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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 343 records · Page 19Linked to original sources
PubMed1995

The inhibitory mechanisms of nicorandil in isolated rat urinary bladder and femoral artery.

Nicorandil or cromakalim inhibited contractile responses to acetylcholine and KCl in detrusor muscles of rat urinary bladder, whereas nitroglycerin inhibited only the responses to acetylcholine. In the detrusor muscles contracted by electrical stimulations, relaxations caused by nicorandil and cromakalim were inhibited by glyburide, but not by nitroglycerin or apamin. Methylene blue slightly potentiated the nicorandil-relaxation without affecting the cromakalim-relaxation. NG-Monomethyl-L-arginine also did not affect the relaxation induced by nicorandil. The level of cGMP was increased by both nicorandil and nitroglycerin. In rat femoral arteries contracted by phenylephrine, the relaxation induced by nicorandil was inhibited by methylene blue, glyburide and apamin. The relaxation induced by cromakalim was inhibited by glyburide, but not by apamin or methylene blue. These results suggest that the effect of nicorandil is due to activation of KATP channels in rat detrusor muscles and is due to the activation of guanylate cyclase, KATP and KCa channels in rat femoral arteries. The effect of cromakalim is due to the activation of KATP channels in both smooth muscles.

Acetylcholine↗
PubMed1995

Glutathione protects against hypoxic/hypoglycemic decreases in 2-deoxyglucose uptake and presynaptic spikes in hippocampal slices.

The effects of glutathione, its analogue: YM737 (N-(N-gamma-L-glutamyl-L- cysteinyl) glycine l-isopropyl ester sulfate monohydrate), a monoester of glutathione, and N-acetyl-L-cysteine on hypoxia/hypoglycemia-induced decreases in CA1 presynaptic fiber spikes and 2-deoxyglucose uptake were investigated using rat hippocampal slices. The drugs were added to normal medium for 30 min before the incubation under hypoxic/hypoglycemic conditions (20 min), and, after a 3-h washout, presynaptic potential or 2-deoxyglucose uptake in hippocampal slices was measured. Treatment with glutathione, YM737 and N-acetyl-L-cysteine produced an attenuation of the hypoxia/hypoglycemia-induced decrease in presynaptic fiber spikes and 2-deoxyglucose uptake. The order of potency for neuroprotective action was YM737 > or = N-acetyl-L-cysteine > glutathione. The present results suggest a role for glutathione in improving hypoxia/hypoglycemia-induced dysfunction of hippocampal regions.

Acetylcysteine↗
PubMed1995

Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.

Adult↗
PubMed1995

Use of a new oligonucleotide probe for detection of colonization factor antigen III gene in enterotoxigenic Escherichia coli.

An alkaline phosphatase-labeled 30-mer oligonucleotide probe was designed to detect the gene for pilus colonization factor antigen III (CFA/III) of the human type of enterotoxigenic Escherichia coli (ETEC). The CFA/III probe was used to identify CFA/III-producing ETEC among 303 Escherichia coli obtained from subjects with traveler's diarrhea. Six isolates positive for the CFA/III gene were found. This result was confirmed immunologically by using a specific monoclonal antibody developed against CFA/III. These six isolates, isolated from travelers returning from India, Pakistan and China, were all positive for the gene of heat-labile enterotoxin and possessed an identical serotype (025:H-).

Antigens, Bacterial↗
PubMed1995

Expression of the small heat shock protein (hsp) 27 in human astrocytomas correlates with histologic grades and tumor growth fractions.

1. Cellular expression and distribution of the stress response small heat shock protein 27 (hsp27) in 39 high-grade astrocytomas (27 glioblastoma multiformes, 12 anaplastic astrocytomas) and in 27 low-grade astrocytomas (grade I-II) were analyzed immunohistochemically. 2. The correlation between hsp27 expression and tumor growth fractions of the astrocytomas was examined following Ki-67 immunostaining. 3. The hsp27 staining was cell cytoplasmic. The hsp27 immunopositive rate was significantly higher in high-grade astrocytomas; the rates was 74% for glioblastomas, 58% for anaplastic astrocytomas, and 37% for low-grade astrocytomas. The small and large tumor cells, especially in glioblastomas, multinucleated tumor giant cells, tumor cells in the pseudopalisading and necrotic areas, cells of the microvascular endothelial proliferations, and tumor vascular smooth muscles were usually hsp27 positive. The mean percentage of hsp27-positive cells was significantly higher in the glioblastomas alone and in the combined high-grade astrocytomas, compared to the low-grade, and in recurrent rather than in primary high-grade astrocytomas. 4. The high-grade astrocytomas had a highly statistical significant Ki-67 labeling index. The Ki-67 labeling indices were significantly higher in the hsp27-positive than the hsp27-negative astrocytomas, irrespective of the histological grade. In the high-grade astrocytomas with a Ki-67 labeling index of five and above, 81% of those tumors were hsp27 positive. 5. Thus, a large number of human astrocytomas express hsp27, and hsp27 expression correlates with histological grades of astrocytoma and with tumor growth fractions. This being the case, hsp27 is likely to have a role in the growth of human astrocytomas.

Adolescent↗
PubMed1995

Endothelin receptor in microvessels isolated from human meningiomas: quantification with radioluminography.

1. We characterized specific 125I-endothelin-1 (125I-ET-1) binding sites in microvessels isolated from human meningiomas, using an in vitro quantitative receptor autoradiographic technique coupled to a radioluminographic imaging plate system. 2. This newly developed and highly sensitive method revealed high-affinity ET receptors present in pellet sections of the microvessels from all the meningiomas studied, regardless of histological subtypes (dissociation constant, 1.2 +/- 0.3 nM; maximum binding capacity, 185 +/- 56 fmol/mg; means +/- SE for nine tumors). 3. In five cases of meningiomas, ET-3 competed for 125I-ET-1 binding to microvessels from those tumors with a low affinity [50% inhibiting concentration (IC50) of 1.6 +/- 0.4 x 10(-6) M], and a selective ETB receptor agonist, sarafotoxin S6c, up to 10(-6) M, did not displace ET binding from the sections. 4. In the sections of microvessels from four other tumors, biphasic competition curves were obtained in the case of incubation in the presence of increasing concentrations of ET-3, with an IC50 of 1.1 +/- 0.2 x 10(-9) M for the high-affinity component and 1.6 +/- 0.3 x 10(-6) M for the low-affinity component, respectively. In addition, S6c competed for ET binding to those sections (IC50 = 2.3 +/- 0.2 x 10(-10) M) and 10(-6) M S6c displaced 30% of the control, corresponding to the high-affinity component of competition curves obtained in the presence of ET-3. 5. Our results suggest that (a) capillaries in human meningiomas express a large number of high-affinity ETA (non-ETB) receptors with a small proportion of ETB receptors, and (b) ET may have a role in neovascularization, tumor blood flow, and/or function of the blood-tumor barrier in meningioma tissues by interacting with specific receptors present on the surface of the endothelium.

Adolescent↗
PubMed1995

Chemical structure of the carbohydrate moiety of fucose-rich glycopeptides from human pancreatic juice.

Human pancreatic juice, obtained from nine patients after partial excision of the pancreas for bile duct cancer, was fractionated in order to isolate its glycopeptides. Three glycopeptides were purified employing ion-exchange chromatography and gel filtration. All the glycopeptides were found to be free of sialic acid and galactosamine but to have an unusually high content of L-fucose. The chemical structures of the three glycopeptides were determined using 500-MHz [1H]-NMR spectroscopy. One of them, glycopeptide, GP-4, possessed a biantennary structure with three L-fucose residues. The second glycopeptide, GP-3, had a triantennary structure with four L-fucose residues, and the third one, G-2, had a tetra-antennary structure with five L-fucose residues. The chemical compositions of these glycopeptides, including the absence of sialic acid and the high L-fucose content, indicate that they represent a new class of glycopeptide present in the normal human pancreas.

Carbohydrate Sequence↗
PubMed1995

A histochemical study of apoptosis in the reduced ameloblasts of erupting mouse molars.

Apoptotic reactions were demonstrated with a commercial detection kit in the reduced ameloblasts around the tip of the cusp just before and after exposure to the mouth but, as tooth eruption advanced, they were no longer seen in the remainder of the reduced ameloblasts. Although some of the reduced ameloblasts appear to be expelled as a consequence of apoptosis, the remainder appear to constitute the junctional epithelium.

Ameloblasts↗
PubMed1995

Attenuating effect of arecoline and physostigmine on an impairment of mealtime-associated activity rhythm in old rats.

In the present study, we examined whether cholinergic drugs such as arecoline and physostigmine attenuated an impairment of time perception presented by daily scheduled feeding in aged rats. When feeding was restricted to a single meal at a fixed time of day (13:00-17:00) for 6 successive days, young rats exhibited intense locomotor activity from 1-3 h before feeding time. Intense locomotor activity was observed between 12:00-17:00 in young animals even on the fasting day (on day 7) (mealtime-associated activity). However, this mealtime-associated activity was impaired in old rats. Daily injection of arecoline (10 mg/kg) or physostigmine (0.1 and 0.2 mg/kg) at 17:00 for 6 successive days attenuated the impairment of mealtime-associated activity on the fasting day in a dose-dependent manner in old rats, whereas daily treatment with D-glucose (100 or 2000 mg/kg) did not. The results of the present study suggest that cholinergic drugs attenuate the impairment of the manifestation of mealtime-associated anticipatory activity related to 'temporal learning' in old rats.

Activity Cycles↗
PubMed1995

Attenuating effect of bifemelane on an impairment of mealtime-associated activity rhythm in aged and MK-801-treated rats.

In the present experiment, we examined the attenuating effect of bifemelane hydrochloride (BF), 4-(o-benzyl phenoxy)-N-methylbutylamine hydrochloride, on the impairment of time perception caused by daily scheduled feeding using aged and MK-801-treated rats. When feeding was restricted to a single meal at a fixed time of day (1300-1700 h) for six successive days, young rats exhibited intense locomotor activity 1-3 h before feeding time. Intense locomotor activity was observed for 1200-1700 h even on the fasting day (day 7; mealtime-associated activity). Mealtime-associated activity was impaired in 24-mo-old rats and also in N-methyl-D-aspartate receptor antagonist, MK-801-treated rats. Daily injections of bifemelane at 1700 h for six successive days significantly attenuated the impairment of mealtime-associated activity on the seventh day in a dose-dependent manner in aged rats. In addition, cotreatment of MK-801 with bifemelane blocked the MK-801-induced impairment of mealtime-associated activity. The present study suggests that bifemelane has an enhancing effect on learning and memory performance, such as spatial and temporal perception.

Aging↗
PubMed1995

Long-term enhancement of dopamine release by high frequency tetanic stimulation via a N-methyl-D-aspartate-receptor-mediated pathway in rat striatum.

We studied the effects of high frequency tetanic stimulation of the striatum on the KCl (20 mM)-evoked dopamine release in rat striatal slices. The KCl-evoked dopamine release was potentiated by high frequency tetanic stimulation (10-20 Hz) of the striatum including the corticostriatal fibers, and this potentiation was observed until 3 h after high frequency tetanic stimulation. Potentiation of dopamine release after high frequency tetanic stimulation was induced not only by KCl but also by glutamate in Mg(2+)-free medium, N-methyl-D-aspartate in Mg(2+)-free medium, and by DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. 2-amino-5-phosphovalerate, 3-[(+/-)-2-carboxypiperazine-4-yl]-propyl-1-phosphonate or dibenzocycloheptaneimine, N-methyl-D-aspartate receptor inhibitors, abolished enhancement by tetanus, whereas, 6,7-dinitroquinoxaline-2,3-dione, an antagonist of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ionotropic receptors, or L-2-amino-4-phosphonobutyrate, an antagonist of glutamate metabotropic receptors, showed no effect. Moreover, pretreatment with glutamate or N-methyl-D-aspartate in the absence of Mg2+ also facilitated dopamine release evoked by KCl concentrations. When extracellular Ca2+ was removed from the medium during pretreatment, potentiation by glutamate disappeared. We conclude that activation of N-methyl-D-aspartate receptors on dopaminergic nerve terminals in the striatum produces the long-term changes in efficacy of the response to KCl or glutamatergic agents. That is, plastical phenomena could exist at presynaptic levels between glutamatergic neurons and dopaminergic neurons in striatum.

Animals↗
PubMed1995

Potentiating effect of nicorandil, an antianginal agent, on relaxation induced by isoproterenol in isolated rat aorta: involvement of cyclic GMP-inhibitable cyclic AMP phosphodiesterase.

In rat aortic rings, isoproterenol (ISO) 10(-9)-3 x 10(-6)M relaxed the contraction induced by phenylephrine (PE) 3 x 10(-7)M. Pretreatment with nicorandil 3 x 10(-7) and 3 x 10(-6) M potentiated the relaxation induced by ISO. Nicorandil 3 x 10(-6) M also potentiated the relaxations induced by forskolin 3 x 10(-9) - 10(-6) M and dibutylyl-cyclic AMP 3 x 10(-6) - 3 x 10(-4) M. Nitroglycerin (NTG) 10(-8) M, but not cromakalim 3 x 10(-8) M, also potentiated the ISO relaxation. Pretreatment with glyburide 10(-6) M or apamin 10(-6) M did not affect the potentiating action of nicorandil 3 x 10(-6) M. Pretreatment with methylene blue (MB) 10(-6) M, but not with NG-monomethyl-L-arginine (NMMA), however, markedly inhibited the potentiating effect of nicorandil. Removal of endothelium impaired the relaxation induced by ISO but did not inhibit the potentiating effect of nicorandil. In addition, in the presence of MCl-154 (10(-7) M), which itself potentiated ISO-induced relaxation, nicorandil 3 x 10(-6) M did not further potentiate the relaxing response to ISO. Furthermore, nicorandil 3 x 10(-6) M potentiated the increase in the tissue level of cyclic AMP caused by ISO 3 x 10(-7) M, whereas the nicorandil-induced increase in cyclic GMP levels were not affected by ISO. These results suggest that the potentiating effect of nicorandil on the relaxation induced by ISO is most likely due to inhibition of phosphodiesterase III (PDE III) by increased cyclic GMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Detection of beta cell-specific DNA damage in streptozotocin-treated rats by in situ nick translation with immunostaining of alpha cells.

In situ nick translation with immunostaining of alpha cells could demonstrate the specific localization of streptozotocin- (STZ) induced DNA damage in beta cells using in vivo materials. The extent of DNA damage was determined through autoradiography by counting the number of grains in the nucleus of the alpha, beta, and exocrine cells of the rat pancreas. Subsequently, in situ nick translation with immunostaining of alpha cells was carried out in a pancreas pretreated with STZ. The number of grains observed in the beta cells of the STZ-treated groups was significantly higher than that in the control group. DNA damage of pancreatic beta cells due to STZ could be detected visually using in situ nick translation with immunostaining of alpha cells. Moreover, it was also possible to compare the DNA damage in the individual cells of the pancreas.

Animals↗
PubMed1995

Effect of acetazolamide on regional cerebral oxygen saturation and regional cerebral blood flow.

BACKGROUND AND PURPOSE: To verify whether the monitoring of regional cerebral oxygen saturation (rSO2) with transcranial near-infrared spectroscopy would successfully reflect changes in intracranial hemodynamics but not changes in extracranial compartment, we measured rSO2 and regional cerebral blood flow (rCBF) simultaneously in seven patients with cerebral ischemia and five normal volunteers before and after acetazolamide administration. SUMMARY OF REPORT: The baseline values of rSO2 and rCBF were 64.2 +/- 5.6% and 53.9 +/- 11.1 mL/100 g per minute, respectively. rCBF increased by 44.4 +/- 23.3% and rSO2 significantly increased to 69.6 +/- 5.6% after acetazolamide administration. Bilateral simultaneous measurement of rSO2 indicated a tendency that the larger the delta rSO2, the greater the delta%rCBF. The relationship between rSO2 level and rCBF value fit significantly on the theoretical curve calculated from Fick's equation. CONCLUSIONS: It is suggested that monitoring of rSO2 with INVOS-3100 could be a useful indicator in the evaluation of intracranial hemodynamic changes.

Acetazolamide↗
PubMed1995

Antitumorigenic activities of chalcones. I. Inhibitory effects of chalcone derivatives on 32Pi-incorporation into phospholipids of HeLa cells promoted by 12-O-tetradecanoyl-phorbol 13-acetate (TPA).

More than forty chalcone derivatives were synthesized to examine their structure-activity relationship against tumorigenesis. As a primary screening test, the inhibitory activities of the chalcones for the 32Pi-incorporation into phospholipids of HeLa cells enhanced by 12-O-tetradecanoyl-phorbol 13-acetate (TPA) were examined. 3-Hydroxy-chalcone derivatives possessing methyl group in 3'-, 4'-, or 2'-position and isoliquiritigenin homologs showed potent inhibitory activities in the phosphorylation test, which suggests their antitumorigenic effects.

Animals↗
PubMed1995

The emergence of free radicals after acoustic trauma and strial blood flow.

The effect of acoustic trauma on cochlear strial circulation was investigated immunohistologically in the guinea pig. Kanamycin was used as a tracer of blood flow. Moreover, histochemical examinations were made to reveal the emergence of free radicals in the cochlea following acoustic trauma. At 5 min (5 min after intense sound exposure 120-125 dB SPL, 3 h) the blood flow in the stria vascularis was greatly diminished. At 2 h the strial blood flow started to recirculate and at 6 h it appeared to have returned to normal. Superoxide anion radicals (O2-) emerged along the luminal membrane of the marginal cells of the stria vascularis at 5 min. O2- disappeared at 30 min, but reappeared at 2 h. The cause of its emergence at 5 min was obscure. However, the strange phenomenon that O2- emerged again at 2 h seemed ascribable to the re-circulation of strial blood flow after sound exposure.

Animals↗