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Biomedical subjects

H Kawata

Publications and source records attributed to H Kawata.

At least 145 records · Page 8Linked to original sources

Rectal absorption of insulin suppositories in rabbits.

When insulin solutions (100 U kg-1) at various pH values were placed in the rectum of rabbits, a large decrease in blood glucose concentration was observed except at the pH close to the iso-electric point of insulin. The effect of surface-active agents on the rectal absorption of insulin was examined by measuring the blood glucose concentration after the administration of 2 or 5 U kg-1. Non-ionic ether type, anionic, cationic and amphoteric surfactants as well as bile acids increased the absorption. The optimal effect with suppositories was reached with the addition of 1% polyoxyethylene (9) lauryl alcohol ether. Insulin suppositories containing agents enhancing rectal absorption were compared with the insulin for intravenous, intramuscular and subcutaneous injection. The changes of blood glucose and plasma immuno-reactive insulin concentration after rectal administration of insulin were similar to those after intravenous injection.

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Contractility of the frog ventricular myocardium in sodium-free lithium solution.

The effects of Na-free Li solution on the electrical and mechanical activities were examined in a bullfrog's ventricular strip. The action potential showed a triphasic change during Na-free perfusion: the initial decrease in the overshoot and duration, the secondary restoration and the gradual decrease in the membrane potential. The twitch contraction also changed in a triphasic manner: the initial rapid decrease with a transient development of contracture and the secondary slow decrease followed by a partial recovery. A negative staircase, which was accompanied by full-sized twitch contractions, was induced by lowering the stimulation rate in this medium, indicating an involvement of some intracellular Ca releasing sites for activating the well-maintained contractile proteins. When CaCl2 was omitted during Na-free Li perfusion the twitch decreased only slightly down to 71.8% whereas in Na-containing medium it decreased to 11.9%. The sensitivity of twitch to the external Ca was thus greatly diminished in the Na-free condition. A fairly large contracture could be elicited by high K solution in Ca-free Li solution even after a prolonged Ca-free perfusion. Modification of the action potential by passing a hyperpolarizing current did not affect the twitch occurring in the Li solution, in contrast to its marked effect on the muscle perfused with normal Ringer. From these results it is concluded that the twitch is activated mainly by Ca released from some intracellular site in the Na-free Li solution. The inhibitory effect of Mn on this contraction was discussed in relation to its intracellular action.

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Effects of hypertonic perfusion on the ultrastructure of frog cardiac muscle.

The ultrastructural changes induced by hypertonic perfusion were investigated using the ventricular muscle of the bullfrog. It was demonstrated that the fixative tonicity critically affects the ultrastructure. Effects of sucrose-, NaCl- and urea-hypertonicities were investigated and compared. In both sucrose- and NaCl-hypertonic media, although the cardiac muscle strongly shrank and the extracellular spaces markedly increased according to increasing tonicity the width of the intercalated disc cleft remained unchanged and the cleft was never separated even in 3 times hypertonicity. The sucrose-hypertonicity made the feature of the fine structure extremely obscure and the electron densities in both the Z-line and the intercalated disc region markedly decreased. When both the perfusate and fixative were made hypertonic by urea, which is known to easily penetrate the cell membrane, a shrinkage of the myocardial cells was observed but to a lesser extent as compared with sucrose or NaCl. The striation pattern was disordered in this condition though the intercalated discs were never affected.

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Inhibitory action of hypertonic urea solution on the potassium contracture of the heart ventricular muscle.

Effects of hypertonic urea solution on potassium contracture were investigated in a bullfrot ventricular strip. In a medium of three times hypertonic urea, the contracture induced by 100 mM potassium solution was markedly inhibited whereas the twitch contraction was augmented in the hypertonic urea solution. The extent, as well as the time course, of the membrane depolarization produced by high potassium solution was essentially identical in both isotonic and hypertonic conditions. Endogeneous catecholamine does not seem to participate in this inhibition since the treatment with propranolol did not modify the results. Thus, the possibility of the well-known catecholamine-induced inhibition of potassium contracture can be excluded. The myocardial contractility was never suppressed, or even augmented, at this stage of urea perfusion although a prolonged hypertonic urea perfusion gradually suppressed the contractility. It was suggested that hypertonic urea exerts its negative inotropic action on the potassium contracture independently of its positive inotropism on the twitch contraction by accelerating the uptake of the activator calcium ion to some undefined intracellular sites.

Action Potentials↗

Effects of hypertonic urea solution on the contractility of the bullfrog ventricle.

UNLABELLED: The effects of hypertonic urea solution on the excitation-contraction coupling of the bullfrog's heart muscle were investigated. MATERIALS AND METHODS: Small strips obtained from the ventricular wall of Rana catesbiana were used. Contractile tension as well as transmembrane action potential were recorded in the single sucrose-gapped arrangement. The muscle weight was measured in order to check the changes in the dimension of muscle fiber both during isotonic and hypertonic perfusions. Light microscopic study was also performed to compare the effect of hyperosmolar urea with that of sucrose. RESULTS AND CONCLUSIONS: 3.0 T-urea solution exerted a triphasic change in twitch tension during hypertonic perfusion and a biphasic change during the recovery perfusion. An initial rapid decline was restored to the original level within 10 min and after an overshoot a secondary gradual decrease was observed during hypertonic perfusion. In spite of parallel change in the action potential duration with the time to peak tension there was an increase in dp/dt during the restoration phenomenon. The calcium sensitivity was altered in the 3.0 T-urea solution and thus in Ca-free solution the rate constant of the slow component of twitch decline was decreased. The muscle weight remained decreased during the whole period of hypertonic perfusion. Histological study revealed that the fiber bundles soaked in hypertonic urea solution show normal appearance whereas those in sucrose exhibit a marked shrinkage. These results show that urea can penetrate the heart muscle membrane easily and that urea has some augmenting action on the E-C coupling process.

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Effects of tonicity on the resting tension in bullfrog ventricle.

INTRODUCTION: A study of the effects of hyper -and hypotonic media on resting tension were examined in ventricular muscle of the bullfrog was undertaken because only few studies on resting tension from the viewpoint of E-C coupling in the heart muscle are available. MATERIALS AND METHODS: Thin strips obtained from the bullfrog ventricle were perfused in the sucrose-gapped chamber, which allowed the effective stimulation and the simultaneous measurement of the contractile tension and the intracellular membrane potential. RESULTS AND CONCLUSIONS: Hypertonic solutions up to 3.0 T, prepared by adding NaCl or sucrose, induced a triphasic response, namely an initial rapid decline, a secondary slow development of contracture and a final transient off-contraction. Both the second and the final responses were strongly sensitive to the calcium concentration of the bathing medium and were completely abolished by depleting external calcium ions. The initial decreasing phase was not sensitive to external calcium but was progressively augmented by increasing the initial muscle length, whereas the dehydration process, estimated by measuring the muscle weight, was unaffected by muscle stretch. The changes in the membrane potential were not essential for these responses. It was concluded that the initial tension decline results from the passive process due to volume change while the sustained contracture as well as the transient off-contraction are produced by some active process involved in E-C coupling. Hypotonic solutions induced a monophasic contracture which is insensitive both to the external calcium concentration and muscle stretch. The possible mechanism for the genesis of the response was discussed.

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Multiple mycobacterial antigens in diagnostic tuberculins.

Guinea-pig antisera containing IgG1 antibodies have been prepared either with killed mycobacterial in paraffin oil or living BCG or intradermal injections of fractions of unheated culture filtrate. Sera, found to contain antibodies specific for different mycobacterial antigens are used in passive cutaneous anaphylaxis (PCA) in 12 times the dilution-to-extinction titer. Animals prepared with sera respond in all sites when unheated culture filtrate, strain H37Rv, is injected intravenously (i.v.) at 17-20 hours. Injection of diagnostic tuberculins i.v. into parallel recipients, in selected amounts, reveals, through reacting sites, the presence of the corresponding antigens and some information on relative amounts. Tuberculins of PPD type are precipitated from heated culture filtrate by ammonium sulfate or trichloroacetic acid (TCA) or benzoic acid. Old Tuberculins are made classically by long heating and evaporation. In all products heat-labile antigens are absent or present in small amount; yet, PPD-S was found to possess five antigens. In all PPD products, there was one dominant antigen, absent from Old Tuberculins. The dominant antigen of OT's was excluded from the TCA-PPD's but was present in most ammonium sulfate-type PPD's. It can be concluded that diagnostic testing made with OT detects a particular delayed-type sensitivity that is different in specificity from that which reacts to TCA-PPD's. Many but not all of the ammonium sulfate PPD's test for both specificities. Several different delayed-type sensitivities are acquired during infection. Supported by Grant AI 01258 of the National Institute of Health.

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Effects of osmolarity change on the excitation-contraction coupling of bullfrog ventricle.

The effect of hyper- and hypotonic solutions on the electrical as well as the mechanical activities of the bullfrog ventricle were investigated. Hypertonic solutions up to 400% tonicity, made by adding sucrose, showed two kinds of inhibitory effect; i.e. a consistent, rapid shortening of the action potential duration and a slowly progressing suppression of contractile tension. The inhibitory effect of the hypertonic solution up to 300%, made by adding NaCl, was more pronounced on the contractile process than on the electrical phenomena. In this condition, the inhibition of the twitch tension occurred with two time constants. The first, rapid decline seems to be related to the suppressive effect on some superficial site while the slower decreasing phase showed a similar time course as the development of contracture. Hypotonic (33.3% and 12.5%) perfusion revealed triphasic changes in the time course of single twitch without accompanying any parallel change in the action potential. From these results it was concluded that the bullfrog ventricular muscle has some superficial site for Ca regulation which is very sensitive to osmolarity change.

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A study on the electrical resistance of the frog sartorius muscle.

Four different methods of measuring the resistance of a muscle fiber have been applied to the frog sartorius muscle. The methods, in which the resistance of the microelectrode entered the calculation of the effective resistance of the fiber, resulted in values which were 8 times higher than the resistance values obtained with methods independent of the electrode resistance. A simple cable model of a muscle fiber could not account for the discrepancy in the effective resistance found in these measurements; therefore, an enlarged cable model for a muscle fiber has been proposed, and its biological implications have been discussed. The effective resistance (measured with the two different groups of methods) decreased when the potassium concentration in the bath increased. Using the proposed enlarged cable model for the interpretation of these results, it is shown that not only the membrane resistance but also the myoplasmic resistance decreases with an increasing potassium concentration in the Ringer solution.

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