Effects of eicosapentaenoic acid on hemostatic function and serum lipids in humans.
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Biomedical subjects
Publications and source records attributed to Y Tamura.
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Flow velocities at the right ventricular outflow tract were recorded for 36 patients including 12 with pulmonary hypertension. Doppler indexes [right ventricular preejection period (RPEP), right ventricular ejection time (RET), right ventricular acceleration time (RAT), RPEP/RET, RET/RAT] were calculated from flow velocity profiles, and noninvasive estimation of pulmonary hypertension was attempted using these indexes. The etiology of ejection flow velocity in pulmonary hypertension was studied using a simulation model. The following results were obtained. RAT shortened proportionately with an increase of pulmonary arterial pressure. RET/RAT correlated most significantly with pulmonary arterial pressure (r = 0.83, p less than 0.001). RET/RAT correlated inversely with stroke volume (SV) (r = -0.48, p less than 0.01); therefore, attention should be paid to SV, when estimating pulmonary arterial pressure, using the value of RET/RAT. The diagnostic value for pulmonary hypertension using RET/RAT was excellent; the predictive accuracy was 100%, sensitivity 75%, and specificity 100%, and it was possible to evaluate pulmonary hypertension using this method. According to the simulation model, an increase of both the pulmonary pulse wave velocity and the reflection of the pulse wave made the interval between the onset and the time of the peak flow velocity shorter. A flow velocity pattern similar to that of pulmonary hypertension was obtained.
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The ATPase activity, light chains and isoenzymes of myosin from specialized myocardial tissue (the A-V node, bundle of His, and right and left bundle branches) of bovine heart were compared with those of atrial and ventricular myosins. The order of Ca2+-activated ATPase activity was atrial greater than specialized myocardial tissue greater than ventricular myosin. SDS-polyacrylamide gel electrophoresis showed that myosin from the specialized myocardial tissue contained the light chains of both atrial and ventricular myosins. On the other hand, the specialized myocardial tissue contained one V3 isomyosin and showed no difference from ventricular myocardial tissue on pyrophosphate gel.
In order to measure muscle stiffness changes with a high time resolution and with minimal disturbance to the contractile mechanism per se, we constructed an apparatus with which the propagation velocity of ultrasonic waves (MHz region) in the longitudinal or transverse direction was measured to serve as a measure of muscle stiffness. The longitudinal muscle stiffness started to increase on stimulation before the onset of isometric force, and reached a maximum before the peak twitch force. Analysis of experimental data indicated that, during an isometric tetanus, the increment of muscle longitudinal stiffness was about 6 X 10(7)N/m2, a value similar to those obtained by Truong (1974) and Ford et al. (1981) with sinusoidal vibrations (3 kHz) and length steps respectively. This suggests that the increment of muscle longitudinal stiffness during the activation of the contractile system results from the recruitment of an almost non-dispersive elastic component. In the case of transverse muscle stiffness, on the other hand, it started to decrease on stimulation before the onset of isometric force, and reached a minimum before the peak twitch force. Possible causes of this unexpected result is discussed in relation to the molecular mechanism of muscle contraction.
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The protective antigen present on the flagella of Clostridium chauvoei was studied by the mouse protection test. A partially purified flagella preparation (PPF) showed protective antigenicity after two intraperitoneal injections of 2 micrograms as protein, while the protective antigenicity of nonflagellated mutants (NFM) was 100-fold less than that of the flagellated parent strain. Although the protective effect of antisera against the whole cells and PPF, in terms of ED50 values, was mostly lost after absorption with the parent strain, that of antisera after absorption with NFMs showed no appreciable loss. These results suggest that the flagella of Cl. chauvoei play some role in inducing protective immunity in mice.
Specific antiflagellar serum of Clostridium chauvoei showed a powerful protective effect which prevented bacterial growth in the liver, but not in infected muscle, against intramuscular challenge with calcium chloride-activated spores in normal mice. No protective effect was observed in mice with polymorphonuclear leucocytes depleted by cyclophosphamide treatment. The antiflagellar serum had approximately the same protective effect in mice with macrophages blocked selectively by carrageenan as it did in normal mice. We suggest that the antiflagellar serum exerted its effect by opsonic function and that opsonized C. chauvoei was eliminated mainly by polymorphonuclear leucocytes rather than by macrophages.
The regulation of cholesterol metabolism in rat adrenal glands, especially the effect of ACTH, cholesterol, and corticosteroids on acyl-coenzyme A (CoA) synthetase and cholesterol ester hydrolases was investigated. A significant increase in acyl-CoA synthetase activity and decrease in cholesterol ester hydrolase activities were observed in 24-h hypophysectomized rats. Acute injection of ACTH, however, reversed these changes, whereas dexamethasone administration had no effect. When 4-aminopyrazolo[3,4-d]pyrimidine was given to rats, adrenal cholesterol ester content and the acyl-CoA synthetase activity declined and the activities of the cholesterol ester hydrolases were increased in association with the rise of plasma ACTH concentration. When dexamethasone, which suppresses ACTH secretion, was simultaneously administered with 4-aminopyrazolo[3,4-d]pyrimidine no changes except for a decrease in plasma cholesterol level occurred. In hyperlipidemic rats the acyl-CoA synthetase activity increased when a high cholesterol diet was given and the plasma cholesterol level was increased. These results suggest that acyl-CoA synthetase is under the influence of ACTH and also the plasma cholesterol concentration, and that cholesterol ester hydrolases are mainly regulated by ACTH.
We examined the effects of serum from a patient with pseudohypoparathyroidism type II and Sjögren's syndrome on renal function in rats. Infusion of 50-100 mg of the patient's immunoglobulin G (IgG) fraction inhibited the PTH-induced increase in urinary phosphate excretion, but had no effect on the PTH-induced increase in urinary cAMP excretion. Infusion of the IgG fraction obtained from the sera of control subjects did not affect PTH-induced increases in urinary excretion of either cAMP or phosphate. Binding of the patient's serum IgG fraction to the membrane of isolated rat renal cortical tubules was observed by immunofluorescent techniques. We conclude that the IgG fraction from the serum of this patient with pseudohypoparathyroidism type II and Sjögren's syndrome contains an autoantibody(ies) reacting with a component(s) of renal tubular plasma membranes and blocking PTH-induced phosphaturia.
We evaluated long-term combined vasodilator therapy (hydralazine or ecarazine + isosorbide dinitrate) in 29 patients with chronic congestive heart failure resistant to the optimal conventional therapy. There were 24 men and 5 women, aged 28 to 76 years (mean 52 y/o). The etiology of heart failure was congestive cardiomyopathy in 24 patients, ischemic cardiomyopathy in 4 patients and advanced mitral regurgitation due to calcified mitral annulus in 1 patient. There were 21 patients in NYHA class III and 8 patients in NYHA class IV. All patients continued their previous therapeutic regimen during the period of this study. Hemodynamic measurements were performed with a triple lumen flow-directed balloon-tipped catheter in 20 patients to evaluate the effects of vasodilator therapy. In the rest of 9 patients, heart rate, blood pressure, chest X-ray examination for heart size (CTR) and M-mode echocardiograms for ejection fraction (EF) were monitored. The hemodynamic responses to the combined vasodilator therapy in 20 patients showed significant decreases in afterload and preload concomitant with an increase in cardiac output. The noninvasive evaluation of combined vasodilator therapy in 9 patients resulted in significant improvement in CTR and EF. We also noted a significant improvement in their symptoms of 29 patients. Side effects and drug toxicity were uncommon during vasodilator therapy. It is concluded that the combined vasodilator therapy is most useful adjunctive therapy in the management of severe refractory heart failure. Moreover, long-term nonparenteral vasodilators can be administered even at outpatient clinic without hemodynamic monitoring.
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Early alterations in fluid, electrolytes, and their regulating hormones were investigated in men exposed to 6,000 m simulated altitude (2 h-ascent, 2 h-sojourn, 2 h-return). Hematocrit and serum protein rose with elevated serum osmolality and reduced urine flow upon arrival at 6,000 m, suggesting decreased plasma volume probably due to hypotonic fluid shift to intracellular spaces. Serum K declined reflecting respiratory alkalosis. The exposure raised plasma antidiuretic hormone (ADH), plasma renin activity (PRA), serum cortisol and aldosterone. Increases both in ADH and aldosterone showed close correlations with that in cortisol, suggesting that ADH may be elevated by hypoxic stress in addition to elevated serum osmolality and decreased plasma volume, and that increased secretion of adrenocorticotropin may be the main cause of increased aldosterone, though PRA involvement cannot be excluded. These rises in ADH and aldosterone may act to retain body water, and the latter may exaggerate alkalosis; thus, these hormonal changes may be related to acute mountain sickness.