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Biomedical subjects

M Ninomiya

Publications and source records attributed to M Ninomiya.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effects of S-312, a new calcium antagonist, on the mechanical and electrophysiological responses of isolated cardiovascular preparations.

S-312, a new calcium antagonist with a bicyclic dihydrothienopyridine structure, potently relaxed the helical strips of various isolated rabbit arteries precontracted with high K+-depolarization, serotonin (5-HT) and U46619 (thromboxane A2 analogue), and it competitively inhibited Ca++-induced contractions in depolarized basilar and femoral arteries. These effects of S-312 were more potent than nifedipine and almost comparable to or slightly more potent than those of nicardipine. In comparison with nifedipine and nicardipine, the calcium antagonistic effect and the relaxant effect on 5-HT-induced contractions of S-312 were most prominent in the basilar artery. The potent vasodilating action of S-312 in the high K+-depolarized basilar artery was not easily reversed by washing. S-312 did not affect Ca++-induced contraction in the skinned fiber of guinea pig taenia caecum. The negative inotropic effect of S-312 in isolated guinea pig left atria was much less potent than those of nifedipine and nicardipine. S-312 above 10(-7) M preferentially increased AV nodal conduction time in Langendorff-perfused isolated rabbit hearts; and above 3 x 10(-8) M, it mainly decreased the maximum upstroke velocity of the action potential in isolated rabbit sinus node preparations. In summary, the present results indicate that S-312 is a potent new calcium antagonist possessing vasculoselectivity, especially for cerebral vessels.

Animals↗
PubMed1989

Effects of S-1389 (711389-S), a new antiarrhythmic agent, on the conduction in perfused guinea pig hearts.

In the His bundle and ventricular electrograms of Langendorff-perfused guinea pig hearts driven at a cycle length of 450 or 700 msec, S-1389 (711389-S), a new antiarrhythmic agent, above 3 x 10(-7) or 10(-6) M increased the basal conduction times in the following order: His-Purkinje system greater than ventricular and atrial muscles greater than atrioventricular (AV) node. Slowing of the ventricular and AV nodal conduction of extrasystoles with variable coupling intervals was also caused by S-1389. S-1389 above 10(-6) or 3 x 10(-6) M significantly prolonged the functional and/or effective refractory periods of the AV node and ventricle. Disopyramide (3 x 10(-6)-3 x 10(-5) M) also produced similar effects, but they were much less potent than those of S-1389. Although disopyramide did not produce the rate-dependent increases in the atrial and AV nodal conduction times and in the AV nodal refractory period, S-1389 increased these parameters rate-dependently.

Animals↗
PubMed1989

[Thrombotic thrombocytopenic purpura which was effectively treated by plasma exchange therapy--involvement of vWF and endothelial cell injury].

A 49-year-old man with a one-week history of general fatigue and several other symptoms, including hematuria, numbness of the mouth, anemia and thrombocytopenia, was admitted because of an episode of convulsions and unconsciousness after blood transfusion. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was then made, and treatment with steroids, anti-platelet agents, transfusion of fresh frozen plasma was started. However, since no improvement was seen, on the third day of admission, treatment with plasma exchange was instituted (total plasma exchange volume was 18.1 iota), and his clinical and hematological conditions improved markedly. Since then, he has been in a remission state for about three years. Laboratory examinations during the acute phase showed increase of vWf: Ag, decrease of RCof/vWf: Ag, increase of vWf large multimers and a high endothelial cell injury activity by the patient's serum. In the next day following the plasma exchange therapy, RCof/vWf: Ag improved, but not to the normal range. One and a half years later, while in the remission phase, the vWf multimers and endothelial cell injury activity normalized. Thus, these findings show further evidence on the involvement of endothelial cell injury and vWf in the pathogenesis of TTP.

Endothelium, Vascular↗
PubMed1989

[A ten-year-old autistic girl with neuroleptic malignant syndrome caused by neuroleptic agents].

We reported a ten-year-old autistic girl who had developed neuroleptic malignant syndrome (NMS) caused by administration of neuroleptic agents, haloperidol and chlorpromazine, because of her behavioral disorders. She had fever (38.4 degrees C) and elevated CK (796 IU). Her extrapyramidal symptoms and autonomic disturbance improved gradually after discontinuation of these drugs. However, altered consciousness did not change for three months despite treatment with L-DOPA, bromocriptine, dantrolene Na, biperiden, diltiazeM HCL and diazepam. Administration of amantadine HCL dramatically cleared not only the persistent symptom but also extrapyramidal symptoms and autonomic disturbance. She recovered from NMS one month later. The study of this case indicated that these neuroleptic drugs could cause NMS also in children. Therefore, the use of them in children with behavioral problems should be carefully evaluated clinically. It was concluded that NMS in this case occurred due to a defective dopamine release from presynaptic vesicles because L-DOPA was not effective and amantadine HCL was effective against these symptoms.

Autistic Disorder↗
PubMed1988

Similar, potent tumor-promoting activity of all isomers of teleocidins A and B in a two-stage carcinogenesis experiment on the skin of CD-1 mice.

Teleocidin, isolated from mycelia of Streptomyces mediocidicus is a mixture of two teleocidin A isomers with molecular weights of 437 (A-1 and A-2) and four teleocidin B isomers with molecular weights of 451 (B-1, B-2, B-3, and B-4). Previously we found that each purified isomer of teleocidins A and B had approximately the same activity as teleocidin in an irritant test on mouse ear, in inductions of ornithine decarboxylase in mouse skin and adhesion of human promyelocytic leukemia (HL-60) cells, and in inhibition of the specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to a mouse skin particulate fraction. This paper reports the strong activation of protein kinase C in vitro by each isomer of teleocidins A and B at a concentration of 1 microgram/ml. Detailed studies on the potent tumor promoting activities of the two teleocidin A isomers and four teleocidin B isomers in a two-stage carcinogenesis experiment on mouse skin are also reported, including histological findings on the tumors. Treatment of mice with 100 micrograms of 7,12-dimethylbenz(a)anthracene and then 2.5 micrograms of any one of the six isomers of teleocidins A and B twice a week induced tumors in 80.0 to 91.7% of the mice with 2.8 to 5.2 tumors/mouse in week 30. Scarcely any tumors developed in groups treated with 7,12-dimethylbenz(a)anthracene or any one of the isomers of teleocidins A or B alone. The percentages of incidences of mice bearing papillomas and carcinomas in the six groups treated with 7,12-dimethylbenz(a)anthracene plus one isomer of teleocidins A or B were 90.9 to 98.3% and 1.7 to 9.1%, respectively. These results indicate that all of the isomers of teleocidins A and B have potent tumor promoting activity on mouse skin, irrespective of the structural differences between teleocidins A-1 and A-2, and among the four isomers of teleocidin B. The structure-activity relationship of teleocidins A and B is discussed on the basis of our recent results. Based on the structures of related compounds, we propose a revised numbering system for compounds of the teleocidin class.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Specific binding of [3H]retinoids to cellular retinoid-binding proteins.

The specific binding of [3H]retinoids to cellular retinoid-binding proteins was measured directly by the cold acetone filtration method. After incubation of purified cellular retinoid-binding proteins with [3H]retinoids with or without competitors for 2-4 h, bound ligands were separated from free by filtration using cold acetone. Nonspecific binding of the ligands was reduced sufficiently to allow measurement of specific binding of [3H]retinoids to cellular retinoid-binding proteins. This method has the advantages of being rapid and practical and giving reproducible results.

Adrenal Glands↗
PubMed1988

Inhibition of ornithine decarboxylase induction by retinobenzoic acids in relation to their binding affinities to cellular retinoid-binding proteins.

Retinobenzoic acids induce differentiation of human promyelocytic leukemia cells (HL-60). Like retinoic acid, 14 retinobenzoic acids inhibited the induction of ornithine decarboxylase (ODC) by teleocidin in mouse skin. The mechanism(s) of inhibition of ODC induction by 7 retinobenzoic acids, Am 80, Am 81, Am 580, Am 590, Am 68, Sa 80, and Ch 55 was compared with those by all-trans-retinoic acid and the arotinoid compound 19. Application of 114 nmol of Am 80, Am 81, Am 580, Am 590, Am 68, Sa 80, or Ch 55, 10 min before 11.4 nmol of teleocidin, resulted in 76.7%, 82.0%, 76.2%, 28.3%, 48.4%, 58.6%, and 85.1% inhibition of ODC induction, respectively. Since all-trans-retinoic acid and compound 19 were also inhibitory, we determined whether retinobenzoic acids bind to cellular retinoic acid-binding protein (CRABP) isolated from bovine adrenal glands. Am 80 and Am 580 inhibited the specific binding of 3H-retinoic acid to CRABP, but also showed less affinity than authentic unlabeled retinoic acid and compound 19. Am 81, Am 590, Am 68, Sa 80, and Ch 55 at up to 10 microM were not effective competitors of the binding of either 3H-retinoic acid or 3H-retinol. These results suggest that the inhibition of ODC induction can be mediated by pathways that do not involve CRABP or the cellular retinol-binding protein.

Animals↗
PubMed1988

Inhibitory effects of synthetic acidic retinoid and polyprenoic acid on the development of hepatoma in rats induced by 3'-methyl-N, N-dimethyl-4-aminoazobenzene.

A study was conducted to investigate the inhibitory effects of acidic retinoid (trimethylmethoxyphenyl analog of retinoic acid ethylester or TMMP) and polyprenoic acid (3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid or E-5166) on the development of hepatoma induced by 3'-methyl-N, N-dimethyl-4-aminoazobenzene (3'-MeDAB) in rats. Morphometric analysis of liver specimens was employed to evaluate the antitumor effects of the compounds in detail, and revealed significant decreases in the number and area of tumors in the TMMP- and E-5166-treated groups. As for adverse effects, retarded growth and marked hypertriglyceridemia were observed only in TMMP-treated rats. During the hepatocarcinogenesis, cellular retinoid-binding protein, F-type or CRBP(F) and cellular retinoic acid-binding protein or CRABP newly appeared in the tumor tissue, particularly in hyperplastic nodules which are the precancerous state of hepatoma. These results suggest that the polyprenoic acid is a good candidate for clinical chemoprevention of hepatoma, targetting its precancerous stage when intracellular receptors for acidic retinoid have emerged.

Animals↗
PubMed1988

Intracellular sodium and potassium concentrations in erythrocytes of patients with primary aldosteronism.

Intracellular concentration of sodium ([Na]i) and potassium ([K]i), and the ouabain sensitive sodium efflux rate constant (ERCos) in erythrocytes were determined in patients with primary aldosteronism, before and after the surgical removal of the adrenocortical adenoma and in comparison to those in healthy controls. Without treatment, [Na]i was higher and ERCos was lower in patients with primary aldosteronism than in controls (10.60 +/- 0.96 vs. 8.25 +/- 0.89 mmol/l cells, p less than 0.01; 0.156 +/- 0.040 vs. 0.255 +/- 0.047/hour, p less than 0.01, respectively). After the surgery, [Na]i was decreased to 7.70 +/- 0.64 mmol/l cells and ERCos was increased to 0.273 +/- 0.031/hour and these values were similar to those in controls. [K]i in primary aldosteronism was not affected by the surgery (from 96.79 +/- 2.03 to 98.8 +/- 3.84 mmol/l cells) and was not different from that in controls (99.11 +/- 3.42 mmol/l cells). In 2 patients, normalization of the serum potassium following an oral potassium chloride supplement caused only partial improvement in [Na]i and ERCos. These results suggest that an inhibition of sodium pump activity resulting in elevated [Na]i may play an important role in the pathogenesis of high blood pressure in patients with primary aldosteronism.

Adenoma↗
PubMed1988

Physical properties of flowing blood.

The changes of viscosity, optical reflection and electrical resistivity of blood due to flow are dependent on the orientation and deformation of red cells. From electrical point of view, it can be assumed that blood is suspension of small insulating particles (red cells) in conductive fluid (plasma) when the frequency of supplied voltage is lower than several hundreds KHz. When blood flows, red cells deform and orient in flow direction. Therefore, flowing blood shows anisotropic electrical and optical properties. In steady flow, blood resistivity longitudinal to flow decrease with flow rate, and transverse one increases. Blood flow in living body is not steady but pulsatile. We measured both longitudinal and transverse resistivity changes, optical reflection change and viscosity change of sinusoidally flowing blood in a rectangular conduit. The results are 1) during one period of sinusoidal flow the longitudinal resistivity change is opposite to that of transverse one, 2) the waveform of reflection light change is similar to that of resistance change, and 3) minimum points of both longitudinal resistivity and viscosity changes do not appear at the moment when flow is zero but are delayed. When the amplitude of sinusoidal flow is small and oscillation frequency is high, the phase difference between the zero crossing period of flow and the period of minimum change in resistivity, increases up to 90 degrees. Viscosity of blood decreases with increase of amplitude and frequency of sinusoidal flow.

Animals↗
PubMed1987

Effects of presensitization of antiheart serum on the rat embryonic heart.

After sensitization by rabbit anti-rat-heart serum (AHS), Wistar rats were injected with 9 ml/kg of AHS on day 9 of gestation. The incidence of malformations was 31.5% and that of cardiovascular malformations was 21.8%. The main malformations were microphthalmia, ventricular septal defect, pulmonary stenosis, and general edema. No antinuclear antibody was detected in the maternal sera by the fluorescent antibody technique. No complete heart block was found in the fetuses by electrocardiography. The fluorescent antibody technique demonstrated localization of rat IgG and rat C3 on the maternal myocardium, but a light-microscopic study revealed no myocarditis or endocarditis in either the maternal or the fetal heart. The types of malformation were similar to those observed after a single administration of antikidney serum, which presumably involves yolk sac dysfunction. These results show that both the existence of the immune complexes of antibodies against AHS and the administration of AHS on day 9 are necessary to cause yolk sac dysfunction or other teratogenic changes.

Abnormalities, Multiple↗
PubMed1986

Absence of phosphorylation of retinoid-binding proteins by protein kinase C in vitro.

Cellular retinol-binding protein, cellular retinoic acid-binding protein, and fetal cellular retinol-binding protein were purified to homogeneity and each polypeptide had a molecular weight of 16,000. Their apoproteins were not phosphorylated under the same conditions. Their holoproteins did not inhibit the phosphorylation of histone III-S by protein kinase C. Each of these observations is contrary to the results reported by Cope et al. (Biochem. Biophys. Res. Commun., 120, 593-601, 1984).

Animals↗