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Biomedical subjects

Y Sugimoto

Publications and source records attributed to Y Sugimoto.

At least 163 records · Page 9Linked to original sources
PubMed1999

Backward movements of cross-bridges by application of stretch and by binding of MgADP to skeletal muscle fibers in the rigor state as studied by x-ray diffraction.

The effects of the applied stretch and MgADP binding on the structure of the actomyosin cross-bridges in rabbit and/or frog skeletal muscle fibers in the rigor state have been investigated with improved resolution by x-ray diffraction using synchrotron radiation. The results showed a remarkable structural similarity between cross-bridge states induced by stretch and MgADP binding. The intensities of the 14.4- and 7.2-nm meridional reflections increased by approximately 23 and 47%, respectively, when 1 mM MgADP was added to the rigor rabbit muscle fibers in the presence of ATP-depletion backup system and an inhibitor for muscle adenylate kinase or by approximately 33 and 17%, respectively, when rigor frog muscle was stretched by approximately 4.5% of the initial muscle length. In addition, both MgADP binding and stretch induced a small but genuine intensity decrease in the region close to the meridian of the 5.9-nm layer line while retaining the intensity profile of its outer portion. No appreciable influence was observed in the intensities of the higher order meridional reflections of the 14.4-nm repeat and the other actin-based reflections as well as the equatorial reflections, indicating a lack of detachment of cross-bridges in both cases. The changes in the axial spacings of the actin-based and the 14.4-nm-based reflections were observed and associated with the tension change. These results indicate that stretch and ADP binding mediate similar structural changes, being in the correct direction to those expected for that the conformational changes are induced in the outer portion distant from the catalytic domain of attached cross-bridges. Modeling of conformational changes of the attached myosin head suggested a small but significant movement (about 10-20 degrees) in the light chain-binding domain of the head toward the M-line of the sarcomere. Both chemical (ADP binding) and mechanical (stretch) intervensions can reverse the contractile cycle by causing a backward movement of this domain of attached myosin heads in the rigor state.

Actomyosin↗
PubMed1999

Impaired duodenal bicarbonate secretion and mucosal integrity in mice lacking prostaglandin E-receptor subtype EP(3).

BACKGROUND & AIMS: To examine the involvement of EP(3) receptors in physiological regulation of duodenal HCO(3)(-) secretion, we disrupted the gene encoding EP receptors in mice by homologous recombination and evaluated acid-induced HCO(3)(-) secretion, which is physiologically important in the mucosal defense against acid injury, using EP(1)- and EP(3)-receptor knockout mice. METHODS: The experiments were performed in the following 3 groups of mice after 18 hours of fasting: wild-type [WT (+/+)] mice, EP(1)-receptor knockout [EP(1) (-/-)] mice, and EP(3)-receptor knockout [EP(3) (-/-)] mice. Under urethane anesthesia, the proximal duodenal loop was perfused with saline that was gassed with 100% O(2), heated at 37 degrees C, and kept in a reservoir, and HCO(3)(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 5 mmol/L HCl. RESULTS: The duodenum of WT (+/+) mice increased HCO(3)(-) secretion in response to luminal perfusion of prostaglandin E(2) and forskolin as well as mucosal acidification. The latter effect was significantly inhibited by prior administration of indomethacin. HCO(3)(-) response to acid was observed in EP(1) (-/-) mice but disappeared totally in EP(3) (-/-) animals, although the acidification increased mucosal PGE(2) generation by similar degrees in all groups. The HCO(3)(-) stimulatory action of PGE(2) was also absent in EP(3) (-/-) but not EP(1) (-/-) mice, but forskolin effect was observed in both groups of animals, similar to WT (+/+) mice. Perfusion of the duodenum with 20 mmol/L HCl for 4 hours caused severe damage in EP(3) (-/-) mice and WT (+/+) animals pretreated with indomethacin, but not in EP(1) (-/-) mice. CONCLUSIONS: The presence of EP(3)-receptors is essential for maintaining duodenal HCO(3)(-) secretion and mucosal integrity against luminal acid.

Animals↗
PubMed1999

Effects of intracerebroventricular injection of alpha-fluoromethylhistidine on radial maze performance in rats.

The effects of alpha-fluoromethylhistidine (alpha-FMH) on spatial cognition were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (ICV) injection of alpha-FMH resulted in spatial memory deficits characterized by an increase in the number of total errors (TE) and a decrease in the number of initial correct responses (ICR). There was a strong correlation between increases in the number of TE and decreases in histamine contents of the cortex and hippocampus regions of the brain, which are known to participate in learning and memory. On the other hand, both histamine (50-100 ng, ICV) and thioperamide (10 microg, ICV) significantly ameliorated the memory deficit induced by alpha-FMH. However, metoprine showed no significant effect on the alpha-FMH-induced memory deficit. Pyrilamine and R-(alpha)-methylhistamine enhanced the memory deficit induced by alpha-FMH, at doses that had no appreciable effect when administered alone. In contrast, no significant influence on alpha-FMH-induced memory deficit was observed with zolantidine.

Animals↗
PubMed1999

Applicability of bovine microsatellite markers for population genetic studies on African buffalo (Syncerus caffer).

The applicability of bovine autosomal microsatellite markers for population genetic studies on African buffalo was investigated. A total of 168 microsatellite markers were tested for PCR amplification on a test panel of seven African buffalo. Amplification was observed for 139 markers (83%), and 101 markers were studied further with 91 (90%) being polymorphic. The mean number of alleles per marker was 5.0 (SE = 0.2) and the mean heterozygosity per marker was 0.61 (SE = 0.03). Considering the overall high level of polymorphism, it was concluded that most bovine microsatellite markers are applicable in African buffalo.

Alleles↗
PubMed1999

Roles of prostaglandin E receptors in mesangial cells under high-glucose conditions.

BACKGROUND: High glucose reportedly stimulates prostaglandin (PG) E2 production and DNA synthesis in mesangial cells (MCs). However, the pathophysiological significance of PGE2 in MCs has remained unclear. METHODS: The effects of prostanoids on [3H]-thymidine uptake and cAMP production in rat MCs cultured with 5.6 mM glucose, 25 mM glucose, or 5.6 mM glucose supplemented with 19.4 mM mannitol were examined. The gene expression of PGE2 receptor (EP) subtypes in MCs was analyzed with Northern blotting techniques. RESULTS: Northern blotting indicated EP1 and EP4 gene expression in MCs. EP1 agonists and PGE2 stimulated [3H]-thymidine uptake in MCs. EP1 antagonists dose dependently attenuated high-glucose-induced [3H]-thymidine uptake, which suggests EP1 involvement, by an increase in intracellular Ca2+, in DNA synthesis of MCs. On the other hand, forskolin, db-cAMP, and 11-deoxy-PGE1, an EP4/EP3/EP2 agonist, significantly decreased DNA synthesis in MCs. These inhibitory effects are thought to be mediated via EP4 as a result of an increase in cAMP synthesis. The effects via EP4 seem to be particularly important because PGE2-induced cAMP synthesis was significantly attenuated in the high-glucose group compared with the mannitol group, in which [3H]-thymidine uptake did not increase in spite of augmented PGE2 production. CONCLUSION: The increase in DNA synthesis in MCs under high-glucose conditions can be explained, at least in part, by the high-glucose-induced inhibition of cAMP production via EP4, which augments EP1 function in conjunction with the overproduction of PGE2.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. Comparison with plasma angiotensin II and endothelin-1.

AIMS: To evaluate the level of plasma brain natriuretic peptide as a predictor of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. METHODS: We measured plasma levels of atrial natriuretic peptide, brain natriuretic peptide, norepinephrine, angiotensin II, and endothelin-1 and monitored haemodynamic parameters in 290 consecutive patients with asymptomatic or minimally and newly symptomatic left ventricular dysfunction (functional classes I-II, mean left ventricular ejection fraction=37%). All patients were followed up for a median period of 812 days. The Cox proportional hazards model was used to assess the association of variables with mortality and morbidity. RESULTS: At the end of the follow-up, 24 patients had suffered cardiac death and 25 had been hospitalized for worsening heart failure during the follow-up period. Among 21 variables such as clinical characteristics, treatment, haemodynamics, and neurohumoral factors, high levels of plasma brain natriuretic peptide (P<0.0001), norepinephrine (P=0.042), left ventricular end-diastolic volume index (P=0.0035), and left ventricular end-diastolic pressure (P=0.033) were shown to be independent predictors of mortality and morbidity by stepwise multivariate analysis. Moreover, only a high level of plasma brain natriuretic peptide (P<0.0001) was shown to be an independent predictor of mortality in these patients. CONCLUSIONS: These results indicate that a high plasma brain natriuretic peptide level provides information about mortality and morbidity in patients with asymptomatic or minimally symptomatic left ventricular dysfunction.

Adolescent↗
PubMed1999

Formation of the myosin.ADP.gallium fluoride complex and its solution structure by small-angle synchrotron X-ray scattering.

In the presence of MgADP, a novel phosphate analogue of gallium fluoride (GaFn) forms a ternary complex with the myosin subfragment-1 (S-1), in the same way that has been previously reported with aluminum fluoride (AlF4-), beryllium fluoride (BeFn), scandium fluoride (ScFn), and vanadate (Vi), and this complex formation may mimic different states along the ATPase kinetic pathway. This novel complex has been characterized and compared with other complexes to ascertain whether it forms a transition-state analogue of myosin ATPase. The complex formed quickly, although several times slower than the BeFn complex. The half-life of the myosin.ADP.GaFn complex was about 50 h at 4 degreesC. The formation of the myosin.ADP.GaFn complex was accompanied by an increase in tryptophane fluorescence, similar to that observed upon the addition of ATP, but slightly lower than that of the M**.ADP.Pi complex. Upon addition of GaFn to acto-myosin.ADP, acto-myosin did not dissociate, and the S-1.ADP.GaFn complex was scarcely decomposed by actin, like the AlF4- and ScFn complexes but unlike the BeFn and Vi complexes. The conformations at the localized region of SH1, SH2, and RLR, which are very accessible to the binding of ATP, were studied by fluorescent labeling and chemical modification, and the results suggested that these conformations are very similar to that of the M**.ADP.Pi state. Small-angle X-ray solution scattering showed that the radius of gyration value decreases by about 3 A when S-1 forms an S-1.ADP.GaFn complex, suggesting that the shape of the complex becomes compact or rounded in shape, similar to that in the presence of ATP or complexes with other phosphate analogues, and thus mimics the myosin**.ADP.Pi state closely. The overall results may indicate that the complex mimics a somewhat different transient state from that of other complexes but has a similar global conformation along the ATPase kinetic pathway.

Actins↗
PubMed1999

Binding pockets of the beta(1)- and beta(2)-adrenergic receptors for subtype-selective agonists.

We examined the subtype-selective binding site of the beta-adrenergic receptors (betaARs). The beta(1)/beta(2)-chimeric receptors showed the importance of the second and seventh transmembrane domains (TM2 and TM7) of the beta(2)AR for the binding of the beta(2)-selective agonists such as formoterol and procaterol. Alanine-substituted mutants of TM7 of the beta(2)AR showed that Tyr(308,) located at the top of TM7, mainly contributed to beta(2) selectivity. However, Tyr(308) interacted with formoterol and procaterol in two different ways. The results of Ala- and Phe-substituted mutants indicated that the phenyl group of Tyr(308) interacted with the phenyl group in the N-substituent of formoterol (hydrophobic interaction), and the hydroxyl group of Tyr(308) interacted with the protonated amine of procaterol (hydrophilic interaction). In contrast to beta(2)AR, TM2 is a major determinant that beta(1)-selective agonists such as denopamine and T-0509 bound the beta(1)AR with high affinity. Three amino acids (Leu(110), Thr(117), and Val(120)) in TM2 of the beta(1)AR were identified as major determinants for beta(1)-selective binding of these agonists. Three-dimensional models built on the basis of the predicted structure of rhodopsin showed that Tyr(308) of the beta(2)AR covered the binding pocket formed by TM2 and TM7 from the upper side, and Thr(117) of the beta(1)AR located in the middle of the binding pocket to provide a hydrogen bonding for the beta(1)-selective agonists. These data indicate that TM2 and TM7 of the betaAR formed the binding pocket that binds the betaAR subtype-selective agonists with high affinity.

Adrenergic beta-1 Receptor Agonists↗
PubMed1999

Prostanoid receptors: structures, properties, and functions.

Prostanoids are the cyclooxygenase metabolites of arachidonic acid and include prostaglandin (PG) D(2), PGE(2), PGF(2alpha), PGI(2), and thromboxne A(2). They are synthesized and released upon cell stimulation and act on cells in the vicinity of their synthesis to exert their actions. Receptors mediating the actions of prostanoids were recently identified and cloned. They are G protein-coupled receptors with seven transmembrane domains. There are eight types and subtypes of prostanoid receptors that are encoded by different genes but as a whole constitute a subfamily in the superfamily of the rhodopsin-type receptors. Each of the receptors was expressed in cultured cells, and its ligand-binding properties and signal transduction pathways were characterized. Moreover, domains and amino acid residues conferring the specificities of ligand binding and signal transduction are being clarified. Information also is accumulating as to the distribution of these receptors in the body. It is also becoming clear for some types of receptors how expression of their genes is regulated. Furthermore, the gene for each of the eight types of prostanoid receptor has been disrupted, and mice deficient in each type of receptor are being examined to identify and assess the roles played by each receptor under various physiological and pathophysiological conditions. In this article, we summarize these findings and attempt to give an overview of the current status of research on the prostanoid receptors.

Animals↗
PubMed1999

Slow wave sleep-inducing effects of first generation H1-antagonists.

The present study was performed to see if first-generation histamine H1-antagonists are useful sedative-hypnotic drugs. Increases in electroencephalogram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex and theta band (4-8 Hz) at the hippocampus in rats were used as an indexes of sleep. The H1-antagonists used in this study resulted in a decrease in sleep latency and an increase in sleep duration (slow wave sleep). The rate of REM (rapid eye movement) sleep during slow wave sleep was decreased by H1-antagonists and brotizolam. The order of potency of H1-antagonists for the reduction in sleep latency (from greatest to least) was promethazine>chlorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyrilamine. Brotizolam was more potent than these H1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.

Animals↗
PubMed1999

Effect of propolis extract on D-galactosamine-induced hepatic injury in rats.

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

Alanine Transaminase↗
PubMed1999

Involvement of serotonin in zimelidine-induced hyperglycemia in mice.

Effects of a selective serotonin reuptake inhibitor, zimelidine, on plasma glucose was studied in mice. Zimelidine dose-dependently induced hyperglycemia, although it did not change insulin levels. To determine the involvement of the serotonergic system in zimelidine-induced hyperglycemia, effects of the 5-HT depleter p-chlorophenylalanine(pCPA) were examined. pCPA significantly reduced zimelidine-induced hyperglycemia. This suggests that zimelidine-induced hyperglycemia is mediated by the serotonergic system through its 5-HT reuptake inhibition.

Animals↗
PubMed1999

Effects of fujibitol, a remedy for nasal symptoms of immediate and delayed type allergic reactions.

The effects of Fujibitol, a remedy for the nasal symptoms of immediate and delayed type allergic reactions were studied. Fujibitol inhibited active systemic anaphylaxis in mice, heterologous passive cutaneous anaphylaxis (PCA) in rats, Masugi's nephritis in rats and delayed type hypersensitivity induced by picryl chloride in mice, but did not affect homologous PCA or immune complex-induced glomerulonephritis in rats. These results suggested that Fujibitol is effective for treatment of allergy-induced inflammation since IgG and type IV allergic reactions were inhibited.

Anaphylaxis↗
PubMed1999

Effects of levocabastine on lipid mediator release from guinea pig lung fragments.

The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release.

Animals↗
PubMed1999

Expression of p120 nucleolar proliferating antigen in human gliomas and growth suppression of glioma cells by p120 ribozyme vector.

p120 is a nucleolar proliferating antigen which is expressed in tumor cells but not normal resting cells. The expression and localization of p120 in human gliomas were studied by Northern blot analysis, Western blot analysis and immunohistochemistry. All five of the glioma cell lines and all of the glioma specimens we investigated expressed p120 at both the mRNA and protein levels. p120 expression was not detected in adjacent brain tissues. A ribozyme vector was constructed to cleave the first GUC sequence in the coding region of p120 mRNA. This p120 ribozyme vector was transfected into the glioma cell line SF188, which expresses p120. The reduced p120 expression of the transfectant at both the mRNA and protein levels was confirmed. An MTT assay indicated that the transfected cells grew more slowly than control cells. These results indicate that i) p120 has an important role in the proliferation of gliomas, and ii) the ribozyme against p120 mRNA can suppress glioma cell growth.

Base Sequence↗
PubMed1999

[Prototype of a new pediatric emergency scale tape: PES tape].

Drug dosage and appropriate size of medical equipment for emergency pediatric patients are determined by age, body weight and/or height. In an emergency situation, however, such information about the patients is not always clear. Body height is easily measured when the patient lies down supine. Furthermore, child's height could be a better parameter than age to predict appropriate endotracheal tube (ETT) size and body weight. We propose a new pediatric emergency scale tape (PES Tape). PES Tape is graduated in centimeters to measure body height in supine position. Height-based body weight, drug dosage, energy dosage for defibrillation, appropriate size of ETT and lip-tip distance (LTD) are printed on the tape. We studied the reliability of this tape in pediatric anesthesia. Body weight estimated from the tape was accurate, and predicted size of ETT and LTD was appropriate. PES Tape is a reliable tool in pediatric emergency.

Body Weights and Measures↗
PubMed1999

Prostaglandin E receptor subtypes involved in stimulation of gastroduodenal bicarbonate secretion in rats and mice.

We investigated prostaglandin E (EP) receptor subtypes responsible for the HCO3- stimulatory action of prostaglandin E2 (PGE2) in the gastroduodental mucosa, by examining the effects of various prostanoids with subtype specific EP receptor agonists in rats and those of PGE2 in knockout mice lacking EP1 or EP3 receptors. In rats, gastric HCO3- secretion was stimulated by i.v. administration of PGE2, 17-phenyl PGE2 the selective EP1 agonist as well as sulprostone the EP1 and EP3 agonist, but was not affected by other EP agonists such as butaprost the selective EP2 agonist, ONO-NT-012 the selective EP3 agonist or 11-deoxy PGE1 the EP3 and EP4 agonist. In contrast, the HCO3- secretion in rat duodenums was stimulated by PGE2, sulprostone, ONO-NT-012 as well as 11-deoxy PGE1 but not affected by either 17-phenyl PGE2 or butaprost. The HCO stimulatory effect of sulprostone in the stomach was significantly inhibited by ONO-AE-829, the selective EP1 antagonist. On the other hand, PGE2 applied topically to the mucosa for 10 min caused a dose-dependent increase of HCO3- secretion in both the stomach and duodenum of wild-type mice. The HCO3- stimulatory action of PGE2 in the stomach was also observed dose-dependently in knockout mice lacking EP3-receptors but was absent in EP1-receptor knockout mice, while the stimulatory effect in the duodenum was observed in EP1-receptor knockout mice, similar to wild-type animals, but not in knockout mice lacking EP3-receptors. These results indicate that PGE2 stimulates HCO3- secretion via different EP receptor subtypes in the stomach and duodenum; the former is mediated by EP1-receptors, while the latter mediated by EP3-receptors.

Animals↗