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REVIEW : Immunological Abnormalities in the Pathogenesis of Inflammatory Bowel Disease
( Tadakazu Hisamatsu ),( Yohei Mikami ),( Katsuyoshi Matsuoka ),( Takanori Kanai ),( Toshifumi Hibi ) 대한장연구학회 2012 Intestinal Research Vol.10 No.4
Crohn`s disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinfl ammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-α. In addition, the CD14+ macrophages contributed to interferon (IFN)-γ production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-γ-positive feedback loop in IBD patients. We also discuss IFN-γ and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th 17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR)γt, the master regulator of Th 17 cells, and are differentiated ‘alternative Th 1 cells.’ In addition to Th 1 cells, mucosal NK cells are also important sources of IFN-γ. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD. (Intest Res 2012;10:317-323)
( Tadakazu Hisamatsu ),( Yasuo Suzuki ),( Mariko Kobayashi ),( Takashi Hagiwara ),( Takeshi Kawaberi ),( Haruhiko Ogata ),( Toshiyuki Matsui ),( Mamoru Watanabe ),( Toshifumi Hibi ) 대한장연구학회 2021 Intestinal Research Vol.19 No.4
Background/Aims: Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods: This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remis-sion, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results: The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malig-nancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained >70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years >2 to ≤3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n=102) at baseline to 26.9 (n=84) at 4 weeks. Conclusions: Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting. (Intest Res 2021;19:408-418)
( Tadakazu Hisamatsu ),( Hyo Jong Kim ),( Satoshi Motoya ),( Yasuo Suzuki ),( Yoshifumi Ohnishi ),( Noriyuki Fujii ),( Nobuko Matsushima ),( Richuan Zheng ),( Colleen W. Marano ) 대한장연구학회 2021 Intestinal Research Vol.19 No.4
Background/Aims: We aimed to evaluate the efficacy and safety of ustekinumab (UST) in the East-Asian population with mod-erate to severely active ulcerative colitis (UC). Methods: This sub-analysis was conducted on data from East-Asian patients included in the UNIFI program (NCT02407236). UNIFI consisted of two double-blind, placebo-controlled trials: an 8-week induction study and a 44-week randomized withdrawal maintenance study. Results: Of 133 East-Asian patients (Japanese: 107, Korean: 26) who underwent randomization, 131 completed induction study and 111 entered maintenance study. In the main-tenance study, 78 patients were randomized. Patients who received UST 130 mg and UST 6 mg/kg showed numerically higher clinical remission at week 8 in the induction study (5/44 [11.4%] and 5/45 [11.1%], respectively) compared with those who re-ceived placebo (0/44, 0%). The proportion of patients achieved clinical remission at week 44 was numerically higher in the UST 90 mg q12w group (10/21, 47.6%), but similar in the UST 90 mg q8w group (5/26, 19.2%) compared to placebo (7/31, 22.6%). Serious adverse events were reported in 1 patient in UST 130 mg group, but no patient in UST 6 mg/kg group through week 8 in the induction study, and 1 patient in UST 90 mg q12w group and 5 patients in the UST 90 mg q8w group in the maintenance study. No deaths were reported in East-Asian patients throughout the study. Conclusions: UST induction and maintenance treatments were effective in East-Asian patients with moderate to severe UC; the efficacy and safety profiles were consistent with the overall population. (Intest Res 2021;19:386-397)
Treatment and outcomes: medical and surgical treatment for intestinal Behcet`s disease
( Tadakazu Hisamatsu ),( Mari Hayashida ) 대한장연구학회 2017 Intestinal Research Vol.15 No.3
Behcet`s disease (BD) is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD. (Intest Res 2017;15:318-327)