閉塞性動脈硬化症による跛行患者に対する運動療法前後での生体力学解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 鄭 雄一, 東京大学教授 牛田 多加志, 東京大学准教授 筑田 博隆, 東京大学講師 篠田 裕介, 東京大学講師 石原 聡一郎University of Tokyo(東京大学

Autonomic Nervous System Changes in Term Infants during Early Skin-to-skin Contact (SSC) : Examination of SSC Effectiveness and the Influence of Meconium-stained Amniotic Fluid

Article信州医学雑誌 67(2): 91-103(2019)journal articl

Competences in Project Management: A Case Study in Osaka Institute of Technology

This chapter briefly explains the distributed project management of four joint departments for first-grade joint project-based learning (PBL). That is, conventional studies and purpose, capital, competence and ability of four kinds of distributed project management were presented, and relations among them are shown after describing background (included prehistory of PBL in Osaka Institute of Technology (O.I.T.)). Then, consideration and analysis about communication, interaction, cooperation, merit, week-point, effect and inference were discussed. Some case studies were described about open innovation and competences in stakeholder management. They were distinctive and superior in first-grade PBL of O.I.T. Finally, some future themes were presented

Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5

Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K mvalue of 140 μm, and naringin inhibited the uptake with an IC 50value of 18 μm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC 50 value of 7.5 μm by the Ussing-type chamber method. The estimated IC 50 values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp. Copyright © 2012 John Wiley & Sons, Ltd

Validation Study of the International Association for the Study of Lung Cancer Histologic Grading System of Invasive Lung Adenocarcinoma

[Introduction] A histologic grading system for invasive lung adenocarcinoma (ADC) has been proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee in June 2020. This study evaluated the prognostic value of the IASLC histologic grading system (the IASLC system) in a large Japanese cohort. [Methods] We performed comprehensive histologic subtyping using the semiquantitative estimation of five major patterns and complex glandular patterns in patients with a completely resected lung ADC and determined the histologic grade using the IASLC system. Concordance index and receiver-operating characteristic curves were used to evaluate the clinical utility of the IASLC system for recurrence and death; the comparison was performed with the architectural-pattern system (the Arch system) and the grading system on the basis of the two most predominant patterns (the Sica’s system). [Results] Of 1002 patients with invasive ADC, 235 had recurrent disease and 166 died of lung cancer. The concordance index and area under the curve of the IASLC system were 0.777 and 0.807 for recurrence and 0.767 and 0.776 for death, respectively. These were similar to those of the Arch system (0.763 and 0.796 for recurrence, 0.743 and 0.755 for death) and the Sica’s system (0.786 and 0.814 for recurrence, 0.762 and 0.773 for death). [Conclusions] We reported that the IASLC system for invasive lung ADC has prognostic significance by evaluating a large Japanese cohort. We believe that the IASLC grading system will provide physicians with better information for postsurgery treatment

Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1, 057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC. Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as disease-free survival (DFS) and overall survival (OS). Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4–113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death. Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs

Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016

Highly pathogenic avian influenza viruses (HPAIVs) A(H5N6) were concurrently introduced into several distant regions of Japan in November 2016. These viruses were classified into the genetic clade 2.3.4.4c and were genetically closely related to H5N6 HPAIVs recently isolated in South Korea and China. In addition, these HPAIVs showed further antigenic drift

Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney

Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor(+) (p75NTR(+)) fibroblasts and homeostatic chemokine-producing fibroblasts inside TLTs, and retinoic acid-producing fibroblasts around TLTs. Deletion of CD4(+) cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly.</p

女子大生の咀嚼の実態と心身の各種因子との関係について

咀嚼を含めた食行為が女子大生の心身に与える影響を把握するため、マシュマロとチャーハンにおける咀嚼回数の測定並びに、生活習慣および心理状況調査を実施した。また、咀嚼回数の測定と併せて口腔部のサイズや容量、1口の食物投入量、咀嚼数、咀嚼スピード、スプーンの移動回数を測定し、体重や体脂肪量などの各種身体情報の調査も行った。　咀嚼の状況と身体特性との関係性を相関分析により検討したところ、相関関係は確認できなかった。咀嚼の状況と生活習慣との関連の検討において、メタボリックシンドロームに対するリスクと有意な負の相関関係が見られた項目は、スプーン移動回数、チャーハン摂取量、1分あたりの摂取量であった。　以上のように咀嚼の状況と生活習慣および心理状況調査結果との関係については、関連性が示唆される傾向が見られた