Biomedical subjects
Publications and source records attributed to M Kihara.
Explore the source record for details and available documents.
The changes of hemodynamics were measured in spontaneously hypertensive rats (SHR) of increasing ages. Male SHR and Wistar rats of the Kyoto strain (WKY) at 4, 12, 24 and 48 weeks of age were used. The right jugular vein and the left femoral artery were cannulated and a thermistor was placed in the ascending aorta. After 24-hour rest, heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were measured. The ratio of left ventricular weight (LVMI) of 4 week-old SHR had already increased significantly when compared to WKY. The HR in 4-week-old SHR was significantly higher than WKY. The increased HR in young SHR indicates the hypersensitivity of the sympathetic nervous system. Increased CO in 4 week-old SHR was due to high HR. The ratio of heart work to left ventricular mass (HW/LVM) of SHR at all age groups was not different from that of WKY, although the ratio of heart work to body weight (HWI) had a tendency to rise in SHR as compared to that in WKY. Our conclusion is that the development of LVM adapts to HW.
Effects of synthetic alpha human atrial natriuretic polypeptide (alpha-hANP) on diuresis, natriuresis and mean arterial blood pressure (MAP) were compared between 4-5 month-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) under ether anesthesia. In both groups, the peptide injected (0.5 micrograms/100g body weight, i.v.) caused potent (about ten fold), rapid and short-acting (for 15 min) increases in sodium (Na+) and chloride excretions and also an increase in urine flow and potassium excretion with lesser magnitude. Although ratios of the maximum response to basal value were much the same, net increases in urine flow and Na+ output were significantly greater in SHR than in WKY. As to the effect on MAP, a rapid (within 2 min) fall observed in the two groups. These results suggest that the atrial natriuretic peptide may be involved in the altered regulatory mechanism of fluid and electrolyte balance in SHR models with genetic hypertension.
Explore the source record for details and available documents.
A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10-year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P less than 0.05); the mean survival time of the IOR group was 4.6 +/- 2.6 (SD) and that of the control group 2.5 +/- 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.
Using a synthetic common carboxy-terminal fragment of alpha-human atrial natriuretic polypeptide (alpha-hANP) and alpha-rat atrial natriuretic polypeptide (alpha-rANP), we have produced an antiserum for alpha-ANP(17-28) and established a radioimmunoassay (RIA) for alpha-ANP that recognizes alpha-hANP and alpha-rANP equally. High performance gel permeation chromatography coupled with the RIA revealed that alpha-hANP-like immunoreactivity (alpha-hANP-LI) in the human atrium consists of three major components, gamma-hANP, alpha-hANP and another. On the other hand, alpha-rANP-LI in the rat atrium comprised at least two components, 13K alpha-rANP-LI and 3K-5K alpha-rANP-LI, which were presumably gamma-rANP and beta-rANP, respectively. Thus, considerable amounts of gamma-hANP and gamma-rANP are present in human right auricles and rat atria, respectively. The RIA established in this study provides a useful tool to investigate the pathophysiological significance of alpha-ANP and related peptides in cardiovascular disorders and shows that gamma-ANP is not only a precursor of alpha-ANP but acts as an important hormone.
A series of digitoxigenin glycosides was studied: five with beta-D-sugars varying stepwise in sugar structure from beta-D-digitoxose to beta-D-galactose, including one beta-D/alpha-D pair. I50 values for these glycosides and digitoxigenin were determined with hog kidney Na+, K+-ATPase. These data suggest a major and unexpected role for 4'-OH conformation in the sugar. All the glycosides with an equatorial 4'-OH were more active than the two with the 4'-OH axial [digitoxigenin beta-D-galactoside (6) I50 = 6.45 X 10(-8) M; digitoxigenin 2'-deoxy-alpha-D-ribo-hexopyranoside (alpha-3a) I50 = 9.33 X 10(-8) M; digitoxigenin I50 = 1.17 X 10(-7) M]. Stereochemistry of the 3'-OH had much less of an activity role than that of the 4'-OH, in contrast to existing models of "sugar-site" binding.
This study was designed to evaluate trace metal metabolism in adults with thyroid diseases. Erythrocyte zinc values were significantly lower than normal in hyperthyroidism and higher in hypothyroidism. A significantly higher than normal urinary excretion of zinc was observed in hyperthyroidism. The mean concentrations of plasma and erythrocyte copper were significantly above normal in hyperthyroidism. Plasma selenium levels were significantly lower than normal in hyperthyroidism. No statistically significant difference was found in plasma zinc, erythrocyte manganese, or urine copper values between patients with thyroid diseases and healthy controls. The erythrocyte manganese content correlated well with thyroxine and triiodothyronine levels. Plasma prealbumin and retinol-binding protein correlated well with the erythrocyte zinc content but not with plasma zinc levels. There was no correlation between erythrocyte superoxide dismutase activity and erythrocyte copper or zinc concentrations. The results of this study suggest that the metabolism of zinc, copper, manganese, and selenium is abnormal in thyroid diseases.
The usefulness of the thermodilution method for measuring cardiac output (CO) was evaluated in awake rats by comparison with electromagnetic flowmetry. CO was measured in 3- and 6-month-old conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The correlation co-efficient between CO obtained by the two methods was 0.66 (p less than 0.01). Although CO values obtained by the thermodilution technique tended to be overestimated in comparison with those determined by electromagnetic flowmetry, this method was shown to be useful for measuring CO in unanesthetized rats because of its technical simplicity. Left ventricular mass (LVM) and the ratio of CO to LVM were significantly greater in SHR than in WKY at both ages and CO/LVM increased with increasing age in SHR. The ratio of heart work (HW) to body weight (HW/BW) was increased only in 3-month-old SHR compared with WKY and there was no difference in HW/LVM in 3- and 6-month-old SHR compared with age-matched WKY. The present results suggest that the development of cardiac hypertrophy in SHR is an adaptation to the increased HW due to high afterload.
'Aliquot cups' a newly devised tool for collecting 24-hour urine samples were useful and accurate enough for the estimation of individual 24-hour excretion of sodium and potassium. Data from 24-hour collections for 31 days for 5 healthy volunteers showed relatively large intra- and inter-individual variation. These data suggest that at least 5 consecutive days of urine collection would be needed to make a reasonable estimate of daily intake.
Explore the source record for details and available documents.
Experimental studies in animals and epidemiological studies have suggested that the interaction between genetic and environmental factors is important in hypertension associated with excess salt intake and other dietary factors such as K, protein and fatty acid intake greatly modify the effect of salt on blood pressure in individuals with low or high salt sensitivity. Thus, the detection of salt sensitivity and the modification of salt intake as well as other dietary factors are expected to contribute to the primary prevention of cardiovascular diseases associated with hypertension.
The genetically hypertensive rat models, spontaneously hypertensive rats (SHR) and especially stroke-prone SHR (SHRSP), both develop arterial fat deposits quickly when fed high cholesterol diets. Therefore the morphological and functional characteristics of cultured vascular smooth muscle cells (SMC) from the aorta of SHR, SHRSP and normotensive Wistar-Kyoto (WKY) rats have been compared in order to demonstrate the common cellular mechanisms which induce hypertension and atherosclerosis. Cultured SMC became differentiated after short-term foetal calf serum exclusion from the medium, and despite the general concept of their noncontractility there was opticometric evidence that subcultured SMC contract spontaneously. Smooth muscle cells from SHR, but especially from SHRSP, showed enhanced proliferation which was inhibited by a Ca-antagonist, and accelerated lipid incorporation. It is concluded that these SMC are primarily predisposed to hypertension as well as to atherosclerosis.
The synthesis and properties of a radiolabeled glycoside photoaffinity probe, [3H]-(3 beta,5 beta,14 beta, 20E)-24-azido-3-[(2,6-dideoxy-beta-D-ribo-hexopyranosyl) oxy]-14-hydroxy-21-norchol-20(22)-en-23-one, containing the photoactive group at the C-17 side chain of the steroid moiety are reported. The molecule binds to the sodium- and potassium-activated adenosinetriphosphatase from porcine kidney outer medulla under type II binding conditions [5 mM MgCl2, 3 mM phosphate, 2 mM ethylenediaminetetraacetic acid, 30 mM tris(hydroxymethyl)aminomethane, pH 7.2, 37 degrees C] in the dark with an equilibrium dissociation constant of (1.4 +/- 0.3) X 10(-7) M. Ultraviolet irradiation of a solution of enzyme plus 3H-labeled probe, followed by analysis of covalently incorporated radiolabel, shows ouabain-displaceable labeling exclusively of the alpha subunit of the sodium- and potassium-activated adenosinetriphosphatase. These data indicate that the binding site of the C-17 side group of cardiac glycosides is located on or near the alpha subunit of this enzyme.
Five cardioactive steroid genins 1a to 5a of widely varying C17 beta-side groups were converted by modified Koenigs-Knorr reactions into the corresponding beta-D-glucosides 1c to 5c and beta-D-galactosides 1e to 5e. The genins included digitoxigenin (3 beta, 14-dihydroxy-5 beta, 14 beta-card-20-(22)-enolide, 1a); (20R)-20, 22-dihydrodigitoxigenin (3 beta, 14-dihydroxy-5 beta, 14 beta, 20R-cardanolde, 2a); 3 beta, 14-dihydroxy-22-methylene-5 beta, 14 beta, 20S-cardanolide (3a); methyl 3 beta, 14-dihydroxy-5 beta, 14 beta-pregn-20(E)-ene-21-carboxylate (4a); and methyl 3 beta, 14-dihydroxy-21-methylene-5 beta, 14 beta-pregnane-21-carboxylate (5a).
Most of apogalanthamine analogs were more specific in alpha-adrenolytic activity than in anti-serotonin activity. In this report, 1,2,11-trimethoxy-N-methyl-5,6,7,8-tetrahydrodibenz[c,e]azocine(abbreviated as K-35) was found to be stronger in activity against serotonin (pA2 = 7.11 +/- 0.08) than against adrenaline (pA2 = 6.24 +/- 0.06). Apogalanthamine analogs have a tetrahydrodibenz[c,e]azocine structure, in which one benzene can be regarded as a part of benzylamine and other as a part of phenethylamine. From the pharmacological point of view, various azocine compounds were tested, the phenethylamine in the azocine structure is demonstrated to contribute toward the alpha-adrenolytic activity and the benzylamine having two methoxy groups contributes toward the anti-serotonin activity.
Effects of low concentrations of guanethidine, bretylium and tetracaine were comparatively studied with regard to inhibitory responses of rabbit ileum to periarterial nerve stimulation at 5, 10 and 20 Hz. Guanethidine 2 X 10(-7) to 10(-6) M and bretylium 3 X 10(-6) to 3 X 10(-5) M dose-dependently and preferentially reduced responses to lower frequencies, whereas tetracaine 10(-5) to 3 X 10(-5) M reduced responses, in a dose- and frequency-dependent manner. In conclusion, the mode of adrenergic neuron blocking action of guanethidine and bretylium differs from that of local anesthetics.
Explore the source record for details and available documents.