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Biomedical subjects

Kohei Sato

Publications and source records attributed to Kohei Sato.

17 recordsLinked to original sources

Oxygen uptake kinetics following 20 days of unilateral lower limb suspension.

The purpose of the present study was to examine the effect of unilateral lower limb suspension (ULLS) deconditioning on oxygen uptake kinetics. Eight healthy males underwent ULLS for 20 days and performed a series of 6-min square-wave transitions from rest to 60-W single-leg cycling exercises just before and after ULLS. To characterize the kinetics of the oxygen uptake response, a single exponential model was applied to the data until the end of the fast component omitted the first 15 s of the on-transit using a nonlinear least-squares fitting procedure. The following results were found: (i) the time constant of oxygen uptake was unchanged before and after ULLS; (ii) although there was no significant difference in the baseline and the asymptotic amplitude of the fast component, the asymptote, i.e., the absolute asymptotic amplitude of the fast component (the sum of the baseline and the asymptotic amplitude), and the end exercise oxygen uptake were decreased after ULLS; (iii) the contribution of the slow component to the total response of oxygen uptake was unchanged at pre- and post-ULLS. In conclusion, the asymptote in the fast component and the end exercise oxygen uptake were decreased after 20-d ULLS, though the response speed and the amplitude of the slow component of oxygen uptake were not changed. It is suggested that deconditioning as a result of limb disuse affects oxygen uptake response.

Adaptation, Physiological↗

Ventilatory and circulatory responses at the onset of exercise after eccentric exercise.

The purpose of this study was to clarify whether delayed onset muscle soreness (DOMS) and muscle damage after eccentric exercise (ECC) could affect the ventilatory and circulatory responses at the onset of exercise, and whether those effects would continue after the disappearance of DOMS. Ten males participated in this study. We measured ventilatory and circulatory responses at the onset of exercise, for the first 20 s, during knee extension-relaxation voluntary exercise (VOL) and passive movement (PAS), which was achieved by the experimenter alternatively pulling ropes connected to the subjects' ankles for the same period and frequency as during VOL. VOL and PAS were performed before, 2 days after, and 7 days after ECC. The following results were found: (1) the gain of minute ventilation at the onset of VOL at 2 days after ECC was significantly larger than that of before ECC; (2) the gain of minute ventilation at 7 days after ECC during both VOL and PAS was also enhanced significantly as compared to that of before ECC; and (3) heart rate and blood pressure responses were unchanged throughout the experimental period. In conclusion, ventilatory response at the onset of exercise is augmented during DOMS and EIMD after ECC and the enhanced ventilatory response continued after the disappearance of DOMS. It is suggested that enhanced ventilatory response during exercise after ECC is attributed to at least the changes in neural factors and that the mechanisms inducing these augmented ventilatory responses should be different during the period after ECC.

Adult↗

Changes in ventilatory responses to hypercapnia and hypoxia after intermittent hypoxia in humans.

The purpose of this study was to clarify the changes in hypercapnic and hypoxic ventilatory responses (HCVR and HVR) after intermittent hypoxia and following the cessation of hypoxic exposure. Twenty-nine males were assigned to one of four groups, i.e., a hypoxic (EX1-H, n=7) or a control (EX1-C, n=7) group in Experiment 1, and a hypoxic (EX2-H, n=8) or a control (EX2-C, n=7) group in Experiment 2. In each experiment, the hypoxic tent system was utilized for intermittent hypoxia, and the oxygen levels in the tent were maintained at 12.3+/-0.2%. In Experiment 1, the EX1-H group spent 3 h/day in the hypoxic tent for 1 week. HCVR and HVR were determined before and after 1 week of intermittent hypoxia, and again 1 and 2 week after the cessation of hypoxic exposure. In Experiment 2, the subjects in the EX2-H group performed 3 h/day for 2 weeks in intermittent hypoxia. HCVR and HVR tests were carried out before and after intermittent hypoxia, and were repeated again after 2 weeks of the cessation of hypoxic exposure. The slope of the HCVR in the EX1-H group did not show a significant increase after 1 week of intermittent hypoxia, while HCVR in the EX2-H group increased significantly after 2 weeks of intermittent hypoxia. The HCVR intercept was unchanged following 1 or 2 weeks of intermittent hypoxia. There was a significant increase in the slope of the HVR after 1 and 2 weeks of intermittent hypoxia. The increased HCVR and HVR returned to pre-hypoxic levels after 2 weeks of the cessation of hypoxia. These results suggest that 3 h/day for 2 weeks of intermittent hypoxia leads to an increase in central hypercapnic ventilatory chemosensitivity, which is not accompanied by a re-setting of the central chemoreceptors, and that the increased hypercapnic and hypoxic chemosensitivities are restored within 2 weeks after the cessation of hypoxia.

Adaptation, Physiological↗

Effect of a repeated series of intermittent hypoxic exposures on ventilatory response in humans.

The purpose of this study was to elucidate the magnitude and the time course of ventilatory changes resulting from a repeated series of hypoxic exposures. Eight healthy males participated in the present study. The subjects spent 1 h/day in normobaric hypoxia (12% inspired oxygen). Inspired minute ventilation (V(I)), end-tidal partial pressure of carbon dioxide (P(ET(CO2))), and arterial oxygen saturation (SaO2) were measured in a hypoxic tent. These measurements were taken for 10 consecutive days (series 1), and were taken again after the subjects had been away from hypoxic exposure for 1 month (series 2). P(ET(CO2)) decreased and SaO2 increased progressively in the hypoxic tent during the 10 days of intermittent hypoxia in series 1. At the onset of series 2 (days 1 to 3), P(ET(CO2)) was significantly lower and SaO2 was significantly higher than those on day 1 during series 1. These results suggest that humans who have had previous hypoxic exposure adapt sooner to hypoxic condition due to an increase in the magnitude of hyperventilation in the first few days of a series of reexposures to hypoxia.

Acclimatization↗

Five-year follow-up study of mother-to-child transmission of Helicobacter pylori infection detected by a random amplified polymorphic DNA fingerprinting method.

Recent studies have speculated on the possible role of the mother in transmitting Helicobacter pylori infection to their children. In an attempt to either prove or disprove this supposition, we investigated the rates of infection of children born to H. pylori-positive mothers from birth to 5 years of age using serology and the stool antigen test. When infection of the children did occur, the strains from the children were compared to those of their mothers using DNA analysis. Sixty-nine of the 350 pregnant mothers (19.7%) had a positive serology for H. pylori. Fifty-one children underwent serological examinations and stool antigen tests at 4 to 6 days after birth, followed by 1, 3, and 6 months. They were continuously given the stool antigen test at 4- to 6-month intervals until the age of 5 years. Gastric juice samples were collected from the infected children and their mothers for culture and DNA analyses using a random amplified polymorphic DNA fingerprinting method. None of the 51 children acquired H. pylori infection during the first year of life. Of the 44 children enrolled in a 5-year follow-up study, five (11%) acquired H. pylori infection. They acquired the infection at the age of 1 year 2 months, 1 year 3 months, 1 year 6 months, 1 year 8 months, and 4 years 4 months. Random amplified polymorphic DNA fingerprinting confirmed that the strains of the five children exhibited DNA fingerprinting patterns identical to those of their mothers. These findings suggest that mother-to-child transmission is the most probable cause of intrafamilial spread of H. pylori.

Antibodies, Bacterial↗

Vestibulo-cardiorespiratory responses at the onset of chair rotation in endurance runners.

Stimulation of the vestibular system has been reported to elicit ventilatory and circulatory changes in humans. The purpose of this study was to clarify the characteristics of vestibular-mediated ventilatory and circulatory responses in male endurance runners at the onset of passive chair rotation, which selectively stimulates the semicircular canals. Fourteen runners and 14 male untrained subjects participated. The vestibular stimulus test, which consists of 180 degrees chair rotations (left or right half-turns on an earth-vertical axis) for a duration of 2 s, was carried out on each subject. Inspiratory minute ventilation, tidal volume, respiratory frequency, heart rate, and blood pressure were measured by breath-by-breath and beat-to-beat techniques before, during, and after the chair rotation for a total of 60 s. It was found in this study that (i) the relative change of minute ventilation response in the endurance runners was significantly (P < 0.05) greater than in the untrained subjects during and after the rotation, and that (ii) no significant group differences were observed in heart rate and mean blood pressure responses during and after the rotation. In conclusion, vestibular-mediated ventilatory response, but not circulatory response, at the onset of the chair rotation in the endurance runners was significantly greater than that in the untrained subjects. The results from the present study suggest that an increase in vestibulo-ventilatory response would be attributed to an adaptation to long-term endurance training.

Adaptation, Physiological↗

Intensive cycle training with artificial gravity maintains muscle size during bed rest.

INTRODUCTION: The present study aimed to investigate the effect of intensive cycle training with short-arm centrifuge-induced hypergravity during bed rest on muscle size and function. METHODS: This study involved 10 healthy men who were divided into 2 groups: a countermeasure group, BR-CM (n = 5); and a control group, BR-Cont (n = 5). The BR-CM subjects partook in intensive cycle training (to 90% of maximum HR) with short-arm centrifuge-induced artificial gravity on alternate days during 20-d bed rest. Muscle volume of the thigh and maximum voluntary contraction (MVC) during isometric knee extensions was measured before and after bed rest. Muscle functional magnetic resonance imaging (mfMRI) and electromyogram (EMG) of the quadriceps femoris were obtained during submaximal knee extension exercises at a load of 30% MVC. RESULTS: The volume of the total thigh muscles was maintained in the BR-CM group (-1%), whereas it was not in the BR-Cont group (-9%, p < 0.05). MVC decreased in the BR-CM (7%) and BR-Cont groups (23%). EMG activity in the BR-CM group after bed rest was significantly lower than that of before; however, no significant change was found in the BR-Cont group. There were no significant changes in the resting and exercised mfMRI signals in either the BR-CM or BR-Cont groups. CONCLUSION: These results suggest that intensive cycle training with hypergravity maintained the size of human skeletal muscles during bed rest.

Adult↗

Ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in sprinters.

The purpose of this study was to clarify the characteristics of ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in sprinters. Eleven male university sprinters and 11 male untrained subjects participated in the present study. Voluntary exercise consisted of leg extension-flexion movement for 20 s with weights corresponding to 5% of each subject's body mass attached to each ankle. Passive movement was achieved without weights by the experimenter alternately pulling ropes that were connected to the subject's ankles for the same period and frequency as during voluntary exercise. In the present study, the following results were found: (1) the magnitude of relative changes (gain) of minute ventilation at the onset of passive movement in the sprinters was significantly smaller than that in the untrained subjects [mean (SEM) 33.3 (2.9) vs 61.7 (6.4)%, P<0.05]; (2) the time for reaching one-half of the gain (response time) of heart rate at the onset of voluntary exercise and passive movement in the sprinters was significantly slower than that in the untrained subjects [2.5 (0.2) vs 1.7 (0.2) s in voluntary exercise and 3.4 (0.8) vs 1.5 (0.1) s in passive movement, P<0.05]; (3) the gain and response time of mean blood pressure at the onset of voluntary exercise and passive movement showed no significant differences between the two groups. It is concluded that sprinters show slowed heart rate response at the onset of voluntary exercise, and attenuated ventilatory and slowed heart rate responses at the onset of passive movement as compared with untrained subjects.

Adaptation, Physiological↗

Effect of intermittent hypoxia on oxygen uptake during submaximal exercise in endurance athletes.

The purpose of the present study was to clarify the following: (1) whether steady state oxygen uptake (VO(2)) during exercise decreases after short-term intermittent hypoxia during a resting state in trained athletes and (2) whether the change in VO(2) during submaximal exercise is correlated to the change in endurance performance after intermittent hypoxia. Fifteen trained male endurance runners volunteered to participate in this study. Each subject was assigned to either a hypoxic group (n=8) or a control group (n=7). The hypoxic group spent 3 h per day for 14 consecutive days in normobaric hypoxia [12.3 (0.2)% inspired oxygen]. The maximal and submaximal exercise tests, a 3,000-m time trial, and resting hematology assessments at sea level were conducted before and after intermittent normobaric hypoxia. The athletes in both groups continued their normal training in normoxia throughout the experiment. VO(2) during submaximal exercise in the hypoxic group decreased significantly (P<0.05) following intermittent hypoxia. In the hypoxic group, the 3,000-m running time tended to improve (P=0.06) after intermittent hypoxia, but not in the control group. Neither peak VO(2) nor resting hematological parameters were changed in either group. There were significant (P<0.05) relationships between the change in the 3,000-m running time and the change in VO(2) during submaximal exercise after intermittent hypoxia. The results from the present study suggest that the enhanced running economy resulting from intermittent hypoxia could, in part, contribute to improved endurance performance in trained athletes.

Adaptation, Physiological↗

2',6'-dimethylphenylalanine (Dmp) can mimic the N-terminal Tyr in opioid peptides.

Substitution of 2',6'-dimethyltyrosine (Dmt) for the N-terminal Tyr in opioid peptides has recently been shown to be a promising tool for improving opioid receptor affinity and biological activity. We have also demonstrated that another unnatural amino acid, 2',6'-dimethylphenylalanine (Dmp), is not only an excellent substitute for Phe at position 3 but also can mimic the aromatic N-terminal Tyr residue in a micro opioid receptor-selective dermorphin analogue (YRFB: Tyr-D-Arg-Phe-betaAla-NH(2)). To further evaluate the value of Dmp in opioid peptides, we investigated Dmp(1)-substituted analogues of the delta receptor ligands, deltorphin II (DLT: Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH(2)) and enkephalin (ENK: Tyr-Gly-Gly-Phe-Leu). In the receptor binding assay, both [Dmp(1)]DLT and [Dmp(1)]ENK bound to the delta-receptor with high affinity and selectivity, and were nearly as effective as the parent peptides. The potency of the Dmp(1)-peptides on the MVD and GPI assays correlated well with the receptor binding affinity data. These results are in contrast to the tendency of corresponding Dmt(1)-analogues to have poor receptor selectivity. Taken together with the results with YRFB, we conclude that the Dmp(1)-peptide is superior to the corresponding Dmt(1)-peptide in its receptor selectivity. [Dmp(1)]DLT and [Dmp(1)]YRFB may serve as pharmacological tools for the studies of ligand recognition and opioid receptor signal transduction.

Animals↗

Ventilatory and heart rate responses at the onset of chair rotation in man.

In the present study, we attempted to confirm whether pulmonary ventilation and heart rate increased immediately after passive chair rotation in man. Inspiratory minute volume (V(I)), tidal volume (V(T)), respiratory frequency (f), and heart rate (HR) were determined by breath-by-breath and beat-by-beat techniques before, during, and after rotation for a total of 45 s. It was found that V(I) significantly increased immediately after chair rotation, but HR remained almost constant. These results suggest that the activation of horizontal semicircular canals is one causal factor of ventilatory response at the onset of exercise with rotational movement in healthy subjects, but heart rate response is not.

Adult↗

Ventilatory and cardiovascular responses to hypercapnia after 20 days of head-down bed rest.

INTRODUCTION: Few studies have attempted to investigate the influence of prolonged head-down bed rest (HDBR) on hypercapnic ventilatory chemosensitivity, and there are no data available regarding associated changes in arterial BP and heart rate (HR). The aim of this study was to clarify the influence of prolonged HDBR on ventilatory and cardiovascular responses to hypercapnia. METHODS: There were five healthy men who participated in this study. Resting ventilatory and cardiovascular responses to hypercapnia were measured by means of Read's CO2 rebreathing method 4 d before and on the 19th day of HDBR. Measured variables included systolic and diastolic BP (SBP and DBP, respectively), inspired minute ventilation (VI), and end-tidal partial pressure of CO2 (PETCO2). RESULTS: Ventilatory response to hyperoxic hypercapnia (deltaVI/ deltaPETCO2) decreased significantly on the 19th day of HDBR (1.42 +/- 0.65 to 0.90 +/- 0.41 L x min(-1) x torr(-1), p < 0.05). On the other hand, SBP, DBP, and HR responses (deltaSBP/deltaPETCO2, deltaDBP/deltaPETCO2, and deltaHR/deltaPETCO2) were unchanged. DISCUSSION: The results from this study suggest that prolonged HDBR leads to diminished central hypercapnic ventilatory chemosensitivity.

Adult↗

Acceleration with exercise during head-down bed rest preserves upright exercise responses.

INTRODUCTION: This study was designed to elucidate the effect of short-arm centrifuge-induced artificial gravity with exercise training during ground-based simulated spaceflight, i.e., prolonged head-down bed rest (HDBR), on respiratory and cardiovascular responses to upright exercise. METHODS: There were 10 healthy men who underwent 20 d of -6 degrees HDBR, and were assigned to either a countermeasure (CM) group (n = 5) or a no countermeasure (No-CM) group (n = 5). The subjects in the CM group performed two sessions (20 min each session, 40 min total) of short-arm centrifuge-induced artificial gravity with exercise training in a supine position on alternate days (10 d total) during HDBR. The first session was set at 0.8-1.4 G load at heart level with a constant exercise intensity (60 W), and the second session began with a 0.3 G load at heart level with an interval exercise protocol (40-80% peak oxygen uptake; VO2peak). The measurements of respiratory and cardiovascular responses to incremental exercise were performed pre- and post-HDBR. RESULTS: The 20 d of HDBR increased minute expired ventilation, heart rate, and respiratory exchange ratio and decreased stroke volume during submaximal exercise in the No-CM group, whereas these parameters were unchanged in the CM group. In the No-CM group, VO2peak decreased significantly (47.0 +/- 8.6 to 34.8 +/- 6.8 ml x kg(-1) x min(-1), p < 0.05), whereas VO2peak in the CM group did not show a significant decrease following 20 d of HDBR (47.7 +/- 10.0 to 43.9 +/- 8.9 ml x kg(-1) x min(-1)). These results suggest that short-arm centrifuge-induced artificial gravity with exercise training is effective in maintaining respiratory and cardiovascular responses to upright exercise.

Adolescent↗

Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient.

HESX1/Hesx1 is a member of the paired-like class of homeobox genes and is essential for pituitary and forebrain development. Mice with a targeted homozygous deletion of the Hesx1 show severe central nervous system defects, absence of optic vesicles, and a very small anterior pituitary gland. This phenotype is similar to the abnormalities observed in the human disorder called septo-optic dysplasia, a syndromic form of congenital hypopituitarism. To date, four missense mutations in the human HESX1 have been described in individuals with phenotypes ranging from severe septo-optic dysplasia, relatively mild combined pituitary hormone deficiency (CPHD), to isolated GH deficiency. Here we report a Japanese patient with CPHD (GH, TSH, LH, FSH, and ACTH deficiency) due to a novel sporadic HESX1 mutation. Brain magnetic resonance imaging examination revealed hypoplastic anterior pituitary, ectopic posterior lobe, and left optic nerve hypoplasia. Molecular analysis identified the insertion of a heterozygous mutation (306/307ins AG) in the exon 2 of the HESX1. This mutation changes a reading frame and introduces a premature stop codon soon after the mutation site. Therefore, this mutation would be predicted to generate a protein lacking the carboxyl-terminal homebox domain (DNA-binding domain) and cause the disease. Family analysis demonstrated that neither of the patient's parents harbored this mutation, indicating that the mutation had arisen de novo. In conclusion, a de novo heterozygous frameshift mutation in exon 2 of the HESX1 causes severe CPHD with optic nerve hypoplasia in a human.

Asian People↗

Cardiorespiratory responses to hypoxia and hypercapnia at rest in vocalists.

In order to clarify whether or not ventilatory and circulatory responses to hypoxia and hypercapnia at rest in male vocalists (n = 11) are identical to those of untrained subjects (n = 11), ventilatory responses to hypoxia (HVR) and hypercapnia (HCVR) were estimated as the slope of regression relating .VI to SaO(2) (Delta.VI/DeltaSaO(2)) or the slope factor (A) for the .VI-PETO(2) curve, and as the slope of regression relating .VI to PETCO(2) (Delta.VI/DeltaPETCO(2)), respectively. The respiratory frequency (f), tidal volume (VT), heart rate (HR), and blood pressure (BP) responses to hypoxia and hypercapnia were also estimated as the slope of the line calculated by linear regression related to SaO(2) and PETCO(2). Mean values of Delta.VI/DeltaSaO(2) and A as an index of hypoxic ventilatory response were lower in the vocalist group (0.39 +/- 0.25 l.min(-1).%(-1) and 76.8 +/- 55.7 l.min(-1).torr(-1)) than that in the control group (0.56 +/- 0.46 l.min(-1).%(-1) and 101.6 +/- 85.4 l.min(-1).torr(-1)), and there was no statistically significant difference. The Deltaf/DeltaSaO(2) was significantly (plt;0.05 ) lower in the vocalist group (-0.02 +/- 0.39 breaths.min(-1).%(-1)) than that in the control group (0.43 +/- 0.65 breaths.min(-1).%(-1)). In contrast, mean values of Delta.VI/DeltaPETCO(2) per body mass index were significantly (p<0.05) lower in the vocalist group (0.05 +/- 0.03 l.min(-1).torr(-1)) than those in the control group (0.10 +/- 0.06l.min(-1).torr(-1)). There were also significant differences in DeltaVT/DeltaPETCO(2) and Deltaf/DeltaPETCO(2) between the two groups (p<0.05). However, no significant differences in HR and BP responses to hypoxia and hypercapnia between the two groups were observed. These results suggest that the magnitude of ventilatory response, but not HR and BP, to hypoxia and hypercapnia at rest in vocalists is reduced by chronic vocal training, including breath control and elongation of phonation for long periods.

Adult↗

Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene.

Gain-of-function mutations of the calcium-sensing receptor (CaR) gene cause autosomal dominant and/or sporadic hypocalcemia with hypercalciuria. Because treatment of the hypocalcemia with vitamin D and/or calcium in patients with such mutations results in increased hypercalciuria, nephrocalcinosis, and renal impairment, its use should be limited to alleviating the symptoms of symptomatic patients. Because thiazide diuretics have been successfully used to treat patients with hypercalciuria and hypoparathyroidism, they are theoretically useful in reducing urine calcium excretion and maintaining serum calcium levels in patients with gain-of-function mutations of the CaR gene. In this study, we report on the clinical course, molecular analysis, and effects of hydrochlorothiazide therapy in two Japanese patients with gain-of-function mutations of the CaR gene. Within a few weeks after birth, they developed generalized tonic seizures due to hypocalcemia (serum calcium values: 1.1 mmol/liter and 1.3 mmol/liter, respectively). Despite treatment with the standard dose of 1,25-dihydroxyvitamin D(3) in one patient and 1alpha-hydroxyvitamin D(3) in the other, acceptable serum calcium levels near the lower limit of normal were not established, and their urinary calcium excretion inappropriately increased. Addition of hydrochlorothiazide (1 mg/kg) reduced their urinary calcium excretion and maintained their serum calcium concentrations near the lower limit of normal, allowing the 1,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(3) doses to be reduced, and it alleviated their symptoms. A heterozygous missense mutation was identified in both patients. In one patient, the mutation was A843E in the seventh transmembrane domain of the CaR, and in the other it was L125P in the N-terminal extracellular domain. In vitro transient transfection of their mutant CaR cDNAs into HEK293 cells shifted the concentration-response curve of Ca(2+) to the left. In conclusion, two sporadic cases of hypercalciuric hypocalcemia were due to de novo gain-of-function mutations of the CaR gene. Hydrochlorothiazide with vitamin D(3) successfully reduced the patients' urinary calcium excretion and controlled their serum calcium concentrations and symptoms. Thiazide diuretics are effective in patients with gain-of function mutations of the CaR gene.

Adolescent↗