Biomedical subjects
T Satake
Publications and source records attributed to T Satake.
Vasodilative effect of nicorandil on coronary artery.
Vasodilative effects of nicorandil (2-nicotinamidoethylnitrate) and verapamil were compared using isolated canine coronary arterial strips contracted with either high potassium or prostaglandin F2 alpha (PGF2 alpha). When the vasodilative effects of these drugs were determined at 15 min after the application, nicorandil induced a dose-dependent relaxation of the strips contracted with high K. Vasodilative effect of nicorandil was inversely proportional to the concentration of K used to contract the arteries, showing 82 +/- 3.0% (mean +/- SE) and 21 +/- 3.6 of relaxation at the highest concentration of this drug (10(-5) mol/l) when the strips were contracted with 20 and 100 mmol/l K, respectively. Vasodilative effect of nicorandil on PGF2 alpha-induced contraction was found to be almost the same as that on 30 K-induced contraction. In contrast to nicorandil, verapamil induced a potent vasodilation of the coronary strips contracted with high K by a dose-dependent manner. Verapamil at the concentration of 10(-5) mol/l was found to induce a potent relaxation (87 +/- 0.8%) of the strips contracted with 100 K. However, verapamil showed a weak vasodilative effect on the strips contracted with PGF2 alpha (10(-5) mol/l), i.e., 10(-5) mol/l verapamil induced 22 +/- 1.1% relaxation of PGF2 alpha-induced coronary strips. These results suggest that nicorandil can exert its vasodilative effect against the coronary arterial contraction induced not only by high K, which is induced by a voltage dependent Ca influx, but also by PGF2 alpha, which is considered to be through the specific receptor of the membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of selective thromboxane synthetase inhibitor OKY-046 on plasma prostaglandins in patients with coronary artery disease during exercise.
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[A case of primary myelofibrosis with nephrotic syndrome and pulmonary fibrosis terminating in acute leukemia].
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[A case of pheochromocytoma associated with the variant form of angina].
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Studies on the pharmacokinetics of theophylline in asthmatic patients following multiple oral dosing of a sustained-release theophylline tablet formulation.
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Mechanism of liver mitochondrial dysfunction associated with bile duct obstruction.
To elucidate the mechanism of liver mitochondrial dysfunction induced by obstructive jaundice, the following experiments were performed. In vivo study: Using Wistar male rats, bile ducts were ligated, and serum levels of total bilirubin (T-Bil), GOT, GPT, mitochondrial GOT (mGOT) and total bile acids (TBA) were measured at 3 and 7 days after the ligation. Then, the liver was isolated to determine mitochondrial functions and to measure the content of fatty acids in mitochondrial phospholipids by high performance liquid chromatography. The levels of T-Bil, GOT, GPT, mGOT and TBA were elevated by the bile duct ligation. Mitochondrial functions were deteriorated, and contents of arachidonic acid, palmitic acid and stearic acid in mitochondrial phospholipids decreased. Pretreatment with coenzyme Q10 (E-0216, CoQ10), an antidetergent agent, prevented not only the development of mitochondrial dysfunction and the decrease in mitochondrial phospholipids but also the elevation of GOT, GPT, and mGOT although CoQ10 did not prevent the elevation of T-Bil and TBA levels. In vitro study: Using intact rat liver mitochondria, the effect of taurocholic acid (TCA), one of the physiological bile salts, on the mitochondrial function and on mitochondrial phospholipids was examined. Incubation of mitochondria with TCA induced a dose-dependent deterioration of mitochondrial function and the increase in the content of solubilized phospholipids. The protective effect of CoQ10 was also observed in the in vitro study. These results indicate that degradation of mitochondrial phospholipids by bile acids is responsible for the early phase of liver dysfunction induced by obstructive jaundice.
[Properties of the tracheal smooth muscle].
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[Correlation between pulmonary function tests and morphological changes in small airways in mildly damaged cases].
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Mechanism of leukotriene-induced contraction of isolated guinea pig tracheal smooth muscle.
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Multiple hemangioblastomas accompanied by syringomyelia in the cerebellum and the spinal cord.
The present report covers an autopsied case of multiple hemangioblastomas in the cerebellum and the spinal cord, which did not involve the retinas and other organs. An intramedullary hemangioblastoma was found at the C3-4 level of the spinal cord and similar small tumors were present at the C-7 and Th-4 levels. Multiple cysts were located from the C1-2 to the lumbar level; some of these seemed to be longitudinally continuous, like syringomyelic cavities. These findings appear only rarely in published reports of autopsied cases of hemangioblastomas in the spinal cord.
Clinical evaluation of theophylline binding to plasma protein in bronchial asthmatic patients.
Theophylline binding to plasma protein was studied with seven bronchial asthmatic inpatients. The extent of protein binding was monitored using an ultrafiltration device, EMIT FreeLevelTM System 1, whose performance is pH independent between 7.5 and 8.5 and concentration independent between 2 and 10 mcg/ml. When protein-free theophylline solutions are used a linear pH dependency was observed between 7.0 and 8.3. With theophylline-spiked human plasma using the same samples, the binding was found to be concentration-independent in the range 5 to 40 mcg/ml. The intra- and inter-individual variations in theophylline binding to plasma proteins were relatively large. A calculation procedure for predicting free fractions at normal physiological plasma pH, 7.4, using the observed free fraction at a given plasma pH is proposed. A good correlation was obtained between plasma and salivary theophylline concentrations. Salivary levels alone, however, are unreliable for monitoring theophylline therapy.
Argyrophil cells in the urachal epithelium and urachal adenocarcinoma.
Urachal adenocarcinoma, normal urachus, and urinary bladder were studied by histochemical methods and electron microscopy. Many argyrophil cells were found in urachal adenocarcinoma and urachal epithelium. Autofluorescence and immunoperoxidase examinations showed that the argyrophil cells possessed serotonin, glucagon, and secretin. Some of the carcinoma cells and urachal epithelial cells contained fairly large amount of mucosubstances. On the other hand, only a few argyrophil cells and very weakly PAS positive cells were observed in the urinary bladder mucosa. This study showed that there were close similarities in the histochemical and electron microscopical features between the urachal carcinoma and urachal epithelium, and suggested that the undifferentiated stem cells were able to differentiate to both glandular and endocrine cells.
Increased plasma cyclic nucleotide concentrations in congestive heart failure.
Plasma concentrations of cyclic nucleotides (adenosine monophosphate (AMP) and guanosine monophosphate (GMP) were measured by an ultrasensitive radioimmunoassay in 138 patients with heart failure due to various causes. Measurements were related to the New York Heart Association classification of symptoms, plasma noradrenaline concentrations, and mean pulmonary artery pressures. Serial concentrations of cyclic AMP and GMP were also measured daily in four patients treated for acute left ventricular failure. Plasma concentrations of cycle AMP were related to the severity of the heart failure, plasma noradrenaline concentrations, and pulmonary artery pressures. Cyclic AMP concentrations fell rapidly after treatment of acute left ventricular failure. Plasma concentrations of cyclic GMP also depended on the severity of heart failure and the pulmonary artery pressure, and decreased sharply with treatment although remaining at a high value. The cyclic GMP concentrations were significantly higher in patients with mitral stenosis than in those with other types of heart failure.
The effects of beta-blocking agents on mitochondrial function in ischemic myocardium.
We investigated the protective effects of beta-adrenergic blocking agents on ischemia-induced mitochondrial dysfunction in 42 anesthetized mongrel dogs. The animals, divided into 6 groups of 7 dogs each, were premedicated with either saline for the controls, or D, L-propranolol (0.5 mg/kg), D-propranolol (0.5 mg/kg), D, L-acebutolol (2.5 mg/kg), D, L-pindolol (0.1 mg/kg), or L-isoproterenol (0.2 microgram/kg/min, for 10 min). Myocardial mitochondria were prepared from both the normal and the ischemic areas after 30 min of coronary ligation. The concentration of long-chain acyl-CoA was measured enzymatically. Respiratory control index, ADP/O, and the rate of oxygen consumption in State III of mitochondria were also measured. In the control group, acyl-CoA in ischemic mitochondria increased significantly compared with that in normal mitochondria, and mitochondrial dysfunction was observed. Administration of L-isoproterenol further increased acyl-CoA level and accelerated the dysfunction, whereas premedication with beta-blocking agents reduced the elevation of acyl-CoA level and prevented the dysfunction. Premedication with D-propranolol had no effect on mitochondria. Since the accumulation of acyl-CoA interferes with normal mitochondrial function, these results suggest that the protective effects of beta-blocking agents are based, at least in part, on the prevention of the accumulation of acyl-CoA esters.
Effects of excessive noradrenaline on cardiac mitochondrial calcium transport and oxidative phosphorylation.
Mitochondrial oxidative phosphorylation, calcium transport activity and calcium content were investigated in dog hearts injured by excessive noradrenaline (NA). Diffuse cardiac injury was produced by a 5-hour infusion of NA (2 or 5 micrograms/kg/min), and the injury was evaluated based on ECG and hemodynamic changes. Mitochondrial calcium uptake and binding activities measured in the presence of ATP showed no significant differences between the control and NA groups. However, the calcium content of heart mitochondria isolated from the NA groups, state 3 respiration and the respiratory control index were significantly depressed without any change in the ADP/O ratio. These results suggest that excessive NA causes the intracellular calcium overload and the depression of mitochondrial respiration, and the both of these changes may play a key role in the pathogenesis of myocardial injury through the insufficient control of cytosolic calcium levels.
The role of phospholipase in mitochondrial dysfunction after coronary reperfusion in the canine myocardium.
The left anterior descending coronary artery of a dog was occluded for 15 min followed by a 5 min reperfusion in order to investigate the mechanism responsible for the paradoxical exacerbation of heart mitochondrial dysfunction caused by reperfusion. The mitochondrial function was assessed and the concentration of Ca++, phospholipids and free fatty acids (FFA) were determined. The relative importance of mitochondrial lysophospholipids was also investigated. Eleven dogs (30.6%) developed "reperfusion arrhythmia" (arrhythmia group) but 25 did not (control group). Although mitochondrial dysfunction was observed in the reperfused area even in the control group, a greater impairment of mitochondrial function was observed in the reperfused area in the arrhythmia group. There was no significant difference in the contents of FFA and phospholipids in the mitochondria from the normal area of both groups and from the reperfused area of the control group. However, a marked increase in eight FFA and a significant decrease in phospholipids were observed in the mitochondria from the reperfused area of the arrhythmia group. A significant increase in Ca++ content both in the myocardium and the mitochondria from the reperfused area was observed in the arrhythmia group but not in the control group. In separate experiments, the mitochondria prepared from dog left ventricle were incubated with either phospholipase C (PhC) or phospholipase A2 ( PhA2 ). Both phospholipases induced severe mitochondrial dysfunction. PhC induced a significant increase in FFA, quite analogous to the changes in mitochondrial FFA caused by reperfusion in vivo. PhA2 also induced a tremendous increase in FFA but only in the content of unsaturated FFA. Although PhC did not affect the lysophospholipid profiles, PhA2 induced lysophosphatidyl choline. These results indicate that mitochondrial damages characteristic of the early phase of coronary reperfusion may be caused by the action of PhC, activated by increased intracellular Ca++, which in turn induces degradation of the mitochondrial membrane.
Long-term effects of triiodothyronine and thiouracil on myocardial beta-adrenergic receptor numbers and cyclic AMP concentration in rats.
Long-term (35 days) effects of thyroid hormone on the number of myocardial beta-adrenergic receptors and the c-AMP concentration were studied in the rat. The ventricles from triiodothyronine-administered rats (T3 rats) showed an increase in the number of beta-receptors compared to controls (54.3 +/- 3.1 vs 39.3 +/- 1.8 fmole of [125I]-iodohydroxybenzylpindolol (IHYP) binding sites/mg protein p less than 0.001) on the 35th day. Conversely, the ventricles from thiouracil-administered rats (TU rats) showed a decrease in the number of beta-receptors compared to controls (31.4 +/- 1.6 vs. 38.4 +/- 2.6 fmole/mg protein, p less than 0.05). The equilibrium dissociation constants (Kd) for the interaction of receptors with IHYP did not differ significantly (0.10 to 0.15 nM). The myocardial concentration of cyclic AMP was not significantly different (T3 rats, 1.09 +/- 0.09 nM/g wet weight tissue; T3 controls, 1.12 +/- 0.07; TU rats, 1.13 +/- 0.07; TU controls, 1.16 +/- 0.12) on the 35th day. On serial effects of triiodothyronine from the first to the 35th day, the number of beta-receptors of T3 rats increased significantly on the 24th and the 35th day, but the c-AMP concentration was not significantly different from that in control rats. These results demonstrated that thyroid hormone affects the number of myocardial beta-receptors in rats, and suggested a different mechanism of action of thyroid hormone on the myocardium from that of catecholamines.