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Biomedical subjects

M Shibasaki

Publications and source records attributed to M Shibasaki.

At least 37 records · Page 2Linked to original sources
PubMed2002

Sweating response in physically trained men to sustained handgrip exercise in mildly hyperthermic conditions.

To investigate the effects of physical training on heat loss response to sustained handgrip exercise (non-thermal factors), we compared the sweating response during isometric handgrip exercise to mild hyperthermia in physically trained and untrained subjects. Seven trained and untrained male subjects (maximal oxygen uptake 62.7 +/- 2.4 and 42.7 +/- 1.6 mL kg-1 min-1, respectively, P < 0.05) performed isometric handgrip exercises at 20, 35 and 50% maximal voluntary contraction (MVC) for 60 s. The study was conducted in a climatic chamber with a regulated ambient temperature of 35 degrees C and relative humidity of 50% to induce sweating response at rest by rising skin temperature without a marked change in internal temperature. Sublingual and mean skin temperatures (thermal factors) in both trained and untrained groups were essentially constant throughout all exercise intensities. Changes in heart rate, mean arterial blood pressure, and rating of perceived exertion with increased exercise intensity were similar in both groups. Sweating rate (SR) on the limbs (mean value of forearm and thigh) was significantly greater in the trained group than in the untrained group at 50% MVC (P < 0.05). In addition, the slopes of the relationship between increased SR and exercise intensity (% MVC) on the trunk (chest) and limbs were significantly greater in the trained group than in the untrained group (P < 0.05). Our results suggest that the sweating response caused by non-thermal factors against a background of changing thermal factors was enhanced by physical training. It is also thought that the enhanced sweating response may be especially evident on the limbs than on the trunk, such as improvement of sweating response associated with thermal factors.

Adult↗
PubMed2002

Sweating responses to a sustained static exercise is dependent on thermal load in humans.

The purpose of this project was to test the hypothesis that internal temperature modulates the sweating response to sustained handgrip exercise. Ten healthy male subjects immersed their legs in 43 degrees C water for 30-40 min at an ambient temperatures of 30 degrees C and a relative humidity of 50%. Sweating responses to 50% maximal voluntary contraction isometric handgrip exercise (IH) were measured following the onset of sweating (i.e. following slight increases in internal temperature), and after more pronounced increases in internal temperature. Oesophageal temperature (Tes) was significantly lower during the first bout of exercise (37.54 +/- 0.07 degrees C) relative to the second bout (37.84 +/- 0.12 degrees C; P < 0.05). However, the increase in mean sweating rate (SR) from both the chest and forearm (non-glabrous skin) was significantly greater during the first IH bout relative to the second bout (P < 0.05). Increases in mean arterial blood pressure and palm SR (glabrous skin) did not differ significantly between exercise bouts, while heart rate and rating of perceived effort were significantly greater during the second bout of IH. As Tes and mean skin temperature did not change during either bout of exercise, the changes in SR from non-glabrous skin between the bouts of IH were likely because of non-thermal factors. These data suggest that sweating responses from non-glabrous skin during IH vary depending on the magnitude of thermal input as indicated by differing internal temperatures between bouts of IH. Moreover, these data suggest that the contribution of non-thermal factors in governing sweating from non-glabrous skin may be greatest when internal temperature is moderate (37.54 degrees C), but has less of an effect after greater elevations in internal temperature (i.e. 37.84 degrees C).

Adult↗
PubMed2001

Enantioselective 1,4-addition of unmodified ketone catalyzed by a bimetallic Zn-Zn-linked-BINOL complex.

1,4-Addition (Michael addition) of 2-hydroxy-2'-methoxyacetophenone (2) to various alpha,beta-unsaturated ketones was efficiently promoted by a bimetallic Zn-Zn-linked-BINOL complex 3 with good yield (up to 90%) and excellent enantiomeric excess (up to 99% ee). The resulting 2-hydroxy-1,5-diketones were successfully converted to synthetically more versatile esters and amides. [reaction: see text]

Journal Article↗
PubMed2001

Zirconium alkoxides in catalysis.

This paper presents recent advances in the reactions catalyzed by zirconium alkoxide. Catalytic asymmetric reactions with chiral zirconium catalysts and redox reactions are first discussed. The diverse characteristics of zirconium alkoxides as Lewis acids, Brönsted bases, and nucleophiles, are key for promoting these unique reactions. Our recent development of novel reactions, one-pot synthesis of trans-1.2-diol derivatives and trans-beta-cyanohydrins from olefins, is also described. These reactions cannot be produced using other metals.

Journal Article↗
PubMed2001

Catalytic enantioselective Reissert-type reaction: development and application to the synthesis of a potent NMDA receptor antagonist (-)-L-689,560 using a solid-supported catalyst.

Full details of the first catalytic enantioselective Reissert-type reaction are described. Utilizing the Lewis acid-Lewis base bifunctional catalyst 5 or 6 (9 mol %), the Reissert products were obtained in 57 to 99% yield with 54 to 96% ee. Electron-rich quinolines produced better yields and enantioselectivities than electron-deficient substrates. Kinetic studies indicated that the reaction should proceed via the rate-determining acyl quinolinium formation, followed by the attack of a cyanide. The catalyst does not facilitate the first rate-determining step; however, it strongly facilitates the second cyanation step. The reaction was successfully applied to an efficient catalytic asymmetric synthesis of a potent NMDA receptor antagonist (-)-L-689,560. A key step is the one-pot process using the Reissert-type reaction from quinoline 1f, followed by stereoselective reduction of the resulting enamine 2f. This step gave the key intermediate 20 in 91% yield with 93% ee, using 1 mol % of 6. The enantiomerically pure target compound was obtained through 10 operations (including recrystallization) in total yield of 47%. Furthermore, 6 was immobilized to JandaJEL, and the resulting solid-supported catalyst 11 afforded 20 in a comparable yield to the homogeneous 6, but with slightly lower enantioselectivity.

Aminoquinolines↗
PubMed2001

Evidence for metaboreceptor stimulation of sweating in normothermic and heat-stressed humans.

1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood pressure, and both remain elevated during post-exercise ischaemia. The purpose of this study was to identify whether the elevation in arterial blood pressure during post-exercise ischaemia contributes to the increase in sweating. 2. In normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal voluntary contraction, followed by 2 min post-exercise ischaemia, was performed with and without bolus intravenous administration of sodium nitroprusside during the ischaemic period. Sodium nitroprusside was administered to reduce blood pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was monitored over two microdialysis membranes placed in the dermal space of forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine, while the other was perfused with the vehicle. 3. In normothermia, IHG exercise increased sweat rate at the neostigmine-treated site but not at the control site. Sweat rate remained elevated during post-exercise ischaemia even after mean arterial blood pressure returned to the pre-IHG exercise baseline. Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG exercise levels. Sweat rate during post-exercise ischaemia without sodium nitroprusside administration followed a similar pattern. 4. During whole-body heating, IHG exercise increased sweat rate at both neostigmine-treated and untreated sites. Similarly, regardless of whether mean arterial blood pressure remained elevated or was reduced during post-exercise ischaemia, sweat rate remained elevated during the ischaemic period. 5. These results suggest that sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by metaboreflex stimulation and not via baroreceptor loading.

Adult↗
PubMed2001

Direct catalytic enantio- and diastereoselective aldol reaction using a Zn-Zn-linked-BINOL complex: a practical synthesis of syn-1,2-diols.

[reaction: see text] The direct catalytic enantio- and diastereoselective aldol reaction with 2-hydroxy-2'-methoxyacetophenone proceeded smoothly using as little as 1 mol % of a dinuclear zinc catalyst, Zn-Zn-linked-BINOL complex 2, to afford alpha,beta-dihydroxy ketones in a highly syn-selective manner (up to syn/anti 97/3) and in excellent yields (up to 95%) and ees (up to 99%). Efficient transformations of the alpha,beta-dihydroxy ketone into an alpha,beta-dihydroxy ester and an alpha,beta-dihydroxy amide via regioselective rearrangements are also described.

Journal Article↗
PubMed2001

Catalytic asymmetric epoxidation of enones using La-BINOL-triphenylarsine oxide complex: structural determination of the asymmetric catalyst.

The catalytic asymmetric epoxidation of enones using the La-BINOL-Ph(3)As=O complex generated from La(O-i-Pr)(3), BINOL, and Ph(3)As=O in a ratio of 1:1:1 is described herein. Using 1-5 mol % of the asymmetric catalyst, a variety of enones, including a dienone and a cis-enone, were found to be epoxidized in a reasonable reaction time, providing the corresponding epoxy ketones in up to 99% yield and with more than 99% ee. The possible structure of the actual asymmetric catalyst has been clarified by various methods, including X-ray crystal structure analysis. This is the first X-ray analysis of an alkali-metal free lanthanoid-BINOL complex. Although La(binaphthoxide)(2)(Ph(3)As=O)(2) (7) was observed as the major complex in the complexes' solution, generated from La(O-i-Pr)(3), BINOL, and Ph(3)As=O in a ratio of 1:1:1, the possible active species turned out to be the La-BINOL-Ph(3)As=O complex in a ratio of 1:1:1. A probable reaction mechanism of the catalytic asymmetric epoxidation of enones is also proposed, suggesting that preferential formation of a heterochiral complex is the reason for asymmetric amplification. Moreover, the interesting role of La(O-i-Pr)(3) for accelerating the epoxidations while maintaining high ee's is discussed.

Journal Article↗
PubMed2001

Haplotypes of the 5' region of the IL-4 gene and SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma.

IL-4 and IL-13 are important in IgE synthesis and allergic inflammation. Therefore, genes encoding IL-4 and IL-13 are candidates for predisposition to asthma and atopy. A recent study in the YAC transgenic mouse has revealed that one of the conserved noncoding sequences (CNS-1) between IL-4 and IL-13 influences the expression of IL-4, IL-5, and IL-13, suggesting that CNS-1 acts as a coordinate regulator of these genes. This investigation screened for mutations in the 13-kb region between IL-4 and IL-13, which includes the human equivalent of the murine CNS-1. Four single nucleotide polymorphisms (SNPs) were found in the region between IL-4 and IL-13 (IL-4-IL-13SNP1, IL-4-IL-13SNP2, IL-4-IL-13SNP3, and IL-4-IL-13SNP4). There was no mutation in the human CNS-1. We genotyped these and other previously reported polymorphisms in IL-4 and IL-13 using asthmatic families, and examined association by transmission disequilibrium test. Two-locus haplotype analysis revealed that haplotypes composed of the IL-4 RP2del, IL-4 +33T, or IL-4 -589T alleles and either IL-4-IL-13SNP3G or IL-4-IL-13SNP4C are transmitted significantly to asthma-affected children (p = 0.002). This data suggests that haplotypes composed of the 5' region polymorphisms in the IL-4 gene and SNPs in the intergene sequence between IL-4 and IL-13 influence the development of asthma.

Adolescent↗
PubMed2001

Identification of missense mutation in the IL12B gene: lack of association between IL12B polymorphisms and asthma and allergic rhinitis in the Japanese population.

Interleukin-12 (IL-12) is a macrophage-derived cytokine that modulates T lymphocyte responses and can suppress allergic inflammation. In a genome-wide screen, we found strong evidence for linkage of atopic asthma with marker D5S1352, located close to IL12B, with a maximum lod score of 4.34. We screened for mutation in IL12B and found three novel (-4475-4insG, Glu186Asp and Ser226Asn) variants and one previously reported (1188A>C) variant in IL12B, and conducted transmission disequilibrium tests in families identified through children with atopic asthma or allergic rhinitis. Frequencies of the Asn226 and 1188C alleles in the parents were 0.04 and 0.5, respectively. Preferential transmission of either the Ser226/Asn226 or 1188A/C allele to asthma-affected or rhinitis-affected children was not observed (P > 0.1) and was not associated significantly with total serum IgE level (P > 0.1). Our results indicate that polymorphisms in IL12B are not likely to be associated with the development of atopy-related phenotypes.

Adolescent↗
PubMed2001

Association between a new polymorphism in the activation-induced cytidine deaminase gene and atopic asthma and the regulation of total serum IgE levels.

BACKGROUND: Activation-induced cytidine deaminase (AICDA) is a recently identified RNA-editing deaminase that plays an important role in class-switching. Defects in AICDA result in a hyper-IgM phenotype and lack of IgG, IgA, and IgE in both human beings and mice. OBJECTIVE: The aim of this study was to determine whether the AICDA gene is related to regulation of total serum IgE and development of atopic asthma. METHODS: We screened for polymorphisms in the 5;-flanking and coding regions of the AICDA gene in subjects with atopic asthma and analyzed the effect of these polymorphisms on the development of atopic asthma and on total serum IgE levels in Japanese asthmatic families. RESULTS: We identified 3 novel polymorphisms (5923A/G, 7888C/T, and 8578A/C) and 1 rare variant (Arg25Cys) in the AICDA gene. Transmission disequilibrium testing showed that the 7888C allele was transmitted preferentially to asthma-affected children (P =.007). Mean log [total serum IgE] levels of parents with the 7888C/7888C, 7888C/7888T, and 7888T/7888T genotypes were 2.12, 1.99, and 1.77, respectively, and a significant association was observed between the genotypes (P =.02). In RT-PCR experiments, we found 2 novel splice variants of AICDA, one lacking all of exon 4 (variant 1; 367 base pairs) and the other lacking the first 30 base pairs of exon 4 (variant 2; 453 base pairs). These variants were not associated with the 7888C/T polymorphism. CONCLUSION: The 7888C/T polymorphism might be associated with the pathogenesis of atopic asthma and the regulation of total serum IgE levels.

APOBEC-1 Deaminase↗
PubMed2001

Effect of muscle mass on V(O(2)) kinetics at the onset of work.

The dependence of O(2) uptake (V(O(2))) kinetics on the muscle mass recruited under conditions when fiber and muscle recruitment patterns are similar following the onset of exercise has not been determined. We developed a motorized cycle ergometer that facilitated one-leg (1L) cycling in which the electromyographic (EMG) profile of the active muscles was not discernibly altered from that during two-leg (2L) cycling. Six subjects performed 1L and 2L exercise transitions from unloaded cycling to moderate [ VT) exercise. The 1L condition yielded kinetics that was unchanged from the 2L condition [the phase 2 time constants (tau(1), in s) for 0.05; for >VT: 1L = 26.8 +/- 12.0; 2L = 27.8 +/- 16.1, P > 0.05]. The overall V(O(2)) kinetics (mean response time) was not significantly different for the two exercise conditions. However, the gain of the fast component (the amplitude/work rate) during the 1L exercise was significantly higher than that for the 2L exercise for both moderate and heavy work rates. The slow-component responses evident for heavy exercise were temporally and quantitatively unaffected by the 1L condition. These data demonstrate that, when leg muscle recruitment patterns are unchanged as assessed by EMG analysis, on-transient V(O(2)) kinetics for both moderate and heavy exercise are not dependent on the muscle mass recruited.

Electromyography↗
PubMed2001

Effect of local acetylcholinesterase inhibition on sweat rate in humans.

ACh is the neurotransmitter responsible for increasing sweat rate (SR) in humans. Because ACh is rapidly hydrolyzed by acetylcholinesterase (AChE), it is possible that AChE contributes to the modulation of SR. Thus the primary purpose of this project was to identify whether AChE around human sweat glands is capable of modulating SR during local application of various concentrations of ACh in vivo, as well as during a heat stress. In seven subjects, two microdialysis probes were placed in the intradermal space of the forearm. One probe was perfused with the AChE inhibitor neostigmine (10 microM); the adjacent membrane was perfused with the vehicle (Ringer solution). SR over both membranes was monitored via capacitance hygrometry during microdialysis administration of various concentrations of ACh (1 x 10(-7)-2 M) and during whole body heating. SR was significantly greater at the neostigmine-treated site than at the control site during administration of lower concentrations of ACh (1 x 10(-7)-1 x 10(-3) M, P < 0.05), but not during administration of higher concentrations of ACh (1 x 10(-2)-2 M, P > 0.05). Moreover, the core temperature threshold for the onset of sweating at the neostigmine-treated site was significantly reduced relative to that at the control site. However, no differences in SR were observed between sites after 35 min of whole body heating. These results suggest that AChE is capable of modulating SR when ACh concentrations are low to moderate (i.e., when sudomotor activity is low) but is less effective in governing SR after SR has increased substantially.

Acetylcholinesterase↗