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Kobayashi, Yasuo,Koike, Satoshi,Taguchi, Hidenori,Itabashi, Hisao,Kam, Dong K.,Ha, Jong K. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.6
Although gut microbial functions have been analyzed through cultivation of isolated microbes, molecular analysis without cultivation is becoming a popular approach in recent years. Gene cloning studies have partially revealed the mechanisms involved in fiber digestion of individual microbe. The molecular approach finally made it possible to analyze full genomes of the representative rumen cellulolytic bacteria Fibrobacter and Ruminococcus. The coming database may contain useful information such as regulation of gene expression relating to fiber digestion. Meanwhile, unculturable bacteria are still poorly characterized, even though they are main constituents of gut microbial ecosystem. The molecular analysis is essential to initiating the studies on these unculturable bacteria. The studies dealing with rumen and large intestine are revealing considerable complexity of the microbial ecosystems with many undescribed bacteria. These bacteria are being highlighted as possibly functional members contributing to feed digestion. Manipulation of gut bacteria and gut ecology for improving animal production is still at challenging stage. Bacteria newly introduced in the rumen, whether they are genetically modified or not, suffer from poor survival. In one of these attempts, Butyrivibrio fibrisolvens expressing a foreign dehalogenase was successfully established in sheep rumen to prevent fluoroacetate poisoning. This expands choice of forages in tropics, since many tropic plants are known to contain the toxic fluoroacetate. This example may promise the possible application of molecular breeding of gut bacteria to the host animals with significance in their health and nutrition. When inoculation strategies for such foreign bacteria are considered, it is obvious that we should have more detailed information of the gut microbial ecology.
Abatement of Methane Production from Ruminants: Trends in the Manipulation of Rumen Fermentation
Kobayashi, Yasuo Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.3
Methane emitted from ruminant livestock is regarded as a loss of feed energy and also a contributor to global warming. Methane is synthesized in the rumen as one of the hydrogen sink products that are unavoidable for efficient succession of anaerobic microbial fermentation. Various attempts have been made to reduce methane emission, mainly through rumen microbial manipulation, by the use of agents including chemicals, antibiotics and natural products such as oils, fatty acids and plant extracts. A newer approach is the development of vaccines against methanogenic bacteria. While ionophore antibiotics have been widely used due to their efficacy and affordable prices, the use of alternative natural materials is becoming more attractive due to health concerns regarding antibiotics. An important feature of a natural material that constitutes a possible alternative methane inhibitor is that the material does not reduce feed intake or digestibility but does enhance propionate that is the major hydrogen sink alternative to methane. Some implications of these approaches, as well as an introduction to antibiotic-alternative natural materials and novel approaches, are provided.
( Yasuo Suzuki ),( Takashi Hagiwara ),( Mariko Kobayashi ),( Kazuo Morita ),( Tomoyo Shimamoto ),( Toshifumi Hibi ) 대한장연구학회 2021 Intestinal Research Vol.19 No.3
Background/Aims: The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease. Methods: This prospective, all-case, post-marketing study was conducted at 254 centers in Japanese patients with intestinal Behçet’s disease receiving adalimumab. The primary endpoint was incidence of adverse drug reactions. Effectiveness endpoints included global improvement rating and change in C-reactive protein levels. Results: Of the 473 registered patients, 462 and 383 included in the safety and effectiveness populations were administered adalimumab for a mean of 515.3 and 579.5 days, respectively. Overall, 395 patients (85.5%) received adalimumab at the recommended dose. Adverse drug reactions and serious adverse drug reactions were reported in 120 (25.97%) and 51 (11.04%) patients, respectively. The incidence of adverse drug reactions was significantly higher in patients with comorbidities (P<0.0001), patients taking concomitant oral corticosteroids (P<0.0001), and those not self-administering adalimumab (P=0.0257). At study end, global improvement rating was “effective” (n=156, 40.7%) or “markedly effective” (n=168, 43.9%) in 324 patients (overall effective, 84.6%). Mean C-reactive protein levels (mg/dL) decreased from 1.96 at baseline (n=324) to 0.58 at week 24 (n=208) and 0.25 at week 156 (n=37). Conclusions: This large real-world study confirmed the long-term safety and effectiveness of adalimumab in patients with intestinal Behçet’s disease. No new safety concerns were identified. (Clinical trial registration number: NCT01960790) (Intest Res 2021;19:301-312)
Characteristics of second harmonic ECCD on CHS
yasuo Yoshimura,H. Matsushita,H. Igami,K. Nagasaki,K. Matsuoka,K. Ohkubo,K. Nagaoka,M. Isobe,S. Kobayashi,S. Okamura,S. Kubo,S. Nishimura,T. Minami,T. Akiyama,T. Notake,T. Shimozuma,A. Shimizu,C. Suzu 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.49 No.III
Second harmonic electron cyclotron current drive (ECCD) has been investigated on CHS (Compact Helical System) by using a 2-D steerable EC-beam injection system. The direction of the plasma current, which is the sum of bootstrap current and EC-driven current, is clearly reversed by a reversal of the EC-beam injection direction. The direction of driven current is consistent with expectation in the case of low-field side injection of EC wave. So far, a driven current up to 6 kA has been obtained when bootstrap current is less than 2 kA. It is confirmed that right-hand polarization and low density are effective for ECCD.
( Taku Kobayashi ),( Tadakazu Hisamatsu ),( Yasuo Suzuki ),( Haruhiko Ogata ),( Akira Andoh ),( Toshimitsu Araki ),( Ryota Hokari ),( Hideki Iijima ),( Hiroki Ikeuchi ),( Yoh Ishiguro ),( Shingo Kato 대한장연구학회 2018 Intestinal Research Vol.16 No.2
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients. (Intest Res 2018;16:168-177)
Fibrolytic Rumen Bacteria: Their Ecology and Functions
Koike, Satoshi,Kobayashi, Yasuo Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.1
Among rumen microbes, bacteria play important roles in the biological degradation of plant fiber due to their large biomass and high activity. To maximize the utilization of fiber components such as cellulose and hemicellulose by ruminant animals, the ecology and functions of rumen bacteria should be understood in detail. Recent genome sequencing analyses of representative fibrolytic bacterial species revealed that the number and variety of enzymes for plant fiber digestion clearly differ between Fibrobacter succinogenes and Ruminococcus flavefaciens. Therefore, the mechanism of plant fiber digestion is also thought to differ between these two species. Ecology of individual fibrolytic bacterial species has been investigated using pure cultures and electron microscopy. Recent advances in molecular biology techniques complement the disadvantages of conventional techniques and allow accurate evaluation of the ecology of specific bacteria in mixed culture, even in situ and in vivo. Molecular monitoring of fibrolytic bacterial species in the rumen indicated the predominance of F. succinogenes. Nutritive interactions between fibrolytic and non-fibrolytic bacteria are important in maintaining and promoting fibrolytic activity, mainly in terms of crossfeeding of metabolites. Recent 16S rDNA-based analyses suggest that presently recognized fibrolytic species such as F. succinogenes and two Ruminococcus species with fibrolytic activity may represent only a small proportion of the total fibrolytic population and that uncultured bacteria may be responsible for fiber digestion in the rumen. Therefore, characterization of these unidentified bacteria is important to fully understand the physiology and ecology of fiber digestion. To achieve this, a combination of conventional and modern techniques could be useful.
( 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)
Tomoo Nakagawa,Taku Kobayashi,Kiyohiro Nishikawa,Fumika Yamada,Satoshi Asai,Yukinori Sameshima,Yasuo Suzuki,Mamoru Watanabe,Toshifumi Hibi 대한장연구학회 2019 Intestinal Research Vol.17 No.4
Background/Aims: An interim analysis of post-marketing surveillance of CT-P13, an infliximab biosimilar, was performed to evaluate its safety and efficacy in Japanese patients with inflammatory bowel disease. Methods: Patients were prospectively enrolled between November 2014 and March 2017, after the launch of CT-P13 in Japan, and case report forms of patients followed for at least 4 months were analyzed as of July 2018. Results: Of 523 patients in the analysis set, 372 remained on CT-P13 therapy, while 54 (20.2%) of 267 patients with Crohn’s disease, and 97 (37.9%) of 256 patients with ulcerative colitis were withdrawn during follow-up. A total of 144 adverse drug reactions (ADRs) were reported in 106 patients (20.3%). Infusion reaction was the most frequent ADR observed in 49 patients (9.4%). Efficacy parameters decreased immediately after the start of treatment in naïve patients to anti-tumor necrosis factor-α antibody. In the patients switched from originator infliximab for nonmedical reasons, the decreased parameters due to proceeded treatment with the originator were maintained in low ranges, and the treatment continuation rate was high with low ADR incidence. In contrast, in patients switched for medical reasons such as adverse event or loss of response, the incidence of ADRs was high. However, the efficacy parameters were improved, and the treatment continuation rate was not significantly different from that of the naïve patient group. Conclusions: In this interim analysis, CT-P13 was comparable to the originator infliximab with respect to ADRs and efficacy, and is therefore considered to be a cost-efficient interchangeable biosimilar for Japanese patients with inflammatory bowel disease.