Biomedical subjects

M Furuta

Publications and source records attributed to M Furuta.

At least 19 recordsLinked to original sources

PubMed2006

Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers.

Methods to permit more precise delineation of astrocytomas of different grades may have therapeutic utility. The authors selectively microdissected pure populations of cells from normal brain and astrocytomas. They performed two-dimensional protein gel electrophoresis (2DGE) followed by protein sequencing. Differential expression was confirmed immunohistochemically. 2DGE identified proteomic patterns and proteins that differentiated normal brain from tumor and distinguished astrocytomas of increasing grade.

Astrocytoma↗

PubMed2006

Cell transplantation after the coculture of skeletal myoblasts and mesenchymal stem cells in the regeneration of the myocardium scar: an experimental study in rats.

UNLABELLED: In myocardial infarction and Chagas's disease, some physiopathological aspects are common: cardiomyocyte loss due to ischemia leads to a reduction of contractility and heart function. Different cells have been proposed for cellular cardiomioplasty. OBJECTIVE: Our goal was to evaluate the method of co-culture of skeletal muscle (SM) and mesenchymal stem cells (MSC) for cell therapy of heart failure in Chagas's disease (CD) and myocardium postinfarction (MI). METHODS: For MI, 39 rats completed the study at 1 month. Seventeen rats received cell therapy into the scar and 22 rats only medium. For CD, 15 rats completed the study at 1 month including 7 that received cell therapy and eight followed the natural evolution. All animals underwent ecocardiographic analysis at baseline and 1 month. Left ventricular, ejection fraction, end systolic, and end dyastolic volume were registered and analyzed by ANOVA. The co-culture method of SM and MSC was performed at 14 days (DMEM, with 15% FCS, 1% antibiotic, IGF-I, dexamethasone). Standard stain analysis was performed. RESULTS: For MI ejection fraction in the animals that received the co-cultured cells increased from 23.52+/-8.67 to 31.45+/-8.87 (P=.006) versus the results in the control group: 26.68+/-6.92 to 22.32+/-6.94 (P=.004). For CD, ejection fraction in animals that received the co-cultured cells increased from 31.10+/-5.78 to 53.37+/-5.84 (P<.001) versus the control group values of 36.21+/-3.70 to 38.19+/-7.03 (P=0.426). Histopathological analysis of the animals receiving co-cultured cells demonstrated the presence of myogenesis and angiogenesis. CONCLUSION: The results validated the product of SM and MSC co-cultures for treatment of diseases.

Animals↗

PubMed2005

Cell transplantation: differential effects of myoblasts and mesenchymal stem cells.

BACKGROUND: Cellular transplantation has emerged as a novel therapeutic option for treatment of ventricular dysfunction. Both skeletal myoblasts (SM) and mesenchymal stem cells (MSC) have been proposed as ideal cell for this aim. The aim of this study is to compare the efficacy of these cells in improving ventricular function and to evaluate the different histological findings in a rat model of severe post-infarct ventricular dysfunction. METHODS: Myocardial infarction was induced in Wistar rats by left coronary occlusion. Animals with resulting ejection fraction (EF) lower than 40% were included. Heterologous SM were obtained by lower limb muscle biopsy and MSC by bone marrow aspiration. Nine days after infarction, rats received intramyocardial injection of SM (n=8), MSC (n=8) or culture medium, as control (n=11). Echocardiographic evaluation was performed at baseline and after 1 month. Histological evaluation was performed after HE and Gomori's trichrome staining and immunostainig against desmin, fast myosin and factor VIII. RESULTS: There was no difference in baseline EF and left ventricular end diastolic (LVEDV) and systolic volume (LVESV) between all groups. After 1 month a decrease was observed in the EF in the control group (27.0+/-7.10% to 21.46+/-5.96%, p=0.005) while the EF markedly improved in SM group (22.66+/-7.29% to 29.40+/-7.01%, p=0.04) and remained unchanged in the MSC group (23.88+/-8.44% to 23.63+/-10.28%, p=0.94). Histopathology identified new muscular fibers in the group that received SM and new vessels and endothelial cells in the MSC. CONCLUSION: Skeletal myoblasts transplantation resulted in myogenesis and improvement of ventricular function. In contrast, treatment with mesenchymal stem cells resulted in neoangiogenesis and no functional effect.

Animals↗

PubMed2005

Inactivation of Cryptosporidium parvum by ultrasonic irradiation.

The inactivation of Cryptosporidium parvum was investigated by the use of three different sonicators utilizing the squeeze-film effect, which may occur when ultrasound is irradiated into an extremely thin space and generate intensified pressure in the sample suspension. To expand from the small-scale horn-type sonicator to large-scale cylindrical or cleaning bath sonicators, the inactivation effectwas improved. In the case of the cylindrical sonicator (26.6 kHz, 30 W), 97% of the initial concentration of 2260 oocysts mL(-1) was inactivated at33 mL min(-1) (residence time of approximately 5.2 min). Hundreds of cubic meters of water can be treated per day at several kW using this sonicator. In addition, the simultaneous use of sonication and chlorination showed a beneficial effect on inactivation for C. parvum based on the evaluation of infectivity testing and morphological observation.

Animals↗

PubMed2004

Molecular genetic and proteomic analysis of synchronous malignant gliomas.

Described is a patient with concurrent discrete gliomas: a pleomorphic xanthoastrocytoma with anaplastic features and an anaplastic oligoastrocytoma. The distinct and morphologically dissimilar tumors demonstrated similar genetic abnormalities by loss of heterozygosity and comparative genome hybridization. Clonality and proteomic analyses highlighted an independent origin for the two tumors. Proteomic methods may prove useful in cases where the differential diagnosis and pathogenetic origin of tumors are uncertain, as well as more globally for its ability to provide insight into specific expression of proteins that may serve as unique markers of tumorigenesis or as novel targets of therapy.

Brain Neoplasms↗

PubMed2004

Inactivation effect of sonication and chlorination on Saccharomyces cerevisiae. Calorimetric analysis.

The inactivation effects of ultrasonic irradiation at 27.5 kHz and chlorination using sodium hypochlorite solution (NaOCl) on the growth of Saccharomyces cerevisiae (yeast cells) were investigated. In order to evaluate the effect of ultrasound on the growth of the yeast cells, calorimetric analysis was carried out in addition to colony counting. The heat evolution produced by the growth of yeast cells detected by calorimetry showed completely different patterns between sonication and chlorination. In case of sonication, the yeast cells were inactivated almost like a bactericidal effect, i.e. a quantitative change in cell number, at the beginning of sonication. It was similar to patterns obtained on simple dilution of yeast cells. In contrast, longer sonication increased the bacteriostatic effect, i.e. qualitative damage of the cell growth activity, together with the bactericidal effect. These results suggest that the cavitation caused by ultrasonic irradiation initially disrupted the cells located near the cavitation bubble which caused immediate cell death and the growth activity of the surviving cells was gradually damaged by further sonication. On the other hand, only a bacteriostatic effect was observed when the yeast cells were inactivated by chlorination.

Calorimetry↗

PubMed2004

Inactivation of Saccharomyces cerevisiae by ultrasonic irradiation.

We have investigated the inactivation of Saccharomyces cerevisiae (yeast cells) by ultrasonic irradiation. The amplitude on the vibration face contacting the sample solution was used as an indication of the ultrasonic power intensity. The effects of the amplitude on the vibration face and the initial cell numbers on the sonolytic inactivation of yeast cells have been investigated using a horn-type sonicator (27.5 kHz). The inactivation of the yeast cells by ultrasonic irradiation shows pseudo first-order behavior. The inactivation rate constant varied from 0.0007 to 0.145 s(-1) when the amplitude on the vibration face was in the range of 1-7 microm(p-p). The change in the inactivation rate constant as a function of the amplitude on the vibration face was similar to that of the OH radical formation rate under the same conditions. The threshold of this sonicator was 3 microm(p-p) with the amplitude on the vibration face. The initial cell numbers (from 10(2) to 10(5) mL(-1)) had an influence on the inactivation of the yeast cells by ultrasonic irradiation. The inactivation rate constants varied from 0.023 to 6.4 x 10(-3) s(-1), and the inactivation by ultrasonic irradiation was fastest at the lowest initial cell numbers. In a squeeze-film-type sonicator (26.6 kHz), 90% inactivation of the yeast cells was achieved by ultrasonic irradiation for 60 min.

Animals↗

PubMed2004

Inactivation of Escherichia coli by ultrasonic irradiation.

Ultrasonic inactivation of Escherichia coli XL1-Blue has been investigated by high-intensity ultrasonic waves from horn type sonicator (27.5 kHz) utilizing the "squeeze-film effect". The amplitude of the vibration face contacting the sample solution was used as an indication of the ultrasonic power intensity. The inactivation of the E. coli cells by ultrasonic irradiation shows pseudo first-order behavior. The inactivation rate constant gradually increased with increasing amplitude of the vibration face and showed rapid increase above 3 microm (p-p). In contrast, the H2O2 formation was not observed below 3 microm (p-p), indicating that the ultrasonic shock wave might be more important than indirect effect of OH radicals formed by ultrasonic cavitation in this system. The optimal thickness of the squeeze film was determined as 2 mm for the E. coli inactivation. More than 99% of E. coli cells was inactivated within 180-s sonication at the amplitude of 3 microm (p-p) and 2 mm of the thickness of the squeeze film.

Escherichia coli↗

PubMed2003

Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis.

To date, the role of pancreatic hormones in pancreatic islet growth and differentiation is poorly understood. To address this issue, we examined mice with a disruption in the gene encoding prohormone convertase 2 (PC2). These mice are unable to process proglucagon, prosomatostatin, and other neuroendocrine precursors into mature hormones. Initiation of insulin (IN) expression during development was delayed in PC2 mutant mice. Cells containing IN were first detected in knockout embryos on d 15 of development, 5 d later than in wild-type littermates. However, the IN(+) cells of d 15 PC2 mutant mice coexpressed glucagon, as did the first appearing beta-cells of controls. In addition, lack of PC2 perturbed the pattern of expression of transcription factors presumed to be involved in the determination of the mature alpha-cell phenotype. Thus, in contrast to controls, alpha-cells of mutant mice had protracted expression of Nkx 6.1 and Pdx-1, but did not express Brn-4. Islets of adult mutant mice also contained cells coexpressing insulin and somatostatin, an immature cell type found only in islets of the wild-type strain during development. In addition to the effects on islet cell differentiation, the absence of PC2 activity resulted in a 3-fold increase in the rate of proliferation of proglucagon cells during the perinatal period. This increase contributed to the development of alpha-cell hyperplasia during postnatal life. Furthermore, the total beta-cell volume was increased 2-fold in adult mutants compared with controls. This increase was due to islet neogenesis, as the number of islets per section was significantly higher in knockout mice compared with wild-type mice, whereas both strains had similar rates of IN cell proliferation. These results indicate that hormones processed by PC2 affected processes that regulate islet cell differentiation and maturation in embryos and adults.

Age Factors↗

PubMed2002

[Off-pump coronary artery bypass grafting/beating coronary artery bypass grafting for a patient with low left ventricular ejection fraction].

Beating coronary artery bypass grafting could be performed for a 47-year-old man with left ventricular ejection fraction (LVEF) of 9.3%. Post-operative LVEF was improved to 51.6%. Conventional coronary artery bypass grafting (CABG) used to be contraindicative for patients with LVEF below 20%. Recently, such patients are involved to indication of off-pump CABG (OPCAB) or beating CABG, because we consider OPCAB are lower complications than conventional CABG. We were able to bypass the circumflex for the patient while we had been used percutaneous cardio-pulmonary support (PCPS). We could perform beating coronary artery bypass grafting for a patient of the low LVEF.

Coronary Artery Bypass↗

PubMed2001

Intracerebroventricular administration of ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized rats.

Ghrelin, an endogenous growth hormone (GH) secretagogue, is shown to increase food intake, which action is similar to that of orexin, also a hypothalamic peptide. Since orexin suppresses pulsatile LH secretion in ovariectomized (OVX) rats, the present study was undertaken to investigate whether ghrelin also suppresses LH secretion. Effects of intracerebroventricularly injected ghrelin (0.1 nmol/0.3 microl) were examined in OVX rats treated with a small dose of 17beta-estradiol (E(2)). After ghrelin injection, pulsatile LH secretions which were ongoing in these E(2)-treated OVX rats were significantly suppressed for about 1 h, whereas GH secretion increased, peaking at 30 min. The main parameter suppressed by ghrelin was the pulse frequency, not the pulse amplitude, suggesting the hypothalamus as the site of ghrelin action. This study provides evidence that ghrelin acts not only in the control of food intake but also in the control of LH secretion.

Analysis of Variance↗

PubMed2001

Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice.

Mice homozygous for a deletion in the gene encoding prohormone convertase 2 (PC2) are generally healthy but have mild hypoglycemia and flat glucose-tolerance curves. Their islets show marked alpha (A)-cell hyperplasia, suggesting a possible defect in glucagon processing (Furuta, M., Yano, H., Zhou, A., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H., and Steiner, D. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 6646-6651). In this report we have examined the biosynthesis and processing of proglucagon in isolated islets from these mice via pulse-chase labeling and find that proglucagon undergoes essentially no processing in chase periods up to 8 h in duration. Only a small percent of cleavage at the sensitive interdomain site (residues 71 and 72) appears to occur. These observations thus conclusively demonstrate the essentiality of PC2 for the production of glucagon in the islet A-cells. Ultrastructural and immunocytochemical studies indicate the presence of large amounts of proglucagon in atypical appearing secretory granules in the hyperplastic and hypertrophic A-cells, along with morphological evidence of high rates of proglucagon secretion in PC2 null islets. These findings provide strong evidence that active glucagon is required to maintain normal blood glucose levels, counterbalancing the action of insulin at all times.

Animals↗

PubMed2001

Biological cell survival mapping for radiofrequency intracavitary hyperthermia combined with simultaneous high dose-rate intracavitary irradiation.

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose-rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37 degrees C. Radiation dose distribution was calculated with a treatment-planning computer. Cell survival was measured by colony assay with HeLa-TG cells in vitro. Radiation dose response at 1 - 7 Gy and time response with hyperthermia in the range of 40 - 46 degrees C were estimated. Radiation dose-response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46 degrees C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment.

Brachytherapy↗

PubMed2001

Simultaneous intraluminal thermobrachytherapy: an in vitro study.

A multi-institutional study on simultaneous intraluminal thermobrachytherapy (SITB) for advanced esophageal cancer was conducted in Japan. In this study, brachytherapy was administered by a small radioactive source stepping through a catheter in the esophagus, and hyperthermia was also applied by an endoesophageal coil. However, experimental or clinical findings on the spatial distribution of its antitumor effects around the esophagus are not available. Therefore, we developed an in vitro model of SITB using a high-dose-rate iridium-192 stepping source and two human cancer cell lines (WiDr and A549), and determined the spatial distribution of the antitumor effects. According to this model, the antitumor effects steeply decreased as the source-cell distance increased when cells of both cell lines were irradiated with 5 Gy without heat. When WiDr cells, a more resistant cell line to radiation and heat, were simultaneously irradiated and heated for 30 min at 44 degrees C, the effects decreased much less steeply as the distance increased. For A549 cells, a more sensitive cell line, irradiation with hyperthermia even at 42 degrees C made the decrease in the effects smaller. The largest antitumor effects can be expected at 5 - 10 mm beneath the esophageal mucosa, where the endoesophageal coil can heat tissues most effectively. SITB can induce larger antitumor effects than brachytherapy alone, especially in submucosal disease, which would favor treatment of advanced cancer.

Brachytherapy↗

PubMed2001

Plasma levels of agouti-related protein are increased in obese men.

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.

Adult↗

PubMed2001

The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site.

Impaired processing of pro-islet amyloid polypeptide (proIAPP), the precursor of the beta-cell peptide islet amyloid polypeptide (IAPP) (amylin), has been implicated in islet amyloid formation in type 2 diabetes. The prohormone convertase enzymes PC3 (also known as PC1) and PC2 are localized to beta-cell secretory granules with proIAPP and proinsulin and are responsible for proinsulin processing. To determine whether PC2 might be essential for proIAPP processing, we performed Western blot analysis of freshly isolated islets from normal mice and mice lacking active PC2. As expected, the primary species of IAPP immunoreactivity in islets from wild-type mice was fully processed (4-kDa) IAPP, with only small amounts of the 8-kDa precursor (unprocessed proIAPP) present. Islets from heterozygous PC2 null mice were identical to wild-type animals, suggesting that half the normal complement of PC2 is sufficient for normal proIAPP processing. By contrast, in islets from homozygous PC2 null mice, the predominant IAPP-immunoreactive form was of intermediate size (approximately 6 kDa), with no detectable mature IAPP and slightly elevated amounts of the 8-kDa precursor form present. Thus, in the absence of PC2, proIAPP processing appears to be blocked at the level of a proIAPP conversion intermediate. Immunofluorescence of pancreas sections and immunoblotting using antisera raised to the NH2- and COOH-terminal flanking regions of mouse proIAPP demonstrated that the 6-kDa intermediate form was an NH2-terminally extended proIAPP conversion intermediate (processed only at the COOH-terminus). These data indicate that PC2 is essential for processing of proIAPP at the NH2-terminal cleavage site in vivo and that PC3 is likely only capable of processing proIAPP at the COOH-terminal cleavage site.

Amyloid↗

PubMed2001

Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes.

OBJECTIVE: To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (approximately 1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS: Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after ( = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 +/- 0.12 vs. -0.79 +/- 0.09, F = 0.25, P = 0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001). CONCLUSIONS: HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.

Adult↗

PubMed2001

[Orbital development after enucleation without orbital implant in early childhood].

PURPOSE: To evaluate the development of orbital volume in five adults who underwent enucleation without orbital implant during early childhood, using reconstructed computed tomography(CT) images. MATERIALS AND METHODS: The orbital volume of 5 adults who underwent enucleation without orbital implants during early childhood was measured using CT images, and the results were compared between the anophthalmic orbit and the unaffected orbit in each case. The shape of maldevelopmental orbit and the relationship between orbital development and replacement of the prosthesis were also investigated. RESULTS: Orbital development in patients who underwent enucleation without orbital implant during early childhood was delayed in comparison with the unaffected orbit, and the delayed development was especially remarkable at the part of orbit corresponding to the equator of the eyeball. Maldevelopment of the orbit was severer in cases without replacement of the prosthesis than with it. CONCLUSION: For the development of orbital volume in anophthalmos after enucleation, orbital volume in place of the eyeball is required. Therefore, orbital implantation at the time of enucleation and replacement of the prosthesis with larger ones as the body grows are important.

Adult↗