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Biomedical subjects

S Homma

Publications and source records attributed to S Homma.

At least 37 records · Page 2Linked to original sources

Hippocampus in relation to mental sweating response evoked by memory recall and mental calculation: a human electroencephalography study with dipole tracing.

Mental-sweating response (MSR) was observed in the palm when the subject was asked to perform a mentally stressful task such as memory recall or mental calculation. About 4 s before the development of MSR, small MSR-related wavelets (MSR wavelets) and large waves were randomly generated on electroencephalograph. After differentiating the two types of waves, we calculated locations of the current dipole of MSR wavelets using the two-dipole model of the SSB/dipole tracing method. The result showed that one current dipole of MSR wavelets was consistently located in the hippocampus while the other dipole was widely dispersed in the cortex during memory recall and mental calculation.

Adult↗

Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells.

Several reports of clinical trials of immunotherapy using dendritic cells have been published to date. In this study, we investigated the safety and clinical response of immunotherapy with fusions of dendritic and glioma cells for the treatment of patients with malignant glioma. Eight patients with malignant glioma, ranging in age from 4 to 63 years old, participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells of dendritic and glioma cells were prepared with polyethylene glycol, and the fusion efficiency ranged from 9.2 to 35.3% (mean, 21.9%). All patients received the fusion cells every three weeks for a minimum of 3, and a maximum of 7, immunizations. Fusion cells were injected intradermally, close to a cervical lymph node. The percentage of CD16- and CD56-positive cells in peripheral blood lymphocytes slightly increased after immunization in 4 out of 5 cases investigated. Peripheral blood mononuclear cells were incubated with irradiated autologous glioma or U87MG cells and supernatants were harvested. In 6 cases analyzed, the concentration of interferon-gamma in the supernatant increased after immunization. Clinical results showed that there were no serious adverse effects and two partial responses. Although the results of the phase I clinical trial of fusion cells indicated that this treatment safely induced immune responses. we were unable to establish a statistically significant treatment-associated response rate, due to the limited sample population. Therefore, further evaluation of the role of adjuvant cytokines is necessary.

Adult↗

Calf and shin muscle oxygenation patterns and femoral artery blood flow during dynamic plantar flexion exercise in humans.

The effects of dynamic plantar flexion exercise [40, 60, and 80 contractions.min-1 (cpm)] on calf and shin muscle oxygenation patterns and common femoral artery blood flow (Qfa) were examined in six female subjects [mean age 21 (SD 1) years] who exercised for 1 min at 33% of their maximal voluntary contraction at ankle angles between 90 degrees and 100 degrees. Spatially resolved near-infrared spectroscopy was used to measure medial gastrocnemius, lateral soleus (synergist) and anterior tibialis (antagonist) muscle oxygen saturation (SO2, %). Qfa was measured by ultrasound Doppler. The SO2 changed significantly only in the medial gastrocnemius and its decrease (up to about 30%) was independent of the contraction frequencies examined. The increase in Qfa, at the end of exercise, was highest at 80 cpm. When the exercise at 60 cpm was prolonged until exhaustion [mean 2.7 (SD 1.1) min], medial gastrocnemius SO2 decreased, reaching its minimal value [mean 30 (SD 10)%] within the 1st min, and had partially recovered before the end of the exercise with concomitant increases in total haemoglobin content and Qfa. These results suggest that the medial gastrocnemius is the muscle mostly involved in dynamic plantar flexion exercise and its oxygen demand with increases in contraction frequency and duration is associated with an up-stream increase in Qfa.

Adult↗

Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice.

BACKGROUND: The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells. METHODS: Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation. RESULTS: About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells. CONCLUSIONS: These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC.

Animals↗

Postoperative fecoflowmetric analysis in patients with anorectal malformation.

Because conventional methods of evaluating anorectal function do not necessarily provide good correlations between investigative results and symptoms in patients who have undergone surgery for an anorectal malformation (ARM), we recently introduced feco-flowmetry (FFM) to simulate natural anorectal evacuation. The purpose of this study was to embody significant parameters to elucidate the dynamics of anorectal activity on FFM. The parameters of FFM were compared with those of manometry and Kelly's clinical score (KCS) in 24 patients who underwent surgery for an ARM. There were three fecoflow patterns, namely, block (B) type, segmental (S) type, and flat (F) type. The B-type or S-type patterns were seen in patients classified as "clinically good." There were close relationships between the fecoflow pattern and both the operative procedure and the KCS (P = 0.01 and 0.001, respectively). Maximum fecal stream flow rate (Fmax) precisely reflected the tolerance rate of intended normal saline solution in the colorectum (TR), the evacuative rate (ER), and KCS. Fmax > 45 ml/s or TR > 70% or ER > 50% was statistically regarded as the borderline of fecal continence. Thus, the fecoflow pattern might reflect the motor activity of the pelvic floor muscle. FFM provided quantiative and qualitative evaluations concerning anorectal motor activity in patients who had undergone surgery for an ARM.

Adolescent↗

Histopathological modifications of early atherosclerotic lesions by risk factors--findings in PDAY subjects.

To investigate whether histopathological modifications on early atherosclerotic lesions differ according to risk factors, we compared the histological findings of arteries obtained from a multicenter study in the USA (Pathobiological Determinants of Atherosclerosis in Youth, PDAY) with the antemortem risk factors. The materials comprised aortas and left anterior descending (LAD) coronary arteries of 140 male subjects. Measurements of intimal thickness, classification of intimal lesions, and density of foam cells and intimal fibrosis at the determined sites of LAD and aorta were evaluated. In both arteries, intimal thickness of hypertensives was greater than the normotensives with no definite proliferation of foam cells. In aortas, hypercholesterolemia was associated with an increase in foam cells, but not with an increase in intimal thickness. HDL-C value correlated inversely with number of foam cells in both the arteries, and the degree of intimal thickness in LADs, where early appearance of advanced lesion such as preatheroma and atheroma, was also indicated in the low HDL-C group. Smokers had less number of foam cells in both the arteries and more intensive intimal fibrosis in LAD than non-smokers. Our study suggests that there are several ways to advanced atherosclerotic lesions by risk factors.

Adolescent↗

Structural analysis of BAG1 cochaperone and its interactions with Hsc70 heat shock protein.

BAG-family proteins share a conserved protein interaction region, called the 'BAG domain', which binds and regulates Hsp70/Hsc70 molecular chaperones. This family of cochaperones functionally regulates signal transducing proteins and transcription factors important for cell stress responses, apoptosis, proliferation, cell migration and hormone action. Aberrant overexpression of the founding member of this family, BAG1, occurs in human cancers. In this study, a structure-based approach was used to identify interacting residues in a BAG1--Hsc70 complex. An Hsc70-binding fragment of BAG1 was shown by multidimensional NMR methods to consist of an antiparallel three-helix bundle. NMR chemical shift experiments marked surface residues on the second (alpha 2) and third (alpha 3) helices in the BAG domain that are involved in chaperone binding. Structural predictions were confirmed by site-directed mutagenesis of these residues, resulting in loss of binding of BAG1 to Hsc70 in vitro and in cells. Molecular docking of BAG1 to Hsc70 and mutagenesis of Hsc70 marked the molecular surface of the ATPase domain necessary for interaction with BAG1. The results provide a structural basis for understanding the mechanism by which BAG proteins link molecular chaperones and cell signaling pathways.

Adenosine Triphosphatases↗

Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function.

Left ventricular remodeling is a major cause of progressive heart failure and death after myocardial infarction. Although neoangiogenesis within the infarcted tissue is an integral component of the remodeling process, the capillary network is unable to support the greater demands of the hypertrophied myocardium, resulting in progressive loss of viable tissue, infarct extension and fibrous replacement. Here we show that bone marrow from adult humans contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to directly induce new blood vessel formation in the infarct-bed (vasculogenesis) and proliferation of preexisting vasculature (angiogenesis) after experimental myocardial infarction. The neoangiogenesis resulted in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition and sustained improvement in cardiac function. The use of cytokine-mobilized autologous human bone-marrow-derived angioblasts for revascularization of infarcted myocardium (alone or in conjunction with currently used therapies) has the potential to significantly reduce morbidity and mortality associated with left ventricular remodeling.

Adult↗

Lipoprotein metabolism in Japanese centenarians: effects of apolipoprotein E polymorphism and nutritional status.

OBJECTIVES: To assess the complex interaction of apolipoprotein (apo) E polymorphisms and environmental factors on lipoprotein profile in centenarians. DESIGN: Cross-sectional analysis. SETTING: Tokyo metropolitan area. PARTICIPANTS: Seventy-five centenarians and 73 healthy older volunteers (mean age 63.1 +/- 10.0) living in the Tokyo metropolitan area. MEASUREMENTS: Plasma lipids and lipoproteins, cholesteryl ester transfer protein mass, apo E phenotype, body mass index, nutritional indices (serum albumin, prealbumin, transferrin), dietary intake, inflammation markers (C-reactive protein (CRP), interleukin-6 (IL-6)), activities of daily living, and cognitive function. RESULTS: In comparison with older people, the centenarians had low concentrations of total and low-density lipoprotein cholesterol (LDL-C) and a relative predominance of high-density lipoprotein 2 cholesterol. No environmental factor, except the number of apo E epsilon2 alleles, was a significant determinant of LDL-C and apo B, suggesting that the low apo B-containing lipoprotein in centenarians may be attributable to a genetic cause. Centenarians had elevated levels of lipoprotein (a) and decreased high-density lipoprotein cholesterol (HDL-C), which seem to be an unfavorable lipoprotein profile. Lower levels of HDL-C in the centenarians were associated with decreased serum albumin, elevated CRP and IL-6 levels, and cognitive impairment, suggesting that HDL-C could be a sensitive marker for frailty and comorbidity in the oldest old. CONCLUSIONS: Low levels of apo B-containing lipoproteins attributable to a genetic cause may be advantageous for longevity. Lipoprotein profiles in centenarians were consistently related to the subjects' nutritional status, inflammation markers, and apo E polymorphisms. The results provide evidence for the importance of maintaining nutritional status in the very old.

Activities of Daily Living↗

Intra-atrial thrombus after surgical closure of patent foramen ovale.

Patent foramen ovale (PFO) represents a potential path for paradoxical embolism and is associated with cryptogenic stroke. It has been suggested that because a PFO represents a repairable lesion (by surgical or transcatheter methods), repair may be the optimal treatment to prevent recurrent stroke. This report describes a patient with recurrent neurologic and peripheral embolic events, which occurred approximately 6 months after the surgical closure of a PFO. The diagnosis of an intra-atrial thrombus with a small residual PFO was made by subsequent transesophageal echocardiography. Thrombus formation at the closure site needs to be considered in a patient with recurrent embolic events after closure of a PFO.

Echocardiography, Transesophageal↗

Assessment of left ventricular function by real-time 3-dimensional echocardiography compared with conventional noninvasive methods.

Quantitative assessment of left ventricular ejection fraction is an essential component of cardiac evaluation. We performed real-time 3-dimensional echocardiography in 56 consecutive patients who underwent multigated radionuclide angiography. Thirteen patients were excluded for the following reasons: 5 for large size of left ventricle required for image acquisition, 5 for suboptimal image quality in real-time 3-dimensional echocardiography, and 3 for atrial fibrillation. Finally, we compared left ventricular ejection fraction assessed by real-time 3-dimensional echocardiography and conventional 2-dimensional echocardiography with that obtained by multigated radionuclide angiography in 43 patients. Left ventricular ejection fraction was determined by real-time 3-dimensional echocardiography with the use of parallel plane-disks and sector plane-disks summation methods. A good correlation was obtained between both real-time 3-dimensional echocardiography methods and multigated radionuclide angiography (r = 0.87 and 0.90, standard error of estimate = 3.7% and 4.2%), whereas the relation between the 2-dimensional echocardiography method and radionuclide angiography demonstrated a significant departure from the line of identity (P <.001). In addition, interobserver variability was significantly lower (P <.05) for the real-time 3-dimensional echocardiography methods than that by the 2-dimensional echocardiography method. Real-time 3-dimensional echocardiography may be used for quantification of left ventricular function as an alternative to conventional methods in patients with adequate image quality.

Adult↗

Four-year prospective study of pulmonary venous thrombosis after lung transplantation.

The objective of this study was to prospectively assess pulmonary venous anastomosis by transesophageal echocardiography after lung transplantation. Thrombus formation at the pulmonary venous anastomotic site after lung transplantation may have catastrophic consequences, including allograft failure and stroke. Eighty-seven consecutive adult lung transplant recipients underwent transesophageal echocardiography within 48 hours after surgery. Thrombosis of a pulmonary vein was diagnosed in 13 (15%) of 87 patients in the early postoperative period after lung transplantation. Mean thrombus width was 0.9 +/- 0.4 cm (range, 0.5 to 1.7 cm), with an average peak flow velocity at the site of obstruction of 127 +/- 23 cm/s (range, 90 to 150 cm/s). Five patients with pulmonary vein thrombosis died in the perioperative period, yielding a 90-day mortality rate of 38%. Larger thrombus size and greater acceleration of flow through a narrowed pulmonary vein correlated with poor clinical outcome. During each year of the study, the incidence of pulmonary vein thrombosis declined progressively. Pulmonary vein thrombosis is a potentially ominous complication in the early postoperative period after lung transplantation. Transesophageal echocardiography is a valuable tool for detecting abnormalities of the pulmonary venous anastomosis. Thrombus size and flow velocity at the anastomotic site may guide prognosis and clinical management. Complications of the pulmonary venous anastomosis are in part technical in nature.

Adult↗

Patent foramen ovale presenting as platypnea-orthodeoxia: diagnosis by transesophageal echocardiography.

Platypnea-orthodeoxia is a rare syndrome that is often associated with interatrial shunting through a patent foramen ovale or atrial septal defect. We describe the case of a 65-year-old woman with progressive dyspnea and hypoxia when standing and walking, which was relieved by assuming the recumbent position. The diagnosis was confirmed by tilt-table transesophageal echocardiography demonstrating a large right-to-left shunt through a patent foramen ovale while the patient was in a semiupright position and no significant shunt while in a recumbent position. This case demonstrates that platypnea-orthodeoxia caused by a patent foramen ovale can be clearly demonstrated by the technique of contrast transesophageal echocardiography performed on a tilt table.

Aged↗

Acute myocardial infarction caused by paradoxical coronary embolization in a patient with a patent foramen ovale.

We describe the case of a young woman without cardiac risk factors who had an acute inferoapical myocardial infarction. Coronary angiographic appearance was consistent with thrombus in the distal left anterior descending coronary artery. A patent foramen ovale with moderate right-to-left shunting after the Valsalva maneuver was detected by contrast transesophageal echocardiography. No other cardioembolic source was identified. Paradoxical embolization through a patent foramen ovale is a rare phenomenon, which appeared to have resulted in myocardial infarction in this patient.

Adult↗

Erythropoietin modulates angiotensin II- or noradrenaline-induced Ca(2+) mobilization in cultured rat vascular smooth-muscle cells.

BACKGROUND: It has been reported that human recombinant erythropoietin (rHuEpo) modulates the sensitivity of the cardiovascular system to angiotensin II (Ang II) or noradrenaline (NA). In the present study, we explored the effect of rHuEpo on the responsiveness of Ang II- or NA-induced cytosolic free calcium ([Ca(2+)]i) mobilization in cultured rat vascular smooth-muscle cells (VSMC). METHODS: [Ca(2+)]i concentrations in VSMC were measured by using the calcium-sensitive fluorescent dye fura-2. RESULTS: The addition of rHuEpo (250 U/ml) alone induced elevation in [Ca(2+)]i, which remained significantly elevated above basal level for at least 60 min in the presence of extracellular Ca(2+). Pre-incubation with specific protein kinase C (PKC) inhibitor calphostin C (1 micromol/l) significantly reduced the peak and the sustained elevations of [Ca(2+)]i. Pre-treatment with rHuEpo for 60 min increased both basal [Ca(2+)]i and the changes in [Ca(2+)]i by Ang II or NA in a dose-dependent manner in the presence of extracellular Ca(2+). The synergistic effects of rHuEpo with Ang II or NA were also retained when VSMC were bathed in the Ca(2+)-free medium after the pre-incubation of rHuEpo. Conversely, they were diminished in the presence of extracellular Ca(2+) combined with intracellular Ca(2+) release inhibitor 8-(NN-diethylamino)octyl-1,3,4,5-trimethoxybenzoate (TMB-8). The synergistic effects of rHuEpo were also diminished by PKC depletion or by PKC inhibitor. CONCLUSIONS: These observations suggest that rHuEpo has synergistic effects on Ang II- or NA-induced [Ca(2+)]i mobilization, particularly on intracellular Ca(2+) release, in VSMC. This may be a potential mechanism contributing to hypertension associated with rHuEpo therapy.

Angiotensin II↗

LV volume quantification via spatiotemporal analysis of real-time 3-D echocardiography.

This paper presents a method of four-dimensional (4-D) (3-D + Time) space-frequency analysis for directional denoising and enhancement of real-time three-dimensional (RT3D) ultrasound and quantitative measures in diagnostic cardiac ultrasound. Expansion of echocardiographic volumes is performed with complex exponential wavelet-like basis functions called brushlets. These functions offer good localization in time and frequency and decompose a signal into distinct patterns of oriented harmonics, which are invariant to intensity and contrast range. Deformable-model segmentation is carried out on denoised data after thresholding of transform coefficients. This process attenuates speckle noise while preserving cardiac structure location. The superiority of 4-D over 3-D analysis for decorrelating additive white noise and multiplicative speckle noise on a 4-D phantom volume expanding in time is demonstrated. Quantitative validation, computed for contours and volumes, is performed on in vitro balloon phantoms. Clinical applications of this spaciotemporal analysis tool are reported for six patient cases providing measures of left ventricular volumes and ejection fraction.

Cardiac Volume↗

Assessment of segmental wall motion abnormalities using contrast two-dimensional echocardiography in awake mice.

Murine models of cardiac disease are becoming an important tool for studying pathophysiological processes. Development of methods to accurately assess ventricular function are therefore important. The purpose of this study was to evaluate the feasibility of echocardiographic assessment of segmental wall motion abnormalities in a murine model of myocardial infarction. Two-dimensional contrast (C+) and noncontrast (C-) echocardiography were performed in 76 awake mice 2 days before and 2 days after left coronary ligation. The short-axis images obtained with two-dimensional echocardiography and corresponding postmortem cross-sectional histological samples stained with Evans blue dye were each divided into 16 segments, and all matched segments were examined for correlation between wall motion abnormalities and myocardial hypoperfusion. With the use of contrast enhancement, the number of visualized segments was significantly increased (base: C- 86%, C+ 98%; midpapillary: C- 57%, C+ 89%; apex: C- 30%, C+ 74%). Agreement between echocardiographically assessed regional wall motion abnormalities and pathologically determined hypoperfusion in basal, midpapillary, and apical levels were 90%, 93%, and 93%, respectively. Agreement between echocardiographically normal wall motion and pathologically normal findings in basal, midpapillary, and apical levels were 99%, 88%, and 71%, respectively. Thus echocardiographic assessment of segmental wall motion in awake mice was feasible and the accuracy was improved with the use of a contrast agent.

Animals↗

Anesthetic inhibition in ischemic and nonischemic murine heart: comparison with conscious echocardiographic approach.

It is well known that the level of anesthesia obtained by intraperitoneal injection is variable and may alter cardiac function. In this study, we compared the effects of different anesthetics on cardiac function with the conscious state using high-resolution two-dimensional echocardiography in nonischemic and ischemic mice. Eighty-four mice were tested before and after surgery with ligation of the coronary artery. All 84 mice were studied in the conscious state and under high-dose intraperitoneal anesthesia. Twenty-two of 84 mice were studied under low-dose intraperitoneal anesthesia. Another 22 mice were also studied under gas anesthesia and spontaneous breathing. Experiments in the conscious state were performed by two investigators before the administration of anesthesia: one investigator held the animal and the transducer and the other operated the ultrasound equipment. Left ventricular systolic function was measured, and measurements obtained after surgery were compared with infarcted areas assessed by histological staining. Results showed that both high- and low-dose intraperitoneal anesthesia significantly reduced heart rates and left ventricular contractility in both pre- and postsurgical mice as opposed to conscious mice (P < 0.01). There were significantly higher correlation coefficients between mean fractional area change (FAC) and infarcted area in conscious state compared with high-dose intraperitoneal anesthesia (P < 0.05). The correlation coefficient between FAC and infarcted area during gas anesthesia was also significantly higher compared with high-dose intraperitoneal anesthesia (P < 0.05). In conclusion, conscious experiments or the use of gas anesthesia is preferred for echocardiographic assessment of cardiac function in mice because intraperitoneal injection significantly induces a significant reduction in heart rate and left ventricular systolic function.

Anesthetics, Inhalation↗