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Biomedical subjects

M Shibasaki

Publications and source records attributed to M Shibasaki.

At least 55 records · Page 3Linked to original sources
PubMed2001

Function of human eccrine sweat glands during dynamic exercise and passive heat stress.

The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/- 0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42 degrees C under an ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further (P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.

Acclimatization↗
PubMed2001

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans.

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

Adult↗
PubMed2001

Multifunctional asymmetric catalysis.

Two types of general and practical enantioselective catalysts, namely, bimetallic complexes and Lewis acid-Lewis base bifunctional catalysts were developed based on the concept of multifunctional catalysis. In the first part of this review, the first example of a catalytic enatioselective nitro-Mannich reaction as well as a direct catalytic enantioselective aldol reaction of 2-hydroxyacetophenone using bimetallic complexes is discussed. The new complex, composed of ytterbium, potassium, and BINOL in a ratio of 1:1:3, promoted the nitro-Mannich reaction of nitromethane with up to 91% ee. On the other hand, second generation ALB catalyzed an enantioselective and diastereoselective nitro-Mannich reaction of nitroalkanes in up to 83% ee with a diastereomeric ratio up to 7:1. Moreover, the reaction of aldehydes with 2-hydroxyacetophenone in the presence of LLB, KHMDS, and H2O selectively gave the corresponding anti-alpha,beta-dihydroxy ketones in up to 95% ee and, in the presence of the catalyst prepared from linked-BINOL and 2 eq of Et2Zn, selectively afforded the syn-alpha,beta-dihydroxy ketones in up to 86% ee. In the second part, the development of new catalysts displaying a Lewis acidity and a Lewis basicity is described. The Lewis acid of the catalyst activates aldehydes, imines, acyl quinoliniums, and ketones. At the same time, the Lewis base activates the nucleophile (TMSCN). Catalysts of this type produced a highly enantioselective cyanation of these electrophiles. Application of the catalytic enantioselective cyanosilylation of aldehydes to a total synthesis of epothilones is also described.

Catalysis↗
PubMed2001

Comparison of the angiotensin II type 1-receptor antagonist YM358 and the angiotensin-converting enzyme inhibitor enalapril in rats with cardiac volume overload.

We evaluated the effects of chronic oral administration of an angiotensin II type 1 (AT1)-receptor antagonist YM358 and an angiotensin converting enzyme inhibitor enalapril on hemodynamics and cardiac hypertrophy in rats with volume overload-induced heart failure. We assessed changes of cardiac hemodynamics and cardiac hypertrophy at 2 and 4 weeks after administration of YM358 (3, 30 mg/kg per day) or enalapril (30 mg/kg per day) in abdominal aortocaval shunt rats. YM358 (30 mg/kg) attenuated increases of left ventricle (LV)/body weight (BW), left atrium (LA)/BW, right ventricle (RV)/BW and heart/BW ratios, but did not affect cardiac hemodynamics in shunt rats. Enalapril also reduced the increased LV/BW and heart/BW ratios together with significant reductions of systolic blood pressure, left ventricular systolic pressure and the first derivative of left ventricular pressure. These data suggest that the effects on attenuation of the development of cardiac hypertrophy are not different for YM358 and enalapril, although the effects on cardiac hemodynamics are different for the same dosages. The attenuating action of YM358 on cardiac hypertrophy was independent of the action on hemodynamics and indicated the direct action of the AT1 receptor on the heart.

Angiotensin Receptor Antagonists↗
PubMed2000

Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells.

We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investigate the mechanism of this stimulation, we determined the redistribution of insulin-regulatable glucose transporter isotype 4 (Glut4). When fully differentiated C2C12 cells stably expressing myc-tagged Glut4 protein were treated with YM-126414, redistribution was dramatically increased in a dose-dependent manner (EC(50)=21 nM). These results indicate that YM-126414 is a novel glucose uptake stimulator for muscle cells by causing up-regulation of Glut4 redistribution in differentiated muscle cells. Our findings for the in vitro effects of YM-126414 suggest a direction for the development of new drugs for the treatment of type 2 diabetes.

Animals↗
PubMed2000

Concept of improved rigidity: how to make enantioselective hydrophosphonylation of cyclic imines catalyzed by chiral heterobimetallic lanthanoid complexes almost perfect

The catalytic and enantioselective hydrophosphonylation of cyclic imines using cyclic phosphites is described for the first time. In contrast to the application of acyclic phosphites, significant improvements are presented arising from the concept of improved rigidity by utilization of cyclic phosphites in the lanthanoid BINOL complex catalyzed hydrophosphonylation of 3-thiazolines. Cyclic phosphites are shown to provide certain improvements within the catalytic cycle. Influence of parameters such as concentration of the catalyst and the phosphite on the catalysis is examined as well as the effects of the substituents on the starting material. The pharmacologically interesting thiazolidinyl phosphonates are synthesized in excellent optical purities of up to 99% ee and high chemical yields of up to 99%. The required amount of catalyst is reduced to 2.5 mol %. The highest efficiency of the reaction involving cyclic phosphites is achieved using the catalytic system "2.5 mol % (S)-YbPB/2.5 equiv phosphite/50 degrees C/48 h/THF-toluene (1:7)". On the basis of the results a refinement of the proposed catalytic cycle has been provided. For comparison cyclic phosphites were used in hydrophosphonylation with a chiral titanium catalyst.

Journal Article↗
PubMed2000

Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families.

Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.

Adolescent↗
PubMed2000

Catalytic asymmetric synthesis of 19,20-dihydroakuammicine.

An enantiocontrolled total synthesis of 19,20-dihydroakuammicine using a catalytic asymmetric Michael addition of dimethyl malonate to cyclohexenone as the key step is described. The above catalytic asymmetric Michael addition proceeds quite efficiently in the presence of a heterobimetalic asymmetric catalyst (ALB-KO-t-Bu-MS 4A, 0.3 mol%), giving the corresponding Michael adduct in 94% yield and 99% ee.

Journal Article↗
PubMed2000

The novel hypoglycemic agent YM440 normalizes hyperglycemia without changing body fat weight in diabetic db/db mice.

To determine the relationship between hypoglycemic activity and body weight gain induced by insulin sensitizers, we compared the effects of thiazolidinedione analogs (troglitazone and pioglitazone) and the oxadiazolidinedione analog (Z)-1,4-bis4[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phen oxy¿but-2-ene (YM440) in diabetic db/db mice. Oral treatment with YM440(100 mg/kg) for 28 days decreased the blood glucose concentration (control v YM440, 418 +/- 12 v243 +/- 44 mg/dL). The hypoglycemic activity of this agent was comparable to that of troglitazone (300 mg/kg) and pioglitazone (100 mg/kg). There were no changes in food intake among the groups. Troglitazone and pioglitazone, but not YM440, significantly increased body weight gain during treatment (control, 7.2 +/- 0.5 g; YM440, 7.5 +/- 0.8 g; troglitazone, 10.9 +/- 0.8 g; and pioglitazone, 14.5 +/- 1.1 g). To further assess whether the increase in body weight by troglitazone or pioglitazone was due to adipogenesis, the weight of intraabdominal fat tissue (epididymal, retroperitoneal, and perirenal) was determined. There were no differences in the total weight of visceral fat between the control and YM440 treatment (3.53 +/- 0.23 and 3.60 +/- 0.16 g). In contrast, troglitazone and pioglitazone significantly increased the fat weight (4.31 +/- 0.13 and 4.66 +/- 0.19 g). Thiazolidinediones are known as ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor responsible for adipogenesis. Troglitazone and pioglitazone activated PPARgamma and increased triglyceride accumulation and mRNA expression of fatty acid-binding protein (FABP) in 3T3-L1 cells. However, YM440 had no effect on these indices for adipocyte differentiation. These results suggest that the mechanism is different for the hypoglycemic action of YM440 versus the thiazolidinediones. YM440 ameliorates hyperglycemia without changing PPARgamma activity, adipocyte differentiation, or fat weight. Thus, YM440 could be a useful hypoglycemic agent for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) without affecting body weight.

3T3 Cells↗
PubMed2000

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma.

BACKGROUND: IL-4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL-4 gene cluster and asthma and/or asthma-related traits. Interferon regulatory factor 1 (IRF-1) is located approximately 300 kb telomeric to IL-4 and recent study reveals that IRF-1 deficiency results in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of native cell- and Th1-related cytokines. OBJECTIVE: To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5' flanking region of the IRF-1 gene. METHODS AND RESULTS: We have screened the promoter and coding regions of the IRF-1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the -300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF-1 gene. No variants causing amino acid alterations of IRF-1 were detected. The -300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy- or asthma-affected children. CONCLUSION: The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.

Adolescent↗
PubMed2000

Hydrogen peroxide augments eosinophil adhesion via beta2 integrin.

During eosinophil (EOS) accumulation at sites of allergic inflammation, an initial step is the binding of EOS to adhesion molecules expressed on vascular endothelial cells (EC). We have previously observed that adhesion of peripheral blood EOS to recombinant human vascular cell adhesion molecule-1 (rh-VCAM-1) stimulates the respiratory burst of EOS. Although the biological consequence of this activation remains to be elucidated, reactive oxygen species such as hydrogen peroxide (H2O2) may modify the adhesive property of EOS. In the present study, we examined whether H2O2 modifies the adhesive property of EOS. EOS were isolated from the peripheral blood of healthy subjects. Adhesion of the EOS to paraformaldehyde-fixed human umbilical vein EC (HUVEC), stimulated or not stimulated with tumour necrosis factor-alpha (TNF-alpha; 100 pM for 24 hr), was examined in the presence or absence of H2O2. H2O2 significantly enhanced adhesion of EOS to both resting and TNF-alpha-stimulated fixed HUVEC (P < 0.01, respectively). Such enhancing effects were inhibited by anti-beta2 integrin antibody or anti-CD11b antibody, but not by anti-CD11a or anti-alpha4 integrin antibody. H2O2 also enhanced EOS adhesion to rh-intracellular cell adhesion molecule-1 (ICAM-1) but not to rh-VCAM-1. Finally, H2O2 enhanced the expression of both CD11b and CD18 on EOS. These results indicate that H2O2 directly augments the adhesive property of EOS through beta2 integrin.

Adult↗
PubMed2000

Interindividual variation in bromperidol metabolism and relationship to therapeutic effects.

Plasma concentrations of bromperidol (BRP) and reduced bromperidol (RBRP) were determined in 31 patients with schizophrenia who were administered BRP for their psychiatric symptoms. Activities of carbonyl reductase in red blood cells were assayed using BRP as a substrate. Plasma concentrations of BRP and RBRP ranged from 2.2 to 23.5 ng/mL and from 0.2 to 8.2 ng/mL, respectively. RBRP-to-BRP ratios in plasma ranged from 0.01 to 0.94 (mean +/- SD: 0.31 +/- 0.20), values notably lower than the previously reported values of reduced haloperidol to haloperidol (HAL) in the plasma from patients on HAL. The activity of BRP reductase in red blood cells was determined as 6.8-12.3 pmol/hr/10(6) red blood cells, which was at approximately the same level as that of HAL reductase. Patients with positive responses to BRP treatment were evaluated using the Brief Psychiatric Rating Scale. We found that the number of patients who had a positive response to BRP did not increase after BRP plasma levels had reached the level of 12 ng/mL. This finding suggests that a therapeutic plateau in BRP pharmacotherapy of schizophrenia occurs, and there is no advantage to raising the dose once this plateau is reached.

Adolescent↗
PubMed2000

Life threatening coronary artery spasm in childhood Kimura's disease.

A 13 year old boy is described with hypereosinophilia associated with Kimura's disease, who showed repeated life threatening syncopal attacks during daily activities or at rest. Coronary arteriography demonstrated small aneurysms with irregular vessel walls of both coronary arteries, and the absence of organic stenotic lesions. Infusion of a minimal dose of ergonovine into the right coronary artery induced severe spasm of the vessel. Ventricular fibrillation recurred even after administration of nifedipine and isosorbide was started, but was completely inhibited by prednisolone.

Adolescent↗
PubMed2000

Effects of exercise intensity on the sweating response to a sustained static exercise.

To investigate how the sweating response to a sustained handgrip exercise depends on changes in the exercise intensity, the sweating response to exercise was measured in eight healthy male subjects. Each subject lay in the supine position in a climatic chamber (35 degrees C and 50% relative humidity) for approximately 60 min. This exposure caused sudomotor activation by increasing skin temperature without a marked change in internal temperature. After this period, each subject performed isometric handgrip exercise [15, 30, 45, and 60% maximal voluntary contraction (MVC)] for 60 s. Although esophageal and mean skin temperatures did not change with a rise in exercise intensity and were similar at all exercise intensities, the sweating rate (SR) on the forearm increased significantly (P < 0.05) from baseline (0.094 +/- 0.021 mg. cm(-2). min(-1) at 30% MVC, 0.102 +/- 0.022 mg. cm(-2). min(-1) at 45% MVC, 0.059 +/- 0.009 mg. cm(-2). min(-1) at 60% MVC) in parallel with exercise intensity above exercise intensity at 30% MVC (0.121 +/- 0.023 mg. cm(-2). min(-1) at 30% MVC, 0.242 +/- 0.051 mg. cm(-2). min(-1) at 45% MVC, 0.290 +/- 0.056 mg. cm(-2). min(-1) at 60% MVC). Above 45% MVC, SR on the palm increased significantly from baseline (P < 0.05). Although SR on the forearm and palm tended to increase with a rise in exercise intensity, there was a difference in the time courses of SR between sites. SR on the palm showed a plateau after abrupt increase, whereas SR on the forearm increased progressively during exercise. These results suggest that the increase in SR with the increase in sustained handgrip exercise intensity is due to nonthermal factors and that the magnitude of these factors during the exercise may be responsible for the magnitude of SR.

Adult↗
PubMed2000

Release of endothelins and platelet-activating factor by a rat pleural mesothelial cell line.

Thrombin is a multifunctional serine protease. It is generated in inflammatory processes and induces the proliferation and chemotaxis of a variety of cells including mesothelial cells (MTCs). MTCs are epithelial cells derived from the mesoderm, as are the vascular endothelial cells. Since thrombin acts on endothelial cells to produce platelet-activating factor (PAF) and endothelin (ET)-1, it was hypothesized that MTCs also produce PAF and ET via the action of thrombin. Rat pleural MTC (RMTC, 4/4 R.M.-4) monolayers were cultural in tissue culture dishes for various periods. The supernatants were fractionated by means of high-performance liquid chromatography to determine the ET isoforms and PAF species present. Immunoreactive ET was measured using an enzyme-linked immunosorbent assay, and PAF was measured by means of a bioassay using a platelet aggregometer. ET-1, ET-2 and ET-3 were detected in RMTC-conditioned medium, and the predominant isoforms were ET-1 and ET-2. RMTCs mainly released C16:0 PAF into the supernatant. Immunoreactive ET and PAF were released via the action of thrombin. Synthetic PAF significantly induced secretion of ET, but the PAF receptor antagonists, WEB2086 and E6123, failed to modulate thrombin-induced ET release. These results indicate that thrombin acts on pleural rat mesothelial cells to release ET and PAF, which may play a role in the development of pleurisy.

Animals↗