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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 415 records · Page 23Linked to original sources

Effect of pilocarpine on striatal acetylcholine release in dopamine-depleted rats.

We have previously demonstrated that the systemic administration of pilocarpine stimulates striatal acetylcholine (ACh) release in rats using a brain microdialysis technique. In the present study, we investigated whether a nigro-striatal dopaminergic system is involved in the pilocarpine-induced increase in striatal ACh release using dopamine-depleted rats under urethane anesthesia. The application of pilocarpine (0.1-10 mM) via the microdialysis tube increased striatal ACh release in normal rats in a concentration-dependent manner, but it had no effect on the release of glutamate or gamma-aminobutyric acid (GABA) from the striatum. The increase in striatal ACh release caused by pilocarpine (1 mM) was enhanced by reserpine and alpha-methyl-p-tyrosine treatment, which completely depleted dopamine in the striatum. These results suggest that pilocarpine selectively increases striatal ACh release by acting at the striatum, and that the nigro-striatal dopaminergic neurons play an inhibitory role in the pilocarpine-induced ACh release.

Acetylcholine↗

Centrally applied nitric oxide donors inhibit vagally evoked rat gastric acid secretion: involvement of sympathetic outflow.

ntracerebroventricularly (i.c.v.) administered nitric oxide (NO) donors, 3-morpholinosydnonimine (SIN-1) (100-500 microg/animal) and sodium nitroprusside (SNP) (100-250 microg/animal) dose-dependently inhibited the rat gastric acid secretion evoked by vagal stimulation at 3 Hz. Furthermore, the inhibitory effect of SIN-1 (250 microg/animal) was more marked and its onset was more rapid than that of SNP (250 microg/animal). The SIN-1 (250 microg/animal)-induced antisecretory effect was abolished by both splanchnicotomy and phentolamine (5 mg/kg, i.m.), and also by indomethacin (500 microg/animal, i.c.v.). These results suggest that i.c.v. administered NO donors inhibit vagally evoked gastric acid secretion by activation of central sympathetic outflow. Central prostaglandin is probably implicated in this NO-mediated antisecretory effect.

Adrenergic alpha-Antagonists↗

Tacrine improves working memory deficit caused by permanent occlusion of bilateral common carotid arteries in rats.

Effect of tacrine, a cholinesterase inhibitor, on spatial acquisition deficit caused by permanent occlusion of bilateral common carotid arteries (2VO) was examined by using the conventional 8-arm and the 4-arm baited radial maze tasks in rats. Daily administration of tacrine (0.1 and 0.3 mg/kg, i.p.) 1 month after 2VO operation significantly improved the impaired spatial acquisition in the conventional maze task. This treatment also ameliorated the 2VO-induced working but not reference memory deficit in the 4-arm baited radial maze task. These results suggest that tacrine improvement of working memory deficit in the 2VO rats is due to stimulation of central cholinergic systems.

Animals↗

Stimulation by urocortin of growth hormone (GH) secretion in GH-producing human pituitary adenoma cells.

Urocortin (Ucn) possesses high homology with CRH and is considered to be a ligand to type-2 CRH receptor. We investigated the effect of Ucn on hormone release from cultured GH-producing human pituitary adenoma cells in vitro. GH-producing human pituitary adenoma cells were superfused on a Sephadex G-25 column. Both Ucn (10 nM) and CRH (10 nM) elicited an increase in GH release from the pituitary adenoma cells in one patient with acromegaly. In contrast, GH release from the pituitary adenoma cells was stimulated by Ucn but not by CRH in the other patient with acromegaly. These preliminary findings suggest that type-2 CRH receptors are expressed in some population of GH-producing human pituitary adenoma cells and that Ucn might be involved in GH secretion from tumorous tissues in patients with acromegaly.

Adenoma↗

Histopathological improvement of acromegalic cardiomyopathy by intermittent subcutaneous infusion of octreotide.

We studied functional and histopathological changes in acromegalic cardiomyopathy following intermittent subcutaneous infusion of octreotide. A 68-year-old female patient with acromegaly associated with congestive heart failure due to dilated cardiomyopathy was initially treated with cardioactive medication for three months, but it was not effective in correcting echocardiographic abnormalities. Further treatment with intermittent subcutaneous infusion of octreotide (20 microg/2 h) for 12 months not only reduced circulating GH and insulin-like growth factor-I (IGF-I) levels but also considerably improved histopathological changes in the myocardial specimen biopsied. These findings provide the first evidence of the favorable effect of octreotide on histopathological changes in acromegalic cardiomyopathy.

Acromegaly↗

Ethanol sclerosis: one of the best treatments for thymic cyst in very elderly patients?

An 83-year-old female patient with a giant thymic cyst that was successfully treated by percutaneous aspiration and ethanol injection. The patient had complained of coughing and chest discomfort for several years. A chest X-ray film revealed the shadow of a large abnormal mass in the anterior mediastinum. We diagnosed it as a thymic cyst. The patient refused surgery because of her age. We chose a less invasive therapy, namely, ethanol sclerosis of the cyst. The cyst was successfully treated without any complications, and no recurrence was found at the one-year follow-up. This therapy may be one of the best treatments for thymic cysts, especially in very elderly patients.

Aged↗

Cloning and characterization of novel gene, DCRR1, expressed from Down's syndrome critical region of human chromosome 21q22.2.

The new gene, DCRR1, from the proximal part of the Down's syndrome critical region (DCR) was identified by the GRAIL analysis of the 97-kb nucleotide sequence of two P1 DNAs and the cDNA for DCRR1 gene was cloned. A 7.36-kb cDNA encodes the imcompleted open reading frame composed of 1941 amino acid residues (220.2 kDa). The deduced amino acid sequence contains the conserved domain for protein phosphatases at the N-terminus. The domain encoding the rod-like tail of a myosin heavy chain was also found near the C-terminal region besides the signature for an actin binding protein, profilin, suggesting its possible role as a microtuble-associated protein. Two different sizes (7.9 and 9.0 kb) of mRNAs were detected in the poly(A)+ RNA from abundant tissues by the Northern analysis. The smaller transcript was only transcribed at a high level in the testis. The imbalance of the DCRR1 gene dosage may contibute to the pathogenesis of Down's syndrome.

Amino Acid Sequence↗

Glycation and inactivation of aspartate aminotransferase in diabetic rat tissues.

Glycated cytosolic aspartate aminotransferase was detected in the liver and kidney of streptozotocin diabetic rats using a boronate affinity column for adjacent cis-hydroxyl groups and an immunoblotting technique. The enzymatic activity and amount of immunoreactive substance were determined in the liver, kidney, and erythrocytes of diabetic and control rats. The ratio of enzymatic activity to the amount of enzyme was lower in diabetic rat tissue than in that in the control rats. It has been suggested that there is an inactive aspartate aminotransferase molecule in the tissues of diabetic rats. We therefore suggest that the cytosolic aspartate aminotransferase was inactivated in the diabetic rat tissues by a glycation reaction, accompanied by an impairment in glucose utilization.

Alkaline Phosphatase↗

[Reliability and validity of a self-administered questionnaire of patient health care behavior and satisfaction].

The reliability of a self-administered questionnaire of health care behavior and patient satisfaction, and also the validity of measuring patient satisfaction by a single question, were investigated on 754 outpatients and 204 inpatients. In order to assess the reliability and the validity, the questionnaire was administrated twice. Subjects for reliability tests were 194 outpatients and 91 inpatients and validity tests were performed with 280 outpatients and 84 inpatients. To assess the validity of patient satisfaction, supplementary questions about satisfaction (outpatients 22 items, inpatients 14 items) were included in the questionnaire. Reliability was assessed using kappa coefficient and proportion of agreement. To assess validity, principal component analysis was performed, and the correlation between principal-components and the score of patient satisfaction was analyzed. With the exception of patient understanding of the doctor's explanation and patient satisfaction, kappa coefficient and proportion of agreement were high (kappa: 0.4 approximately 0.82), indicating that question contents were objective and easily understood. By making the question categories simple, a higher kappa coefficient and proportion of agreement in patient understanding about doctor's explanation and patient satisfaction were achieved. This suggests that in questionnaire, similar question category must be made simple or similar categories should be put together in analysis. Spearman's correlation coefficient between the question about patient satisfaction and the first principal component (which summarizes all of the questions about patient satisfaction) was high (outpatients: 0.63, inpatients: 0.67). Therefore the validity of measuring general information about patient satisfaction by using a single question is suggested.

Female↗

[Response rates and non-response bias in a health-related mailed survey].

A health-related mailed survey was conducted to investigate the effect of follow-up mailings to response rates. In addition, the answer distributions among early and late respondents were compared to check non-response bias. Approximately 3,000 persons aged 40-64 were randomized into two groups; a questionnaire with four pages (twenty-two questions) was assigned to the first group, and a questionnaire with eight pages (thirty-five questions) to the second group. Both questionnaires contained questions of current health status, health-related practice, smoking status, etc. Follow-up mailings were sent twice to non-respondents. Response rates were increased from 38% to 62% by the first follow-up mail, and to 71% by the second follow-up mail. Although the length of the questionnaire did not affect response rates, response rates among the older subjects was higher than the younger subjects. Positive response to current smoking status was 10% lower among early respondents than late respondents, collected after the second follow-up mailing, and response to regular participation in physical/medical checkup was 15% higher among early respondents, whereas there were few differences for answers to other questions. Odds ratios between current health status and several health-related questions may not be biased by late response. However, increased response rates are needed to prevent non-response bias, because there were some differences in responses from follow-up mailings.

Adult↗

Nitric oxide mediates central activation of sympathetic outflow induced by interleukin-1 beta in rats.

The excitatory mechanism of central sympathetic outflow induced by interleukin-1 beta was investigated in urethane-anesthetized rats. Intracerebroventricular administration of interleukin-1 beta induced a gradually developing elevation of plasma noradrenaline levels in a dose-dependent manner (50, 100 and 200 ng/animal), while the levels of adrenaline were not affected. The elevation of noradrenaline levels induced by interleukin-1 beta (100 ng/animal i.c.v.) was abolished by the following treatments with: (1) a chemical sympathectomizer, 6-hydroxydopamine (15 mg/kg i.v., 3 days before); (2) a prostaglandin synthesis inhibitor, indomethacin (500 micrograms/animal i.c.v.); (3) a nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (100 micrograms plus 10 micrograms/min i.c.v.); and (4) a nitric oxide scavenger, oxyhemoglobin (32.3 micrograms plus 3.23 micrograms/min i.c.v.). In contrast to these results, D-NG-nitroarginine methyl ester, an inactive isomer of L-NG-nitroarginine methyl ester, and methemoglobin, a metabolite of oxyhemoglobin, were without effect. Furthermore, prostaglandin E2 (100 ng/animal i.c.v.) rapidly and markedly elevated the plasma level of noradrenaline but not adrenaline. This prostaglandin E2-induced elevation of plasma noradrenaline levels was not attenuated by L-NG-nitroarginine methyl ester (100 micrograms plus 10 micrograms/min i.c.v.). The present results suggest that nitric oxide is involved in the interleukin-1 beta-induced central activation of sympathetic outflow. Furthermore, there probably exists nitric oxide-linked prostaglandin-generating system in the brain.

Anesthesia, General↗

Central antinociceptive effects of mitragynine in mice: contribution of descending noradrenergic and serotonergic systems.

Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna speciosa Korth, that is known to exhibit narcotic-like activity. In this study, we investigated the roles of central monoaminergic systems in the antinociceptive action of mitragynine by means of the tail-pinch and hot-plate tests in mice. Mitragynine (1.0-10 micrograms) injected i.c.v. exerted a dose-dependent antinociceptive activity in both tests. The activity of mitragynine (10 micrograms, i.c.v.) in the tail-pinch test was antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalnine treatment, whereas the antinociceptive activity of morphine (3 micrograms) given i.c.v. in this test was attenuated by 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine treatment. Moreover, the activity of i.c.v. mitragynine was also antagonized by the alpha 2-adrenoceptor antagonist, idazoxan (10 micrograms), and cyproheptadine (1 microgram) administered intrathecally (i.t.). On the other hand, the antinociceptive action of i.c.v. mitragynine (10 micrograms) in the hot-plate test was abolished by reserpine and 6-hydroxydopamine plus nomifensine, but not by p-chlorophenylalanine treatment. This action was also antagonized by i.t. injection of idazoxan (10 micrograms). These results suggest that both descending noradrenergic and serotonergic systems are involved in the antinociceptive activity of supraspinally administered mitragynine on the mechanical noxious stimulation, while the descending noradrenergic system predominantly contributes to the effect of supraspinal mitragynine on the thermal noxious stimulation. The mechanisms underlying the suppressive action of mitragynine on the nociceptive response may differ from those of morphine in mice.

Adrenergic alpha-2 Receptor Antagonists↗