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Biomedical subjects

Y Kusama

Publications and source records attributed to Y Kusama.

At least 19 recordsLinked to original sources

Observation of nonlinear coupling between small-poloidal wave-number potential fluctuations and turbulent potential fluctuations in Ohmically heated plasmas in the JFT-2M tokamak.

Two types of electrostatic modes with small-poloidal wave numbers (approximately 1 and 10-15 kHz) are observed in the edge region of Ohmically heated plasmas in the JFT-2M tokamak. The envelope of the higher frequency coherent mode is modulated at the frequency of the lower frequency mode. A bispectral analysis revealed that a significant nonlinear coupling among the two types of fluctuations and the broadband background turbulent potential fluctuations occurs inside the last closed magnetic flux surface, suggesting that a nonlinear process such as the parametric-modulational instability is involved.

Journal Article↗

Role of bremsstrahlung radiation in limiting the energy of runaway electrons in tokamaks.

Bremsstrahlung radiation of runaway electrons is found to be an energy limit for runaway electrons in tokamaks. The minimum and maximum energy of runaway electron beams is shown to be limited by collisions and bremsstrahlung radiation, respectively. It is also found that a massive injection of a high-Z gas such as xenon can terminate a disruption-generated runaway current before the runaway electrons hit the walls.

Journal Article↗

Resting ultrasonic tissue characterization and dobutamine stress echocardiography for prediction of functional recovery in chronic left ventricular ischemic dysfunction.

This study was designed to assess the diagnostic accuracy of the percentage of resting systolic wall thickening (WT), dobutamine stress echocardiography (DSE), resting cyclic variation of integrated backscatter (IBS-CV), and low-dose dobutamine stress IBS-CV (DSE-IB) for the prediction of regional function recovery (RFR) in patients with chronic left ventricular (LV) ischemic dysfunction. The study also evaluated whether or not global LV function affected the diagnostic accuracy. All studies were conducted before percutaneous transluminal coronary angioplasty (PTCA) and RFR was assessed after PTCA (mean interval, 10 months) in 30 patients with chronic LV ischemic dysfunction. Patients were divided into 2 groups according to the LV ejection fraction (LVEF): group A, LVEF<40%, n=14; group B, LVEF> or =40%, n=16. Of a total of 480 segments, 37 initially demonstrating akinetic wall motion before PTCA were analyzed. The wall motion of 24 of the 37 segments improved on visual analysis after PTCA. In the prediction of RFR, resting WT, DSE, resting IBS-CV and DSE-IB had sensitivities of 79%, 79%, 92% and 62%, and specificities of 54%, 84%, 83% and 69%, respectively. In particular, the resting IBS-CV in group A, as well as DSE, was an excellent predictor of RFR (sensitivity, 100%; specificity, 86%; vs sensitivity, 82%; specificity, 78%; respectively). Therefore, both resting IBS-CV and DSE are useful predictors for RFR in patients with chronic LV ischemic dysfunction.

Aged↗

Clinical significance of increased plasma concentration of macrophage colony-stimulating factor in patients with angina pectoris.

OBJECTIVES: To determine the effect of macrophage colony-stimulating factor (MCSF) on atherogenesis in patients with coronary artery disease (CAD), we assessed the relation between the plasma concentration of MCSF and the incidence of acute coronary events in patients with CAD. BACKGROUND: Cytokines such as MCSF play a central role in inflammatory and proliferative responses in patients with acute coronary syndromes. However, the effect of MCSF on the clinical course in patients with CAD is still not known. METHODS: We measured the plasma MCSF concentration in 142 patients with documented CAD (62 +/- 9 years) and followed up for a mean period of 14 +/- 6 months. The study included 97 patients with stable angina (SA), 45 patients with unstable angina (UA) and 22 age-matched control subjects. The predictors of coronary events were analyzed by using a Cox proportional hazards model. RESULTS: The mean plasma MCSF concentration in patients with UA was significantly higher than that in patients with SA and in control subjects (981 +/- 277 vs. 693 +/- 223 vs. 680 +/- 158 pg/ml, p < 0.001). The mean plasma MCSF concentration in the 20 patients with coronary events was significantly higher than that in patients without coronary events (1,192 +/- 232 vs. 690 +/- 213 pg/ml, p < 0.001). The predictors of unfavorable outcome were an increased MCSF concentration, the presence of CAD and a low ejection fraction. CONCLUSIONS: These findings suggest that an increased circulating MCSF concentration reflects atherosclerotic progression in patients with CAD and predicts future cardiac events.

Adult↗

A role of angiotensin-converting enzyme gene polymorphism in left ventricular remodeling after myocardial infarction.

BACKGROUND: Left ventricular remodeling (LVR) process is one of the important secondary sequele after acute myocardial infarction (AMI). However, little is known about the relationship between LVR and angiotensin converting enzyme (ACE) gene polymorphism as well as endothelial nitric oxide synthase (ecNOS) gene polymorphism. METHODS: Coronary angiography and left ventriculography were performed within 24 hours and 30+/-7 days after AMI onset. All consecutive 24 patients (57+/-6 years) had acute anterior MI with one vessel disease of left anterior descending artery and successful revascularization therapy during acute phase. Patients were divided into three groups according to the change of end-diastolic volume index (EDVI)(Delta EDVI = EDVI 1 month-EDVI within 24 hrs); LVR(+) (Delta EDVI>7.0 ml/m(2), n = 5), LVR (-)(Delta EDVI<-7.0 ml/m(2), n = 13), and LVR (+/-)(-7.0<Delta EDVI<7.0 ml/m(2), n = 6) groups. The polymorphisms of ACE and ecNOS gene were determined with PCR method after an extraction of genomic DNA from peripheral leukocytes. RESULTS: There were no significant difference among three groups as to baseline characteristics, including coronary risk factors, medications, serum CPKmax and patency of infarct-related artery. The incidence of DD genotype of ACE gene is significantly higher in LVR (+) than in the other two groups (0.60; 0; 0, respectively, chi(2) = 13.150, p<0.01). The incidence of D allele of ACE gene is also significantly higher in LVR (+) than in the other two groups (0.70; 0.17; 0.19, respectively, chi(2) = 10.221, p<0.01). Delta EDVI of DD genotype was significantly greater than in the other two groups (DD genotype = 30.1+/-18.1; ID genotype = -13.0+/-27.4; II genotype = -8.2+/-11.5 ml/m(2), respectively, p<0.05). There was no significant difference in ecNOS gene polymorphism among three groups. By stepwise regression analysis, the significant independent predictors of Delta EDVI were EDVI within 24 hrs and DD genotype (F = 16.88 and 8.641, respectively, p = 0.0024). CONCLUSION: These results showed that left ventricular dilatation is related to DD genotype of ACE gene after successful reperfusion therapy of anterior AMI. Thus, renin-angiotensin system may play an important role in left ventricular remodeling after AMI.

Aged↗

Transient left ventricular aneurysm and hypertrophy accompanied by polymorphic ventricular tachycardia in a patient suspected of acute myocarditis.

A 75-year-old woman presented with recurrent ventricular tachycardia (VT) compatible with torsades de pointes (TdP) based on sinus bradycardia and QT prolongation. Previously she had received pirmenol, at a serum concentration within therapeutic range, for her paroxysmal atrial fibrillation. Emergent cardiac catheterization identified a ventricular aneurysm of the anteroapical and inferior wall along with angiographically normal coronary arteries. A right ventricular endomyocardial biopsy revealed postmyocarditic change. The left ventricular contraction improved after 5 weeks of conservative treatment. A follow-up echocardiogram revealed transient thickening of partial left ventricular wall consistent with the segment of the aneurysm. Several months later, almost all abnormal findings had improved except for sustained deep negative T waves in precordial leads. Acute myocarditis was primarily suspected as the cause of her clinical presentation.

Acute Disease↗

Novel cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups.

The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the N6-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carb onyl group at the N6-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.

Animals↗

Negative U-wave as a predictor of antihypertensive treatment effect on regression of echocardiographic hypertrophy in hypertensive patients.

To clarify the mechanism and the predictors of the reduction in left ventricular mass (LVM) induced by antihypertensive drugs, forty hypertensive patients were classified according to the presence of left ventricular hypertrophy (LVH) as a defined by echocardiographic LVM findings (LVH group: 27 patients, non-LVH group: 13 patients) and according to the presence of negative U-waves (NU) (NU group: 10 patients, non-NU group: 30 patients). Negative U-waves appeared in the LVH group only (10 of 27 patients). The hemodynamic determinants were investigated as a mechanism of LVM reduction in 38 of these patients who were treated for 2 years with antihypertensive drugs. In the LVH group, thickness of interventricular septum (IVST), posterior wall thickness (PWT) and LVM increased significantly compared to the non-LVH group. In the NU group, the left ventricular end-diastolic dimension (LVDD) was significantly larger and the relative wall thickness was significantly smaller compared to the non-NU group in the LVH group, with no difference in LVM between the two groups. Negative U-waves disappeared in all cases after treatment. Significant decreases in LVDD and LV wall thickness were observed in the NU group and significant decrease in LV wall thickness in the non-NU group. LVM index was reduced by 24.0% in the NU group and 9.5% in the non-NU group. The disappearance of negative U-waves was an independent predictor of the reduction of LVH.

Adult↗

[Myocardial distribution of iodine-123-iodophenyl-9-methyl-pentadecanoic acid (9MPA) in patients with acute myocardial infarction: comparison with regional wall motion obtained from technetium-99m-sestamibi gated SPECT].

123I-iodophenyl-9-methyl-pentadecanoic acid (9MPA) is a modified long-chain (15 carbons) fatty acid with a methyl branch on its 9 carbon location. Myocardial SPECT images (two sets, 10 min each) were obtained starting 10 min (early phase) and 50 min (delay phase) after the injection of 160 MBq 123I-9MPA at rest in 10 patients with acute myocardial infarction. The segmental myocardial uptake (% uptake) and clearance (% washout) from early to delay image were calculated by the SPECT data. ECG-gated myocardial SPECT with 99mTc-sestamibi was also performed and segmental left ventricular (LV) wall motion was evaluated using QGS (quantitative gated SPECT) program. The % uptake of LV segments with hypokinetic or akinetic wall motion were significantly lower than those with normokinesis (p < 0.01) for both early and delay phases. The % washout of hypokinetic segments were significantly lower than those of normokinetic regions (p < 0.01), while the % washout of akinetic segments were significantly higher than those of severely hypokinetic segments (p < 0.05). Thus, 123I-9MPA myocardial distribution and clearance thought to be associated with left ventricular regional wall motion.

Fatty Acids↗

[Assessment of left ventricular contraction abnormalities with myocardial infarction using gated technetium-99m sestamibi SPECT: comparison of wall thickening and regional ejection fraction analysis for the detection of coronary artery stenosis].

ECG-gated myocardial Technetium-99m sestamibi SPECT is a useful technique to measure myocardial perfusion and function simultaneously. In this study, wall thickening (WT) and regional ejection fraction (rEF) using ECG-gated SPECT have been studied to determine which parameter would be more sensitive to detect coronary artery stenosis in patients with acute myocardial infarction (AMI). Forty-five patients (36 men, 9 women, mean age 63 +/- 9 years old) with AMI were examined. CAG was performed for all patients. ECG-gated SPECT was performed 60 min after the intravenous injection of 555 MBq 99mTc-sestamibi at rest. Commercially available software (QGS) was used to produce WT and rEF polar maps from acquired SPECT data. The WT and rEF polar maps were evaluated visually and quantitatively. WT indicated higher sensitivity (80.3% vs. 59.1%, p < 0.05) and accuracy (86.7% vs. 74.8%, p < 0.05) than rEF for detecting overall coronary artery stenosis on visual interpretation. On quantitative analysis, WT had higher specificity (91.3% vs. 75.4%, p < 0.05) and accuracy (85.9% vs. 72.6%, p < 0.05) than rEF for detecting overall coronary artery stenosis, and showed a higher specificity (93.8% vs. 59.4%, p < 0.01) and accuracy (88.9% vs. 62.2%, p < 0.01) for detecting LCX stenosis. Moreover, sensitivity of WT for detecting coronary artery stenosis without infarction was higher than that of rEF significantly in quantitative analysis (75.0% vs. 31.3%, p < 0.05). These results suggested that WT was superior to rEF for detecting the coronary artery stenosis in patients with and without myocardial infarction. We concluded that WT is more sensitive indicator to determine localization of regional left ventricular dysfunction in AMI than rEF.

Aged↗

Rapid data acquisition protocol in ECG-gated myocardial perfusion SPECT with Tc-99m-tetrofosmin.

Into 25 patients with heart disorders, 99mTc-tetrofosmin 555-740 MBq was injected intravenously at rest. After 40 minutes, ECG-gated myocardial perfusion SPECT was performed with a two detector gamma camera VERTEX (ADAC), setting up two detectors to form a 90-degree angle. Sixteen frames per R-R interval were acquired during a 180 degree rotation from the RAO 45 degrees to the LPO 45 degrees. A pair of data sets with standard (SDA) and rapid data acquisition (RDA) protocols was collected. In an SDA protocol, SPECT imaging was performed for 50 sec per step in 5 degree angular steps (total acquisition time; 15 minutes). An RDA protocol was conducted with 12 sec per step, 6 degree angular steps (acquisition time, 3 minutes). LVEF (%) and LVEDV (ml) quantitated automatically with a QGS program showed excellent correlations between two protocols with correlation coefficients of 0.980 (p < 0.01) and 0.983 (p < 0.01), respectively. Subsequently visual assessment of regional wall motion based on a four-point grading system was carried out with a 3-D cine LV display. High complete agreement was gained with 158 (90.3%) out of total 175 segments, so that assessment of the global and regional LV function with the RDA protocol demonstrated high reliability and feasibility.

Electrocardiography↗

Coronary hyperreactivity to adrenergic stimulation and increased nocturnal vagal tone trigger coronary vasospasm.

The relationship between autonomic nervous system activity (ANA) and coronary vasoreactivity during transient myocardial ischemia was determined in patients with vasospastic angina (VA). ANA was measured by power spectral analysis of heart rate variability and humoral factors following intravenous infusion of insulin in 24 patients with VA and 6 control patients. Nine (38%) of the VA patients had significant ST segment depression (STD), and 4 of these patients had symptomatic STD. The frequency of anginal episodes in the 9 patients with VA and STD was significantly greater than that in the 15 VA patients without STD (3.4 +/- 3.1 vs 0.5 +/- 0.8 episodes/week, p < 0.05). The increase in the LF/HF ratio 30 min after insulin injection in patients with STD was significantly greater than that in patients without STD (34 +/- 31% vs 4 +/- 34%, p < 0.05). All of the patients with VA and STD had significant coronary vasospasm in response to the infusion of < or = 20 micrograms of acetylcholine, higher levels of nocturnal parasympathetic activity, and greater norepinephrine production in response to insulin stimulation than the VA patients without STD. These findings suggest that increased vagal tone and hyperreactivity to adrenergic stimulation may trigger vasospasm in patients with VA.

Aged↗

[Effect of phenylephrine, endothelin and angiotensin II on reperfusion arrhythmias. A role for Na+/H+ exchanger activation via protein kinase C].

Stimulation of receptors for alpha 1-adrenergic agonist, endothelin (ET) and angiotensin II (AT) activates the cardiac sarcolemmal Na+/H+ exchanger (NHE), perhaps via protein kinase C(PKC)-mediated pathway(s). We tested for the ability of these extracellular stimuli to exacerbate reperfusion arrhythmias and for the possible role of NHE activation and PKC in such phenomena. Isolated rat hearts (n = 12/group) were subjected to dual coronary perfusion. After 15 min of aerobic perfusion, flow to the left coronary bed was reduced to 5% of basal values for 12 min, and the same bed was then reperfused for 5 min. An alpha 1-adrenergic agonist phenylephrine (PE) at 1 or 10 mumol/L, ET at 0.5 or 5nmol/L or AT at 1 or 10mumol/L was infused selectively into the left coronary bed during 12 min of regional low flow ischemia. The incidence of reperfusion-induced ventricular fibrillation (VF) was increased from 17% in control to 33% and 75%* with 1 and 10 mumol/L PE(*p < 0.05 vs control) from 8% in control to 8% and 12% with 0.5 and 5 nmol/L of ET. However, AT had no effect. The selective NHE inhibitor NOE642 at 1 mumol/L, infused concomitantly with 10 mumol/L PE, reversed the proarrhythmic effects of PE; VF incidence was reduced from 67% to 8%*. However, glibenclamide (a blocker for the ATP-sensitive K+ channel) at 1 mumol/L did not affect the proarrhythmic effects of PE. Infusion of a specific PKC inhibitor GF109203X(GF) at 30 or 300 nmol/L, starting from 5 min before ischemia and maintained throughout ischemia concomitantly with 10 mumol/L of PE, was partially effective in reducing VF incidence; which reduced from 75% in control to 42% with 300 nmol/L of GF. These results suggest that, in rat hearts subjected to regional low-flow ischemia and reperfusion, stimulation of alpha 1-adrenergic receptor can exacerbate reperfusion-induced VF, whose mechanism(s) may involve NHE activation. Moreover, PKC activation does not appear to be the sole signaling mechanism for this phenomenon.

Adrenergic alpha-Agonists↗

Increased accumulation of acidic fibroblast growth factor in left ventricular myocytes of patients with idiopathic cardiomyopathy.

To clarify the pathophysiologic role of fibroblast growth factors in idiopathic cardiomyopathy, we evaluated endomyocardial biopsy specimens obtained from 24 patients (nine with hypertrophic cardiomyopathy [HCM], 12 with dilated cardiomyopathy [DCM], and three with hypertensive hypertrophy) and six controls. All the specimens were stained for acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) with immunohistochemistry. In situ hybridization was carried out for detection of aFGF mRNA. The average diameter of the myocytes, the percent area of interstitial fibrosis, and capillary vessel density were assessed in each biopsy specimen with morphometric methods. Positive staining of aFGF was observed in the myocytes of the biopsy specimens taken from 15 of 21 (71%) patients with cardiomyopathy (six of nine HCM, nine of 12 DCM) and all hypertensive hypertrophy patients but in none of the controls (p < 0.01). The average diameter of the myocytes was significantly larger in the patients with positive aFGF staining than in those with negative staining (23.1 +/- 1.5 versus 18.3 +/- 1.2 microm, p < 0.05). The percent area of fibrosis and the density of capillaries did not differ between the two groups. Intense expression of aFGF mRNA was observed in the myocytes from the patients with positive aFGF protein. In conclusion, the expression of FGF was significantly increased in myocytes obtained from the left ventricle of patients with cardiomyopathy. Acidic FGF may contribute to the hypertrophy of myocytes as the repair response to myocardial injury in patients with idiopathic cardiomyopathy.

Adult↗

Dobutamine stress echocardiography for the detection of coronary artery disease and viable myocardium.

Dobutamine stress echocardiography has become a diagnostic tool for the evaluation of coronary artery disease and the detection of myocardial viability. In the diagnosis of significant coronary artery disease, it provides similar accuracy to exercise stress thallium-201 myocardial perfusion scintigraphy. Dobutamine stress echocardiography is also a promising modality for predicting the recovery of hibernating myocardium from contractile dysfunction after coronary angioplasty or bypass surgery. This article, reviews our recent clinical experience with the detection of coronary artery disease and viable myocardium by dobutamine stress echocardiography.

Cardiotonic Agents↗

[Assessment of left ventricular systolic function derived from ECG-gated myocardial SPECT with 99mTc-tetrofosmin: automatic determination of LV epi- and endocardial surface].

Non-invasive assessment of ischemic heart disease requires information of both LV function and myocardial perfusion. Recently, ECG-gated myocardial SPECT with technetium-labeled radiopharma-ceuticals can provide both of them. Gated myocardial SPECT were performed in thirty-three patients with cardiac disease using a two-headed rotating gamma camera system (ADAC; VERTEX), 30-60 minutes after resting injection of 555-740 MBq of 99mTc-Tetrofosmin. Then, the SPECT data were used to determine the LV epi- and endocardial surface, and LV volume for measurement of LVEF was calculated automatically. This entire computational process required only 210 seconds per 16 frame study. Interobserver agreement of EF values obtained from gated SPECT was excellent (r = 0.996, n = 10, p < 0.01). LVEFs obtained from gated SPECT showed good correlation to those calculated from radionuclide ventriculography (MUGA) (r = 0.91, p < 0.01). In conclusion, this automatic method using gated myocardial SPECT data was considered to be useful for assessment of LV function with reproducibility.

Aged↗