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Biomedical subjects

Y Akutsu

Publications and source records attributed to Y Akutsu.

At least 19 recordsLinked to original sources

Vertical density matrix algorithm: a higher-dimensional numerical renormalization scheme based on the tensor product state ansatz.

We present a new algorithm to calculate the thermodynamic quantities of three-dimensional (3D) classical statistical systems, based on the ideas of the tensor product state and the density matrix renormalization group. We represent the maximum-eigenvalue eigenstate of the transfer matrix as the product of local tensors that are iteratively optimized by the use of the "vertical density matrix" formed by cutting the system along the transfer direction. This algorithm, which we call vertical density matrix algorithm (VDMA), is successfully applied to the 3D Ising model. Using the Suzuki-Trotter transformation, we can also apply the VDMA to 2D quantum systems, which we demonstrate for the 2D transverse field Ising model.

Journal Article↗

Inhibition of tumor metastasis by adoptive transfer of IL-12-activated Valpha14 NKT cells.

A unique lymphocyte lineage, the Valpha14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments. Valpha14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti-tumor immunity. Valpha14 NKT cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo. Here, we report that adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL-2, IL-4, and IFN-gamma, which are cytokines produced by activated Valpha14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL-12-injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL-12-injected RAG-1-/- mice failed to inhibit the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be replaced by adoptive transfer of IL-12-activated Valpha14 NKT cells but not by IL-12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated anti-tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine-mediated immune responses at the effector phase of the Valpha14 NKT cell-mediated anti-tumor activity.

Adoptive Transfer↗

Involvement of decidual Valpha14 NKT cells in abortion.

The immunological mechanisms that regulate abortion are largely unknown. Here, we found that a distinct subset of lymphocytes, Valpha14 NKT cells expressing an invariant antigen receptor encoded by Valpha14/Jalpha281 and Vbeta7 segments, accumulated in the decidua during pregnancy and provoked abortion upon stimulation with alpha-galactosylceramide (alpha-GalCer), a specific ligand for Valpha14 NKT cells. The alpha-GalCer-mediated abortion was not observed in Valpha14 NKT-, IFN-gamma-, tumor necrosis factor alpha-, or perforin-knock-out mice and appeared to be due to the degeneration of embryonic trophoblasts mediated by the activated Valpha14 NKT cells whose perforin-dependent killing and production of IFN-gamma and tumor necrosis factor alpha were essential. The possible role of the decidual Valpha14 NKT cells in the pathogenesis of abortion is discussed.

Abortion, Induced↗

Exercise-induced QTc-interval changes for predicting improvement in regional blood flow in ischemic myocardium and cardiac output after coronary angioplasty in patients with right bundle-branch block.

BACKGROUND: We have previously shown that QT-interval changes are more useful than ST-T changes in evaluating the severity of exercise-induced myocardial ischemia in patients with right bundle-branch block (RBBB). HYPOTHESIS: The purpose of this study was to evaluate whether the improvement in regional myocardial blood flow (RMBF) in ischemic areas and cardiac output after percutaneous transluminal coronary angioplasty (PTCA) can be predicted by exercise-induced QT-interval changes prior to PTCA. METHODS: The RMBF and cardiac output were quantified with nitrogen-13 ammonia positron emission tomography at rest and during exercise in 20 patients with RBBB and ischemic heart disease before and 6 months after PTCA, and in 9 healthy volunteers. RESULTS: Before PTCA, exercise-induced prolongation by < 20 ms or shortening of the Bazett-corrected QT (QTc) interval (454 +/- 38 to 451 +/- 41 ms, p = NS) was observed in 13 patients (Group 1) and prolongation by > or = 20 ms (429 +/- 44 to 466 +/- 50 ms, p < 0.002) was observed in 7 (Group 2). The number of regions of exercise-induced ischemia was significantly greater in Group 2 than in Group 1 (4.0 +/- 1.2 vs. 2.1 +/- 1.2, p < 0.01). The RMBF in regions of exercise-induced ischemia and cardiac output at rest was not significantly different between Groups 1 and 2, whereas during exercise both the parameters were significantly lower in Group 2 than in Group 1 (both p < 0.05). After successful PTCA, RMBF both at rest and during exercise improved significantly in Group 1 (0.67 +/- 0.04 to 0.71 +/- 0.06 ml/min/g, 0.74 +/- 0.05 to 0.84 +/- 0.08 ml/min/g; both p < 0.0001), but did not improve significantly in Group 2 (0.63 +/- 0.05 to 0.65 +/- 0.07 ml/min/g, 0.65 +/- 0.04 to 0.69 +/- 0.11 ml/ min/g; both p = NS). Cardiac output during exercise improved significantly in Group 1 (6.4 +/- 0.7 to 7.4 +/- 0.9 l/min; p < 0.002) but not in Group 2 (5.7 +/- 0.6 to 5.9 +/- 0.6 l/min; p = NS). CONCLUSIONS: Our results suggest that the marked prolongation of the QTc interval induced by pre-PTCA exercise may predict a lack of improvement in RMBF in ischemic areas and cardiac output after PTCA in patients with RBBB and ischemic heart disease.

Adult↗

Influence of cetane improvers on the air quality in an urban street canyon.

The concentration distributions of NOx, PM, HC and CO in an urban street canyon have been estimated using a two-dimensional air quality numerical model based on the k-epsilon turbulent model and the atmospheric convection diffusion equation when various cetane improvers were used in diesel fuels. A wind vortex can be found within the street canyon, and the pollutants emitted from the bottom of the street canyon tend to follow the course of the wind field, moving circularly. The addition of cetane improvers can improve the air quality in a street canyon, all of the pollutants were found to decrease with increasing centane number.

Air↗

Exercise-induced ST-segment depression: imbalance between myocardial oxygen demand and myocardial blood flow.

OBJECTIVE: ST-segment depression is believed as a common electrocardiographic sign of myocardial ischemia during exercise testing. Ischemia is generally defined as oxygen deprivation due to reduced perfusion. However, the exact relationship of the ischemic definition to ST-segment depression remains unclear. This study was conducted to evaluate the correlation between myocardial oxygen demand and myocardial blood flow (MBF) when ischemic (horizontal or downsloping) ST-segment depression of > or = 0.1 mV 80 ms after the J point developed during low-level exercise. METHODS AND RESULTS: Seventy-two patients with angiographically proven coronary artery disease (CAD) and 9 healthy volunteers underwent exercise positron emission tomography (PET). Myocardial oxygen demand was defined as a rate-pressure product (RPP, heart rate x systolic blood pressure) during exercise and MBF was quantified by nitrogen-13 ammonia perfusion PET. The myocardial demand-supply balance (MDSB) index was calculated from the MBF ratio (values during exercise/values at rest) against the RPP ratio (values during exercise/values at rest). The MDSB index was significantly lower in patients with ischemic ST-segment depression than in patients with non-ischemic ST depression and healthy volunteers (0.82 +/- 0.16 vs. 1.02 +/- 0.17, p < 0.0001 and vs. 0.99 +/- 0.14, p = 0.0109). Further, the presence of inadequate increase in MBF of < or = 10% (2 SD below the mean % value of healthy volunteers) during exercise in regional myocardium perfused by stenotic CAD significantly correlated with exercise-induced ischemic ST-segment depression (p = 0.0105). CONCLUSIONS: Our study could demonstrate that exercise-induced ischemic ST-segment depression is associated with myocardial ischemia due to exercise-induced imbalance between myocardial oxygen demand and global and regional MBF supply in patients with proven CAD.

Adult↗

Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT cells.

Human V alpha24 NKT cells bearing an invariant V alpha24J alphaQ antigen receptor, the counterpart of the murine V alpha14 NKT cells, are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Here, we demonstrate that the alpha-GalCer-activated V alpha24 NKT cells exert a potent perforin-dependent cytotoxic activity against a wide variety of human tumor cell lines. In addition, we demonstrate that V alpha24 NKT cells and dendritic cells (DCs) from melanoma patients are functionally normal, even in the tumor-bearing status. The potential use of alpha-GalCer-activated V alpha24 NKT cells and/or DCs from patients for cancer immunotherapy is discussed.

Adult↗

Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide.

A unique lymphoid lineage, Valpha14 NKT cells, bearing an invariant Ag receptor encoded by Valpha14 and Jalpha281 gene segments, play crucial roles in various immune responses, including protective immunity against malignant tumors. A specific ligand of Valpha14 NKT cells is determined to be alpha-galactosylceramide (alpha-GalCer) which is presented by the CD1d molecule. Here, we report that dendritic cells (DCs) pulsed with alpha-GalCer effectively induce potent antitumor cytotoxic activity by specific activation of Valpha14 NKT cells, resulting in the inhibition of tumor metastasis in vivo. Moreover, a complete inhibition of B16 melanoma metastasis in the liver was observed when alpha-GalCer-pulsed DCs were injected even 7 days after transfer of tumor cells to syngeneic mice where small but multiple metastatic nodules were already formed. The potential utility of DCs pulsed with alpha-GalCer for tumor immunotherapy is discussed.

Animals↗

Universal asymptotic eigenvalue distribution of density matrices and corner transfer matrices in the thermodynamic limit.

We study the asymptotic behavior of the eigenvalue distribution of the corner transfer matrix (M(CTM)) and the density matrix (M(DM)) in the density-matrix renormalization group. We utilize the relationship M(DM)=M(4)(CTM), which holds for noncritical systems in the thermodynamic limit. We derive the exact and universal asymptotic form of the M(DM) eigenvalue distribution for a class of integrable models in the massive regime. For nonintegrable models, the universal asymptotic form is also verified by numerical renormalization group calculations.

Journal Article↗

Relation between exercise-induced myocardial ischemia as assessed by nitrogen-13 ammonia positron emission tomography and QT interval behavior in patients with right bundle branch block.

Exercise-induced myocardial ischemia is difficult to detect with ST-T changes in patients with right bundle branch block (RBBB). We sought to predict exercise-induced myocardial ischemia with QT interval behavior during exercise in patients with RBBB. Twenty-two patients with angiographically proven coronary artery disease and RBBB and 9 healthy volunteers underwent nitrogen-13 ammonia positron emission tomography with bicycle ergometer exercise at a fixed workload of 25 W. Regional myocardial blood flow (RMBF) and electrocardiographic changes were measured both at rest and after 5 minutes of exercise. The QT interval was measured from the onset of the QRS complex to the offset of the T wave in lead V5. The deltaQT and deltaRMBF, which indicated values after 5 minutes of exercise minus values at rest, were negatively correlated (r = -0.74, p <0.001). Exercise-induced shortening of the QT interval (422 +/- 27 to 381 +/- 38 ms, p = 0.0020) was observed in 15 patients (group 1) and no change or prolongation (411 +/- 45 to 420 +/- 37 ms, p = NS) was observed in 7 patients (group 2). Multivessel disease was significantly more frequent but collateral circulation was significantly less in group 2 than in group 1 (p <0.01, p <0.05, respectively). Cardiac output at rest was significantly lower in groups 1 and 2 than in healthy volunteers (4.52 +/- 0.83 and 4.51 +/- 0.84 vs 6.20 +/- 0.83 L/min; p = 0.0014, p = 0.0003). Although RMBF at rest did not differ significantly among groups 1 and 2 and healthy volunteers (0.63 +/- 0.20 vs 0.69 +/- 0.13 and vs 0.77 +/- 0.14 ml/min/g), RMBF after 5 minutes of exercise was significantly lower in group 2 than in group 1 and healthy volunteers (0.78 +/- 0.11 vs 0.96 +/- 0.20 and vs 1.20 +/- 0.18 ml/min/g; p = 0.0289, p <0.0001). The number of regions of critical coronary artery disease was significantly greater in group 2 than in group 1 (4.0 +/- 1.2 vs 2.1 +/- 1.3, p = 0.0039). Our results suggest that the absence of QT interval shortening during exercise may indicate severe myocardial ischemia induced by exercise in patients with RBBB and coronary artery disease.

Ammonia↗

Correlation between exercise-induced ischemic ST-segment depression and myocardial blood flow quantified by positron emission tomography.

BACKGROUND: Ischemic ST-segment depression (horizontal or downsloping) is the most common manifestation of exercise-induced myocardial ischemia. The mechanisms responsible for these types of ST-segment depression are largely unknown. We investigated the relation of these 2 types of exercise-induced ST-segment depression to changes in regional myocardial blood flow (RMBF) by using exercise positron emission tomography (PET). METHODS AND RESULTS: The RMBF was measured with nitrogen-13 ammonia PET both at rest and during low-level supine bicycle exercise in 27 patients with angiographically proven coronary artery disease and in 6 healthy volunteers. ST-segment depression was measured from the isoelectric PR segment 80 ms after the J point. Exercise-induced horizontal ST-segment depression > or =0.1 mV was observed in 9 patients and downsloping depression > or =0.1 mV was observed in 18 patients. Multivessel disease was more frequent and areas of exercise-induced ischemia were larger in patients with downsloping depression than in patients with horizontal depression (P < .02, P < .05). In patients with horizontal ST-segment depression, RMBF in ischemic areas and in surrounding areas increased by a similar amount (31%+/-29% and 32%+/-16%) with exercise. In patients with downsloping ST-segment depression, RMBF was unchanged or decreased in ischemic areas (10%+/-24%) but increased in surrounding areas (46%+/-27%) with exercise. In healthy volunteers, RMBF increased in all areas (56%+/-30%) with exercise. CONCLUSIONS: Compared with horizontal changes in ST-segment morphology, downsloping changes may better indicate severe ischemia and greater differences in the increase of blood flow with exercise in the ischemic myocardium and in the surrounding areas.

Adult↗

Oxidation of cysteamine induced by gas-phase radicals from combustion smoke of poly (methyl methacrylate).

In order to obtain fundamental knowledge on biological damage caused by the smoke from combustion of poly(methyl-methacrylate) (PMMA), we investigated the oxidation of cysteamine induced by PMMA smoke. We suggest that the long-lived and oxygen-centered radicals involved in PMMA smoke should play an important role in the oxidation of cysteamine. The mechanism for the oxidation of cysteamine by combustion smoke of PMMA was postulated as radical initiated chain reactions, taking into account the effect of pH, oxygen and radical concentrations.

Chromatography, High Pressure Liquid↗

Hypertrophic cardiomyopathy with apical left ventricular aneurysm.

We report a case of hypertrophic cardiomyopathy (HCM) with apical left ventricular aneurysm, which is difficult to review because cases are so rare. A 54-year-old Japanese man was first found to have an electrocardiographic abnormality (T-wave inversion at rest) 19 years ago, and non-obstructive apical HCM without identifiable cause was diagnosed by echocardiography, left ventriculography, and clinical findings. After 19 years, he was admitted because of repeated episodes of palpitation and chest oppression at rest. Widespread left ventricular hypertrophy from the anteroseptal wall to the apex with an apical left ventricular aneurysm was detected by echocardiography, left ventriculography, and cardiac magnetic resonance imaging. Histologic examination of the hypertrophic apical myocardium surrounding the aneurysm showed that the myocardial tissue had been extensively replaced by fibrous tissue containing hypertrophic myocardial fibers, and uptakes of [123I]-metaiodobenzyl guanidine (MIBG) and [123I-] beta-methyliodophenyl pentadecanoic acid (BMIPP) in single-photon emission photography images were reduced despite high myocardial perfusion. On the other hand, histologic examination of the hypertrophic anterior wall revealed myocardial hypertrophy with disorganization; myocardial perfusion and the uptakes of MIBG and BMIPP were preserved. Abnormalities of myocardial fatty acid metabolism and sympathetic neuron activity with preserved perfusion flow and histologic changes such as fibrosis in the apical wall are indicative of apical myocardial injury or ischemia (infarction) without coronary artery stenosis; apical aneurysm may have occurred in severe apical HCM with cavity obliteration up to the midventricular level.

Cardiomyopathy, Hypertrophic↗

Correlation between myocardial blood flow and fasting glucose metabolism in ischemic heart disease. Quantitative assessment by nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose positron emission tomography.

Ischemic myocardium avidly incorporates fluorine-18 fluorodeoxyglucose (F-18 FDG) in the fasting state, in contrast to the relative absence of F-18 FDG uptake in normal myocardium with sufficient blood flow in the fasting state. Although many studies have attempted to use F-18 FDG uptake to discriminate ischemic but viable myocardium from scarred myocardium, little is known clinically about the correlation between blood flow and F-18 FDG uptake in ischemic myocardium. We studied the critical level of blood flow that causes avid F-18 FDG uptake in myocardium in 9 patients. All patients had angiographically proven ischemic heart disease but no diabetes. Regional myocardial blood flow (RMBF) was measured quantitatively by positron emission tomography (PET) using nitrogen-13 ammonia in the resting state, in which the normal value was 80.2 +/- 13.0 ml/min/100 cm3. The F-18 FDG uptake in myocardium was assessed with the differential uptake ratio (DUR) scale. We constructed circumferential profiles of radioactivity uptake in myocardium for each study, and chose 780 sections of myocardium in which the relation between the two factors could be analyzed. In moderately ischemic to normal myocardium with RMBF of 50 to 90 ml/min/100 cm3, RMBF and F-18 FDG uptake were negatively correlated (r = -0.44, p < 0.01). When RMBF was 50 to 60 ml/min/100 cm3 (n = 121), the peak DUR value of F-18 FDG uptake was 4.0 +/- 2.0. The two factors were not correlated when RMBF was less than 50 ml/min/100 cm3 or 90 ml/min/100 cm3 or higher. Our results suggest that RMBF and F-18 FDG uptake values as measured with PET may provide valuable information on the possible benefit of intervention in ischemic heart disease.

Aged↗

Correlations between resting regional wall motion and regional myocardial blood flow (at rest and during exercise) in infarct-related myocardium--a study with [13N]ammonia positron emission tomography.

We evaluated quantitatively the correlations between resting wall motion and regional myocardial blood flow (RMBF; at rest and during exercise) in infarct-related myocardium. The study was performed in 28 subjects: 21 patients who had previously suffered myocardial infarction of the anteroseptal wall, and 7 normal individuals. Positron emission tomography (PET) with [13N]ammonia was performed at rest and during low-grade exercise (bicycle ergometer fixed at 25 W for 6.5 min), and RMBF was measured quantitatively from the radioactivity in myocardial tissue and arterial blood. Resting regional wall motion was calculated using the centerline method on left ventriculographic findings. Resting regional wall motion was correlated with RMBF both at rest and during exercise in the infarct areas (anterior walls; y = 2.74 +/- 4.25 x 10(-2)x, r = 0.43, at rest; and y = -2.48 + 3.04 x 10(-2)x, r = 0.48, during exercise, p < 0.05; septal walls; y = -3.61 + 5.64 x 10(-2)x, r = 0.62, at rest; and y = -3.46 + 4.31 x 10(-2)x, r = 0.62, during exercise, p < 0.01). In each infarct-related wall, the coefficient (the slope) during exercise was smaller than that at rest (3.04 vs 4.25 and 4.31 vs 5.64 in each), and the infarct areas with preserved wall motion showed higher RMBF during exercise than those with reduced wall motion. Our results may show that wall motion depends on viable but ischemic myocardium in infarct-related walls.

Adult↗

Significance of downsloping ST-segment depression induced by low-level exercise in severe coronary artery disease. Assessment with myocardial ischemia and collateral perfusion.

Exercise-induced downsloping ST-segment depression is a common manifestation of severe myocardial ischemia. Although greater downsloping ST-segment depression is suspected to indicate more severe ischemia, its exact relationship to regional myocardial blood flow (RMBF) has not yet been clarified. We investigated the relationship between the magnitude of downsloping ST-segment depression and exercise-induced changes in RMBF and collateral perfusion. Nitrogen-13 ammonia positron emission tomography was performed in 6 healthy volunteers and 72 patients with angiographically proven coronary artery disease. The left ventricle was divided into 11 regions of interest, and RMBF in each region was measured at rest and during low-level supine bicycle exercise. Downsloping ST-segment depression of 0.1 mV or more at 80 milliseconds after the J point was accepted as significant. Low-level exercise induced downsloping depression of 0.1 to 0.2 mV in 10 patients (group D1) and downsloping depression of 0.2 mV or more in 8 patients (group D2). Multivessel disease was common in both group D1 (80% of patients) and group D2 (88% of patients). Collateral circulation was significantly more frequent in group D1 (90%) than in group D2 (13%, p < 0.01). Ischemic areas were larger and cardiac function was worse in group D2 than in group D1. The RMBF increased sufficiently in all regions (56 +/- 30%) with exercise in the healthy group. In group D1, RMBF was unchanged or decreased in ischemic areas (10 +/- 23%) but increased sufficiently in surrounding areas (50 +/- 32%). In group D2, RMBF was unchanged in ischemic areas (17 +/- 24%) and increased insufficiently in surrounding areas (41 +/- 21%). Therefore, exercise-induced downsloping ST-segment depression of 0.1 to 0.2 mV may reflect an underlying change in blood flow in viable myocardium with collateral perfusion, and downsloping depression of 0.2 mV or more may reflect more severely impaired myocardium without collateral perfusion.

Adult↗