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Biomedical subjects

S Hosoda

Publications and source records attributed to S Hosoda.

At least 55 records · Page 3Linked to original sources

Sodium--potassium pump current in rabbit sino-atrial node cells.

1. The Na(+)-K+ pump current (Ip) was studied in sino-atrial (SA) node cells of rabbits using the whole-cell patch-clamp technique. 2. With 50 mM Na+ in the pipette solution ([Na+]pip), changing the external K+ concentration (-K+-o) from 0 to 5.4 mM caused the holding current to shift in an outward direction and reach a new steady state. The current-voltage relationships obtained by subtraction of current traces recorded at 0 mM Ko+ from those recorded at 5.4 mM Ko+ revealed time-independent and voltage-dependent characteristics. The external K(+)-induced current was completely blocked by external application of 10 microM ouabain, indicating the existence of Ip in SA node cells of rabbit heart. 3. Ip increased as [K+]o increased. With 30 mM Na+pip, Ip at 0 mV was activated by [K+]o with non-linear least-squares fit parameters for the Hill equation of K0.5 of 1.4 mM and a Hill coefficient (nH) of 1.2 (n = 7). 4. The cation dependence of the K+ site of the Na(+)-K+ pump was examined using various monovalent cations. The sequence was K+ > or = Rb+ > Cs+ > > > Li+. 5. Ip at 0 mV also increased as [Na+]pip was increased from 10 to 150 mM at 5.4 mM Ko+, with a K0.5 value of 14 mM and a nH of 1.3 (n = 54). 6. Ip at 0 mV was reduced by lowering the temperature from 37 to 25 degrees C with 30 mM Na+pip and 5.4 mM Ko+. The temperature coefficient (Q10) for Ip was 2.1 (n = 27). 7. With 10 mM Na+pip and 5.4 mM Ko+, the half-activation voltage of Ip was -52 +/- 16 mV and the current at this voltage was 22.5 +/- 3.5 pA (n = 10), indicating that Ip contributes significantly to the background outward current during the normal pacemaker potential of SA node cells.

Animals↗

Apoptosis and DNA fragmentation in the bulbus cordis of the developing rat heart.

Histologic, ultrastructural and nick end labeling studies were made of the process of apoptosis in the bulbus cordis of rat embryos. Apoptosis was observed between the 14th and 16th days of gestational age, at which time the bulbus cordis undergoes extensive remodeling. Three types of mesenchymal cells were identified in this region: cells undergoing apoptosis, cells engaging in the phagocytic removal of apoptotic cells, and cells not involved in either of these two processes. Fragmentation of DNA, demonstrated by nick end labeling, was found only in the apoptotic cells. The combined use of morphologic and labeling techniques is extremely useful in the evaluation of the contribution of apoptosis to cardiac morphogenesis.

Animals↗

Comparison of clinical outcomes of coronary artery bypass grafting and percutaneous transluminal coronary angioplasty in renal dialysis patients.

BACKGROUND: The leading cause of death in chronic renal dialysis patients is cardiovascular disease. As the number of dialysis patients increases, we are encountering more patients with severe ischemic heart disease requiring coronary intervention. METHODS: A retrospective analysis was performed of the short- and long-term clinical results in 23 coronary artery bypass grafting patients and 20 coronary angioplasty patients undergoing chronic renal dialysis. RESULTS: Among coronary bypass grafting patients, there were no hospital deaths. The graft patency rate was 100% for arterial grafts. There were four late deaths and four cardiac events. In coronary angioplasty patients, the lesion success rate was 76%. There were no hospital deaths and three major complications. The restenosis rate was 70%. There were two late deaths and 14 cardiac events. The 5-year cardiac event-free rate was 70% in coronary bypass grafting patients, significantly better than 18% in coronary angioplasty patients (p < 0.001). CONCLUSIONS: Coronary artery bypass grafting in chronic renal dialysis patients can be accomplished with a better short- and long-term outcome than coronary angioplasty, through an intensive perioperative dialysis program and extensive use of arterial grafts.

Angioplasty, Balloon, Coronary↗

Comparison between Japan and North America in the post-hospital course after recovery from an acute coronary event.

We compared the post-hospital prognosis after an acute coronary event (acute myocardial infarction and unstable angina) in 106 patients in Japan vs. 789 patients in North America who were prospectively enrolled in the Multicenter Study of Myocardial Ischemia and were followed-up for an average of 26 months per patients. Risk factors more frequent in Japan were older age, males and smoking at enrollment, but the rest of many risk factors were similar. After adjusting for differences in clinical and medication variables, Cox analyses indicated patients in North America had a significantly greater risk of experiencing a primary end-point (cardiac death, non-fatal myocardial infarction or unstable angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P = 0.003). There was a non-significant trend in the restricted end-points (cardiac death or non-fatal myocardial infarction) with North America having more frequent events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after recovery from an acute coronary event is more favorable in Japan than in North America, mostly due to a reduction in subsequent hospitalization for unstable angina. The reason for these findings cannot be explained by differences in the measured risk factors or medications.

Adult↗

Endogenous endothelin-1 mediates cardiac hypertrophy and switching of myosin heavy chain gene expression in rat ventricular myocardium.

OBJECTIVES: We investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions. BACKGROUND: Endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture. METHODS: We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group). RESULTS: The ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus FR139317. The right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus FR139317 than in those treated with monocrotaline alone (p < 0.01). As a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. This ratio was increased in all monocrotaline-treated rats but was lower (p < 0.01) in rats given monocrotaline plus FR139317 than in those given monocrotaline alone. The isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by S1 nuclease mapping also was lower (p < 0.025) in rats receiving monocrotaline plus FR139317 than in those receiving monocrotaline alone. CONCLUSIONS: These data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.

Animals↗

[Basic and clinical studies of pazufloxacin on infectious enteritis research group of T-3761 on infectious enteritis].

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

4-Quinolones↗

[Clinical study of prulifloxacin on infectious enteritis. Japan Research Committee of Prulifloxacin, Research Group on Infectious Enteritis].

Prulifloxacin (PUFX), a new quinolone antimicrobial agent, was administered to a total of 122 patients and carriers to investigate its clinical efficacy, safety and usefulness in infectious enteritis (bacillary dysentery, enteritis caused by Salmonella spp. and enteropathogenic E. coli, cholera and so on). In addition, the minimum inhibitory concentration (MIC) of UFX (active compound) was determined against each clinical isolate, and compared with that of ciprofloxacin (CPFX), ofloxacin (OFLX), tosufloxacin (TFLX) and nalidixic acid (NA). The correlation between the concentration of UFX in feces and the change of the fecal microflora were also investigated when PUFX was administered to the patients with acute infectious enteritis. A daily dose of 400 mg of PUFX was administered orally in two divided doses (morning and evening) for 5 days, with the exception of 7 days administration against salmonella enteritis and 3 days administration against cholera. 84 cases were adapted for evaluating the usefulness. The clinical efficacy was 100% in all the enteritis except salmonella enteritis, in which it was 88.9% (8/9 cases). On the bacteriological efficacy, the elimination rate was 100% in all isolates except Salmonella spp., in which it was 75.0% (12/16 cases). As for the adverse effect, uriticaria in moderate degree was observed in 1 (0.9%) of 109 cases. Abnormal changes in laboratory findings were seen in 3 (3.0%) of 100 cases, consisting of 1 with eosinophilia and 2 with elevated S-GPT, although they were all slight in degree. The usefulness rate was 65.5% (55/84 cases) for "very useful" and 95.2% (80/84 cases) for "very useful" and "useful". MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae, was 0.025, 0.05, 0.025 and 0.05 microgram/ml, respectively. These values were the same as those of CPFX and TFLX, and superior to OFLX and NA. UFX concentrations in feces followed by administration of PUFX in 3 cases with acute infectious enteritis were higher than that of MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae. The changes of the fecal microflora, which influence the efficacy and safety of PUFX, were not observed.

Adult↗

Enhancement of the L-type Ca2+ current by mechanical stimulation in single rabbit cardiac myocytes.

Anion conductance is known to be activated by mechanical stimulation, such as osmotic cell swelling or cell inflation via the patch pipette, of canine or rabbit cardiac myocytes. The effects of mechanical stimulation on time-dependent currents, however, remain unsettled. Using the whole-cell voltage-clamp method, we have found that mechanical stimuli enhance the L-type Ca2+ current (ICa,L) in rabbit cardiac myocytes. At every membrane potential, ICa,L was reversibly increased by osmotic cell swelling and by cell inflation caused by applying a positive pressure of 10 to 15 cm H2O via the patch pipette. ICa,L was increased during cell inflation by 37 +/- 21% (mean +/- SD, n = 17) in atrial cells and by 37 +/ -8% (n = 7) in sinoatrial node cells in solution containing 2 mmol/L Ca2+. The current-voltage relationship, the inactivation time constant, the steady state inactivation curve, and the conductance properties of ICa,L were all virtually unaffected by mechanical stimulation except for the open probability, which appears to increase. The increase in ICa,L was not dependent on protein kinase A, since an inhibitor peptide of cAMP-dependent protein kinase failed to prevent the increase in ICa,L during mechanical stimuli (n=5). The increase in ICa,L caused by cell inflation was unaffected by the chelation of intracellular Ca2+ by the addition of 10 mmol/L EGTA or 10 mmol/L BAPTA to the pipette solution, suggesting that the effect was not mediated by changes in intracellular Ca2+. Thus, mechanical stimulation due to cell swelling or inflation may itself directly increase ICa,L in rabbit cardiac myocytes.

Animals↗

Low efficiency of oxygen utilization during exercise in hyperthyroidism.

STUDY OBJECTIVE: The mechanism of exercise intolerance in hyperthyroidism has not been fully elucidated. This study was undertaken to determine if hyperthyroidism reduced the efficiency of sub-maximal exercise. STUDY DESIGN: We measured cardiorespiratory variables up to the anaerobic threshold (AT) during ramp-loading cycle ergometry in 12 patients (New York Heart Association functional class II or III). Studies were performed in the hyperthyroid state and repeated in the euthyroid state after 10 months of medical treatment. In 10-W steps from rest to the AT, we measured oxygen uptake (VO2) as a measure of total body work rate, and pressure rate product (PRP) as a measure of cardiac work rate. Loading watts at AT divided by the increment of Vo2 from rest to the AT (delta Watt/delta VO2) was calculated as an index of work efficiency (where delta means the increment of each value from rest to the AT). RESULTS: VO2 and PRP at the AT were not significantly different between hyperthyroid and euthyroid states (VO2, 16.6 +/- 3.0 vs 17.5 +/- 2.3 mL/min/kg; PRP, 229 +/- 41 vs 218 +/- 28 x 10(2) mm Hg/min). However, loading watts at the AT were significantly lower in the hyperthyroid than the euthyroid state (28 +/- 22 vs 60 +/- 14 W: p < 0.01). VO2 and PRP while hyperthyroid were significantly higher than when euthyroid at every 10-W step during ramp-loading exercise. Furthermore, delta Watt/delta VO2 was significantly lower in hyperthyroid than euthyroid states (p < 0.001). There was a significant inverse correlation-ship between triiodothyronine and delta Watt/delta Vo2 (r = -0.654, p < 0.001). CONCLUSION: Hyperthyroidism causes low work efficiency, which may limit exercise tolerance.

Adult↗

[Acute myocardial infarction and silent myocardial ischemia in the elderly--clinical features and effectiveness of therapy in an era of coronary intervention].

To elucidate the clinical features of acute myocardial infarction (AMI) and post-MI silent myocardial ischemia (SMI) in the elderly, and efficacy of therapy in an era of coronary intervention, a total of 10,607 patients with AMI who were enrolled in a multicenter survey between 1982 and 1992 were examined. The elderly had a higher ratio of females, noncardiac illness, atypical symptoms at the onset of AMI, severe pump failure at admission, cardiac rupture and multivessel disease. Hospital mortality was markedly higher in patients > or = 75 years, and it was 4-fold compared with patients < 65 years. In the last 5 years, the rate of application of coronary angiography and primary PTCA significantly increased even in the very elderly. In contrast, use of thrombolysis highly diminished. Hospital mortality declined (14.6 vs 11.9%, p < 0.001) in every age group compared with the first 5 years, although it was higher in the elderly even in the last 5 years. Investigation of 642 survivors after AMI admitted to one hospital showed that the elderly had a higher incidence of SMI and post-MI angina compared with the non-elderly. Clinical features of SMI were similar in both groups. However, medical treatment was more prevalent and recurrence of MI and cardiac death during follow-up (average 27 months) were more frequent in the elderly. In this retrospective study, characteristics of AMI and SMI, and effectiveness and limitation of therapy in the elderly were clearly demonstrated. It was evident that hospital mortality of the elderly had improved, although it was still higher than the non-elderly.

Aged↗

[A case of dilated cardiomyopathy with early back-diffusion of 123I-BMIPP].

A 28-year-old woman was pointed out cardiomegaly and diffuse hypokinesis of left ventricle by ultrasonography in community hospital. Coronary angiography showed normal coronary artery and, left ventriculography revealed diffuse hypokinesis (LVEF 40%). She was diagnosed idiopathic dilated cardiomyopathy by myocardial biopsy and other clinical information. Myocardial scintigraphy with 201Tl. revealed dilatation of left ventricle and diffuse inhomogeneous accumulation of 201 Tl. Dynamic 123I-BMIPP SPECT image 2 minutes after injection showed BMIPP accumulation in all segment, though, static image 15 minutes after injection indicated reduced BMIPP accumulation. These findings suggested existence of the early back-diffusion in inferior segment. Early back-diffusion of BMIPP may become a marker of abnormal fatty acid metabolism in patient with dilated cardiomyopathy.

Adult↗

[Detection of angina-related coronary artery in patients with unstable angina pectoris by using 123I-BMIPP myocardial scintigraphy].

To evaluate the diagnostic accuracy of detection of angina-related coronary arteries in patients with unstable angina pectoris. Twenty patients with unstable angina pectoris underwent 123I-BMIPP scintigraphy at rest. A mean duration from last anginal attack to 123I-BMIPP scintigraphy was 408 +/- 3.2 days. Seventeen of 20 angina-related coronary territories were detected by reduced 123I-BMIPP uptake. The sensitivity and specificity for detection of angina-related coronary arteries were 85% and 95%, respectively. The decrease in myocardial uptake of 123I-BMIPP agreed with the decrease in regional wall motion by using ultrasonic echocardiography. 123I-BMIPP scintigraphy may be useful for detection of angina-related coronary artery in a routine clinical examination in patients with unstable angina pectoris.

Aged↗

[Changes of coronary artery diameter during follow-up in patients with vasospastic angina: comparison of spastic and non-spastic sites].

The relationship between coronary vasospasticity and the development of atherosclerotic lesion was studied in 24 patients with vasospastic angina. All patients had no organic stenosis initially and underwent follow-up coronary angiography at 66 +/- 9 months after the initial examination. The coronary artery diameter was measured with the contour detection method. The spastic and non-spastic sites were identified at the initial coronary angiography with the acetylcholine provocation test. The change of the luminal diameter (delta LD) and the ratio of the change of luminal diameter (% delta LD) were compared at the spastic and the non-spastic sites. The follow-up examination showed significant decreases of coronary artery diameter in both the spastic (2.35 +/- 0.67 vs 2.16 +/- 0.58 mm, p < 0.001) and non-spastic sites (2.66 +/- 0.91 vs 2.54 +/- 0.84 mm, p = 0.02). However, delta LD and % delta LD were not different between the spastic and non-spastic sites (delta LD: -0.19 +/- 0.40 vs -0.12 +/- 0.46 mm, NS; % delta LD: -6.7 +/- 14.8% vs -3.2 +/- 17.0%, NS). In conclusion, coronary vasospasticity does not promote the development of atherosclerotic lesion.

Aged↗

[Prediction of long-term efficacy of amiodarone for refractory ventricular tachycardia: clinical significance of electrophysiologic study and Holter monitoring].

The usefulness of electrophysiologic study and Holter monitoring for predicting the long-term efficacy of amiodarone was investigated in 31 patients with sustained ventricular tachycardia (VT) and organic heart disease. Patients underwent both electrophysiologic study and Holter monitoring before and during oral administration of amiodarone. These patients were followed up and the difference in the prognosis according to the results of these two tests was examined. During a follow-up period of 887 +/- 678 days, sustained VT recurred in 13 patients and sudden cardiac death in 3. Sustained VT recurred in only one of 11 patients in whom amiodarone was determined effective by electrophysiologic study whereas recurrent VT and/or sudden death occurred in 15 of 20 patients in whom amiodarone was determined ineffective (p < 0.01). Eight of 18 patients in whom amiodarone was determined effective by Holter monitoring, and 8 of 13 in whom it was determined ineffective, suffered recurrent VT and/or sudden cardiac death. Amiodarone was judged effective in 7 patients by both tests (group I) and in 15 by either electrophysiologic study or Holter monitoring (group II). In the remaining nine patients, amiodarone was ineffective by both tests (group III). Recurrent VT or sudden death occurred in none of the patients in group I (0%), in nine group II (60%) and seven in group III (78%). The prognoses of the three groups were significantly different: group I vs II; p < 0.05, group II vs III: p < 0.05, and group I vs III; p < 0.005. The combination of the two drug tests, electrophysiologic study and Holter monitoring, is a useful method for the prediction of the long-term efficacy of amiodarone in patients with sustained VT and underlying heart disease. Patients in whom amiodarone was determined ineffective in both tests, are at high risk for VT recurrence and sudden death, and interventional therapy is recommended.

Administration, Oral↗

[Short-term and long-term outcome of left heart function after cardioverter defibrillator implantation].

The usefulness and problems of implantable cardioverter defibrillators (ICD) were examined in patients with reduced heart function. Of 36 patients who received ICD for refractory ventricular tachycardia (VT) or ventricular fibrillation (VF), VT and/or VF was associated with underlying heart disease in 26 patients, and VF without underlying heart disease in 10. Of the former 26 patients, 13 with left ventricular ejection fraction (LVEF) of less than 30% were assigned to group A, 13 with LVEF of greater than 30% to group B, and the other 10 with idiopathic VF to group C. Intraoperative death, cardiac death due to heart failure, sudden death, functional status of the ICD, exacerbation of heart failure symptoms and complications were compared between the three groups. There were no intraoperative deaths in any of the groups. During the median follow-up period of 36 +/- 22 months, there was only one sudden death in group A. There were no significant differences between the three groups. There were five cardiac deaths in group A, but none in groups B or C. The cardiac death-free rates 12, 24, and 36 months after implantation in group A were 83%, 60% and 50%, respectively. These values significantly differed from those in groups B and C (p < 0.05). The number of patients who received defibrillation therapy was higher in group A (p < 0.05). Defibrillation therapy was administered earlier in group A than in groups B and C (p < 0.05). The incidence of exacerbation of heart failure after implantation was 69%, 23% and 0% in groups A, B, and C, respectively. In group A, defibrillation therapy was administered in all patients with exacerbation of heart failure. The administration of defibrillation therapy significantly differed from that in patients without exacerbation of heart failure (p < 0.05). Exacerbation of heart failure during the postoperative acute stage occurred in both patients in group A in whom an epicardial lead system was used, but not in the four patients in group B or five in group C (p < 0.05). There were no differences in the incidence of other complications between the three groups. In group A, patients with reduced heart function, ICD greatly decreased the risk of sudden death. However, heart failure mortality remained high. Therefore, ICD may have limitations for improved prognosis. In group A patients, defibrillation therapy was administered in all patients with exacerbation of heart failure or death due to heart failure. In patients with reduced heart function, treatment for heart failure and prophylaxis of VT and/or VF should be administered.

Adult↗

[Left ventricular lesions in arrhythmogenic right ventricular dysplasia and 12-lead electrocardiographic findings].

Left ventricular lesions in arrhythmogenic right ventricular dysplasia have not been well described, and the relationship between the left ventricular lesions and the 12-lead electrocardiographic findings has not been analyzed. This study examined whether the presence of left ventricular lesions and the extent of right ventricular lesions due to arrhythmogenic right ventricular dysplasia are predictable by 12-lead electrocardiographic findings. The 12-lead electrocardiograms during sinus rhythm and left and right ventriculography were studied in 29 patients (27 males and 2 females, mean age 42.6 +/- 15.5 years) diagnosed by the current criteria for this disease. After evaluation, patients were divided into two groups: those with normal left ventricles (normal group) and those with left ventricular wall motion abnormalities (abnormal group). Seventeen of the 29 patients (59%) were classified into the abnormal group. Left ventricular wall motion abnormalities were located in the posterolateral (4 patients), apical (1), and posterolateral and apical regions (12). QS patterns of abnormal Q waves in lead I, aVL or V5, V6 rS patterns (R/S ratio < 1) in leads I and V6, and/or R or Rs patterns (R/S ratio > 1) in lead V1 were observed in all patients in the abnormal group, but in none in the normal group. There was a positive correlation between the right ventricular end-diastolic volume index and the number of precordial negative T waves (r = 0.746, p < 0.0001), and the time from onset of the QRS to the terminal portion of the epsilon wave in lead V1 (r = 0.627, p < 0.001). The correlation coefficients showed no significant differences between the groups. A left ventricular lesion associated with arrhythmogenic right ventricular dysplasia was not unusual (59%), and our study suggests that the posterolateral and apical regions are the most frequent sites. The presence of these lesions were predictable by the QRS abnormalities. Moreover, regardless of the presence of such a lesion, the extent of the right ventricular lesion is also predictable by the 12-lead electrocardiographic findings.

Adult↗