Kawasaki University of Medical Welfare

Matsushima, Japan

Kawasaki University of Medical Welfare is a private university in Kurashiki, Okayama, Japan, established in 1991. Wikipedia.

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We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1–specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Eikawa S.,Okayama University of Science | Nishida M.,Okayama University of Science | Mizukami S.,Okayama University of Science | Yamazaki C.,Okayama University of Science | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Metformin, a prescribed drug for type 2 diabetes, has been reported to have anti-cancer effects; however, the underlying mechanism is poorly understood. Here we show that this mechanism may be immune-mediated. Metformin enabled normal but not T-cell-deficient SCID mice to reject solid tumors. In addition, it increased the number of CD8+ tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ. CD8+ TILs capable of producing multiple cytokines were mainly PD-1-Tim-3+, an effector memory subset responsible for tumor rejection. Combined use of metformin and cancer vaccine improved CD8+ TIL multifunctionality. The adoptive transfer of antigen-specific CD8+ T cells treated with metformin concentrations as low as 10 μM showed efficient migration into tumors while maintaining multifunctionality in a manner sensitive to the AMP-activated protein kinase (AMPK) inhibitor compound C. Therefore, a direct effect of metformin on CD8+ T cells is critical for protection against the inevitable functional exhaustion in the tumor microenvironment.

Anno T.,Tohoku University | Sakamoto N.,Tohoku University | Sakamoto N.,Kawasaki University of Medical Welfare | Sato M.,Tohoku University
Biochemical and Biophysical Research Communications | Year: 2012

The linker of nucleus and cytoskeleton (LINC) complex, including nesprin-1, has been suggested to be crucial for many biological processes. Previous studies have shown that mutations in nesprin-1 cause abnormal cellular functions and diseases, possibly because of insufficient force transmission to the nucleus through actin filaments (F-actin) bound to nesprin-1. However, little is known regarding the mechanical interaction between the nucleus and F-actin through nesprin-1. In this study, we examined nuclear deformation behavior in nesprin-1 knocked-down endothelial cells (ECs) subjected to uniaxial stretching by evaluating nuclear strain from lateral cross-sectional images. The widths of nuclei in nesprin-1 knocked-down ECs were smaller than those in wild-type cells. In addition, nuclear strain in nesprin-1 knocked-down cells, which is considered to be compressed by the actin cortical layer, increased compared with that in wild-type cells under stretching condition. These results indicate that nesprin-1 knockdown releases the nucleus from the tension of F-actin bound to the nucleus, thereby increasing allowance for deformation before stretching, and that F-actin bound to the nucleus through nesprin-1 causes sustainable force transmission to the nucleus. © 2012 Elsevier Inc.

Yuan L.,Chongqing University | Yuan L.,Tohoku University | Sakamoto N.,Kawasaki University of Medical Welfare | Song G.,Chongqing University | Sato M.,Tohoku University
Stem Cells and Development | Year: 2013

Mesenchymal stem cells (MSCs) are able to home and migrate into damaged tissues and are thus, considered an optimal therapeutic strategy for clinical use. We previously demonstrated that higher shear stress (>2 Pa) hindered human MSC (hMSC) migration, whereas lower shear stress (0.2 Pa) induced cell migration through mitogen-activated protein kinase (MAPK) pathways. Here the mechanisms underlying shear stress-induced hMSC migration have been studied further. An MSC monolayer was mechanically wounded and subsequently exposed to low-level shear stress of 0.2 Pa. Image analysis was performed to quantify cell migration speeds under both flow and static conditions. hMSCs along both upstream- and downstream edges of the wound migrated at a similar speed to cover the wounded area under static conditions, whereas shear stress induced cells along the downstream edge of the wound to migrate significantly faster than those along the upstream edge. We also found that shear stress upregulated the secretion of stromal-derived factor-1 (SDF-1), which stimulated its receptor CXCR4 expression in hMSCs until the cells covered the wounded area. A CXCR4 antagonist repressed both cell migration and activation of c-Jun N-terminal kinase (JNK) and p38 MAPK but did not affect extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. When MAPK activation in upstream- and downstream hMSCs was evaluated separately, ERK1/2 was activated earlier in downstream than in upstream cells. These results indicate that the SDF-1/CXCR4 axis mediates shear stress-induced hMSC migration through JNK and p38 MAPK pathways and that the difference in migration speeds between upstream- and downstream cells may be due to ERK1/2 activation. © Mary Ann Liebert, Inc.

Kawanishi N.,Waseda University | Mizokami T.,Waseda University | Yano H.,Kawasaki University of Medical Welfare | Suzuki K.,Waseda University
Medicine and Science in Sports and Exercise | Year: 2013

PURPOSE: Obesity is associated with adipose tissue inflammation, which has been attributed to changes in the number and types of leukocytes in adipose tissue. Exercise training is thought to be important for the reduction of adipose tissue inflammation, but the mechanisms by which this may occur are incompletely understood. Here, we evaluated the effect of exercise training on several inflammation-associated changes in adipose tissue, including infiltration of inflammatory macrophages and T cells. METHODS: Four-week-old male C57BL/6J mice were randomly assigned to four groups that received a normal diet (ND) plus sedentary (n = 8), an ND plus exercise training (n = 8), a high-fat diet (HFD) plus sedentary (n = 12), and an HFD plus exercise training (n = 12). Mice were fed the ND or the HFD from 4 to 20 wk of age. Mice in the exercise groups ran on a treadmill for 60 min·d, 5 d·wk over the same points. RESULTS: Mice fed the HFD had increased numbers of macrophage clusters in adipose tissue, which were reduced by exercise training. Similarly, adipose tissue from the HFD sedentary mice contained higher levels of tumor necrosis factor α mRNA and increased numbers of CD11c inflammatory macrophages and CD8 T cells than adipose tissue from the ND mice, and those were also lowered by exercise training. The mRNA levels of monocyte chemoattractant proteins 1 and 2 and macrophage inflammatory proteins 1α and 1β in adipose tissue were lower in the HFD exercise mice than those in the HFD sedentary mice. CONCLUSIONS: The results suggest that exercise training reduces adipose tissue inflammation by suppressing infiltration of inflammatory macrophages and CD8 T cells. Copyright © 2013 by the American College of Sports Medicine.

Hattori K.,Kawasaki University of Medical Welfare | Ishida D.N.,University of Hawaii at Manoa
Nursing and Health Sciences | Year: 2012

Most humans desire a good death, but the nursing literature on culture-specific responses to older life, especially on issues of death and dying among Japanese Americans, is still limited. The pattern of beliefs about a good death held by elderly Japanese Americans living in Hawaii was explored. A qualitative study using ethnography and in-depth interviewing was employed. Eighteen healthy and active elderly participants were interviewed, and data analyzed using ethnography to extract categories and themes, and four supplementary interviews with experts were held for triangulation of the data. Four themes emerged, however, in this paper, the predominate one, not being a burden to family, was discussed. The participants believed burdening someone in their culture has an extremely negative implication. Sufficient preparation for older life and death, family support, friends support, and finance were their strategies to avoid being a burden. Nurses need to understand that the concept of good death is unique to every culture. Such knowledge will help them to plan and provide appropriate end-of-life care, and will reduce the risk of living wills being ignored. © 2012 Wiley Publishing Asia Pty Ltd.

Nagano T.,Kawasaki University of Medical Welfare | Tokita M.,Kyushu University
Food Hydrocolloids | Year: 2011

Heat-induced gels of 11S globulin (11S) or soybean protein isolate (SPI) were prepared using magnesium chloride (MgCl2) as a coagulant. Viscoelastic properties and microstructures of 11S and SPI gels were quantified using dynamic viscoelastic measurement (DVM) and confocal laser scanning microscopy (CLSM). The addition of sodium chloride was necessary for 11S and SPI to form MgCl2-induced gels. DVM indicated that 11S formed stiffer and more solid gels than SPI under all experimental conditions. CLSM showed that the microstructures of 11S gels were coarser and more heterogeneous than SPI gels in comparable conditions. The microstructures of 11S gels were highly affected by MgCl2 concentration whereas those of SPI gels were relatively insensitive to MgCl2 concentration. The microstructures of 11S and SPI gels were analyzed by two parameters: the fractal dimension and the average density of gel networks. Compared to SPI, 11S forms MgCl2-induced gels with a lower fractal dimension and a higher density of network structures. © 2011 Elsevier Ltd.

Ishida H.,Kawasaki University of Medical Welfare | Watanabe S.,Kawasaki University of Medical Welfare
Journal of Bodywork and Movement Therapies | Year: 2013

All lateral abdominal muscles contract more strongly during maximum expiration than during the abdominal drawing-in maneuver (ADIM). However, little is known about which of the lateral abdominal muscles is activated during maximum expiration. Thus, the purpose of this study is to quantify changes in the thickness of the lateral abdominal muscles immediately after the ADIM and maximum expiration. The thickness of the transverse abdominis (TrA), internal oblique (IO), and external oblique (EO) muscles was measured by ultrasound imaging in 30 healthy men before and after the ADIM and maximum expiration. After the ADIM, there was no significant change in the thickness of the lateral abdominal muscles. After maximum expiration, the thickness of the TrA muscle significantly increased, and there was no significant change in the thickness of the IO and EO muscles. Thus, maximum expiration may be an effective method for TrA, rather than IO and EO, muscle training. © 2012 Elsevier Ltd.

Ishida H.,Kawasaki University of Medical Welfare | Watanabe S.,Kawasaki University of Medical Welfare
Journal of Back and Musculoskeletal Rehabilitation | Year: 2014

BACKGROUND: Recent studies have indicated that maximum expiration could be a useful way of performing challenging exercises that include coactivation of the deep and superficial abdominal muscles. However, little is known about the effect of maximum expiration on the activity of the abdominal muscles during lumbar stabilizing exercise. OBJECTIVES: The purpose of our study was to quantify changes in the activities of the abdominal muscles during side bridge exercise in combination with maximum expiration. DESIGN: Experimental laboratory study. METHODS: The activities of the rectus abdominis (RA), external oblique (EO), and internal oblique (IO) muscles were measured using electromyography in 12 healthy men performing 3 tasks: holding the breath after maximum expiration in the prone position, holding the breath after resting expiration during side bridge exercise, and holding the breath after maximum expiration during side bridge exercise.RESULTS: Significant increases in the activities of the abdominal muscles (RA, EO, and IO) occurred with maximum expiration when compared with resting expiration during side bridge exercise (P < 0.05). CONCLUSION: This is the first study to demonstrate the effect of maximum expiration on abdominal muscle activities during a stabilizing exercise, thus contributing to existing knowledge about therapeutic exercise for alternative core training. © 2014 IOS Press and the authors. All rights reserved.

Kakeda T.,Kawasaki University of Medical Welfare
Japan Journal of Nursing Science | Year: 2010

Aim: Sucrose-induced analgesia frequently has been investigated for pain relief during invasive procedures in neonates. This analgesic mechanism is thought to be mediated by the endogenous opioid system, taking advantage of sweet taste. However, few studies have examined the effects of sucrose-induced analgesia in adults. Therefore, this preliminary study examines the analgesic efficacy of a sucrose stimulus on experimentally induced pain in male adults. Methods: A randomized, single-masked, cross-over study was conducted to examine the analgesic effect of a sucrose stimulus in male adults. Experimental pain was induced with the cold pressor test. Prior to and during the cold pressor test, the participants held either a 24% sucrose solution or distilled water as a control in their mouth. The analgesic efficacy was evaluated by using the pain threshold, pain tolerance, Profile of Mood State, and two visual analogue scales of pain intensity and taste pleasantness. Results: The sucrose stimulus reduced the pain response of the participants. The mean threshold increased significantly when using the 24% sucrose solution, compared with distilled water. The mean tolerance also increased under the sucrose condition. In addition, the taste pleasantness score was significantly higher under the sucrose condition than with distilled water. However, neither condition showed a significant difference in the scores of the visual analogue scales for pain. Conclusions: These findings suggest that sucrose stimuli might induce the antinociceptive effects on pain in male adults. More trials are needed to further elucidate these effects before this analgesic method can be used for clinical pain in adults. © 2010 The Author. Journal compilation © 2010 Japan Academy of Nursing Science.

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