Takeoka T.,Kawasaki University of Medical Welfare
Journal of Immunotherapy | Year: 2017
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.
Tabuchi A.,Kawasaki University of Medical Welfare
Neuro-Ophthalmology Japan | Year: 2017
The author was presented with The Outstanding Service in Prevention of Blindness Award at the 31st Asia-Pacific Academy of Ophthalmology annual congress, held in Taipei, Taiwan, in May 2016. The 17 award winners were recommended by their respective ophthalmological organizations. The author in this case was one of the key individuals who contributed to the establishment of the Japanese Society for Low-Vision Research and Rehabilitation in 2000 and served as its president for 10 years. He created an important role for the newly established 'Medical Fee for Low-vision Care' in 2012 during the second presidency of Hiroshi Takahashi. These achievements were among the primary reasons for the recommendation. A historical review of low-vision care initiated by ophthalmologists from the Meiji era to 2000 was presented. In addition, the status of the low-vision clinic in the university hospital and the lowvision education in the university after 2000 were discussed. Low-vision care status in other Asian countries and certain overseas collaborations with Japanese ophthalmologists were also highlighted.
Kosaka M.,Kawasaki University of Medical Welfare
Japan Journal of Logopedics and Phoniatrics | Year: 2016
This study investigated development of narrative abilities through contents and structures in telling stories. The participants were 118 typically developing children (4: 01-6: 11). Two stories and two tasks were prepared. Each child was presented with 10 pages of a wordless picture book extracted from a story entitled, "Frog, Where Are You?" (Mayer, 1969). The other was an original picture story entitled, "A little elephant goes back home with his mother." The children conducted spontaneous speech and retelling tasks. All narratives were recorded with an IC recorder and transcribed for analysis. The results showed that the stories produced by the 4-year-old group contained fewer words and poorer content compared to the over-5-year-old group in both materials and tasks. There were some individual differences in relation to story lengths within the same age group. These findings suggest that children develop contents and structures in telling stories at the same time. Narrative skills have no relation to the materials and tasks. As a group, children from 5 years old and above produce stories rich in structures and contents. The results indicated different narrative skills for each age in preschool.
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.
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.
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.