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Biomedical subjects

S Senda

Publications and source records attributed to S Senda.

At least 19 recordsLinked to original sources

DNA methylation variation in cloned mice.

Mammalian cloning has been accomplished in several mammalian species by nuclear transfer. However, the production rate of cloned animals is quite low, and many cloned offspring die or show abnormal symptoms. A possible cause of the low success rate of cloning and abnormal symptoms in many cloned animals is the incomplete reestablishment of DNA methylation after nuclear transfer. We first analyzed tissue-specific methylation patterns in the placenta, skin, and kidney of normal B6D2F1 mice. There were seven spots/CpG islands (0.5% of the total CpG islands detected) methylated differently in the three different tissues examined. In the placenta and skin of two cloned fetuses, a total of four CpG islands were aberrantly methylated or unmethylated. Interestingly, three of these four loci corresponded to the tissue-specific loci in the normal control fetuses. The extent of aberrant methylation of genomic DNA varied between the cloned animals. In cloned animals, aberrant methylation occurred mainly at tissue-specific methylated loci. Individual cloned animals have different methylation aberrations. In other words, cloned animals are by no means perfect copies of the original animals as far as the methylation status of genomic DNA is concerned.

Animals↗

Ultrasonic tissue characterization can predict beta-blocker efficacy in dilated cardiomyopathy.

The aim was to determine if the combination of cyclic variation of myocardial integrated backscatter (variation IB) and left ventricular mass measurements can predict the efficacy of beta-blocker treatment in dilated cardiomyopathy. In 32 patients, left ventricular mass and variation IB were measured at baseline and during 6 microg/kg/min dobutamine infusion before the initiation of beta-blocker therapy. Variation IB was measured at left and right ventricular halves in the ventricular septum. The baseline left ventricular mass index and transseptal variation IB gradient during dobutamine were significantly greater in the effective group (1.16 +/- 0.18 g/mL and 1.8 +/- 0.6 dB) than in the ineffective group (0.94 +/- 0.28 g/mL, p = 0.032 and 0.4 +/- 0.6 dB, p < 0.005). When both baseline left ventricular mass index > or = 1.05 g/mL and transseptal variation IB gradient during dobutamine > or = 1.5 dB were defined as predictive criteria for the effective group, the sensitivity was 78% and the specificity was 86%. Analysis of transseptal variation IB during dobutamine may provide useful information predicting the efficacy of beta-blocker therapy in dilated cardiomyopathy.

3-Iodobenzylguanidine↗

A potential mechanism for regulating myosin I binding to membranes in vivo.

Myosin Is are associated with specific membranes, however, the mechanism for regulating their intracellular localization is unclear. As a first step towards understanding this mechanism, membrane rebinding assays using Dictyostelium myoB were performed. Crude, cytosolic myoB bound to intact, but not to NaOH-treated plasma membranes. In contrast, partially purified myoB binds to both intact and NaOH-treated plasma membranes. Chemical cross-linking of cytosolic myoB yielded several products, whereas none were found with the partially purified myoB. These results suggest a model where proteins regulating the specific binding of myoB to the plasma membrane may exist both in the cytosol and on the plasma membrane.

Animals↗

Recruitment of a specific amoeboid myosin I isoform to the plasma membrane in chemotactic Dictyostelium cells.

The Dictyostelium class I myosins, MyoA, -B, -C, and -D, participate in plasma membrane-based cellular processes such as pseudopod extension and macropinocytosis. Given the existence of a high affinity membrane-binding site in the C-terminal tail domain of these motor proteins and their localized site of action at the cortical membrane-cytoskeleton, it was of interest to determine whether each myosin I was directly associated with the plasma membrane. The membrane association of a myosin I heavy chain kinase that regulates the activity of one of the class I myosins, MyoD was also examined. Cellular fractionation experiments revealed that the majority of the Dicyostelium MyoA, -B, -C and -D heavy chains and the kinase are cytosolic. However, a small, but significant, fraction (appr. 7. -15%) of each myosin I and the kinase was associated with the plasma membrane. The level of plasma membrane-associated MyoB, but neither that of MyoC nor MyoD, increases up to 2-fold in highly motile, streaming cells. These results indicate that Dictyostelium specifically recruits myoB to the plasma membrane during directed cell migration, consistent with its known role in pseudopod formation.

Amino Acids, Diamino↗

Comparison of left ventricular diastolic filling with myocyte bulk modulus using Doppler echocardiography and acoustic microscopy in pressure-overload left ventricular hypertrophy and cardiac amyloidosis.

BACKGROUND: The myocardial bulk modulus has been described as the constitutive properties of the left ventricular (LV) wall and is measured as rho V2 (rho = density, V = sound speed) using acoustic microscopy. HYPOTHESIS: The study was undertaken to assess the relationship between the myocyte bulk modulus and transmitral inflow patterns in patients with pressure-overload LV hypertrophy (LVH) and cardiac amyloidosis (AMD). METHODS: In 8 patients with LVH, 8 with AMD, and 10 controls without heart disease, the transmitral inflow pattern was recorded by Doppler echocardiography before death, and myocardial tissue specimens were obtained at autopsy. The tissue density and sound speed in the myocytes were measured by microgravimetry and acoustic microscopy, respectively. The diameters of the myocytes were measured on histopathologic specimens stained by the elastica Van Gieson method. RESULTS: In the subendocardium, the myocyte bulk modulus was larger in LVH (2.98 x 10(9) N/m2, p < 0.001) and smaller in AMD (2.61 x 10(9) N/m2, p < 0.001) than in the controls (2.87 x 10(9) N/m2). The myocyte diameter in LVH (26 +/- 1 microns) was larger than that in the control (21 +/- 1 microns, p < 0.001) and AMD (20 +/- 1 microns, p < 0.001). The bulk modulus in the subendocardial myocyte significantly correlated with the deceleration time (DT) of the early transmitral inflow (r = 0.689, p = 0.028 in control, r = 0.774, p = 0.024 in LVH, and r = 0.786, p = 0.021 in AMD). CONCLUSION: The changes in the myocyte elasticity as represented by the bulk modulus were limited to the subendocardial layers and may be related to relaxation abnormalities in LVH and a reduction in LV compliance in AMD.

Acoustics↗

A novel color M-mode Doppler echocardiographic index for left ventricular relaxation: depth of the maximal velocity point of left ventricular inflow in early diastole.

Color M-mode Doppler echocardiography (CMD) has been utilized in assessing left ventricular (LV) filling dynamics. We tested a novel CMD index, the depth of the spatiotemporal maximum of early diastolic inflow (D-maxV) in the left ventricle, to clarify its significance in assessing LV diastolic function. In 26 normal subjects and 32 patients with ischemic heart disease, D-maxV was determined with CMD as the distance from the mitral valve opening point to the center of the aliasing area in early diastole. Transmitral flow velocity was measured with pulsed Doppler. During routine catheterization, high-fidelity LV pressure measurements yielded diastolic variables in patients. D-maxV was significantly lower in the patients than the normals (13.0+/-7.0 vs 23.4+/-6.8 mm, P < 0.0001). D-maxV exhibited significant linear correlations with the minimal first derivative of LV pressure (r = 0.72, P < 0.01), the time constant of isovolumic relaxation (r = -0.67, P < 0.01), and LV minimal pressure (r = -0.53, P < 0.02) in the patients with wide ranges of peak early to late inflow velocity ratio (0.43-3.9) and deceleration time of early filling (79-293 ms). D-maxV showed an inverse correlation with LV end-diastolic pressure (r = -0.53, P < 0.02) and no significant correlation with mean pulmonary capillary wedge pressure. Moreover, Kaplan-Meier analysis focusing on the patients with myocardial infarction revealed that the group with D-maxV < 10.4 mm (n = 13) exhibited a lower cumulative cardiac event-free rate than that with D-maxV > or = 10.4mm (n = 14) (49.4% vs 92.9% at 5 years, P < 0.05). The depth of the spatiotemporal maximum of early diastolic LV inflow velocity reflects LV relaxation and is free of pseudonormalization. Evaluation of the LV relaxation separately from preload may have a prognostic value for myocardial infarction.

Adult↗

A new approach for glomerular lesions: evaluation of scanning acoustic microscopy (SAM) for experimental glomerular disease in rats.

Most pathological evaluations using ordinary optical microscopy are usually qualitative and subjective. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed, indicating the tissue elasticity. In this study, we examined the capability of SAM to evaluate pathological findings in glomeruli using anti-Thy.1 glomerulonephritis. Light microscopic observations of the glomeruli showed severe cell proliferation and mesangial matrix expansion at 10 days after induction of glomerulonephritis and, yet, to a lower extent at day 21 with onset of healing. C-mode scanning of SAM enabled imaging of glomerular structure compatible to findings of ordinary light microscopy. In addition, glomerular propagation speed in nephritic rats was significantly increased at day 10, and then decreased at day 21. These results indicate that SAM evaluation may be a new, useful technique for quantitative evaluation of proliferative glomerular lesions.

Animals↗

Physical properties of the mitral valve tissue assessed by tissue sound speed in cardiac amyloidosis: relationship to the severity of mitral regurgitation.

Cardiac amyloidosis has been documented to show mitral regurgitation (MR) and a thickened mitral valve (MV) due to amyloid deposits. However, the changes in the physical properties of the thickened MV tissue in cardiac amyloidosis, which may be a causative factor of the MR, have not been described. Physical properties of the tissue, which are expressed by the elastic bulk modulus, can be evaluated by tissue sound speed. If biological tissue is assumed to be fluid-like, the tissue sound speed may be given by c= square root of K/rho, where c is the tissue sound speed, K is the elastic bulk modulus, and rho is the density. A reduction in tissue sound speed indicates a reduction in the elastic bulk modulus of the tissue, assuming that there is little change in rho. This suggests that the tissue is less elastic. The purpose of this study was to assess the physical properties of MV tissue by evaluating the sound speed of the MV tissue in cardiac amyloidosis. MV specimens were obtained at autopsy from 20 control adults without cardiovascular diseases and from 20 patients with cardiac amyloidosis. An acoustic microscope operating at 450 MHz was used to measure the tissue sound speed in the tip and basal portions of the MV tissue. The density of MV tissue was measured by microgravimetry. The severity of the MR had been evaluated by Doppler echocardiography before death, and it was compared with the tissue sound speed measured after death. In cardiac amyloidosis showing mild MR, the tissue sound speed of the MV in the tip portion (1605 +/- 19 m/s) and in the basal portion (1791 +/- 64 m/s) were lower than the corresponding values in control subjects (1637 +/- 42 m/s and 1851 +/- 62 m/s). However, these differences were not statistically significant. In cardiac amyloidosis showing moderate MR, the tissue sound speed of MV in the tip portion (1563 +/- 17 m/s) and in the basal portion (1654 +/- 59 m/s) were significantly lower than the corresponding values in the control subjects (p < 0.001) and the patients with mild MR (p < 0.05). No significant differences were observed in the density of MV tissue among the three groups. Therefore, the low value of the MV tissue sound speed in patients with cardiac amyloidosis indicated a reduced elastic bulk modulus, suggesting the less elasticity of the MV tissue. Furthermore, the patients with moderate MR demonstrated the greater reduction in the tissue sound speed than the patients with mild MR. The data suggest that the changes in physical properties of the MV tissue may be one of the causes of MR in cardiac amyloidosis.

Acoustics↗

Evaluation of progression in nonrheumatic aortic valvular stenosis by scanning acoustic microscopy.

To investigate distributions of hardness and thickness in nonrheumatic aortic stenosis (AS), scanning acoustic microscopy was used. The acoustic propagation speed (APS: m/s) and thickness at three sites (tip, middle and base) of aortic valve were measured in 18 cusps from 7 surgical patients with AS (late lesion), 27 showing mild lesions from 9 autopsy cases (early lesion) and 18 healthy from 6 autopsy cases (healthy). These were measured in each layer of cusps: fibrosa (F), spongiosa (S) or ventricularis (V). In early lesions, an increase in APS preceded the thickening and distributed in the tip (1666 +/- 107), the three layers of the middle (F: 1782 +/- 121; S: 1590 +/- 38; V: 1636 +/- 59) and the fibrosa of the base (1736 +/- 203). In late lesions, APS of the tip and three layers of the base were markedly increased. Progressive nonrheumatic AS is characterized by increased hardness that precedes the thickening, and its distribution may be related to mechanical stress.

Adult↗

[Newly developed technology for intravenous contrast echocardiography].

Until now we have not been able to employ a contrast enhancer for ultrasonic echocardiography at the everyday clinical level because the agent itself, composed of microbubbles, was too easily dispersed or even destroyed by several factors. However, contrast echocardiography has made a great leap forward with major developments on two fronts; the application of some new intravenous contrast enhancers, and newly developed machine technology permitting second harmonic imaging, intermittent or triggered imaging, pulse inversion harmonic imaging, and so on. New contrast enhancing agents are proving durability enough to permit greatly enhanced imaging for more than several minutes after injection. Recent new echocontrast specific imaging allows real-time visualizing of myocardial perfusion and assessment of myocardial function.

Contrast Media↗

[Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases].

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.

Aged↗

Relationship between myocardial tissue density measured by microgravimetry and sound speed measured by acoustic microscopy.

If myocardial tissue can be assumed to be fluid-like, myocardial tissue elasticity can be estimated by the sound speed of tissue based on the equation K = rho(c)2, where K is the elastic bulk modulus, rho is density, and c is the sound speed of tissue. However, little data exist regarding the relationship between the sound speed of tissue and tissue density. The purpose of the present study was to evaluate the relationship between the sound speed of tissue and tissue density of various diseased myocardia. Myocardial tissue specimens at autopsy were obtained from 10 control patients without cardiovascular disease, 8 patients with pressure overload left ventricular hypertrophy (POLVH), and 8 patients with cardiac amyloidosis (AMD). Myocardial tissue sound speed was measured using a scanning acoustic microscope operating in the frequency of 450 MHz, and tissue density was measured by microgravimetry. The sound speed in POLVH (1639 +/- 17 m/s) was higher and that in AMD (1565 +/- 11 m/s) was lower than that in control patients (1615 +/- 15 m/s) (p < 0.001) at the temperature of 20-22 degrees C. The density in POLVH (1.087 +/- 0.004 g/cm3) was higher and that in AMD (1.072 +/- 0.003 g/cm3) was lower than that in control patients (1.082 +/- 0.003 g/cm3) (p < 0.001). Tissue density correlated with sound speed in all three groups (r = 0.96, p < 0.001). Therefore, myocardial tissue sound speed data obtained by acoustic microscopy enabled us to evaluate tissue elasticity without measuring tissue density directly.

Acoustics↗

Evaluation of left atrial wall elasticity using acoustic microscopy.

Left atrial wall elasticity is one of the important factors regulating left atrial stiffness and functions. The authors evaluated left atrial wall elasticity by measuring the sound speed through the left atrial wall, based on the hypothesis that high elasticity tissues will yield larger sound speed values through the tissue, and examined age-associated changes in left atrial wall elasticity. Left atrium specimens were obtained from 30 normal subjects (age, 15-95 years) at autopsy. An acoustic microscope, operating at 450 MHz, was used to measure the sound speed in the endocardium and the myocardium of the left atrium. The sound speeds in endocardium and myocardium demonstrated significant correlation with age (r = 0.74, p<0.0001 and r = 0.47, p<0.01, respectively). These findings indicate that left atrial wall elasticity increased with advancing age. These changes may lead to deterioration of left atrial compliance and eventual left atrial failure in older subjects.

Adolescent↗

Cyclic variation of thickness in an age-related thick mitral valve observed by transthoracic echocardiography.

The cyclic variation of thickness during the cardiac cycle in age-related degenerative mitral valve (MV) has not been reported. Transthoracic echocardiography was used to evaluate the cyclic alteration in MV thickness in 40 patients with age-related MV thickening (diastolic MV thickness > or = 4 mm, age 70 +/- 14 years), 10 with mitral valve prolapse (MVP, age 49 +/- 11 years), 10 with rheumatic mitral stenosis (MS, age 66 +/- 9 years), and 31 control subjects (diastolic MV thickness < or = 3.6 mm, 53 +/- 17 years). After determination of the site of maximal thickness during diastole, the maximal and minimal thickness during systole of the anterior MV were measured. The percent change in MV thickness from diastole to systole (%deltaT) was calculated. The mitral regurgitation (MR) area was measured on color Doppler echocardiogram. The %deltaT (mean +/- sd) in age-related thickened MV and MVP groups were similar and significantly greater than that in control (60 +/- 8%, 61 +/- 6% vs 32 +/- 9%, p < 0.001). MR area was significantly greater in the age-related thickened MV group than that in controls (160 +/- 205 mm2 vs 14 +/- 40 mm2, p < 0.05). The %deltaT in MS (10 +/- 6%) was smallest (p < 0.001). A large cyclic alteration in valvular thickness was observed in the age-related degeneration of the MV and may be the cause of large MR despite no leaflet prolapse. The echocardiographic assessment of cyclic variation of MV thickness is feasible for estimating the histologic damage in thick MV.

Adolescent↗

Tissue characterization of myocardial cells by use of high-frequency acoustic microscopy: differential myocyte sound speed and its transmural variation in normal, pressure-overload hypertrophic, and amyloid myocardium.

The purpose of the present study was to evaluate the acoustic properties of myocytes in normal, pressure-overload hypertrophic, and amyloid myocardium. Myocardial tissue specimens at autopsy were obtained from 10 subjects without cardiovascular disease, six patients with left ventricular (LV) hypertrophy, and six patients with cardiac amyloidosis. Sound speed of myocytes was measured at subendocardial and subepicardial regions in myocardium by use of a high-frequency (450 MHz) acoustic microscope. In normal myocardium, the sound speed of myocytes was significantly higher in subendocardial region (1,728+/-19 m/sec) than in subepicardial region (1,645+/-22 m/sec) (p<0.0001). A significantly higher sound speed of myocytes was observed in the subendocardial region in LV hypertrophic myocardium (1,779+/-19 m/sec) than that in normal myocardium (p<0.001). In amyloid myocardium, a significantly lower sound speed of myocytes was observed in subendocardial (1,560+/-8 m/sec) and subepicardial (1,594+/-48 m/sec) regions than that in respective regions of the normal myocardium (p<0.0001 and p<0.05, respectively). Transmural variation in sound speed of myocytes measured by high-frequency acoustic microscopy existed in normal left ventricle. The differential myocyte sound speed and its transmural variation was observed in LV hypertrophic and amyloid myocardium as compared with normal myocardium. High-frequency acoustic microscopy can be a promising technique for myocardial tissue characterization at the myocyte level.

Acoustics↗

[Development and evaluation of a new target heart rate formula for the adequate exercise training level in healthy subjects].

Little data is available recommending the adequate exercise level for physical fitness, so we hypothesized that the anaerobic threshold (AT) point is an ideal exercise level. We aimed to determine a new target heart rate formula for the adequate exercise training level in healthy subjects. This study first developed a new formula in 405 subjects (221 males, 184 females, mean age 48.9 +/- 12.3 years). The AT was determined during cycle ergometer exercise with continuous respiratory gas measurements. The correlation of heart rate at the AT to resting heart rate, age and gender was analyzed by the multiple regression method. Based on this correlation, a new formula calculating target heart rate was established as 74.8 + 0.76 x (resting heart rate) - 0.27 x (age) + 7.3 x S (male: 0 or female: 1). This formula was then compared to Blackburn's method in 210 subjects (139 males, 71 females, mean age 44.5 +/- 14.4 years). The difference between the new target heart rate and the heart rate at the AT was significantly lower than that between the target heart rate by Blackburn's method [(220 - age) x 0.7] and the heart rate at the AT (8.8 +/- 6.3 vs 12.7 +/- 8.2 beat/min, p < 0.001). The resting heart rate and gender are important factors in determining the target heart rate for exercise. This new formula indicates the adequate exercise training level more accurately in healthy subjects.

Adult↗

Evaluation of acoustic properties of the live human smooth-muscle cell using scanning acoustic microscopy.

This study was performed to measure the acoustic propagation speed in live human aortic smooth-muscle cells (HASMC), using scanning acoustic microscopy (SAM) and a novel measurement theory that permits the measurement of the acoustic propagation speed in biological samples of unknown thickness. C-mode and X-Z-mode images of HASMC under three different conditions: growing (G); differential (D); and on hypotonic loading (H), were acquired using 100-MHz, 450-MHz and 600-MHz ultrasound. The images exhibit features related to the cell surface curvature and intracellular structure. The theory supporting the methodology is derived in this article and makes use of the interference fringes within the focusing lens of the high-frequency transducer. The propagation speed in the cells was calculated from the location of the interference fringe on the C-mode images and the fringe shift on the X-Y-mode images with 450-MHz ultrasound. The propagation speed in D (1624 +/- 16 m/s) was significantly higher than those in G (1571 +/- 14 m/s, p < 0.05) and H (1585 +/- 8 m/s, p < 0.05). Scanning acoustic microscope measurements, along with the described theory, are useful for studying the acoustic properties of live cells ex vivo and have applications in both pathophysiology and biomechanics.

Acoustics↗