Biomedical subjects
Publications and source records attributed to H Takaki.
We report a case of malignant lymphoma presenting with tumor thrombus of the portal venous system. Computed tomography showed a mass in the portal vein and mesenteric lymphadenopathy. Filling defects in the dilated portal vein also were identified by angiography. This type of the lymphoma is extremely rare, but it should be considered in the differential diagnosis of portal vein thrombus.
During attempted oesophageal stent placement in a patient with cervical oesophageal cancer in whom swallowing of even saliva was impossible, transoral access to the cervical oesophagus was unsuccessful. Under ultrasound and fluoroscopy guidance, percutaneous gastric puncture was performed, and using an angiographic catheter and guidewire, access to the oesophagus by a retrograde transgastric route was successfully achieved. The obstructed segment of the oesophagus was traversed. It was then possible to pull the guidewire through the mouth and place an oesophageal stent via an antegrade approach.
OBJECTIVE: To elucidate the responsible mechanisms of increased slope of minute ventilation relative to carbon dioxide production (VE/VCO(2)) during exercise after acute myocardial infarction without overt signs of heart failure, patients who had an acute myocardial infarction were examined after participating in a three month supervised exercise training programme. DESIGN: Exercise testing, hypercapnic CO(2) chemosensitivity measurement (rebreathing method), and pulmonary function test were repeated at entry and after three months in 50 acute myocardial infarction patients with neither symptoms nor signs of heart failure who completed the training programme. Ten patients who performed initial inhospital training served as controls. RESULTS: Age, peak oxygen uptake, left ventricular ejection fraction, CO(2) chemosensitivity, respiratory parameters (percentage of predicted normal vital capacity (%VC), forced expiratory volume in one second, and carbon monoxide transfer factor (%TLCO)) were all significantly correlated with VE/VCO(2) slope. Multivariate regression analysis showed that age (beta = 0.29, p = 0.01), %TLCO (beta = -0.27, p = 0.01), and CO(2) chemosensitivity (beta = 0.49, p < 0.001) were independent determinants of VE/VCO(2) slope. After three months, there was no significant change in these parameters in the control group. Peak oxygen uptake, %TLCO, and %VC and attenuation in CO(2) chemosensitivity increased significantly in the training group. The VE/VCO(2) slope decreased marginally (p = 0.11). The changes in VE/VCO(2) slope were correlated only with those in CO(2) chemosensitivity (r = 0.50, p < 0.001). CONCLUSION: After acute myocardial infarction, exercise hyperventilation is seen in association with aging, enhanced hypercapnic CO(2) chemosensitivity, and reduced TLCO, even in the absence of overt heart failure. The correlation of VE/VCO(2) attenuation after training with the reduction in CO(2) chemosensitivity suggests that exercise training may reduce increased VE/VCO(2) slope, at least partially by reducing CO(2) chemosensitivity.
OBJECTIVES: To compare and contrast the gene expression of two LIM-homeobox type transcription factors, Lhx6 and L3/Lhx8, in secondary palate formation. METHODS: In situ hybridization histochemistry with digoxygenin (DIG) labelled cRNA probes specific for Lhx6 and L3/Lhx8. MATERIALS: Serial cryo-sections of embryonic day (E)13.5, 14.5, and 15.5 mice (C57BL/6). OUTCOME MEASURE: Comparison of the signal intensities of NBT/BCIP precipitate by alkaline phosphatase conjugated anti-DIG antibody. RESULTS: From E13.5 to E15.5, Lhx6 and L3/Lhx8 signals are detected in palatal mesenchyme, but the L3/Lhx8 signal is much more intense than the Lhx6 signal. In palatal epithelium, covering the mesenchyme, Lhx6 mRNA is transiently expressed at E14.5, while L3/Lhx8 mRNA expression is never detected throughout the development. CONCLUSION: Lhx6 and L3/Lhx8 functions may be partially redundant in the mesenchyme of the secondary palate, but not in the palatal epithelium.
AIMS: Differences in the sensitivity of the genotype of the congenital long QT syndrome to sympathetic stimulation have been suggested. This study compared the influence of sympathetic stimulation on continuous corrected QT (QTc) intervals between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome. METHODS AND RESULTS: We recorded a 12-lead electrocardiogram continuously before and after bolus injection (0.1 microg x kg(-1)) of epinephrine followed by continuous infusion (0.1 microg x kg(-1) min(-1)) in 12 LQT1, 10 LQT2, 6 LQT3, and 13 control patients. The QT intervals and previous RR intervals of all beats were measured semi-automatically, and the QTc intervals of all beats were calculated by Bazett's method. The dynamic response of the RR interval to epinephrine was no different between the four groups. The QTc was prolonged remarkably (477+/-42 to 631+/- 59 ms; P<0.0005, % delta prolongation =+32%) as the RR was maximally decreased (at peak of epinephrine), and remained prolonged at steady state conditions of epinephrine (556+/-56 ms; P<0.0005 vs baseline, +17%) in LQT1 patients. Epinephrine also prolonged the QTc dramatically (502+/-23 to 620+/-39 ms; P<0.0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened to baseline levels at steady state (531+/-25 ms; P=ns vs baseline, +6%). The QTc was much less prolonged at peak of epinephrine in LQT3 (478+/-44 to 532+/-41 ms; P<0.05, +11%) and controls (394+/-21 to 456+/-18 ms; P<0.0005, +16%) than in LQT1 and LQT2 patients, and shortened to the baseline levels (LQT3; 466+/-49 ms, -3%, controls; 397+/-16 ms, +1%; P=ns vs baseline) at steady state. CONCLUSION: Our data suggest that the dynamic response of ventricular repolarization to sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may explain why the trigger of cardiac events differs between the genotypes.
The OASIS gene, which encodes a novel CREB/ATF family member, was isolated from long-term cultured astrocytes that were employed as an in vitro gliosis model. In the present study, we examined the expression pattern of the OASIS gene in the developing mouse embryo by in situ hybridization histochemistry and compared it with the expression of osteogenesis markers. OASIS mRNA expression was most strongly detected in preosteoblasts of the outer bony cortex of the ribs. Alveolar bone also showed strong signals for OASIS gene expression. OASIS mRNA was also localized to the preodontoblast of tooth buds. Expression began at embryonic day 12 (D12.5), peaked around D14.5-16.5, and continued to D18.5. The pattern of expression was very similar to that of hXBP-1 mRNA, which encodes another CREB/ATF family member. Spatiotemporal patterns of OASIS partly overlapped that of osteopontin, osteonectin, and alpha1 type I procollagen genes. Among these, the time course of OASIS mRNA expression was most similar to that of osteopontin mRNA expression, suggesting that the OASIS protein is involved in the late phase of osteoblast differentiation, as compared to the Cbfa1 that regulates early phases of osteoblast differentiation.
BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.
OBJECTIVE: To assess acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Cardiopulmonary exercise testing was performed in 20 patients with CTEPH before thromboendarterectomy (baseline), one month after (early phase), and four months after (late phase). Peak oxygen uptake (peak VO(2)) and the ventilatory response to carbon dioxide production (VE-VCO(2) slope) were measured for assessment of exercise capacity and ventilatory efficiency. Right heart catheterisation was performed in all patients before and one month after surgery. RESULTS: Baseline peak VO(2) decreased and VE-VCO(2) slope increased along with the increase in pulmonary vascular resistance in patients with CTEPH. After thromboendarterectomy, the VE-VCO(2) slope decreased greatly from baseline to the early phase (mean (SD), 50 (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a continued increase in peak VO(2) was noted from the early to the late phase (16.9 (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in the VE-VCO(2) slope from baseline to the early phase, but not the increase in peak VO(2), correlated strongly with the decrease in pulmonary vascular resistance after surgery (r = 0.75, p < 0.01). CONCLUSIONS: Thromboendarterectomy may cause an immediate improvement in ventilatory efficiency, possibly through its beneficial haemodynamic effects. In contrast, exercise capacity may continue to improve towards the late phase, reflecting peripheral adaptation to exercise.
We examined whether the ACh concentration measured by cardiac microdialysis provided information on left ventricular ACh levels under a variety of vagal stimulatory and modulatory conditions in anesthetized cats. Local administration of KCl (n = 5) and ouabain (n = 7) significantly increased the ACh concentration in the dialysate to 4.3 +/- 0.8 and 7.3 +/- 1.3 nmol/l, respectively, from the baseline value of 0.6 +/- 0.5 nmol/l. Intravenous administration of phenylbiguanide (n = 5) and phenylephrine (n = 6) significantly increased the ACh concentration to 5.4 +/- 0.9 and 6.0 +/- 1.5 nmol/l, respectively, suggesting that the Bezold-Jarisch and arterial baroreceptor reflexes affected myocardial ACh levels. Modulation of vagal nerve terminal function by local administration of tetrodotoxin (n = 6), hemicholinium-3 (n = 6), and vesamicol (n = 5) significantly suppressed the electrical stimulation-induced ACh release from 20.4 +/- 3.9 to 0.6 +/- 0.1, 7.2 +/- 1.9, and 2.7 +/- 0.6 nmol/l, respectively. Increasing the heart rate from 120 to 200 beats/min significantly reduced the myocardial ACh levels during electrical vagal stimulation, suggesting a heart rate-dependent washout of ACh. We conclude that ACh concentration measured by cardiac microdialysis provides information regarding ACh release and disposition under a variety of pathophysiological conditions in vivo.
The relationship between ventilation (VE) and CO2 output (VCO2) is fitted linearly. The steeper gradient implies excessive ventilation. Through an evaluation of the VE-VCO2 slopes, this study investigated whether patients with acute myocardial infarction (AMI) have excessive ventilation and whether it improved in 4 months. The VE-VCO2 slopes were determined in exercise tests at 1 and 4 months in 131 patients with AMI. Patients were divided into 3 groups according to the 1 month VE-VCO2 slope value: (i) normal (<30); (ii) intermediate (30-32); and (iii) excessive (>32). In the normal group (n=76), at 4 months, the slope decreased in 10, increased in 5 and remained unchanged in 61 patients; in the intermediate (n=31) group, 9, 2 and 20; and in the excessive (n=24) group, 15, 3 and 6, respectively, showing that the slope reduction was greater in the excessive group (p<0.01). The slope correlated with age and acute phase heart failure. The percent reduction of the slope did not correlate with these parameters. In conclusion, a substantial fraction of patients with AMI have excessive ventilation that improves in 4 months. The improvement is greater in patients with greater excessive ventilation but is not associated with an improvement in exercise capacity nor hemodynamics.
To understand better the pathophysiological roles of the vagal efferent system in ischemic heart diseases, we examined endogenous acetylcholine (ACh) release in the myocardium in vivo. Acute myocardial ischemia was induced in anesthetized cats by a 60-min occlusion of the left anterior descending coronary artery (LAD). We implanted dialysis probes in the left ventricular free wall and measured the dialysate ACh concentration using liquid chromatography. In the ischemic region, the ACh level increased from 0.68+/-0.12 to 12.3+/-3.3 n M (mean+/-S.E., P<0.01) by LAD occlusion. Bilateral vagotomy did not inhibit ischemia-induced ACh release (20.3+/-6.4 n M). In vagotomized animals, inhibition of the N-type Ca(2+)channel by intravenous administration of omega-conotoxin GVIA (10microg/kg) also failed to suppress ACh release (15.9+/-2.0 n M). However, the inhibition of intracellular Ca(2+)mobilization by local administration of 3,4,5-trimethoxybenzoic acid 8-(dietyl amino)-octyl ester (1 m M) suppressed ACh release (4.4+/-0.8 n M, P<0.05 compared with no pharmacological intervention). In the non-ischemic region, the ACh level increased from 1.9+/-0.4 to 6. 0+/-1.0 n M (P<0.05) by LAD occlusion, which was completely abolished by vagotomy. We concluded that ACh release in the ischemic region was mainly attributed to a local release mechanism, whereas that in the non-ischemic region depended on the presence of intact vagal activity. The local release mechanism would depend on intracellular Ca(2+)mobilization but not on N-type Ca(2+)channel opening.
BACKGROUND: The renin-angiotensin system (RAS) plays a key role in the pathophysiology of chronic heart failure (CHF). In rats, we reported that CHF enhances dipsogenic responses to centrally administered angiotensin I, and central inhibition of the angiotensin-converting enzyme (ACE) prevents cardiac hypertrophy in CHF. This suggests that the brain RAS is activated in CHF. To clarify the mechanism of the central RAS activation in CHF, we examined brain ACE and the angiotensin receptor (AT) among rats with CHF. METHODS AND RESULTS: We created high-output heart failure in 22 male Sprague-Dawley rats by aortocaval shunt. Four weeks after surgery, we examined ACE mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and AT by binding autoradiography. ACE mRNA levels were not significantly increased in the subfornical organ (SFO), the hypothalamus, or in the lower brainstem of CHF rats (n = 5) compared with sham-operated rats (SHM) (n = 6). Binding densities for type 1 AT (AT1) in the SFO (P < .05), paraventricular hypothalamic nuclei (P < .05), and solitary tract nuclei (P < .05) were higher in rats with CHF (n = 5) than in SHM rats (n = 6). Thus, in rats with CHF, AT1 expression is increased in brain regions that are closely related to water intake, vasopressin release, and hemodynamic regulation. CONCLUSIONS: The fact that AT1 expression was upregulated in important brain regions related to body fluid control in CHF rats indicates that the brain is a major site of RAS action in CHF rats and, therefore, a possible target site of ACE-inhibitors in the treatment of CHF.
INTRODUCTION: Brugada syndrome is characterized by an ST segment elevation in leads V1-V3 and a high incidence of ventricular fibrillation (VF). A mutation in a cardiac Na+ channel gene, SCN5A, has been linked to Brugada syndrome, and sodium channel blockers have been shown to be effective in unmasking the syndrome when concealed. The aim of this study was to examine the effects of Na+ channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhythmias in patients with Brugada syndrome. METHODS AND RESULTS: We examined the effects of three different Na+ channel blockers (flecainide, disopyramide, and mexiletine) on the amplitude of the ST segment 20 msec after the end of QRS (ST20), QRS duration, QTc interval measured from 12-lead ECG, and ventricular arrhythmias in 12 Brugada and 10 control patients. Maximum ST20 observed in the V2 or V3 leads under baseline conditions was greater in the Brugada patients than in control patients, whereas QRS duration and maximum QTc interval were no different between the two groups. Flecainide and disopyramide, but not mexiletine, significantly increased maximum ST20 and QRS duration in both groups, although these effects were much more pronounced in the Brugada patients. The increases in ST20 and QRS duration with flecainide were significantly larger than those with disopyramide. An increase of 0.15 mV in ST20 with flecainide separated the two groups without overlap. Ventricular premature complexes developed only with flecainide in Brugada patients (3/12) displaying a marked ST elevation but not widening of QRS. CONCLUSION: Our findings suggest that Na+ channel blockers amplify existing I(Na) and possibly other ion channel defects, with a potency inversely proportional to the rate of dissociation of the drug from the Na+ channel, thus causing a prominent elevation of the ST segment and, in some cases, prolongation of QRS duration in patients with Brugada syndrome.
INTRODUCTION: The clinical characteristics of three patients with spontaneous or inducible ventricular fibrillation (VF) without apparent heart disease, who presented with J wave and ST segment elevation in inferior leads, are described. METHODS AND RESULTS: All patients were male and experienced syncope. Their symptoms occurred at night or early in the morning. Holter ECG revealed infrequent premature ventricular complexes. Injection with disopyramide 2 mg/kg augmented ST segment elevation. CONCLUSION: These characteristics were very similar to those of patients with Brugada syndrome. These three patients with these specific features might have a variant of Brugada syndrome.
To clarify the pathophysiological role of dynamic arterial properties in cardiovascular diseases, we attempted to develop a new control system that imposes desired aortic impedance on in situ rat left ventricle. In 38 anesthetized open-chest rats, ascending aortic pressure and flow waveforms were continuously sampled (1,000 Hz). Desired flow waveforms were calculated from measured aortic pressure waveforms and target impedance. To minimize the difference between measured and desired aortic flow waveforms, the computer generated commands to the servo-pump, connected to a side branch of the aorta. By iterating the process, we could successfully control aortic impedance in such a way as to manipulate compliance and characteristic impedance between 60 and 160% of their respective native values. The error between desired and measured aortic flow waveforms was 70 +/- 34 microl/s (root mean square; 4.4 +/- 1.4% of peak flow), indicating reasonable accuracy in controlling aortic impedance. This system enables us to examine the importance of dynamic arterial properties independently of other hemodynamic and neurohumoral factors in physiological and clinical settings.
Although neck suction has been widely used in the evaluation of carotid sinus baroreflex function in humans, counteraction of the aortic baroreflex tends to complicate any interpretation of observed arterial pressure (AP) response. To determine whether a simple linear model can account for the AP response during neck suction, we developed an animal model of the neck suction procedure in which changes in carotid distension pressure during neck suction were directly imposed on the isolated carotid sinus. In six anesthetized rabbits, a 50-mmHg pressure perturbation on the carotid sinus decreased AP by -27.4+/-4.8 mmHg when the aortic baroreflex was disabled. Enabling the aortic baroreflex significantly attenuated the AP response (-21.5+/-3.8 mmHg, P<0.01). The observed closed-loop gain during simulated neck suction was well predicted by the open-loop gains of the carotid sinus and aortic baroreflexes using the linear model (-0.43+/-0.13 predicted vs. -0.41 +/-0.10 measured). We conclude that the linear model can be used as the first approximation to interpret AP response during neck suction.
A questionnaire-based investigation was performed on 325 Japanese school children with Down syndrome ages 6 to 18. Data on height and body weight, eating habits, physical activity for these children were obtained through their parents. Proportion of obese children was higher among these subjects than the average for Japanese children (34.3% and 7.47% respectively, for the ages from 6 to 14). We examined characteristics of eating habits and physical activities between the obese group (obesity index greater than 20% above the average of Japanese school children) and the non-obese group. Obesity started to increase in the obese group around age 7. The obese group tended to have had a greater intake of sweets, juice and total foods in their preschool days, but unexpectedly had been physically more active in their primary school days.
A 74 year-old man with bladder transitional carcinoma had severe multivascular disease; coronary artery stenosis, abdominal aortic aneurysm and right internal carotid artery stenosis. First, transurethral bladder tumor resection (TUR-Bt) was performed twice but in the second TUR-Bt, no carcinoma cell was found. One stage surgery of minimally invasive direct coronary artery bypass (MIDCAB), abdominal aortic aneurysm (AAA) repair and carotid endarterectomy (CEA) was proposed. MIDCAB was performed first. Inspite of the bradycardia, heart oppression by stabilizer and coronary artery clamping, blood pressure and ST segments were stable. With heparinization and the chest left open, AAA repair was carried out. On aorta clamping and declamping, blood pressure and heart rate were stable. After completion of AAA repair, heparinization was reversed with protamine. Chest and abdominal wounds were closed simultaneously. CEA was performed lastly, because the patient had no cerebral ischemic symptom and no risk of cardiopulmonary bypass. After the operation, no neurologic deficit appeared. This experience of one stage surgery was reported with review of literatures. One stage surgery is a possible approach to the patients with severe multivascular disease.