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Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 505 records · Page 28Linked to original sources

Method for stable measurement of the electrocardiogram in isolated guinea pig heart. Evaluation of the RR-QT relationship and the effect of quinidine.

A method for stable measurement of ECG in an excised guinea pig heart was presented. The effects of quinidine and its major metabolite, 3-OH quinidine, on QT interval were compared using excised guinea pig hearts with A-V nodal rhythm paced at a constant frequency (190 beats/min). The relative potency of 3-OH quinidine to its parent drug was about one-fourth. Taking into account the fact that the free fraction of 3-OH quinidine in blood is larger than quinidine, this metabolite may contribute to the effects of quinidine in man. Changing the frequency of electrical pacing in excised hearts with A-V nodal rhythm, the RR-QT relation was determined to be rather linear, and this relation became more curvilinear after addition of quinidine (2 mg/liter), suggesting that the Bazett's formula for correcting QT interval with the heart rate is not applicable to guinea pig heart and/or after an addition of drug.

Animals↗

Changes in brain thyrotropin-releasing hormone (TRH) of El mice.

The present study showed that DN-1417 had a dose-dependent anticonvulsant activity on El mouse seizure. This finding is consistent with other reports using the kindling model of epilepsy. Since both the El mouse and kindling preparations have been regarded as complex partial seizure with secondary generalization, endogenous brain TRH, as well as exogenous TRH, may act as an anticonvulsant substance to such a seizure type of epilepsy. Moreover, this study showed IR-TRH of the El mouse changed significantly in the striatum or hippocampus genetically or postictally without a change in the TRH receptor binding. A transient decrease in hippocampal IR-TRH after convulsion shown in this study may suggest an increased release of TRH during and after the seizure. Further studies are required to clarify the relationship between a change in the brain TRH system and seizure susceptibility in the El mouse.

Animals↗

Randomized double-blind trial of intracoronary urokinase for acute myocardial infarction: multicenter study.

The efficacy of intracoronary urokinase (UK) in an acute myocardial infarction has not been firmly established in a randomized fashion. Two hundred and ten patients were randomized to UK therapy (107 patients) and placebo (103 patients). Successful recanalization was achieved in 74% of the UK group vs 17% in the placebo group (p less than 0.01). The success rate was dose dependent up to 960,000 I.U. Clinical course was favorable and left ventricular enddiastolic pressure was reduced significantly in the UK group compared with the placebo group (p less than 0.05). Ejection fraction one month after the study was better in the reopened group than in the occluded group. Thus, early administration of UK can establish coronary reflow in a high proportion of patients and appears to favor the clinical course.

Aged↗

Changes in vascular responsiveness to vasoactive agents in the hindlimb of DOCA-salt hypertensive rats.

The responsiveness to vasoactive agents in the perfused hindlimb of DOCA-salt hypertensive rats was examined and compared with that of normotensive rats. The vasoconstrictor responses in the femoral vascular bed to norepinephrine and serotonin were markedly potentiated in DOCA-salt hypertensive rats as compared with those in normotensive rats, and no change was found in the responses to angiotensin II. On the other hand, the vasodilatory response in DOCA-salt hypertensive rats to isoproterenol was attenuated without any marked changes in responsiveness to acetylcholine, nitroprusside and papaverine. These results suggested that the reduced vasodilator responses as well as the increased vasoconstrictor responses occur to some specific vasoactive agents in DOCA-salt hypertensive rats.

Angiotensin II↗

Heterogeneity in vasorelaxant effects of alpha-human atrial natriuretic polypeptide in the dog.

Effects of alpha-human natriuretic polypeptide (ANP) on isolated canine vascular strips were examined in 6 arteries and 5 veins. Under the preconstriction with either methoxamine, prostaglandin F2 alpha or KCl, ANP relaxed the vascular strips to various degrees, depending on the region removed from the circulatory system. The largest relaxation was obtained in the pulmonary artery, suggesting that the pulmonary artery may be an important site of action of ANP.

Anesthesia↗

Effects of 2-[(5-chloro-2-methoxyphenyl) azo]-1H-imidazole (M6434) on alpha adrenergic receptors.

The effects of a newly synthesized compound, 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434) on alpha-adrenergic receptors were investigated by using the atria of normal and hypothyroid rats, rat vasa deferentia and canine arteries. M6434 showed a positive inotropic effect on rat left atria, which was suppressed by phentolamine but not by propranolol and reserpine. M6434 also showed a positive chronotropic effect on rat right atria. These positive inotropic and chronotropic effects of M6434 were enhanced in propylthiouracil-induced hypothyroid rats. M6434 caused contraction of rat vas deferens and increased its spontaneous movement. These effects on vas deferens were suppressed by phentolamine. M6434 induced contraction of canine arteries. The pD2 values for vasoconstrictive effects of M6434 on the aorta, pulmonary artery, renal artery and femoral artery were about equal to those of phenylephrine, and the intrinsic activity of M6434 was somewhat lower than that of phenylephrine. These results suggest that M6434 is an adrenergic alpha-agonist which is about as potent as phenylephrine and that M6434 has neither a beta-stimulating activity nor a catecholamine-releasing one.

Animals↗

Psychomotor performance tests using a microcomputer: evaluation of effects of caffeine and chlorpheniramine in healthy human subjects.

We have developed two kinds of microcomputer programs for evaluation of psychomotor function in man. In one (simple test), two single-digit random numbers are displayed, and the subject inputs the last figure of their sum from the keyboard. The performance during two sequential trial periods of 5 min with a rest interval of 1 min is evaluated. In the other (complicated test), four single-digit random numbers are displayed and the test is performed in the same manner. With the latter we intended to decrease the efficacy of performance by about 50% as compared with the former. A validation study of these programs was conducted in 20 healthy volunteers (14 males and 6 females) with caffeine as a central nervous stimulant. The study was a double-blind, placebo controlled and cross-over one. The subjects performed both of the above tests prior to and 1 h after an oral administration of a capsule containing either placebo or caffeine (230 mg) at an interval of 24 h. The numbers of correct answers during 10 min of trial were used for the evaluation of performance. The relationship between the performance of the simple test and that of the complicated test was linear and, as expected, the efficacy of the latter was about a half (48%) of the former in the total 40 performances of control. The concentration of caffeine in plasma was measured with and HPLC technique to be 4.4 +/- 1.7 micrograms/ml (mean +/- SD) 40 min after administration. Caffeine significantly (P less than 0.05) increased the performances of both tests 1 h after the administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reciprocal potentiation of a vasoconstrictor response between 5-hydroxytryptamine and clonidine in the perfused mesenteric vascular bed of the rat.

The interaction between 5-hydroxytryptamine (5-HT) and clonidine, an alpha 2-adrenoceptor agonist, was investigated in the isolated perfused mesenteric vascular bed of the rat. Clonidine itself did not cause vasoconstriction even at 300 micrograms. However, clonidine in the presence of 5-HT (10 and 100 nM) caused a marked vasoconstriction in a dose range of 0.1 micrograms to 300 micrograms. Prazosin inhibited the clonidine response, whereas yohimbine did not. The potency of prazosin against clonidine was less than that against an alpha 1-adrenoceptor agonist phenylephrine. Therefore, it is suggested that clonidine activated alpha 1-like adrenoceptors. 5-HT also potentiated the vasoconstrictor response to perivascular nerve stimulation, exogenous norepinephrine (NE) and phenylephrine. Calcium entry blockade by nicardipine (0.1 microM) reduced the response to clonidine in the presence of 5-HT, whereas that to phenylephrine in the presence or absence of 5-HT was not reduced. On the other hand, clonidine (0.01-1 microM) potentiated the vasoconstrictor effect of 5-HT more than NE did. Ouabain (1 microgram/ml) enabled clonidine to exhibit an agonistic action, and also enhanced the contractile response to 5-HT. In conclusion, 5-HT modulated the vasoconstrictor effect of clonidine, and the vasoconstriction with 5-HT was also facilitated by clonidine reciprocally. It is possible that a partial depolarization of the cell membrane is the common mechanism for their reciprocal potentiation.

Animals↗

Responses of cerebellar cortex to electrical stimulation of the glossopharyngeal nerve in the frog.

In the frog cerebellar cortex, electrical stimulation of the glossopharyngeal (IXth) nerve induced negative field potentials with a peak latency of 57 ms whose distribution was bilateral with ipsilateral predominance. The site where the maximum negativity was induced by IXth nerve stimulation was histologically located within the molecular layer near the Purkinje cell layer. In extracellular recording, electrical stimulation of the IXth nerve induced complex and/or simple spike discharges of Purkinje cells. Such evoked potentials and unitary spikes in the cerebellum were attributed to the excitation of the IXth nerve afferents of higher threshold which are mainly composed of fibers sensitive to taste stimulation. These results suggest that gustatory information projects to the cerebellum, as well as those of other kinds of senses, such as touch, visual and auditory sensation.

Animals↗

Prognostic factors in giant cell tumor of bone. A modified histological grading system useful as a guide to prognosis.

An analysis of 26 patients with giant cell tumor of bone was carried out to determine the clinical and pathological factors affecting the prognosis of the tumor, with a follow-up program of more than 3 years. The physical characteristics of the pathological features were measured objectively using an image analyzer. A significant correlation between the therapeutic procedures and recurrence of the tumor was found, but no pathological variables were significantly correlated. Excision or resection en bloc should be performed for the initial treatment of the tumor. Local recurrence could not be predicted on the basis of histological grading. Stromal cell atypia was significantly correlated with metastasis, but multinucleated giant cells bore no correlation to either recurrence or metastasis. The use of a modified histological grading system based not on variations of the stroma and giant cells but only on the atypia of mononuclear stromal cells, either malignant or classical, is recommended for the clinical assessment of the tumor.

Adolescent↗

Alternation in refractoriness and in conduction delay in the ischemic myocardium associated with the alternation in the ST-T complex during acute coronary occlusion in anesthetized dogs.

The effective refractory period (ERP) during the period of the alternation of the ST-T complex (STTA) in the ischemic myocardium was determined using a synchronized system of electrical stimulators and a bipolar epicardial electrode during acute coronary occlusion in anesthetized dogs. Epicardial unipolar electrograms (UP), epicardial bipolar electrograms (BP) and monophasic action potentials (MAP) were also recorded from ischemic areas. ERP in ischemic areas was prolonged, as ischemia progressed, and during the period of STTA ERP also alternately changed. A lower or negative deflection of the ST-T complex was accompanied by a longer ERP, and a higher or monophasic ST-T complex was accompanied by a shorter ERP. A good correlation was observed between the degrees of alternation in ERP and of STTA. MAP also showed an alternation in its duration and its amplitude. The alternation in duration preceded the alternation in amplitude. A lower or negative deflection of the ST-T complex corresponded to a MAP with a longer duration and a larger amplitude. During the period of STTA, a long conduction delay followed the negative deflection of the ST-T complex. A marked conduction delay appeared only during a period of STTA. Diltiazem and nifedipine inhibited STTA and an alternation in ERP. In conclusion, STTA is associated with an alternation in ERP and in conduction delay, and calcium antagonists attenuate both STTA and an alternation in ERP.

Action Potentials↗

Change in brain thyrotropin-releasing hormone (TRH) mechanism of amygdaloid kindled rats.

We reported previously that DN-1417, a potent analog of thyrotropin-releasing hormone (TRH), suppressed both the progression of amygdaloid (AM) kindling and AM kindled seizure. To study a functional role of the cerebral TRH mechanism in AM kindling, immunoreactive TRH (IR-TRH) and specific TRH receptor binding were examined in the rat brains kindled from the left AM. The IR-TRH concentration elevated significantly in the amygdala plus piriform cortex and the hippocampus 24 and 48 hours after the AM kindled convulsion. Such an elevation of IR-TRH was not found 7 days after the last convulsion, indicating that the elevation of IR-TRH was a transient change seen after the AM kindled convulsion. By contrast, the specific TRH receptor binding in the striatum increased 48 hours, 7 and 21 days after the AM kindled convulsion. This indicates that the increase of the specific TRH binding in the striatum was a long-lasting change. The present study suggests that the change in the striatal TRH receptors may be associated with a long-lasting seizure susceptibility of AM kindled rats.

Amygdala↗