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Biomedical subjects

A Koike

Publications and source records attributed to A Koike.

At least 37 records · Page 2Linked to original sources

Percutaneous transluminal coronary angioplasty improves oxygen uptake kinetics during the onset of exercise in patients with coronary artery disease.

STUDY OBJECTIVES: Although percutaneous transluminal coronary angioplasty (PTCA) is known to have beneficial effects on exercise capacity, its effects on the cardiovascular response during the onset of exercise have not been clarified. The present study was undertaken to determine the effects of PTCA on the kinetics of oxygen uptake (VO(2)) during constant-work-rate exercise in patients with coronary artery disease, as well as on their indexes of maximal work capacity. METHODS: Seventeen patients with coronary artery disease who received successful PTCAs performed a 50-W constant-work-rate exercise test for 6 min and a symptom-limited incremental exercise test both before and 4 months after the PTCA procedure. VO(2) was calculated from breath-by-breath analysis of respired gases. The time constant of VO(2) kinetics during the onset of 50-W exercise was determined by fitting a single exponential function to the VO(2) response. RESULTS: In 14 patients without coronary restenosis, the time constant of VO(2) kinetics was significantly shortened from (mean +/- SD) 57.4 +/- 12.6 before PTCA to 48.2 +/- 9.5 s after PTCA (p = 0. 0035), indicating improved kinetics of the VO(2) response. In these subjects, the peak VO(2) obtained during maximal exercise testing also increased from 23.1 +/- 3.5 to 26.5 +/- 3.2 mL/min/kg, respectively (p = 0.0005). However, there was no improvement in these indexes in the patients who had restenosis after undergoing PTCA (n = 3). CONCLUSION: Indexes of cardiopulmonary exercise testing, which reflect an efficiency of oxygen flow to the exercising muscle, can be used as an objective, noninvasive, and cost-effective guide for understanding which patients will not have coronary restenosis following PTCA.

Aged↗

Novel missense mutation (Leu466Arg) of the DAX1 gene in a patient with X-linked congenital adrenal hypoplasia.

We identified a DAX1 missense mutation, a substitution of arginine for leucine at codon 466 (Leu466Arg), in an infant with X-linked congenital adrenal hypoplasia (AHC). A heterozygous substitution, Leu466Arg, was also identified in his mother and sister. Since leucine at position 466 is well conserved among other orphan nuclear hormone receptor superfamilies and Leu466Arg was not detected among 50 normal Japanese control individuals, the mutation is most likely responsible for X-linked AHC. It is interesting to note that Leu466Arg among all mutations ever reported is located at the most C-terminal region of the DAX-1 protein. Most mutations identified previously were located in the C-terminal presumptive ligand binding domain. Hence, the C-terminal end of the DAX-1 protein may play an important role in the biological function, such as in normal adrenal embryogenesis.

Adrenal Insufficiency↗

Effects of posture on left ventricular diastolic filling during exercise.

BACKGROUND: Measuring the transmitral flow velocity with Doppler echocardiography is a useful method for evaluating left ventricular diastolic function. However, there are few data regarding the effect of posture during exercise on transmitral flow velocity. METHODS: The transmitral flow velocity with pulsed-wave Doppler echocardiography was measured during supine and upright bicycle ergometer exercise in 10 normal young men without cardiac disease (26.7 +/- 5.5 yr). RESULTS: The ratio of the early rapid filling wave to the atrial filling wave (E/A) was gradually decreased with increasing exercise intensity. At rest and during recovery, the E/A ratio was significantly higher (P < 0.01) in the supine position than in the upright position. This difference was caused mainly by the higher E wave in the supine position. However, E wave and E/A ratio did not differ between the upright and supine position during exercise. CONCLUSION: Although measurement of left ventricular filling is completely noninvasive and clinically useful for evaluating diastolic function, it was found that the E/A ratio was profoundly influenced by posture and exercise intensity. These results suggest that the potential influences of posture and exercise intensity on the filling velocities should be taken into account when interpreting diastolic function by Doppler echocardiography.

Adolescent↗

Differential subcellular localization of DNA-dependent protein kinase components Ku and DNA-PKcs during mitosis.

The Ku protein is a complex of two subunits, Ku70 and Ku80. Ku plays an important role in DNA-PKcs-dependent double-strand break repair and V(D)J recombination, and in growth regulation, which is DNA-PKcs-independent. We studied the expression and the subcellular localization of Ku and DNA-PKcs throughout the cell cycle in several established human cell lines. Using immunofluorescence analysis and confocal laser scanning microscopy, we detected Ku70 and Ku80 in the nuclei in interphase cells. In mitotic cells (1) most of Ku protein was found diffused in the cytoplasm, (2) a fraction was detected at the periphery of condensed chromosomes, (3) no Ku protein was present in the chromosome interior. Association of Ku with isolated chromosomes was also observed. On the other hand, DNA-PKcs was detected in the nucleus in interphase cells and not at the periphery of condensed chromosomes during mitosis. Using indirect immunoprecipitation, we found that throughout the cell cycle, Ku70 and Ku80 were present as heterodimers, some in complex with DNA-PKcs. Our findings suggest that the localization of Ku at the periphery of metaphase chromosomes might be imperative for a novel function of Ku in the G(2)/M phase, which does not require DNA-PKcs.

Antigens, Nuclear↗

Kinetics of pulmonary gas exchange during and while recovering from exercise in patients after anterior myocardial infarction.

The effect of exercise intensity on gas exchange kinetics was investigated during exercise and recovery, as well as the relationship between the kinetics during exercise and recovery. Twenty-three patients with a history of anterior myocardial infarction performed low-intensity (38.7+/-8.3 W) and high-intensity (68.8+/-15.0 W) exercise for 6 min. The time constants of oxygen uptake (VO2), carbon dioxide output (VCO2) and minute ventilation (VE) were significantly prolonged during high intensity exercise compared with low-intensity exercise (61.2+/-8.6 vs 52.3+/-10.3 s, p<0.005 for the time constant of VO2). The time constant of VO2 was similar during exercise and during recovery from exercise of high (61.2+/-8.6 vs 66.2+/-12.2 s) as well as low intensity (52.3+/-10.3 vs 55.0+/-10.1 s). However, the time constants of VCO2 and heart rate were significantly shorter during recovery than during exercise. The time constants of VCO2 and VE were significantly longer than that of VO2 during both exercise and recovery. In the present study, it was found that (1) the gas exchange kinetics were influenced by the intensity of exercise; (2) the kinetics during recovery did not necessarily reflect the kinetics during exercise except for VO2; and (3) the kinetics of VCO2 and VE were delayed as compared with the VO2 kinetics. These characteristics should be taken into account when using gas exchange kinetics to estimate cardiopulmonary responses to exercise in patients with left ventricular dysfunction.

Adult↗

Mechanism of overshoot in cardiac function during recovery from submaximal exercise in man.

BACKGROUND: A sudden increase (overshoot) in the left ventricular ejection fraction during the recovery from maximal exercise has been reported in patients with coronary artery disease, but its mechanism has not been fully clarified. We investigated whether this phenomenon may occur in normal subjects, and whether it depends on the intensity of exercise. METHODS: Thirteen normal subjects (mean [+/- SD] age, 59 +/- 8 years old) performed two levels (25 W and 50 W) of mild-intensity, constant-work-rate exercise for 6 min on a cycle ergometer. Left ventricular function was monitored continuously during the recovery from exercise using a computerized cadmium telluride detector. RESULTS: An overshoot was observed in the ejection fraction during the first minute of recovery compared with the end-exercise value. The overshoot in the ejection fraction during recovery after the 50-W exercise was greater than that seen after the 25-W exercise. An overshoot phenomenon in stroke volume was also observed during the recovery from 50-W exercise. CONCLUSIONS: The overshoot in cardiac function observed during the early phase of recovery, which was caused mainly by an immediate decrease in end-systolic volume, occurred even after exercise of mild intensity. This phenomenon appears to suggest the existence of a transient mismatch between cardiac contractility and afterload reduction during the recovery from mild-intensity exercise, even in normal subjects.

Aged↗

Onset age-dependent variations of three islet specific autoantibodies in Japanese IDDM patients.

The age related incidence rate of insulin-dependent diabetes mellitus shows a bimodal distribution, not only in Caucasians but also in Japanese. To evaluate the onset age-related autoimmune profile at presentation in insulin-dependent diabetes mellitus (IDDM), glutamic acid decarboxylase (GAD) autoantibody, islet cell antibody (ICA), and insulin autoantibody (IAA) were measured in 137 newly diagnosed Japanese IDDM patients with onset ages between 0-29 years. The prevalence of GAD autoantibody was significantly increased from the lowest (32%) in the 0-5 years onset age group to 75% in the 13-19 years onset age group (P < 0.05), whereas the IAA prevalence significantly decreased from the peak (48%) in the 6-12 years onset age group to 10% in the 20-29 years onset age group (P < 0.05). The ICA prevalence was increased from the lowest (32%) in the 0-5 years onset age group to the highest (53%) in the 20-29 years onset age group similar to that for the GAD autoantibody. Such results demonstrate that there was age-related autoimmune characteristics at presentation of IDDM in Japanese as well as in Caucasians.

Adolescent↗

Delayed kinetics of oxygen uptake during recovery after exercise in cardiac patients.

PURPOSE: Little is known about cardiovascular responses during recovery from exercise in patients with cardiovascular disease. The aim of this study was to determine the time constants of the kinetics of oxygen uptake and heart rate during recovery from exercise and to evaluate the influence of resting cardiac function on these kinetics in patients with left ventricular dysfunction. METHODS: A moderate exercise test was performed by 40 patients (57+/-10 yr old) with prior myocardial infarction at a constant work rate (40+/-8 W) for 6 min on a cycle ergometer. The time constants of oxygen uptake and heart rate during 6 min of recovery were compared in patients whose left ventricular ejection fractions were > or =35% (group 1, N = 20) and those with ejection fractions <35% (group 2, N = 20). RESULTS: The time constant of the decrease in oxygen uptake during exercise recovery was significantly prolonged (oxygen requirement was increased) in group 2 compared with group 1. Heart rate during recovery was consistently higher, and its time constant was prolonged in group 2 compared with group 1. The time constant of oxygen uptake was positively correlated with the time constant of heart rate. CONCLUSION: The recovery of oxygen uptake after exercise was significantly delayed, associated with delayed recovery of heart rate, in patients with severely impaired left ventricular function.

Aged↗

Effects of isosorbide dinitrate on oxygen uptake kinetics in cardiac patients.

PURPOSE: Although nitrates are known to improve indices of exercise capacity in patients with coronary artery disease, their effects on oxygen uptake kinetics during the onset of exercise have not been clarified. We evaluated the acute effects of isosorbide dinitrate on the kinetics of oxygen uptake during the onset of exercise at a constant work rate in patients with coronary artery disease. METHODS: We studied 14 patients with coronary artery disease who performed 6 min of low-intensity exercise at a constant work rate on a cycle ergometer 30 min after oral administration of 10 mg of isosorbide dinitrate or placebo in a double-blind, crossover manner. Oxygen uptake was calculated from breath-by-breath analysis of respired gases. The time constant of oxygen uptake kinetics during the onset of exercise was determined by fitting a single exponential function to the oxygen uptake response. RESULTS: Heart rate was significantly increased at rest, and systolic blood pressure was significantly decreased both at rest and during exercise after administration of isosorbide dinitrate. The time constant of oxygen uptake was significantly shorter (the kinetics were faster) after administration of isosorbide dinitrate (39.4+/-10.1 vs 44.5+/-10.5 s, P = 0.038). CONCLUSIONS: Isosorbide dinitrate was found to speed the kinetics of the increase in oxygen uptake during constant work-rate exercise. The time constant of oxygen uptake, which reflects the rapidity of cardiovascular adaptation at the onset of exercise, seems to be a useful parameter of the effectiveness of therapy in patients with coronary artery disease.

Adult↗

Descriptive epidemiology of IDDM in Hokkaido, Japan: the Childhood IDDM Hokkaido Registry.

OBJECTIVE: To identify the incidence of IDDM with regard to sex, age, family history of diabetes, season, and 5-year period of childhood IDDM among children ages 0-14 years from a population-based epidemiological study in Hokkaido, Japan, from 1973 to 1992. RESEARCH DESIGN AND METHODS: Registration of all new IDDM cases in Hokkaido was conducted by the Childhood IDDM Hokkaido Registry Study Group from 1973 to 1992. The cases were selected from among 1) patients who were admitted to the member hospitals of the study group, 2) patients who answered a questionnaire distributed to hospitals and diabetic clinics throughout Hokkaido, and 3) patients whose cases were recorded in free-treatment medical records of urban and rural districts. The case ascertainment rate was estimated to be 100%. Differences in incidence with regard to sex, age, family history of diabetes, season, and year period were analyzed by the Poisson regression analysis by GENMOD. RESULTS: During the 20-year period studied, 396 cases (181 boys, 215 girls) of abrupt-onset IDDM were registered. Statistically significant differences in annual incidence were found according to sex (female), age (8-14 years), history (having no diabetes in family), season (spring), and 5-year period. CONCLUSIONS: This is the first population-based, long-term epidemiological study of childhood IDDM from Japan. We observed a significantly higher annual incidence (per 100,000/year) of IDDM in female subjects (1.81), older age-groups (2.25 for 8-14 years), subjects with no family history of diabetes (1.26), diabetes onset in the spring (2.20), and an increased trend over the 20 years. In addition, the heterogeneity of IDDM among Japanese children needs to be elucidated.

Adolescent↗

Lung function and exercise gas exchange in chronic heart failure.

BACKGROUND: The ventilatory response to exercise in patients with chronic heart failure (HF) is greater than normal for a given metabolic rate. The objective of the present study was to determine the mechanism(s) for the high ventilatory output in patients with chronic HF. METHODS AND RESULTS: Centers in Germany, Italy, Japan, and the United States participated in this study. Each center contributed studies on patients and normal subjects of similar age and sex. One hundred thirty patients with chronic HF and 52 healthy subjects participated. Spirometric and breath-by-breath gas exchange measurements were made during rest and increasing cycle exercise. Arterial blood was sampled for measurement of pH, PaCO2, PaO2, and lactate during exercise in 85 patients. Resting forced expiratory volume in 1 second (FEV1) and vital capacity (VC) were proportionately reduced at all levels of impairment. Patients with more severe HF had greater tachypnea and a smaller tidal volume (VT) at a given exercise expired volume per unit time (VE). This was associated with an expiratory flow pattern characteristic of lung restriction. VE and VCO2 as a function of VO2 were increased during exercise in HF patients. The increases were greater the lower the peak VO2 per kilogram of body weight. The ratio of VD (physiological dead space) to VT and the difference between arterial and end tidal PCO2 at peak VO2 also increased inversely with peak VO2/kg. In contrast, the difference between alveolar and arterial PO2 and PaCO2 were both normal, on average, at peak VO2 regardless of the level of impairment. The more severe the exercise limitation, the higher the lactate and the lower the HCO3- at a given VO2, although pH was tightly regulated. CONCLUSIONS: The increase in VE in chronic HF patients is caused by an increase in VD/VT due to high ventilation/perfusion mismatching, an increase in VCO2 relative to VO2 resulting from HCO3- buffering of lactic acid, and a decrease in PaCO2 due to tight regulation of arterial pH. With regard to the excessive VE in HF patients, the increases in VD/VT and VCO2 relative to VO2 are more important as the patient becomes more exercise limited. Regional hypoperfusion but not hypoventilation typifies lung gas exchange in HF. This and other mechanisms might account for the restrictive changes leading to exercise tachypnea in HF patients.

Carbon Dioxide↗

Cardiomyopathy in a case of Crow-Fukase syndrome.

Crow-Fukase syndrome or POEMS syndrome is a variant of plasma cell dyscrasia that is characterized by polyneuropathy, organomegaly, endocrinopathy, the presence of M-protein in serum, and dermatological changes. A 60-year-old man presented with features of Crow-Fukase syndrome, such as the presence of M-protein in serum, dermatological changes, and osteosclerotic changes, but did not have polyneuropathy. To our knowledge, this is the first case of Crow-Fukase syndrome in which the presence of hypertrophic cardiomyopathy has been confirmed by a left endomyocardial biopsy. The findings suggest that hypertrophic cardiomyopathy may be a manifestation of organomegaly in patients with Crow-Fukase syndrome.

Cardiomyopathy, Hypertrophic↗

Prognostic value of preoperative immunosuppressive acidic protein in patients with gastric carcinoma. Findings from three independent clinical trials. Tumor Marker Committee for the Study Group of Immunochemotherapy with PSK for Gastric Cancer.

BACKGROUND: Immunosuppressive acidic protein (IAP) has been reported to have close correlation with the impairment of host immune response. To evaluate the significance of IAP in clinical studies, the prognostic value of preoperative IAP was investigated in clinical trials of patients with gastric carcinoma after curative resection. METHODS: An appropriate IAP threshold value of 580 micrograms/mL was determined using Cox's proportional hazards model. Five-year survival rates were estimated for high and low IAP groups in three different clinical studies. Meta-analysis was performed based on individual patient data, and summarized hazard ratios were estimated using a stratified proportional hazards model. RESULTS: Meta-analysis of the three clinical trials demonstrated that patients with preoperative IAP levels above the threshold had significantly poorer cancer related survival (P = 0.0039) and absolute survival (P = 0.0023), even after adjustment for the major prognostic factors. CONCLUSIONS: Gastric carcinoma patients with an IAP value above the threshold level of 580 micrograms/mL have a higher risk of cancer death and absolute death than patients with an IAP value below the threshold value.

Adult↗

Relation between oxygen uptake and carbon dioxide output during constant work rate exercise in patients with mild congestive heart failure.

The gas exchange (anaerobic) threshold, a useful index of exercise capacity, is determined as the oxygen uptake (VO2) value at which the ratio of the increase in carbon dioxide output (VCO2) to the increase in VO2 becomes > 1 during incremental exercise (V-slope method). However, this method has not been applied to the constant work rate exercise. We evaluated whether a similar threshold phenomenon (i.e., the gas exchange threshold) could be detected during exercise performed at a constant work rate. Thirty-seven patients with a variety of cardiovascular diseases and 27 normal subjects performed symptom-limited incremental exercise and 6 minutes of 50 W constant work rate exercise. The gas exchange threshold could be determined during both symptom-limited incremental exercise (GETi) and constant work rate exercise (GETc) in all subjects, except for 3 normal subjects, by using the V-slope method. There was a significant correlation between GETc and GETi (r=0.80, p<0.0001). GETc was significantly correlated with peak VO2 obtained during the incremental exercise test (r=0.69, p<0.0001). The results suggest that the gas exchange threshold during constant work rate exercise, which does not require the subject's maximal effort, is a useful measure of exercise capacity in patients with cardiovascular disease.

Adult↗

Prospective adjuvant therapy with mitomycin C and carmofur (HCFU) for colorectal cancer, 10-year follow-up: Tokai HCFU Study Group, the first study for colorectal cancer.

A joint study was performed by the Tokai HCFU study group, which included 41 institutions to study the usefulness of the concomitant therapy with Mitomycin C (MMC) and Carmofur (HCFU) as a postoperative adjuvant chemotherapy in patients with colorectal cancer who had curative resection. Patients were divided into two groups, Group MMC and Group MMC+HCFU, using the "envelope" method. Among the 172 patients who had the envelope opened, 149 evaluable cases were analyzed for evaluation of the drug. The cumulative 10-year survival rates of Group MMC+HCFU had a statistically significant increase in survival rate compared with Group MMC. In particular, the rate was statistically significant in patients with colorectal cancer who had lymph node invasion. There were no severe side effects due to the adjuvant chemotherapy with MMC+HCFU. Thus the adjuvant chemotherapy with MMC+HCFU is suggested to be a useful and safe postoperative adjuvant chemotherapy.

Adult↗

Protective effects of dimethyl amiloride against postischemic myocardial dysfunction in rabbit hearts: phosphorus 31-nuclear magnetic resonance measurements of intracellular pH and cellular energy.

The effects of 5-(N,N-dimethyl)amiloride, a potent and specific Na(+)-H+ exchange inhibitor, were investigated in isolated perfused rabbit hearts subjected to ischemia and reperfusion. Phosphorus 31-nuclear magnetic resonance spectroscopy was used to monitor intracellular pH, creatine phosphate, beta-adenosine triphosphate, and inorganic phosphate. After cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees C) global ischemia was induced for 45 minutes, and the hearts were reperfused for 50 minutes. Dimethyl amiloride at 10 mumol/L, which has minimal inotropic and chronotropic effects on the nonischemic heart, was added to the cardioplegic solution. Treatment with dimethyl amiloride reduced the elevation of left ventricular end-diastolic pressure during and after the ischemia and improved the postischemic recovery of developed pressure from 76% +/- 3.2% at 30 minutes of reperfusion in control hearts (n = 6) up to 99% +/- 1.9% in hearts treated with dimethyl amiloride (n = 8). Dimethyl amiloride did not affect the decline in intracellular pH during ischemia for up to 30 minutes but enhanced the intracellular acidosis thereafter. The intracellular pH at the end of ischemia was 6.21 +/- 0.05 in control hearts compared with 5.24 +/- 0.17 in hearts treated with dimethyl amiloride (p < 0.05). During reperfusion, intracellular pH of hearts treated with dimethyl amiloride was less than control for 5 minutes, but subsequent recovery of intracellular pH was similar to control. Treatment with dimethyl amiloride did not affect creatine phosphate breakdown, inorganic phosphate accumulation, and beta-adenosine triphosphate depletion during 45 minutes of ischemia. The creatine phosphate resynthesis and inorganic phosphate reduction during reperfusion were also unaffected. These findings suggest that Na(+)-H+ exchange plays an important role not only during reperfusion but also during ischemia for the development of postischemic cardiac dysfunction most likely by inducing primary Na+ and secondary Ca2+ overload. Specific Na(+)-H+ exchange inhibitors like dimethyl amiloride would have a potential therapeutic profile in cardiac surgery, especially if added before ischemia.

Acidosis↗

Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction?

OBJECTIVE: The objective of the present study was to determine whether appropriate endurance exercise training improves cardiac function in patients with prior myocardial infarction. METHODS: Twenty-nine patients with prior myocardial infarction were divided into three groups (Group 1: control, Group 2: low-intensity training, Group 3: high-intensity training). Low and high training intensities were determined according to the gas exchange threshold of each patient. The patients in Groups 2 and 3 performed 15 min of home-based physical training safely, twice a day, 5 days a week for 2 months. Prior to and following this training, each patient performed two constant work rate tests (moderate and heavy intensity) and a symptom-limited incremental exercise test. RESULTS: Heart rates at rest and during exercise were decreased significantly after 2 months in all three groups. Stroke volume at rest increased significantly after 2 months only in Group 3. Stroke volume after 6 min of heavy-intensity exercise increased significantly in Groups 2 and 3. However, the ejection fraction at 6 min of heavy-intensity exercise increased significantly only in Group 3. The maximal work rate attained during incremental exercise testing increased significantly in Groups 2 and 3. This parameter did not significantly change in the control group. CONCLUSIONS: Effects of physical training on maximal exercise capacity were noted in both exercise training groups. However, improvement in cardiac function (such as stroke volume), both at rest and during exercise, was noted only in the high-intensity training group. Our results suggest that relatively high-intensity training may improve exercise capacity and cardiac function of patients with prior myocardial infarction.

Adult↗