足関節の視覚性運動錯覚中に活動する脳領域

Abstract. [Purpose] This study sought to localize the brain activity prompted by visual motor illusion (VMI) of the ankle movement. [Participants and Methods] We randomly applied VMI condition to the left and right lower limbs of 13 healthy subjects. The VMI condition required watching a video to induce VMI; the recording featured an ankle dorsiflexion movement on the non-measuring side in the first-person perspective. The left and right VMI conditions were measured three sets using a rest-task-rest block design using functional near-infrared spectroscopy. Oxygenated hemoglobin (oxy - Hb) during rest and task was measured under two conditions. Oxy - Hb of the two conditions were calculated average values of three sets and compared left and right VMI condition. During the VMI condition, a visual analog scale (VAS) was evaluated the degree of kinesthetic illusion. VAS of both VMI condition was compared using t test. [Results] VAS of the left VMI condition was higher when compared with the right VMI condition. In both conditions, oxy - Hb in the premotor area was significantly increased during the VMI condition. [Conclusion] VMI of the ankle movement induces increased oxy - Hb in the premotor area of healthy subjects.東京都立大学学位論文甲第1066号副論

視覚性運動錯覚が安静時脳機能結合に与える即時効果

東京都立大

Brain and muscle activation patterns during postural control affect static postural control

東京都立大学Tokyo Metropolitan University博士（理学療法学）doctoral thesi

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

Isoflavones are a class of flavonoids present in legumes and are called phytoestrogens because of their estrogen-like activity. Endogenous estrogen is well known to regulate mammary gland morphogenesis during pregnancy. Each isoflavone also has different physiological activities. However, it is difficult to investigate the direct effect of each isoflavone in mammary morphogenesis in vivo because isoflavones are metabolized into different isoflavones by enteric bacteria. In this study, investigated are the direct influences of coumestrol, daidzein, and genistein on mammary structure development and future milk production ability of mammary epithelial cells (MECs) using in vitro culture models. Mouse MECs are cultured in Matrigel with basic fibroblast growth factor and epidermal growth factor to induce ductal branching and alveolar formation, respectively. Coumestrol and genistein inhibit ductal branching and alveolar formation by affecting the proliferation and migration of MECs with the induction of apoptosis. Daidzein hardly influences mammary structure development. Furthermore, pretreatment with coumestrol adversely affects the induction of milk production ability of MECs. These results suggest that each isoflavone differentially influences mammary morphogenesis and future milk production by affecting MEC behaviors. These results also suggest that the culture models are effective to study mammary epithelial morphogenesis in vitro

Effect of Types of Disease on Change in Care Levels in Home-visit Rehabilitation Users

【目的】訪問リハビリテーション利用者の要介護度変化について，特に疾患の種類と併存疾患に着目し検討した。【方法】対象は訪問リハビリテーション利用中の66 名（78.0 ± 9.3 歳）とした。解析は要介護度軽度化および重度化有無で基本情報，併存疾患有無，各疾患種類の群間比較とロジスティック回帰分析を行った。【結果】併存疾患は要介護度変化に影響しなかった（軽度化p=0.218，重度化p=0.925）。要介護度軽度化の関連要因に運動器疾患（オッズ比（OR）=4.76，95% 信頼区間（CI）：1.05–21.50 ，p<0.05）が，阻害要因に呼吸循環器疾患以外の内部障害（OR=0.19，CI：0.05–0.83，p<0.05）が，重度化の関連要因に認知症（OR=8.82，CI：1.08–72.20，p<0.05）が抽出された。【結論】疾患により訪問リハビリテーション実施後の要介護度変化の傾向が異なることが示された。Objective: We investigated factors associated with changes in care levels of home-visit rehabilitation users and focused especially on the types of disease and the existence of comorbidity.Method: Sixty-six patients (78.0 ± 9.3 years) who used home-visit rehabilitation for longer than three months and took the renewal survey of care levels more than once were included. We compared the difference in care levels between the beginning of home-visit rehabilitation and at the time of this investigation. Furthermore, a logistic regression analysis was conducted to investigate the factors associated with changes in care levels.Result: Care levels did not significantly change at the time of investigation compared with at the start of home-visit rehabilitation (p=0.72). Factors that were associated with improvement in care levels were the presence of musculoskeletal diseases (odds ratio [OR] = 4.76, 95%confidence intervals [CI]: 1.05–21.50, p < 0.05) and, on the other hand as an inhibiting factor, the presence of internal failure, with the exception of cardiorespiratory disease (OR=0.19, CI: 0.05–0.83, p<0.05). A factor that deteriorated care levels was the presence of cognitive impairment (OR=8.82, CI: 1.08–72.20, p<0.05). Comorbidity did not affect changes in care levels.Conclusion: The influence of difference in disease types on the changes in care levels should be considered.東京都立大学学位論文甲第1252号　副論文journal articl

訪問リハビリテーション利用者の要介護度変化に対する疾患の影響

【目的】訪問リハビリテーション利用者の要介護度変化について，特に疾患の種類と併存疾患に着目し検討した。【方法】対象は訪問リハビリテーション利用中の66 名（78.0 ± 9.3 歳）とした。解析は要介護度軽度化および重度化有無で基本情報，併存疾患有無，各疾患種類の群間比較とロジスティック回帰分析を行った。【結果】併存疾患は要介護度変化に影響しなかった（軽度化p=0.218，重度化p=0.925）。要介護度軽度化の関連要因に運動器疾患（オッズ比（OR）=4.76，95% 信頼区間（CI）：1.05–21.50 ，p<0.05）が，阻害要因に呼吸循環器疾患以外の内部障害（OR=0.19，CI：0.05–0.83，p<0.05）が，重度化の関連要因に認知症（OR=8.82，CI：1.08–72.20，p<0.05）が抽出された。【結論】疾患により訪問リハビリテーション実施後の要介護度変化の傾向が異なることが示された。Objective: We investigated factors associated with changes in care levels of home-visit rehabilitation users and focused especially on the types of disease and the existence of comorbidity.Method: Sixty-six patients (78.0 ± 9.3 years) who used home-visit rehabilitation for longer than three months and took the renewal survey of care levels more than once were included. We compared the difference in care levels between the beginning of home-visit rehabilitation and at the time of this investigation. Furthermore, a logistic regression analysis was conducted to investigate the factors associated with changes in care levels.Result: Care levels did not significantly change at the time of investigation compared with at the start of home-visit rehabilitation (p=0.72). Factors that were associated with improvement in care levels were the presence of musculoskeletal diseases (odds ratio [OR] = 4.76, 95%confidence intervals [CI]: 1.05–21.50, p < 0.05) and, on the other hand as an inhibiting factor, the presence of internal failure, with the exception of cardiorespiratory disease (OR=0.19, CI: 0.05–0.83, p<0.05). A factor that deteriorated care levels was the presence of cognitive impairment (OR=8.82, CI: 1.08–72.20, p<0.05). Comorbidity did not affect changes in care levels.Conclusion: The influence of difference in disease types on the changes in care levels should be considered.東京都立大学学位論文甲第1252号　副論