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| 1 | Treating inflammatory bowel disease by adsorptive leucocytapheresis:A desire to treat without drugs显示文摘Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease(IBD),which afflicts millions of individuals throughout the world with debilitating symptoms,impairing function and quality of life.Current medications are aimed at reducing the symptoms or suppressing exacerbations.However,patients require life-long medications,and this can lead to drug dependency,loss of response together with adverse side effects.Indeed,drug side effects become additional morbidity factor in many patients on long-term medications.Nonetheless,the efficacy of anti-tumour necrosis factors(TNF)-αbiologics has validated the role of inflammatory cytokines notably TNF-αin the exacerbation of IBD.However,inflammatory cytokines are released by patients’own cellular elements including myeloid lineage leucocytes,which in patients with IBD are elevated with activation behaviour and prolonged survival.Accordingly,these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis(GMA)with an Adacolumn.Based on this background,recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries.Efficacy rates have been impressive as well as disappointing.In fact the clinical response to GMA seems to define the patients’disease course,response to medications,duration of active disease,and severity at entry.The best responders have been first episode cases(up to 100%)followed by steroid nave and patients with a short duration of active disease prior to GMA.Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA.It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD.Additionally,GMA is very much favoured by patients for its good safety profile.GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates.However,in patients with IBD,there is a scope for removing from the body the sources of proinflammatory cytokines and achieve disease remission.The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications,many patients should respond to GMA and avoid pharmacologics.This should fulfill the desire to treat without drugs. | Abbi R Saniabadi Tomotaka Tanaka Toshihide Ohmori Koji Sawada Takayuki Yamamoto Hiroyuki Hanai | 2014 | World Journal of Gastroenterology2014，20，29： | 11 |
| 2 | Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis显示文摘Ulcerative colitis (UC) and Crohn’s disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor (TNF)-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin (IL)-1β, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages (GM) are major sources. Further, in IBD, peripheral GMs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GM by receptor-mediated adsorption (GMA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid na?ve patients (the best responders), GMA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GMA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short diseaseduration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile. | Hiroyuki Hanai | 2006 | World Journal of Gastroenterology2006，12，47： | 9 |
| 3 | Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis显示文摘瞄准:调查在临床的活动索引的 ulcerative (UC )( 蔡) 和 IL-1ra, IL-10, IL-6 和 IL-18 的传播层次之间的关系。方法:IL-1ra, IL-10, IL-6 和 IL-18 的血层次与活跃 UC 在 31 个病人被测量,吝啬的蔡是 11.1,从 5-25 ;并且是的 12 个健康个人控制。病人们与 Adacolumn 被给粒细胞和单核白血球 adsorptive 词首字母的脱落(GMA ) 。忍受 FcgammaR 并且补充受体的白细胞被吸附到列 leucocytapheresis 搬运人。每个病人能在 8 wk 上收到多达 11 个 GMA 会议。结果:我们发现了在蔡和 IL-10 之间的强壮的关联(r = 0.827, P <
0.001 ) , IL-6 (r = 0.785, P <
0.001 ) 并且 IL-18 (r = 0.791, P <
0.001 ) 。IL-1ra 没与蔡一起被相关。后面的 GMA 治疗, 31 个病人中的 24 个完成了宽恕,所有 4 cytokines 的层次掉在健康控制里到层次。进一步, IL-1ra 和 IL-10 的血层次在从遵守了搬运人的白细胞建议版本的 60 min 在列流出和流入增加了。 | Hiroyuki Hanai Takayuki Iida Masami Yamada Yoshihiko Sato Ken Takeuchi Tatsuo Tanaka Kenji Kondo Masataka Kikuyama Yasuhiko Maruyama Yasushi Iwaoka Akiko Nakamura Kazuhisa Hirayama Abby R Saniabadi Fumitoshi Watanabe | 2006 | World Journal of Gastroenterology2006，12，21： | 8 |
| 4 | Decrease of reactive-oxygen-producing granulocytes and release of IL-10 into the peripheral blood following leukocytapheresis in patients with active ulcerative colitis显示文摘AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients.METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP.RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytoline IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP.CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactiveoxygen-producing neutrophils from the peripheral blood. | Hiroyuki Hanai Takayuki Iida Ken Takeuchi Fumitoshi Watanabe Yasuhiko Maruyama Masataka Kikuyama Tatsuo Tanaka Kenji Kondo Kou Tanaka Kenji Takai | 2005 | World Journal of Gastroenterology2005，11，20： | 7 |
| 5 | Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial显示文摘 | Hiroyuki Hanai Takayuki Iida Ken Takeuchi Fumitoshi Watanabe Yasuhiko Maruyama Akira Andoh Tomoyuki Tsujikawa Yosihihide Fujiyama Keiichi Mitsuyama Michio Sata Masami Yamada Yasushi Iwaoka Kazunari Kanke Hideyuki Hiraishi Kazuhisa Hirayama Hajime Arai Shi | 2006 | Clinical Gastroenterology and Hepatology2006，，12： | 2 |
| 6 | Regulation of endocytosisi of activin type II receptors by a novel PDZ protein through Ral/Ralbinding protein 1 -dependent pathway 显示文摘 | Matsuzaki T Hanai S Kishi H | 2002 | J Biol Chem2002，277，19： | 1 |
| 7 | Realtime PD identification in diagnosis of gis using symmetric and asymmetric UHF sensors显示文摘 | Toshihiro Hoshino Kenichi Nojima Masahiro Hanai | 2004 | IEEE Trans on Power Delivery2004，19，3： | 1 |
| 8 | Current topics and endoscopic characteristics for the diagnosis how to detect in early gastric or colon cancer显示文摘 | Hanai H Kaneko E | 1996 | Nippon Rin-sho1996，54，12： | 1 |
| 9 | Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels 显示文摘 | ATSUMI S HANAI T LIAO J C | 2008 | Nature2008，451，7174： | 1 |
| 10 | Targeting lactate dehydro- genase-A inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initi- ating cells显示文摘 | Xie H Hanai J Ren J G | 2014 | Cell Metabolism2014，19，5： | 1 |
| 11 | Molecular cloningand characterization of OsPSK, a gene encoding a precursor 显示文摘 | Yang H Matsubayashi Y Hanai H | 2000 | Plant Mol Bio 12000，44，63： | 1 |
| 12 | Endostatin causes G1arrest of endothelial cells through inhibition of cyclin D1 显示文摘 | Hanai J Dhanabal M Karumanchi SA | 2002 | J Biol Chem2002，277，16： | 1 |
| 13 | Systematic review on the short-termefficacy and safety of nicorandil for stable angina pectoris in comparison withthose ofβ-blockers,nitrates and calcium antagonists显示文摘 | Hanai Y Mita M Hishinuma S | 2010 | J PharmaceuticalSociety of Japan2010，130，： | 1 |
| 14 | Discrepancies in cytogenetic results between amniocytes and postnatally obtained blood :trisomy 9 mosaicism显示文摘 | Kosaki R Hanai S Kakishima H | 2006 | Congenit Anom (Kyoto)2006，46，： | 1 |
| 15 | Anterior decompression for myelopathy resulting from thoracic ossification of the posterior longitudinal ligament 显示文摘 | Hanai K Ogikubo O Miyashita T | 2002 | Spine ( Phila Pa 1976 )2002，27，10： | 1 |
| 16 | Should gastric cancer patients more than 80 years of age undergo surgery? Comparison with patients not treated surgically concerning prognosis and quality of life显示文摘 | Matsushita I Hanai H Kajimura M | 2002 | J Clin Gastroenterol2002，35，1： | 1 |
| 17 | Changing incidence of hepatocellular carcinoma in japan显示文摘 | Okuda K Fujimoto I Hanai A | 2007 | Cancer Res2007，47，： | 1 |
| 18 | Telomere length and telomerase activity in intestinal metaplasia adenoma and well-differentiated adenocarcinoma of the stomach显示文摘 | MaruyamaY Hanai H Kaneko E | 1998 | Nippon Rinsho1998，56，5： | 1 |
| 19 | Should gastric cancer patientsmore than 80 years of age undergo surgery? Comparison with patients not treated surgically concerning prognosis and quality of life显示文摘 | Matsushita I Hanai H Kajimura M | 2002 | J Clin Gastroenterol2002，35，1： | 1 |
| 20 | Relationship between fecal calprotectin,intestinal inflammation,and peripheral blood neutrophils in patients with active ulcerative colitis显示文摘 | Hanai H | | 0，，9： | 1 |
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