脱脂米糠抽出物のヒト由来食細胞に対する免疫賦活性の検討

The present report describes the effect of the three kinds of degreasing rice bran extracts (rice bran (Rb), rice bran extract E (RbE), and rice bran heat water extract (RbhS) on the immune response of human cells. Samples of Rb and RbE were processed by fermentation with Enterococcus sp. and Pichia sp. at 37°C for 3 to 5 days, subsequently, RbE samples were treated with hemicellulose enzyme. While RbhS samples were heattreated and used as the control. We studied the effect of inactive Staphylococcus aureus cells coated with the three kinds of rice bran extracts on phagocytosis and phagosome-lysosome fusion by human leukocytes in vitro. Rice bran extracts increased phagocytic activity and phagosome-lysosome fusion in neutrophils and monocytes in a doseresponse manner. The rate of phagocytosis of RbE-coated S. aureus by neutrophils was significantly higher, by approximately 3.6 times, than that of uncoated S. aureus. The rate of phagocytosis of RbE-coated S. aureus by monocytes was about 1.6 times higher than that of the control. The phagosome-lysosome fusion index (FI) for RbE-coated bacteria by neutrophils was higher, by approximately 6 times, than that of the control. The ratio of the FI to the phagocytic index (PI) in human neutrophils showed that 83% of phagocytosed cells were digested the fused phagolysosomes when the S. aureus coated with RbE at a concentration of 25 μg/ml. These results show that RbE has immune-enhancing activity. Although degreasing rice bran is traditionally discarded, if processed with Enterococcus sp., Pichia sp. and hemicellulose enzyme, it becomes consumable and can be used as a health food material to enhance immune activity in humans3種類の方法で調製した脱脂米糠抽出物について免疫賦活性(貧食活性と食胞融合性)の視点から,未利用資源としての活用可能性を検討した。　(1)ライフペップ(Rb)は乳酸菌・酵母処理(37℃ ・3～5日)。　(2)ライフペップE(RbE)は乳酸菌・酵母処理後　酵素(ヘミセルラーゼ)処理。　(3)熱水抽出物(RbhS)はオートクレープ処理。　何れの処理サンプルも,凍結乾燥後試験に供した。その結果,ヒト好中球に対する貧食活性は,3試料とも,濃度に依存して貧食作用が上昇した。RbEでは5μg/mlプラトーに達し,コントロールに比べ3.6倍(p<0.001)の活性を示した。また,単球に対する貧食活性では,RbEが1.6倍(p<0.001)活性を示した。RbEは,脱脂米糠の熱水抽出物(RbhS)とRbより高い活性を示した。　最も貧食活性の強かったRbEの食胞融合能は,コントロールに対して6倍の食胞融合性を示し,25μg/mlの濃度で貧食された菌のうち約8割が殺菌されることが確認できた。この結果,脱脂米糠を乳酸菌・酵母処理後酵素(ヘミセルラーゼ)処理すると,貧食活性を促進できることがわかり,免疫賦活作用を示す利用資源として役に立つことが明確となった

首都圏在住成人女性（20～59歳）の年齢階級および体型別栄養摂取状況と背景因子

The relationship between the situation of nutrient intake and eating habits was studied in 527 women (aged 20s to 50s; 59% married, 41% unmarried) who lived in a metropolitan area of Japan. The characteristics of the subjects were as follows: height, 158

Analysis of the Optimum Tapering Angle in Microanastomosis Using Computational Fluid Dynamics

Background: In free flap transfer, size discrepancy between the vascular pedicle and recipient vessel can create a problem for microsurgeons and sometimes induces postoperative thrombus formation. When there is a major difference between the diameters of the vascular pedicle and the recipient vessel, the larger vessel is often tapered to perform the anastomosis properly. However, the decision on the tapering angle used depends mostly on the operator’s experience. In this study, computational fluid dynamics (CFD) was used to investigate the optimum tapering angle. Methods: Using ANSYS ICEM 16.0 (ANSYS Japan, Tokyo, Japan), simulated vessels of diameters 1.5 mm and 3.0 mm were designed and then used to produce four anastomosis models with the 3.0-mm vessel tapered at angles of 15º, 30º, 60º, and 90º (no tapering). Venous perfusion with a mean value of 13.0 mL/min was simulated, and this was passed through the four anastomosis models in both the forward direction (F), from the smaller to the larger vessel, and the retrograde direction (R), from the larger to the smaller vessel. The velocity, wall shear stress (WSS), and oscillatory shear index (OSI) were measured in these eight patterns and then analyzed using OpenFOAM version 5. Results: The decrease in velocity was limiting. The WSS was greater in the R direction than the F direction at every tapering angle. The OSI also tended to be almost the same in the F direction, and lower at smaller tapering angles in the R direction. And, it was greater in the F direction than in the R direction at every tapering angle. The OSI values for 15º and 30º were almost identical in the R direction. Conclusion: The risk of thrombus formation is thought to be lower when tapering is used for anastomosis if the direction of flow is from the larger to the smaller vessel, rather than vice versa. These results also suggest that the optimum tapering angle is approximately 30º in both directions

Immune function in a patient with aspergillosis after lung transplantation: Case Report

We report a case that was successfully treated invasive pulmonary aspergillosis after living donor lobar lung transplantationand monitored patients\u27 immune function with ImmuKnow® assay. A 43-year-old woman underwent living donor lobar lungtransplantation for pulmonary alveolar proteinosis. Two healthy her relatives donated each lower lobe. Six months after transplantation,she was diagnosed as invasive pulmonary aspergillosis (IPA). During the anti-fungal treatment, one immunosuppressantwas withdrawn and the trough level of calcineurin inhibitor was reduced to the minimum. Despite of such a lowimmunosuppressive status, Immuknow® assay showed that immune function was maintained in the moderate range, whichencouraged us to keep this strategy for IPA. Immune evaluation by Immuknow® is useful method for monitoring and controllingpatients\u27 immune status especially in the infected condition, which revealed moderate immune level could be maintained withonly two immunosuppressant drugs in the patient after recovery from IPA

Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia

Simple Summary Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). Recently, TKIs were discontinued in patients with CML with deep molecular remission, and some patients have been reported to be able to maintain long-term treatment-free remission (TFR). However, there is no certainty regarding which patients can maintain TFR. We focused on immunity in the TFR phase and investigated the immunological mechanism of continuous TFR or recurrence. Our results suggest that the group that maintains the TFR is immunologically activated. In addition, regulatory T cells can be used as a biomarker. These results may have important implications for future strategies for maintaining TFR in CML treatment. Treatment-free remission (TFR) has become a therapeutic goal in chronic myeloid leukemia (CML), and approximately half of the patients with chronic phase-CML (CML-CP) with deep molecular remission (DMR) by tyrosine-kinase inhibitors (TKIs) have achieved TFR. However, the mechanism of continuous TFR is still unclear, as there are fluctuate patients who have BCR-ABL-positive leukemia cells but do not observe obvious relapse. We focused on the immune response and conducted an immune analysis using clinical samples from the imatinib discontinuation study, JALSG-STIM213. The results showed that, in the group that maintained TFR for 3 years, changes in regulatory T (Treg) cells were observed early after stopping imatinib treatment. The effector Treg (eTreg) cells increased transiently at 1 month after stopping imatinib and then returned to baseline at 3 months after stopping imatinib treatment. There was no difference in the Treg phenotype, and CD8(+) T cells in the TFR group were relatively activated. High concentrations of imatinib before stopping were negatively correlated with eTreg cells after stopping imatinib. These data suggest immunological involvement in the maintenance of the TFR, and that Treg cells after stopping imatinib might be a biomarker for TFR. Furthermore, high imatinib exposure may have a negative immunological impact on the continuous TFR

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)

Introduction: In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC. Methods and analysis: This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoint are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias. Ethics and dissemination: This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)

Introduction In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis issuspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCCremains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC.Methods and analysis This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias.Ethics and dissemination This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the correspondingauthor on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo