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81.
82.
Masato Kiyoshi Hiroko Shibata Akira Harazono Tetsuo Torisu Takahiro Maruno Michiko Akimaru Yuuka Asano Mai Hirokawa Keisuke Ikemoto Yukari Itakura Takafumi Iwura Aya Kikitsu Takashi Kumagai Naoki Mori Hiroaki Murase Hirotaka Nishimura Atsushi Oda Taiichiro Ogawa Akiko Ishii-Watabe 《Journal of pharmaceutical sciences》2019,108(2):832-841
The evaluation of subvisible particles, including protein aggregates, in therapeutic protein products has been of great interest for both pharmaceutical manufacturers and regulatory agencies. To date, the flow imaging (FI) method has emerged as a powerful tool instead of light obscuration (LO) due to the fact that (1) protein aggregates contain highly transparent particles and thereby escape detection by LO and (2) FI provides detailed morphological characteristics of subvisible particles. However, the FI method has not yet been standardized nor listed in any compendium. In an attempt to assess the applicability of the standardization of the FI method, we conducted a collaborative study using FI and LO instruments in a Japanese biopharmaceutical consortium. Three types of subvisible particle preparations were shared across 12 laboratories and analyzed for their sizes and counts. The results were compared between the methods (FI and LO), inter-laboratories, and inter-instruments (Micro Flow Imaging and FlowCam). We clarified the marked difference between the detectability of FI and LO when counting highly transparent protein aggregates in the preparations. Although FlowCam provided a relatively higher number of particles compared with MFI, consistent results were obtained using the instrument from the same manufacturer in all 3 samples. 相似文献
83.
Shinichi Kako Yoshinobu Kanda Makoto Onizuka Nobuyuki Aotsuka Kensuke Usuki Takayoshi Tachibana Takeshi Kobayashi Jun Kato Shingo Yano Hiroaki Shimizu Katsuhiro Shono Masatsugu Tanaka Shokichi Tsukamoto Takehiko Mori Etsuko Yamazaki Yuho Najima Akira Hangaishi Takumi Hoshino Reiko Watanabe Kenji Matsumoto Shinichiro Okamoto for Kanto Study Group for Cell Therapy 《American journal of hematology》2020,95(3):251-257
The optimal pre-transplant conditioning for aplastic anemia (AA) remains unclear. We performed a prospective study on allogeneic transplantation from a related or unrelated donor for adult patients with AA. We assessed whether reduced-dose cyclophosphamide (CY) could decrease toxicity while maintaining engraftment, and low-dose thymoglobulin could safely prevent graft-vs-host disease (GVHD). The pre-transplant conditioning regimen consisted of fludarabine 120 mg/m2, CY 100 mg/kg, and thymoglobulin 2.5 mg/kg with or without 2 Gy of total body irradiation. Twenty-seven patients with a median age of 36 years were analyzed. Sixteen patients received graft from related donors. The stem cell source was bone marrow in 26 patients. All of the patients but one, who died early, achieved neutrophil engraftment at a median of 19 days. Mixed chimerism was observed in six and five patients at days 30 and 90, respectively. Only one patient experienced secondary engraftment failure with complete donor-type chimerism. None of the patients developed severe acute GVHD. The cumulative incidence of chronic GVHD was 37.7% at 1 year. The overall survival rate was 96.3% at 1 year and 3 years. A high EB virus-DNA load was detected in one patient at days 60. No one developed EBV-lymphoproliferative disorder within a year. The results suggest that the conditioning regimen in this study was safe and effective. However, relatively high incidence of chronic GVHD needs further improvement. 相似文献
84.
85.
Hiroki Ito Futoshi Sano Takehiko Ogawa Masahiro Yao 《International journal of urology》2014,21(1):108-112
We investigated the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of lower urinary tract symptoms using silodosin. In addition, the ability of the Core Lower Urinary Tract Symptom Score to detect overactive bladder in male patients with lower urinary tract symptoms was examined. The present study included 241 males with benign prostatic hyperplasia treated at 31 medical facilities between June 2009 and December 2010. All patients were given silodosin, and the effects of silodosin intake were measured using four questionnaires: the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score, Overactive Bladder Symptom Score and Quality‐of‐Life index. The efficacy of silodosin for treating lower urinary tract symptoms was validated according to the total scores of all four questionnaires weighted equally (P < 0.05). Spearman's ρ among the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score and Overactive Bladder Symptom Score showed a mild‐high correlation. However, the correlation between the baseline values of the Core Lower Urinary Tract Symptom Score and Quality‐of‐Life index was low in the groups with benign prostatic hyperplasia (ρ = 0.314) and benign prostatic hyperplasia/overactive bladder (ρ = 0.244). Our findings showed the Core Lower Urinary Tract Symptom Score, both its total score and each subscore, is able to show the efficacy of silodosin, similar to other questionnaires. The Core Lower Urinary Tract Symptom Score is also useful for identifying overactive bladder symptoms in patients with benign prostatic hyperplasia. As the Core Lower Urinary Tract Symptom Score does not correlate well with the Quality‐of‐Life index, these two questionnaires might be better used in combination to assess treatment outcomes. 相似文献
86.
Erika Ishihara Yuya Nagaoka Toshiaki Okuno Satoshi Kofuji Mari Ishigami‐Yuasa Hiroyuki Kagechika Kenya Kamimura Shuji Terai Takehiko Yokomizo Yukihiko Sugimoto Yasuyuki Fujita Akira Suzuki Hiroshi Nishina 《Genes to cells : devoted to molecular & cellular mechanisms》2020,25(3):197-214
Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition. 相似文献
87.
88.
89.
Kazuya Tamai Minoru Yamato Takehiko Yamaguchi Wataru Ohno 《Arthritis \u0026amp; Rheumatology》1994,37(8):1151-1157
Objective. To investigate whether the findings of magnetic resonance imaging (MRI) reflect rheumatoid synovitis. Methods. Dynamic imaging enhanced with gadolinium—diethylenetriamine pentaacetic acid was performed on 10 affected knees of 9 patients with rheumatoid arthritis. Changes in signal intensity were correlated with pathologic findings in synovial biopsy specimens obtained during total knee arthroplasty. Results. Enhancement was greater in regions with a higher degree of fibrin exudation, cellular infiltration, villous hypertrophy, vascular proliferation, and granulation formation. Conclusion. Dynamic MRI can be used for assessing local disease activity in rheumatoid synovium. 相似文献
90.
Kohei Yamaguchi Tomomoto Ishikawa Shimpei Mizuta Takumi Takeuchi Hidehiko Matsubayashi Shoji Kokeguchi Toshihiro Habara Kentaro Ichioka Masakazu Ohashi Sumihide Okamoto Toshihiro Kawamura Satoru Kanto Hisanori Taniguchi Fumiko Tawara Tetsuaki Hara Hatsuki Hibi Hiroshi Masuda Takehiko Matsuyama Hiroaki Yoshida 《Reproductive Medicine and Biology》2020,19(2):158-163