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Stem cell-based therapy for inflammatory bowel disease
Hiromichi Shimizu,Kohei Suzuki,Mamoru Watanabe,Ryuichi Okamoto 대한장연구학회 2019 Intestinal Research Vol.17 No.3
Inflammatory bowel disease (IBD) is an idiopathic, multi-etiological disease characterized by inflammation and mucosal destruction of the gastrointestinal tract. Despite the remarkable advance in immunomodulating therapies, there still remains a certain population of patients who are refractory to conventional as well as biologic therapies and fail to achieve mucosal healing. To improve the prognosis of those patients, at least 2 types of stem cells have been tested for their potential therapeutic use. Transplantation of hematopoietic stem cells or mesenchymal stem cells have been tested in several clinical studies, but their beneficial effect still remains controversial. In this review, we would like to overview the recent clinical challenges of stem cell-based therapies in IBD and also introduce our new therapeutic plan of intestinal stem cell transplantation for IBD, based on our ex vivo intestinal organoid culture technique.
Rapid prediction of 1-year efficacy of tofacitinib for treating refractory ulcerative colitis
( Hiromichi Shimizu ),( Toshimitsu Fujii ),( Shuji Hibiya ),( Maiko Motobayashi ),( Kohei Suzuki ),( Kento Takenaka ),( Eiko Saito ),( Masakazu Nagahori ),( Kazuo Ohtsuka ),( Mamoru Watanabe ) 대한장연구학회 2021 Intestinal Research Vol.19 No.1
Hiromichi Shimizu,Yuko Aonuma,Shuji Hibiya,Ami Kawamoto,Kento Takenaka,Toshimitsu Fujii,Eiko Saito,Masakazu Nagahori,Kazuo Ohtsuka,Ryuichi Okamoto 대한장연구학회 2024 Intestinal Research Vol.22 No.3
Background/Aims: The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. Methods: A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Results: Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Conclusions: Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.
Masahiko Hayashi,Toru Kaiwa,Yoshiaki Matsushima,Makoto Shimizu,Takekazu Ishida,Kazuo Satoh,Tsutomu Yotsuya,Hiromichi Ebisawa 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.54 No.1
It is shown that the spatial resolution of scanning superconducting quantum interference device (SQUID) microscope, which is considered naively to be limited by the size of the pickup coil (typically grater than of the order of ㎛), can be improved by applying a mathematical transformation to the obtained data. The resolution of the image is improved at best to the scanning step size (can be less than of the order of ㎛) even in the presense of the noise. Problems to be solved in applying the method to visualize the uxons in superconducting network structures are discussed by use of numerical simulations and of real experimental data.
Ami Kawamoto,Kento Takenaka,Shuji Hibiya,Yoshio Kitazume,Hiromichi Shimizu,Toshimitsu Fujii,Eiko Saito,Kazuo Ohtsuka,Ryuichi Okamoto 대한장연구학회 2024 Intestinal Research Vol.22 No.1
Background/Aims: Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy.Methods: One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed.Results: Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.Conclusions: The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.
Kawahara, Manabu,Wakai, Takuya,Yamanaka, Ken-Ichi,Kobayashi, Jin,Sugimura, Satoshi,Shimizu, Takashi,Matsumoto, Hiromichi,Kim, Jin-Hoi,Sasada, Hiroshi,Sato, Eimei BioScientifica 2005 Reproduction Vol.130 No.3
<P>When the nucleus in G0/G1 phase is transferred to an enucleated oocyte by nuclear transfer (NT), its nuclear envelope is broken, followed by condensation of chromosome structure by maturation promoting factor (MPF). This morphological remodeling of the transferred interphase nucleus seems to be essential for subsequent development of NT embryos. In this study, we treated porcine NT embryos with caffeine, which has been reported to increase MPF activity, to keep their MPF level high during NT. When 2.5 mM caffeine was added to the handling medium, the proportion of NT embryos showing condensed chromosome increased significantly (P < 0.05). In NT embryos treated with caffeine, the activity of p34(cdc2) kinase was significantly (P < 0.05) higher than in those without caffeine at 3 h post-injection. In addition, the rate of development to the blastocyst stage after activation was significantly (P < 0.05) higher in NT embryos treated with caffeine. These results indicate that caffeine treatment can increase not only the rate of chromosome condensation but also the developmental rate to the blastocyst stage of porcine NT embryos. This action is most likely due to the support/increase of MPF activity throughout the process of NT.</P>