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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 397 records · Page 22Linked to original sources
PubMed1994

Possible mechanisms of vasoinhibitory effects of mequitazine, an antiallergic agent, on the contractions of isolated rat aorta induced by K+, phenylephrine, 5-hydroxytryptamine, and Ca2+.

Mequitazine, 10-(3-quinuclidinylmethyl) phenothiazine, inhibited contractile responses to KCl, phenylephrine (PE), 5-hydroxytryptamine (5-HT), and Ca2+ in rat aorta. Indomethacin or removal of endothelium did not affect the inhibitory effect of mequitazine on the responses to PE. In Ca(2+)-free medium containing EGTA and nifedipine, mequitazine inhibited both residual response to PE and subsequent response to Ca2+ in the presence of PE. Mequitazine potentiated the relaxation to nitroglycerin (NTG) and isoproterenol. In the presence of forskolin, mequitazine did not cause further potentiation of NTG relaxation. Mequitazine relaxation was slightly inhibited by nifedipine and was potentiated by theophylline. The relaxation was not affected by zaprinast, methylene blue, W-7, propranolol, cimetidine, glyburide, or tetraethylammonium. Tissue level of cyclic AMP in rat aorta was increased by mequitazine. These results suggests that mequitazine may inhibit voltage-operated Ca2+ channels (VOC) and increases the level of cyclic AMP.

Animals↗
PubMed1994

Apoptosis induced in mouse hepatitis virus-infected cells by a virus-specific CD8+ cytotoxic T-lymphocyte clone.

Morphological changes of mouse hepatitis virus-infected J774.1 cells cocultured with cloned mouse hepatitis virus-specific CD8+ cytotoxic T lymphocytes were examined by electron microscopy. Condensation and margination of chromatin, cellular shrinkage with severe vacuolar degeneration, and blebbing were observed. In addition, fragmentation of cellular DNA was observed, and a decrease in virus titer was accompanied by those changes. These findings show that the cloned cytotoxic T lymphocytes induce in the target cell an internal degradation program termed apoptosis, which results in virus clearance.

Animals↗
PubMed1994

N-methyl-D-aspartate induces phase shifts in circadian rhythm of neuronal activity of rat SCN in vitro.

The suprachiasmatic nucleus (SCN) acts as a pacemaker for mammalian circadian rhythms. Receptors for excitatory amino acids like N-methyl-D-aspartate (NMDA) and non-NMDA receptors have both been found to play an important role in the transmission of photic information from the retina to the SCN. Therefore, we investigated whether the application of glutamate receptor agonists could reset the phase of the circadian rhythm of SCN firing activity in vitro. Treatment with NMDA (0.1-10 microM) for 15 min or 1 h during the early part of the subjective night produced phase delay, whereas treatment during the late subjective night caused an advance in phase. The phase-response curve for NMDA was similar to that previously obtained in response to light pulses in vivo. Application of DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (1 or 10 microM), a non-NMDA-receptor agonist, also produced a dose-dependent phase delay of SCN activity. The NMDA-induced phase delay was antagonized by an NMDA-receptor antagonist MK-801. These findings suggest that both NMDA and non-NMDA receptors may be involved in the transmission of information to the SCN via the retinohypothalamic tract. In addition, both the advances and delays in phase caused by NMDA were potentiated by cotreatment with neuropeptide Y, whereas AMPA-induced phase delay was not potentiated by neuropeptide Y. This points to a functional link between NMDA and neuropeptide Y receptor-mediated mechanisms in the SCN.

Animals↗
PubMed1994

Calmodulin inhibitors produce phase shifts of circadian rhythms in vivo and in vitro.

The effect of calmodulin inhibitors on the circadian rhythm of locomotor activity and on the rhythm of suprachiasmatic nuclear (SCN) neuron firing rate recorded in vitro from hypothalamic slices was examined. Trifluoperazine produces changes in a dose-dependent manner in the phase of the activity rhythm, with phase advances throughout most of the subjective day extending into the subjective night. These phase changes in the activity rhythm occur rapidly and without induction of locomotor activity at the time of treatment. Similarly, trifluoperazine and the naphthalenesulfonamide W-7 produce changes in phase delays in the subjective night extending into early subjective day. The effects are greater with respect to amplitude when measured acutely after treatment than in the next cycle, and both the acute and next-day effects are greater than those observed in vivo, indicating that data from in vitro studies need to be interpreted with caution. These observations indicate that calmodulin inhibitors affect rhythms directly in vivo by altering SCN neuron pacemaker function, as this reflects involvement of calcium-calmodulin binding with activation of a calmodulin-dependent kinase, either to alter intracellular cAMP levels or to alter gene expression directly to modulate the phase of the SCN clock.

Animals↗
PubMed1994

[Pharmacological study on circadian rhythms in mammals].

Living organisms including humans drive circadian rhythm, and this rhythm influences the social structure and daily life of human beings. The suprachiasmatic nucleus (SCN) has been established as a pacemaker for mammalian circadian rhythm. There are many kinds of neurotransmitters and neuromodulators in this nucleus. The circadian systems are involved in oscillation, input (entrainment) and output (overt rhythm). Therefore in this review, pharmacological characteristics of circadian systems in relation to the SCN are discussed by focussing especially upon the roles of various neurotransmitters and modulators.

Animals↗
PubMed1994

Observation study on natural walking in the Tokyo metropolitan.

In this study, data on walking speed, step numbers, cadence of natural walking were collected and their relations to foot wear, clothing, luggage carried and time of the day as well as crowdedness were investigated. This survey was held in Shinjuku, Tokyo in 1991. Six thousand three hundred and seventy nine walking people were observed from 10:00 am to 5:00 pm. Ten students who were trained to observe the walking were employed for the data collection. The observed subjects were divided into three age groups, namely young (less than 30 years), middle (31-60 years) and elder (over 61 years), and their age groups were decided by the students based on their appearance. For the analysis, they were further classified into male and female groups. The factors which affect walking speed, step number and cadence were taken into consideration. It was found that young people were more sensitive to their factors in their natural walking and old people showed lower flexibility to these factors.

Adult↗
PubMed1994

[Responses of electroencephalogram to different odors].

The responses of electroencephalogram (EEG) to different odors and their densities were studied on four men and two women at rest while sitting. The odors examined were citrus, floral and lavender, and their densities were 100 ppb and 200 ppb. The odors were released for ten minutes from a duct to fill the room completely. The subjective estimation indicated that citrus had a tendency to be the most comfortable odor in this study, but it was not significant. To evaluate changes of EEG, the power spectra of frequency-fluctuation of alpha wave (Fz) and the rate of alpha, beta, and beta/alpha wave (Oz, Fz) were calculated. The rate of alpha wave (Oz) in the period of giving out the citrus at 100 ppb was significantly (p < 0.05) higher than that of the lavender. The rate of beta wave (Oz) in the period of giving out the floral at 200 ppb was significantly (p < 0.05) higher than that of the lavender. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave in the period of giving out the lavender at 100 ppb was significantly higher than those in the other periods of the experiment. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave for lavender given out at 200 ppb was significantly (p < 0.01) higher than those for the other odors given out. It seems that the regression coefficient of the power spectra of frequency-fluctuation of alpha wave can be used for the evaluation of psychophysiological responses.

Adult↗
PubMed1994

Effect of suramin on 125I-insulin-like growth factor-I binding to human meningiomas and on proliferation of meningioma cells.

Suramin, a polyanionic compound, has been shown to inhibit the binding of various growth factors to cell surface receptors. The effects of suramin on 125I-insulin-like growth factor (IGF)-I binding to human meningioma tissues and IGF-I-induced deoxyribonucleic acid (DNA) synthesis in cultured meningioma cells were examined using the quantitative receptor autoradiographic method and 3H-thymidine incorporation, respectively. Suramin inhibited specific 125I-IGF-I binding to meningioma tissue sections in concentration-dependent manner, with a 50% inhibiting concentration (IC50) of 8.7 +/- 0.5 x 10(-5) M. The addition of 10(-3) M suramin to the incubation buffer potently dissociated 125I-IGF-I previously bound to meningioma tissue as a function of time (dissociation half-life (T1/2) 6.8 minutes). After preincubation of tissue sections with 10(-3) M suramin for 120 minutes, there was no inhibition of the subsequent 125I-IGF-I binding to meningiomas. Suramin inhibited the IGF-I-induced incorporation of 3H-thymidine into meningioma cells in a dose-dependent manner, with an IC50 of 4.6 +/- 1.4 x 10(-5) M. The growth rate of meningioma cells (determined 4 days after seeding) was reduced by 10%, 20%, and 50% of the control culture in the presence of 10(-6), 10(-5), and 10(-4) M suramin, respectively. These results suggest that suramin interferes with IGF-I binding to meningioma tissue and inhibits proliferation of cells, at least partially by preventing IGF-I-induced DNA synthesis and probably by interacting with IGF-I directly rather than with its binding sites.

Aged↗
PubMed1994

Expression of a functional endothelin (ETA) receptor in human meningiomas.

Endothelin (ET) receptor subtypes (ETA and ETB) in human meningiomas were characterized using quantitative receptor autoradiography. A single class of high-affinity 125I-ET-1 binding sites was localized in all meningioma tissue studied (dissociation constant: 2.4 +/- 0.3 nM, maximum binding capacity: 319 +/- 66 fmol/mg (mean +/- standard error of the mean for 13 tumors)). Unlabeled ET-1 showed a strong affinity for 125I-ET-1 binding to tissue sections of the tumors with a 50% inhibiting concentration (IC50) of 2.9 +/- 0.7 x 10(-9) M, whereas ET-3 showed a much lower affinity (IC50: 8.4 +/- 2.5 x 10(-6) M). Sarafotoxin S6c, a selective agonist for the ETB receptor, could not compete for 125I-ET-1 binding to meningiomas. Endothelin-1 significantly stimulated deoxyribonucleic acid (DNA) synthesis in a dose-dependent manner in cultured human meningioma cells. In contrast, no significant stimulation of DNA synthesis occurred with an S6c concentration up to 10(-7) M. Pretreatment of the meningioma cells with pertussis toxin, a bacterial toxin that adds adenosine 5'-diphosphate-ribose to the alpha subunit of guanine nucleotide binding (G) proteins such as Gi or G(o), induced a concentration-dependent reduction in ET-stimulated DNA synthesis in meningioma cells, but did not affect the epidermal growth factor-induced DNA synthesis. These observations suggest that the ETA receptor is predominantly expressed in human meningioma tissue and that ET may act as a growth factor on the meningioma cells by interacting with the ETA receptor and by pertussis toxin-sensitive mechanisms.

Adolescent↗
PubMed1994

Alteration of beta-D-glucan from edible mushroom after injection into mouse peritoneal cavity.

Tritium-labeled antitumor beta-D-glucan derivative (T-labeled glucan) was prepared from the branched beta-1,3-D-glucan of an edible mushroom, Volvariella volvacea, by its periodate oxidation followed by reduction with NaBT4. Twenty-three hours after T-labeled glucan had been injected into the mouse peritoneal cavity, about 3% of the total radioactivity injected was found in the mouse serum. In spite of the fact that T-labeled glucan had no affinity to the anion-exchange column before injection, about 50% of the labeled beta-D-glucan in the serum thus obtained was adsorbed onto the column. The labeled beta-D-glucan fraction eluted from the column by salt gradient showed antitumor activity in vivo.

Animals↗
PubMed1994

[Basic and clinical studies on biapenem (L-627) in obstetrics and gynecology].

UNLABELLED: We investigated biapenem (BIPM, L-627) a newly carbapenem antibiotic, for its antibacterial activity, tissue penetration, clinical efficacy and bacteriological effect in obstetric and gynecological infections, and obtained the following results. 1. Antibacterial activity: MICs of L-627 against 149 strains isolated from 80 patients in this clinical trial were examined and compared with those of imipenem (IPM) and ceftazidime (CAZ). The MIC50 and MIC90 of L-627 against the isolates were 0.2 and 12.5 micrograms/ml, respectively. Those of IPM were 0.2 and 6.25 micrograms/ml, respectively. The antibacterial activity of L-627 was quite similar to that of IPM, and was superior to that of CAZ. 2. Tissue and retroperitoneal fluid penetration: The peak levels in venous and uterine arterial sera were 24.0 and 26.2 micrograms/ml, respectively, after 300 mg drip infusion. The peak levels in the uterine or adnexal tissues were 2.39-9.60 micrograms/g, and 0.2 microgram/g of L-627 was detected at 275 minutes after administration. Peak levels in retroperitoneal fluid were 8.7 +/- 1.7 micrograms/ml at 1 hour after the completion of 30 minutes drip infusion (300 mg) and 7.9 +/- 0.2 micrograms/ml at 30 minutes after 300 mg 60 minutes drip infusion (300 mg). These levels expected the MICs against main pathogenic organisms. 3. CLINICAL RESULTS: L-627 was given to the following 144 patients (No. of analytical subjects) at a daily dose of 0.3-1.2 g for 2-13 days: intrauterine infections (54), adnexitis (36), parametritis (17), pelvic peritonitis (27), bartholins abscess (6) and other infections (4). The clinical efficacy was 93.1% (134/144) and the eradication rate against isolated organisms was 88.7% (110/124). Side effects were observed in 2 patients: eruption (1) and vomiting with numbness of the tongue (1). Abnormal change in laboratory test results included increase in eosinophils in 1, increase in GOT, GPT and gamma-GTP in 1 and increase in GPT and A1-P in 1, but all of these abnormalities were very mild and withdrawal of the drug was not required. Our results suggest that this drug is useful in the treatment of gynecological infections.

Adolescent↗
PubMed1994

Nephrosis augments contractile response to adrenoceptor agonists by the decrease in release of endothelium-derived relaxing factor from the endothelial cells.

The thoracic aorta was taken from nephrotic rats on the 40th day after a single i.v. injection of daunomycin (10 mg/kg). In the endothelium-intact aorta, the contractions induced by norepinephrine or B-HT 933, an alpha-2 adrenoceptor agonist, were significantly greater in nephrotic rats than in normal animals. However, such a difference was not observed in the KCl- or U46619-induced contractions. The difference in norepinephrine-induced contraction between nephrotic and normal preparations was enhanced by zaprinast, a cyclic GMP phosphodiesterase inhibitor. The contractions elicited by norepinephrine and B-HT 933 were potentiated by either removal of the endothelium or pretreatment with methylene blue, a guanylate cyclase inhibitor. The difference in the contractile response to these agonists between nephrotic and normal preparations was eliminated completely by either treatment. The cyclic GMP level in the endothelium-intact aorta in the presence of zaprinast was significantly lower in nephrotic rats than in normal animals. In the presence of zaprinast, norepinephrine, but not B-HT 933, caused an increase in the cyclic GMP level, which was abolished completely by pretreatment with prazosin, but not by yohimbine. These results suggest that the augmented contractile response to norepinephrine observed in nephrotic aorta may be due to the decrease in the stimulated release of endothelium-derived relaxing factor from the endothelial cells via the stimulation of endothelial alpha-1 adrenoceptors, whereas the augmented response to B-HT 933 may be due, at least in part, to the decrease in spontaneously released endothelium-derived relaxing factor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Neuropeptide Y and optic chiasm stimulation affect suprachiasmatic nucleus circadian function in vitro.

The retinohypothalamic tract (RHT) is a direct pathway from the retina to the suprachiasmatic nucleus (SCN). Electrical stimulation of the optic nerve or optic chiasm activates the RHT and produces shifts in phase of a circadian rhythm in SCN neuron activity in rat hypothalamic slices in vitro. The phase response curve (PRC) for this effect is very similar to that obtained from administration of light pulses to intact animals maintained in constant darkness. The effect of optic chiasm stimulation is blocked by tetrodotoxin. In addition to the RHT, there is a second entraining pathway, the geniculohypothalamic tract, which arises from neuropeptide Y (NPY)-containing neurons of the intergeniculate leaflet of the lateral geniculate complex. In contrast to optic chiasm stimulation. NPY produces phase shifts in the rhythms of SCN neuron firing rate in vitro with a PRC that similar to that for NPY infusion into the SCN in intact animals as well as that produced by a series of treatments that induce locomotor activity. These results indicate that phase shifts of the circadian rhythm of SCN neuron activity may be produced by activation of two different entraining pathways and that the physiological actions of these pathways on pacemaker function are markedly different.

Animals↗
PubMed1993

Facilitatory effect of phorbol ester on 2-deoxyglucose uptake in rat hippocampal slices.

It is well known that synaptic potentiation in the hippocampus can be produced by phorbol ester, a protein kinase C activator. The 2-deoxyglucose uptake is an index of regional glucose utilization which predominantly reflects activity in the axonal terminal of neuronal pathways. In the present experiment, therefore, we examined whether application of phorbol ester produces a facilitatory effect on 2-deoxyglucose uptake by the rat hippocampus in vitro. The application of phorbol-12,13-dibutyrate (PdBU) produced an elevation of 2-deoxyglucose uptake, while pretreatment with PdBU for 60 min eliminated the pdBU-induced elevation. Pretreatment with protein kinase C inhibitors, K252a (0.1 and 1 microM) or staurosporine (0.1 and 1 microM), was found to block significantly the PdBU-induced elevation of 2-deoxyglucose uptake. In addition, the facilitatory effect of glutamate, quisqualate and carbachol on 2-deoxyglucose uptake was reduced by pretreatment with PdBU. In the present experiment, we demonstrated that application of phorbol ester caused an elevation of 2-deoxyglucose uptake, which is linked in turn to neuronal activity, suggesting a positive relationship between protein kinase C activation and energy consumption.

Alkaloids↗
PubMed1993

Working memory deficits following muscarinic blockade combined with depletion of brain somatostatin in rats.

In a working memory task with three-panel runway paradigm, cysteamine, a depletor of somatostatin, at 100 or 200 mg/kg i.p. given 24 h before testing, had no effect on the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). Cysteamine at 100 mg/kg caused a significant reduction in somatostatin-like immunoreactivity in the rat brain, including the hippocampus and cerebral cortex. Working memory errors were significantly increased by scopolamine, a muscarinic receptor antagonist, at 0.32 mg/kg i.p. given 20 min before testing, whereas errors were not affected by the 0.1 mg/kg dose. Combined administration of 100 mg/kg cysteamine and 0.1 mg/kg scopolamine significantly increased the number of working memory errors. However, cysteamine at 100 mg/kg and scopolamine at 0.1 mg/kg had no effect on reference memory errors, whether they were administered alone or in combination. These results suggest that depletion of brain somatostatin aggravates working memory deficits induced by blockade of muscarinic receptors.

Animals↗
PubMed1993

Tetrodotoxin does not affect circadian rhythms in neuronal activity and metabolism in rodent suprachiasmatic nucleus in vitro.

Single unit activity of suprachiasmatic nucleus (SCN) neurons recorded from hamster and rat hypothalamic slices in vitro exhibits a circadian rhythm in firing rate. Tetrodotoxin (TTX) produces electrical silence during the period of administration but has no effect on the oscillatory activity of the circadian pacemaker in both hamster and rat SCN. TTX does not affect either the phase of the rhythm in firing rate at any time of the circadian day, or that of the rhythm in glucose metabolism as demonstrated by the 2-deoxyglucose method. These data are in accord with the view that SCN neuron firing rate and glucose utilization is an expression of pacemaker activity but that pacemaker function is maintained in the SCN independent of neuronal function manifested by sodium dependent action potentials.

Animals↗