance ; Lateral elastic stress ; Lipid bilayers ; Lipid-channel interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The ubiquity of cholesterol in cell membranes and changes in its concentration during development, aging and in various diseases suggest that it plays an important role in modulating cell function. We examined this possibility by monitoring the effects of cholesterol on the activity of the calcium-activated potassium (BK) channel reconstituted into lipid bilayers from rat brain homogenates. Increasing the cholesterol concentration to 11% of total lipid weight resulted in a 70% reduction in channel mean open time and a reduction of the open probability of the channel by 80%. Channel conductance was reduced by 7%. Cholesterol is known to change the order state and the modulus of compressibility of bilayers. These physico-chemical changes may be translated into an overall increase in the structural stress in the bilayer, and this force may be transmitted to proteins residing therein. By examining the characteristics of the BK channel as a function of temperature, in the presence and absence of cholesterol, we were able to estimate the activation energy based on Arrhenius plots of channel kinetics. Cholesterol reduced the activation energy of the BK channel by 50% for the open to closed transition. This result is consistent with an increased stress energy in the bilayer and favors the channel moving into the closed state. Taken together, these data are consistent with a model in which cholesterol induces structural stress which enhances the transition from the open to the closed state of the channel. We suggest that this is an important mechanism for regulating the activity of membrane-integral proteins and therefore membrane function, and that the concept of structural stress may be relevant to understanding the modulation of ion channel activity in cell membranes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00232523
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  • 2
    Electronic Resource
    Electronic Resource
    Self-expanding metallic stents in the management of pyloric dysfunction after gastric pull-up operations (1999)
    Springer
    European radiology 9 (1999), S. 1123-1125 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Pylorus ; Stenosis ; Surgery complications ; Stents and prostheses ; Oesophagus ; Stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The purpose of this paper is to report the use and benefits of self-expanding metallic stents employed in pyloric dysfunction. Four patients treated with oesophagectomy and gastric pull-up for oesophageal carcinoma failed to respond to balloon dilatation for pyloric dysfunction. Three of the patients were thought to have residual tumour at sites remote from the pylorus prior to stenting, but the fourth, who had undergone surgery 8 years previously, was thought to be cured. All were treated with self-expanding metallic stents. All four patients responded well with resolution of their symptoms. Over a mean follow-up of 6 months there has been no recurrence of symptoms. Stent insertion represents a potentially valuable method of treatment in patients with post-surgical pyloric dysfunction in whom simple balloon dilatation has failed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300050804
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  • 3
    Electronic Resource
    Electronic Resource
    Microstimulation of movements from cerebellar-receiving, but not pallidal-receiving areas of the macaque thalamus under ketamine anaesthesia (1998)
    Springer
    Experimental brain research 123 (1998), S. 387-396 
    Details
    ISSN: 1432-1106
    Keywords: Key words Thalamus ; Basal ganglia ; Cerebellum ; Electrical stimulation ; Movement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The motor thalamic areas receiving input from the globus pallidus (VA) and the cerebellar nuclei (VL) appear to have different roles in the generation and guidance of movements. In order to further test these differences, we used electrical stimulation to map the ventro-anterior and ventro-lateral nuclei of the thalamus in three ketamine anaesthetised monkeys. Movements were readily evoked from VL at currents of down to 10 μA. The movements were typically multi-joint, and stimulation could evoke arm and trunk or arm and facial movement at the same current threshold. Evoked arm movements often involved multiple joints, with or without finger movements. Facial movements included the lips, tongue, jaw, eyebrows and, occasionally, the eyes. The thalamic map was topographic, but complex with at least two separate regions related to arm movement. Very few sites within the VA could stimulate movement, even at high currents. We therefore suggest that the cerebellar projections to motor regions of the cortex, which pass through the VL thalamic nuclei, have a different relationship and are closer to movement execution than the projections from basal ganglia via the ventro-anterior nucleus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050584
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  • 4
    Electronic Resource
    Electronic Resource
    Molecular Membrane Interactions of a Phospholipid Metabolite. Implications for Alzheimer's Disease Pathophysiology (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Alzheimers's disease is characterized by changes in phospholipid metabolism leading to a perturbation in the levels of phosphomonoesters, including L-Phosphoserine (L-PS). These early changes in lipid metabolism may result in a defect in membrane bilayer structure, leading to increased rates of β-amyloid formation. To investigate the effect of L-PS on membrane lipid bilayers, small angle x-ray diffraction and high resolution differential scanning calorimetry (DSC) approaches were used with liposomes composed of lecithin and cholesterol. A one-dimensional electron density profile of a control dimyristoyl phosphatidylcholine (DMPC)/cholesterol lipid bilayer with a unit cell dimension of 52 Å at 370C was generated from the x-ray diffraction data. Following incubation with 2.0 mM L-PS, a broad decrease in electron density ±4-12Å from the lipid bilayer center was observed concomitant with an increase in the width of the phospholipid headgroup electron density and a 3Å reduction in lipid bilayer width. The interactions of L-PS with DMPC lipid bilayers were concentrationdependent, highly affected by cholesterol content and reproduced in egg phosphatidylcholine/cholesterol liposomes. DSC analysis showed that millimolar (1.0-5.0 mM) L-PS levels decreased the phase transition cooperative unit size of DMPC liposomes in a highly concentration-dependent manner which was significantly greater in preparations containing 10 mol% cholesterol. These data provide direct evidence that phosphomonoester levels modulate the biophysical properties of the membrane lipid bilayer which may, in turn, lead to altered structure/function relationships in AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1996.tb34447.x
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  • 5
    Electronic Resource
    Electronic Resource
    Dissociation of Striatal GTPase and Dopamine Release Responses to Muscarinic Cholinergic Agonists in F344 Rats: Influence of Age and Dietary Manipulation (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: There is evidence that dietary lipids and age both influence neuronal membrane composition and receptor G protein-linked signal transduction, but very little information is available on the interaction between these two factors. To investigate this, we obtained striata from 2, 12, and 22-month-old male F344 rats who were fed either a high-cholesterol, high-saturated fat or low-fat diet for 1 month. The striata were assayed for muscarinic agonist-stimulated low-Km GTPase activity using 10−3M carbachol and 10−5M oxotremorine and for KCl-evoked dopamine release enhancement by 10−5M oxotremorine. Membrane cholesterol and phospholipid content and phospholipid class composition were also determined. Mature animals showed significant but divergent changes in GTPase activity and dopamine release for high-cholesterol and low-fat diets: GTPase activity decreased, whereas dopamine release increased in these groups. Alterations in GTPase activity but not in dopamine release were inversely correlated with the cholesterol/phospholipid molar ratio. Old control animals showed reductions in both GTPase activity and oxotremorine-enhanced dopamine release compared with young animals. Whereas none of the experimental diets affected GTPase activity in old animals, the low-fat diet produced a marked decrease in dopamine release. In contrast to mature and old groups, young rats showed no significant change in either GTPase or dopamine release, suggesting a relative “resistance” to such dietary lipid modulation. The observed dissociation in GTPase and dopamine release responses to diet may reflect differing effects of these diets on discrete membrane lipid domains that preferentially influence different signal transduction components. The substantial age-related differences in striatal membrane response to dietary lipid modulation may represent the effects of underlying age differences in membrane lipid metabolism, structure, and/or dynamics. Our findings support the work of other groups that have shown that brain membranes are susceptible to modification by exogenous lipids. They also suggest the need for a more systematic examination of the influence of age on the response to other types of dietary lipid changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.64062755.x
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  • 6
    Electronic Resource
    Electronic Resource
    Inhibition of Excessive Neuronal Apoptosis by the Calcium Antagonist Amlodipine and Antioxidants in Cerebellar Granule Cells (1999)
    Oxford UK : Blackwell Science Ltd
    Journal of neurochemistry 72 (1999), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neuronal cell death as a result of apoptosis is associated with cerebrovascular stroke and various neurodegenerative disorders. Pharmacological agents that maintain normal intracellular Ca2+ levels and inhibit cellular oxidative stress may be effective in blocking abnormal neuronal apoptosis. In this study, a spontaneous (also referred to as age-induced) model of apoptosis consisting of rat cerebellar granule cells was used to evaluate the antiapoptotic activities of voltage-sensitive Ca2+ channel blockers and various antioxidants. The results of these experiments demonstrated that the charged, dihydropyridine Ca2+ channel blocker amlodipine had very potent neuroprotective activity in this system, compared with antioxidants and neutral Ca2+ channel blockers (nifedipine and nimodipine). Within its effective pharmacological range (10-100 nM), amlodipine attenuated intracellular neuronal Ca2+ increases elicited by KCl depolarization but did not affect Ca2+ changes triggered by N-methyl-D-aspartate receptor activation. Amlodipine also inhibited free radical-induced damage to lipid constituents of the membrane in a dose-dependent manner, independent of Ca2+ channel modulation. In parallel experiments, spontaneous neuronal apoptosis was inhibited in dose- and time-dependent manners by antioxidants (U-78439G, α-tocopherol, and melatonin), nitric oxide synthase inhibitors (N-nitro-L-arginine and N-nitro-D-arginine), and a nitric oxide chelator (hemoglobin) in the micromolar range. These results suggest that spontaneous neuronal apoptosis is associated with excessive Ca2+ influx, leading to further intracellular Ca2+ increases and the generation of reactive oxygen species. Agents such as amlodipine that block voltage-sensitive Ca2+ channels and inhibit cellular oxidative stress may be effective in the treatment of cerebrovascular stroke and neurodegenerative diseases associated with excessive apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1999.721448.x
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  • 7
    Electronic Resource
    Electronic Resource
    Foam-buffered spherical implosions at 527 nm (1997)
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 4 (1997), S. 1379-1384 
    Details
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Creation of a low density, high temperature plasma buffer between the absorption and ablation layers of a directly driven inertial confinement fusion implosion capsule has been proposed as a means to reduce "early time" imprint from laser nonuniformities. This thermal smoothing blanket might be created from a low density foam layer wrapped around the deuterium–tritium filled microballoon. Preliminary spherical implosion tests of this concept using a polystyrene foam layer surrounding a glass microballoon were performed at the Nova laser [Rev. Sci. Instrum. 57, 2101 (1986)], using a 527 nm drive wavelength. Comparison of capsule yield and imploded core symmetry showed promising improvements in overall target performance, relative to one-dimensional undegraded hydrodynamic simulations, when the foam-buffer layer was present. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.872568
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  • 8
    Electronic Resource
    Electronic Resource
    High-intensity illumination of an exploding foil (1997)
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 4 (1997), S. 3006-3011 
    Details
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: In an experiment relevant to the fast ignitor fusion concept, a preformed plasma simulating the corona of a fusion target has been probed with laser intensities exceeding 1018 W/cm2. It is seen that the f number of the probe beam is increased as it propagates through the target plasma—a channeling of the power. The transmission and backscatter of the probe beam have been examined, and the analysis suggests anomalous absorption of laser light in shorter scale length plasmas. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.872435
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  • 9
    Electronic Resource
    Electronic Resource
    Computational study of laser imprint mitigation in foam-buffered inertial confinement fusion targets (1998)
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 5 (1998), S. 211-221 
    Details
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Recent experiments have shown that low density foam layers can significantly mitigate the perturbing effects of beam nonuniformities affecting the acceleration of thin shells. This problem is studied parametrically with two-dimensional LASNEX [G. B. Zimmerman and W. L. Kruer, Comments Plasma Phys. Controlled Fusion 2, 51 (1975)]. Foam-buffered targets are employed, consisting typically of 250 Å of gold, and 50 μm of 50 mg/cm3 C10H8O4 foam attached to a 10 μm foil. In simulation these were characteristically exposed to 1.2 ns, flat-topped green light pulses at 1.4×1014 W/cm2 intensity, bearing 30 μm lateral perturbations of up to 60% variation in intensity. Without the buffer layers the foils were severely disrupted by 1 ns. With buffering only minimal distortion was manifest at 3 ns. The smoothing is shown to derive principally from the high thermal conductivity of the heated foam. The simulation results imply that (1) the foam thickness should exceed the disturbance wavelength; (2) intensities exceeding 5×1013 W/cm2 are needed for assured stability beyond 2 ns; (3) longer foams at lower densities are needed for effective mitigation with shorter wavelength light; (4) the gold layer hastens conversion of the structured foam to a uniform plasma. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.872690
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  • 10
    Electronic Resource
    Electronic Resource
    Wavelength scaling of high-intensity illumination of an exploded foil (1998)
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 5 (1998), S. 4005-4008 
    Details
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A preformed plasma simulating the corona of a fast ignitor target has been probed with 527 nm and 1054 nm lasers exceeding the critical power for ponderomotive electron cavitation. For both colors, the f number of the probe beam is increased as it propagates through the plasma. Transmission of the diffraction-limited beams is higher for the green than for the 1 μm case. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.873122
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