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Biomedical subjects

T Toyo-Oka

Publications and source records attributed to T Toyo-Oka.

29 records · Page 2Linked to original sources

Identification of two new calcium dependent hydrolases in the human heart.

We have identified and isolated two new calcium-activated neutral hydrolases from human ventricular muscles. The one is an esterase, of which molecular weight was 300,000, required millimolar concentration of Ca2+, hydrolyzed Ac-Tyr-OEt X H2O, optiaml pH at 7.0. The other is an amidase, of which molecular weight was 70,000, also required millimolar concentration of Ca2+, hydrolyzed a synthetic substrate for chymotrypsin, Suc-Leu-Leu-Val-Tyr-MCA, with optimal pH at 7.2. Both enzymes did not degrade casein or contractile proteins (myosin, actin, troponin and tropomyosin). Their activities were not inhibited by exogenous protease inhibitors, leupeptin, antipain, monoiodoacetic acid and chymostatin, while the amidase activity was blocked by the endogenous inhibitor against calcium-activated neutral protease (CANP). Thus, their characters are different from chymotrypsin or CANP and they seems to be new hydrolases in the human heart.

Amidohydrolases↗

The cardiovascular effects of xamoterol, a beta 1-adrenoceptor partial agonist, in healthy volunteers at rest.

The cardiovascular effects of three single intravenous doses of a beta 1-adrenoceptor partial agonist, xamoterol (0.025, 0.05 and 0.1 mg kg-1) and placebo were studied in six healthy volunteers at rest using a single-blind design. In addition to heart rate and blood pressure measurements, cardiac contractility was measured by means of M-mode echocardiography and systolic time intervals. Ambulatory 24 h Holter-monitoring of the electrocardiogram was performed. Plasma concentrations of xamoterol were measured. Compared to baseline, xamoterol (0.025 mg kg-1) increased heart rate (61 +/- 3-68 +/- 3 beats min-1, means and SEM) and systolic blood pressure (119 +/- 3-138 +/- 5 mm Hg) but decreased pre-ejection period (100 +/- 4-76 +/- 5 msec). Stroke volume (88 +/- 6-104 +/- 10 ml), cardiac output (4.8 +/- 0.4-6.6 +/- 0.61 min-1), velocity of circumferential fibre shortening (1.15 +/- 0.06-1.50 +/- 0.06 circ s-1) were increased by xamoterol. No significant changes were produced by placebo. No dose-dependent effects were seen and maximum effects were produced by 0.025 mg kg-1 xamoterol. Significant effects were observed for 2 h. The areas under the plasma concentration curves (AUC0-12) showed a linear dose response. No adverse effects attributable to xamoterol were seen in haematological, biochemical, urinalysis or electrocardiographic tests. Four volunteers were aware of a more forceful heart beat after xamoterol, but this was mild and transient. It is concluded that xamoterol has a positive inotropic action.

Adrenergic beta-Agonists↗

Ca2+ sensitivity change and troponin loss in cardiac natural actomyosin after coronary occlusion.

Ca2+ sensitivity of natural actomyosin (NAM) isolated from both the intact left ventricular free wall and an area of myocardial infarction (MI) was analyzed by use of superprecipitation response from 2 to 48 h after left anterior descending coronary artery ligation in the dog. NAM from the intact tissue showed normal superprecipitation and normal Ca2+ sensitivity. Four hours after coronary ligation, Ca2+ sensitivity was lowered only in the endocardial half of MI region; it was markedly decreased both in the epicardial and endocardial halves at 6 h and completely lost at 24 and 48 h. A superprecipitation response was, however, demonstrated in all samples, indicating that both myosin and actin preserved their functions in the course of MI. With polyacrylamide gel electrophoresis in sodium dodecyl sulfate, NAM from the MI region revealed moderate decrease of the tropomyosin-binding subunit of troponin(TN-T) and the Ca2+-binding subunit of troponin(TN-C) and drastic decrease of the inhibitory subunit of troponin(TN-I). This resulted in the formation of extra bands of low molecular weights. These results suggest that degradation of troponin subunits occurs relatively early (4 h after coronary artery occlusion) and from the endocardial half of MI region. This degradation may be caused by one or several proteases that preferentially degrade the regulatory proteins among myofibrillar proteins.

Actomyosin↗

Influence of hyperthyroidism on the superprecipitation response and Ca2+-sensitivity of natural actomyosin in cardiac and skeletal muscle.

In cardiac natural actomyosin prepared from hyperthyroid rabbits, the time of onset of the superprecipitation response was shortened by 58% and the rate of response was increased 4-fold compared with euthyroid animals. However, Ca2+-sensitivity of cardiac natural actomyosin prepared from either euthyroid or hyperthyroid rabbits was not changed over the range of 10(-7) to 6.6 . 10(-5) M free Ca2+ concentrations. Skeletal natural actomyosin prepared from either euthyroid or hyperthyroid rabbits showed a far higher Ca2+-sensitivity than cardiac natural actomyosin, but there was no difference in either time of onset or rate of superprecipitation response.

Actomyosin↗

Effects of various concentrations of MgATP on the superprecipitation and ATPase activity of scallop striated muscle myosin B1.

1. The superprecipitation and ATPase activity of scallop striated muscle myosin B showed essentially the same biphasic pattern as that of vertebrate skeletal muscle myosin B in its responses to changes in the MgATP concentration. Ca2+ had no effect at MgATP concentrations less than 10(-5) M. 2. The superprecipitation of gizzard myosin B showed a weak biphasic pattern, but its ATPase activity showed no sign of a biphasic pattern up to 3 x10(-3) M MgATP, in accord with the result of Bremel (1974). 3. Thus scallop striated muscle is classified into the same group as vertebrate skeletal muscle as far as its response to changes in MgATP concentration is concerned. Gizzard is distinct from the other two kinds of muscle.

Actomyosin↗

Gizzard Troponin.

Native tropomyosin from the gizzard was separated into troponin and tropomyosin. The mode of action of the troponin-tropomyosin system of gizzard was shown to be distinclty different from that of skeletal muscle.

Animals↗

X-linked hypoxanthine-guanine phosphoribosyltransferase deficiency without neurological disorders. a report of a family.

A patient is reported with X-linked hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency. He had gout but no neurological symptoms. The patient had negligible HGPRT activity as determined by thin layer chromatography and liquid scintillation counting. Autoradiography of fibroblast cultures revealed no uptake of -3H-hypoxanthine. His mother and two sisters were shown to be heterozygotes.

Adolescent↗