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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 1,027 records · Page 57Linked to original sources

Structure and function of the interleukin 2 receptor: affinity conversion model.

We cloned cDNAs of the human and mouse IL-2 receptors. Comparison of their structures allowed us to identify several conserved regions localized to exons 2 and 4, the cytoplasmic portion and the transmembrane portion. These regions might be important for the functions of the IL-2 receptor. The human IL-2 receptor, which was expressed on an IL-2-dependent murine T-cell line, CTLL-2, by cDNA transfection, was shown to be functionally active by blocking the endogenous mouse IL-2 receptor with monoclonal antibodies. On the other hand, the human IL-2 receptors expressed on non-lymphoid cells were functionally inactive. They were unable to mediate the growth signal, were of low affinity species and aberrant in internalization. We postulated that the dysfunction of the IL-2 receptors in non-lymphoid cells would be due to the absence of the putative converter protein which is expressed specifically in lymphoid cells. Since the human IL-2 receptor is active in the murine T cell, the converter may interact with the receptor at the portions conserved between man and mouse. We proposed the affinity conversion model that explained the high affinity state of the receptor by the ternary complex formation between IL-2, the IL-2 receptor and the converter.

Allosteric Regulation↗

Effect of dibutyryl cyclic adenosine monophosphate on canine pelviureteral discharge potentials.

An electromyographic study of the responses of the pelviureter to dibutyryl cyclic AMP was performed using isolated canine pelviureteral preparations. Dibutyryl cyclic AMP caused a marked increase in the amplitude of discharge potential in the pelvicalyceal pacemaker region and this was associated with a decrease in renal pelvic pressure. The frequency of the pacemaker discharge did not increase. On the other hand, in the lower pelvis and ureter, dibutyryl cyclic AMP caused a small but significant decrease in the amplitude of discharge potentials and this was associated with a marked decrease in discharge frequencies in the lower pelvis and ureter.

Animals↗

Cardiovascular effects of nipradilol, a beta-adrenoceptor blocker with vasodilating properties.

In anesthetized dogs, an intravenous injection of nipradilol produced a long lasting fall in mean arterial blood pressure which was accompanied by transient decreases in peripheral vascular resistance and sustained decreases in heart rate, cardiac output and left ventricular (LV) dP/dt. LV end-diastolic pressure (LVEDP) was not changed while LV diameters and central venous pressure were slightly increased. Under propranolol pretreatment conditions, nipradilol no longer affected the heart rate, but the drug still induced a transient reduction in peripheral vascular resistance, and sustained decreases in arterial blood pressure and cardiac output. Furthermore, indicators of LV preload (LVEDP, LV end-diastolic diameter and central venous pressure) were significantly reduced, suggesting a direct dilating action of nipradilol on capacitance vessels. In intact conscious dogs, nipradilol caused a sustained reduction in LVEDP, while propranolol increased LVEDP. After administration of nipradilol, coronary blood flow in anesthetized dogs decreased in association with diminished myocardial oxygen consumption, and large coronary vessel resistance also decreased. Nipradilol competitively antagonized the isoproterenol-induced positive chronotropic response (DR10: 0.04 mg/Kg, i.v.) and the phenylephrine-induced vasopressor response (DR10: 3.95 mg/Kg, i.v.). In conclusion, nipradilol, in contrast to propranolol, possesses the properties to decrease arterial blood pressure, LV preload and large coronary vessel resistance through its dilating action on arterial and venous vessels. It is proposed that nipradilol may be beneficial for the treatment of hypertension and coronary heart disease.

Adrenergic beta-Antagonists↗

Effect of dobutamine on adenylate cyclase activity in rabbit renal pelvis and ureter.

The adenylate cyclase activity in the rabbit renal pelvis and ureter was measured by the method of Salomon et al. (1974). The dobutamine-induced increase of adenylate cyclase activity is more prominent in the renal pelvis including the pacemaker region than in the ureter that is non-pacemaker region in the upper urinary tract. Therefore, it is thought that the pacemaker region is different from other regions in the upper urinary tract with regard to responses to dobutamine.

Adenylyl Cyclases↗

Effects of forskolin on contractility and cyclic AMP levels in rabbit detrusor muscle.

Forskolin caused a concentration-dependent relaxation and increase in cyclic AMP levels in rabbit detrusor muscle. Propranolol, a beta-adrenoceptor antagonist, did not affect the relaxation induced by forskolin. 3-isobutyl-1-metylxanthine (IBMX), a cyclic nucleotide phosphodiesterase inhibitor, potentiated the relaxation induced by forskolin. These data suggest that the relaxation of rabbit detrusor muscle induced by forskolin is mediated by cyclic AMP accumulation resulting from activation of adenylate cyclase.

1-Methyl-3-isobutylxanthine↗

Characterization of functional beta-adrenoceptor subtypes in rabbit urinary bladder smooth muscle.

Spontaneous contractile force of muscle strips isolated from male rabbit urinary bladder dome (detrusor) and base (trigonal muscle) was significantly inhibited by isoproterenol (10(-7)-10(-5) M), a non-specific beta-adrenoceptor agonist or by terbutaline (10(-8)-10(-5) M), a selective beta 2-adrenoceptor agonist. The EC50 values for isoproterenol and terbutaline in detrusor were the same as those in trigonal muscle but the maximum relaxant response to isoproterenol or terbutaline was significantly greater in detrusor than in trigonal muscle. Dobutamine (10(-5)-10(-4) M), a relatively specific beta 1-adrenoceptor agonist caused a small but significant relaxant response in trigonal muscle but no change in detrusor. In trigonal muscle the relaxant response to dobutamine was less than that to terbutaline. The relaxant response to 10(-6) M isoproterenol in detrusor was completely blocked by butoxamine (10(-4) M), a selective beta 2-antagonist or by propranolol (10(-6) M), a non-specific beta-antagonist but not by metoprolol (10(-6)-10(-4) M), a selective beta 1-antagonist. Relaxation of trigonal muscle induced by 10(-6) M isoproterenol was inhibited by 10(-5) M metoprolol by 30%, by 10(-4) M butoxamine by 70%, or completely by 10(-6) M propranolol. These findings are consistent with the view that the density of beta-adrenoceptors is higher in the detrusor than in trigonal muscle, and that the relaxant response to beta-adrenoceptor stimulation is mediated by beta 2-subtype in the detrusor and by both of beta 1- and beta 2-subtypes in trigonal muscle of the male rabbit.

Animals↗

[Regional coronary outflow and coronary reserve assessed by the thermodilution technique: an experimental study].

Coronary blood flow distribution and coronary flow reserve were experimentally evaluated by the thermodilution technique. Using a special catheter with two external thermistors 5 cm apart, the great cardiac vein (GCV) outflow and coronary sinus (CS) outflow were measured. Coronary inflows in the left anterior descending (LAD) and circumflex (LCX) arteries were measured by electromagnetic flow probes during arterial occlusion or bolus arterial injection of nitroglycerin and dipyridamole injection in a peripheral vein. On the LAD side, the venous flow due to the interventions increased both GCV and CS outflows, while the interventions in the LCX increased CS outflow without significant changes in the GCV flow. LAD inflow and GCV outflow, and LCX inflow and (CS-GCV) flow correlated well, and there were significant close correlations between each inflow and outflow. Coronary reserve in the LAD and LCX was studied in successive 70% and 90% stenoses produced by a calibrated constrictor. Maximal coronary flow was obtained during reactive hyperemic response after coronary artery occlusion. Although there was no significant coronary reserve in the coronary inflow or outflow in the basal state, coronary reserve in the GCV and CS decreased significantly in stenoses of the LAD and LCX. These results suggest that this method allows practical assessment of drainage from the LAD and LCX areas and that stenosis greater than 70% can be estimated from the changes in regional venous outflows. This method may be helpful in evaluating regional coronary hemodynamics clinically.

Animals↗