[C-series gangliosides and neuronal differentiation].
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Biomedical subjects
Publications and source records attributed to H Waki.
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The effects of aging on the uptake of calcium channel blockers through brain capillaries to brain parenchyma were investigated. Two different piperazine derivatives, flunarizine and 1-[bis(fluorophenyl)-methyl]-4-(2,3,4-trimethoxybenzyl)piperazine (abbreviated as KB-2796), were orally administered to young and aged rats. The concentrations of the blockers in plasma, endothelial cells of the brain capillaries and synaptosomal fractions of the three brain regions were determined by high-performance liquid chromatography. Flunarizine was more incorporated into brain tissues than KB-2796 in both young and aged rats. The uptake efficiency of KB-2796 from the circulation to the brain decreased more remarkably than that of flunarizine in aged rats. The partition coefficients between n-octanol and water indicated that KB-2796 was less hydrophobic than flunarizine. These results suggest that the uptake of the chemicals seems to be influenced by their hydrophobicity and the age of animals given.
The lipid composition of nerve growth cone membranes isolated from rat fetal forebrain or brainstem by the sucrose density gradient method was analyzed biochemically and immunochemically. In the forebrain, growth cone membrane (GCM) contained lower levels of gangliosides than those from other heavier fractions, but it was not the case in the fetal brainstem at the same developmental stage. The distinctive features in the ganglioside composition of GCM are the predominance of GD3 and the presence of c-series gangliosides that are due to fetal expression in mammals. A unique acidic glycolipid, sulfoglucuronylparagloboside (SGPG), which is not present in adult brains, was first detected in both forebrain and brainstem GCM. Including such minor species, the ganglioside composition in forebrain or brainstem GCM was almost identical to other membrane fractions from the forebrain or brainstem. The compositional ratios of the major lipid classes in membranes, cholesterol and phospholipids, seemed to be common to forebrain GCM and brainstem GCM, as indicated by the identical values of phospholipid-to-protein (PL/Pr), cholesterol-to-protein (Ch/Pr), and cholesterol-to-phospholipid (Ch/PL) ratios for both. This study has revealed that GCM isolated from forebrain which is supposed to be at an earlier stage of neuronal differentiation than brainstem has less amounts of total gangliosides, high proportion of GD3 to GD1a and enriched c-series gangliosides as compared to brainstem GCM.
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To evaluate the effects of atrioventricular pacing interval on hemodynamics, we studied the changes in stroke volume and left ventricular filling dynamics in fourteen consecutive patients with implanted atrioventricular pacemakers using a Doppler echocardiographic technique. Twelve patients had sick sinus syndrome and 2 had complete atrioventricular block. Stroke volume was determined as the time-velocity integral of the pulsed Doppler recordings at the aortic annulus multiplied by the area of the aortic annulus obtained by 2-dimensional echocardiography. Left ventricular filling velocity was measured at the mitral annulus by the pulsed Doppler technique to provide the time-velocity integral of rapid filling (TVI-R) and that of atrial filling (TVI-A). No significant change in stroke volume was noted during the atrioventricular interval manipulation. TVI-R was greater with short atrioventricular intervals than that with the long atrioventricular intervals. On the contrary, TVI-A was greater with long atrioventricular intervals than that with short atrioventricular intervals. These results suggested that there is a compensatory mechanism in the left ventricular filling dynamics to keep the stroke volume constant despite the change in the atrioventricular interval. However, in patients with high atrial filling to rapid filling ratio (A/R), the stroke volume varied with change of atrioventricular interval, suggesting that the compensatory mechanism was not sufficient in such patients. We conclude that Doppler echocardiography is a useful, noninvasive technique to assess the changes in the hemodynamics produced by atrioventricular interval manipulation in patients with implanted atrioventricular pacemakers.
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High-performance liquid chromatographic systems have been developed which use DEAE-Iatrobeads and Aquasil SS or amino-silica gel to attain fine separation of gangliosides in a short time. Two UV-transparent solvent systems containing potassium chloride or tetramethylammonium chloride were devised and optimized, especially for the separation of polysialogangliosides.
New solvent systems consisting of acetonitrile, isopropanol and aqueous 50 mM potassium chloride or 2.5 M ammonium hydroxide were developed for the separation of gangliosides by high-performance thin-layer chromatography. These solvent systems seem to be superior for the resolution of polysialogangliosides such as tetra-, penta- and hexasialo species, as compared to chloroform-methanol-aqueous salt systems. The order of mobility of gangliosides in the ammoniacal solvent system is GD3 greater than GD1a greater than GM1 greater than GT1b greater than GD1b as compared with GM1 greater than GD3, GD1a greater than GD1b greater than GT1b in the neutral septem. A combination of these two solvent systems provides excellent two-dimensional separations of complex ganglioside mixtures. The neutral solvent system, acetonitrile-isopropanol-aqueous 50 mM potassium chloride, can be used for the separation of underivatized gangliosides by high-performance liquid chromatography on an Aquasil SS silica gel column. Ganglioside elution can be monitored at 208 nm because of the good UV-transparency of the effluent.