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(空白) (空白)
2014 年 21 巻 2 号 p.
120-123
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
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Organ Biology による基礎と臨床の融合
島津 元秀
2014 年 21 巻 2 号 p.
125-126
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
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島津 元秀
2014 年 21 巻 2 号 p.
127-133
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
In 1992, we started a program on living-donor liver transplantation(LDLT)at Keio University that aimed to apply basic research to clinical practice. Basic research focused on microcirculation, free radicals, and cytokines to elucidate the mechanism and treatment of ischemiareperfusion injury. Experimental liver transplantations were performed on pigs in preclinical trials,which showed that intraportal administration of prostaglandin E1(PGE1)mitigated ischemiareperfusion injury and helped maintain positive graft liver circulation and function. In addition,
in vivo fluorescence microscopy was used to visualize the beneficial role of PGE1 in the suppression of leukocyte adhesion to the vascular endothelium and in the improvement of microcirculation in the liver. This research was translated to the clinical practice of adult LDLT and intraportal infusion therapy for ABO-incompatible liver transplantation. The first LDLT at Keio University Hospital was performed on April 3, 1995. The patient developed jaundice after the surgery and had to be hospitalized for approximately 3 months, but was later discharged uneventfully and is now in good health. In November 1998, the first adult ABO-incompatible LDLT was performed. To prevent single organ DIC that occurs in the graft, intraportal infusion of PGE1, gabexate mesilate, and steroids was decided based on the aforementioned basic research. In my 11 years at Keio, I performed 119 LDLTs in 116 patients, achieving a 5-year survival rate of 84.3% overall, 87.2% in children, and 82.3% in adults, which were all higher than the corresponding national averages. For the 19 patients (12 adults, 7 children) in whom I performed ABO-incompatible liver transplantationLDLTs, the 5-year survival rate was 78.9%, which is not significantly different from the 83.1% for compatible cases. At Tokyo Medical University, I successfully resumed the LDLT program in 2012 with the assistance of the staff, which had been put on hold.
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半田 宏, 伊藤 拓水, 安藤 秀樹
2014 年 21 巻 2 号 p.
134-140
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Half a century ago, the sedative thalidomide caused one of the worst notorious drug disasters in history, with more than 10,000 babies born with deformities. The drug is now used in the treatment of multiple myeloma. Recently new thalidomide derivatives called immunomodulatory drugs (IMiDs) have been developed. Among them, lenalidomide and pomalidomide have excellent anti-cancer activity. However, the use of them is limited due to its potent teratogenic activity. The mechanism by which IMiDs including thalidomide induce birth defects and therapeutic effects was a long-standing question. Using an affinity beads technology we originally developed, we have identified cereblon(CRBN)as a primary target of IMiDs. CRBN forms an E3 ubiquitin ligase complex. IMiDs alter the activity and induce various biological effects such as teratogenicity, anti-cancer and immunomodulation.Understanding IMiDs and CRBN may lead to uncover new therapeutic pathways for overcoming refractory cancer diseases.
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杉本 真樹
2014 年 21 巻 2 号 p.
141-144
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Our new technology of Bio-Texture Modeling by multi-material 3D printing system enabled manufacturing patient-specific bio-elastic 3D organ models by simultaneous jetting of different types of model materials and compounding water-soluble synthetic resins. Such realistic tangible organ models can be soaked in water to look and feel closer to real organs. We evaluated its feasibility in navigation and simulation for organ transplantation biology.
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寺谷 工, 笠原 尚哉, 小林 英司
2014 年 21 巻 2 号 p.
146-149
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
The role of organ preservation solution is fundamentally important in the transplantation therapy. We have established the effectiveness of the transplantation of mesenchymal stem cell on the alleviation of graft ischemia reperfusion injury in experimental rat model. Since it is well known that organ deterioration during preservation period exacerbate ischemia reperfusion injury, fresh graft is preferably used in transplantation. Thus, we examined whether the factors secreted by mesenchymal stem cells have the potency of elongation of storage time and improvement of graft survival when added to preservation solution.
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中尾 篤典, 野田 健太郎, 川村 知裕, 小濱 圭祐, 山田 太平, 小久保 謙一, 小林 弘祐, 小谷 穣治
2014 年 21 巻 2 号 p.
150-158
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
近年,移植医療において,移植後虚血再灌流障害に対する水素含有保存液の有用性が報告されている.水素含有保存液をつくる方法として,臓器保存液に100%の水素をバブリングし,水素を保存液中に溶け込ませる方法があるが,この方法では保存容器を開放するためコンタミネーションの危険性があり,安定した水素濃度が得られにくく,さらにバブリングでの気泡による機械的な臓器損傷の可能性もある.また,高濃度の水素ガスは常に爆発の危険性を有する.これらの危険を回避するため,この研究ではMIZ 社が開発したhydrogen rich water bath を用い,そのなかで低温下で臓器を保存液ごと持続的に水素に暴露させ,その効果をラット心移植を用いて検討を行った.ドナーラットから心臓グラフトを摘出し,保存液とともにプラスチックバックに入れ,4℃のhydrogen rich water bath,もしくは恒温水槽に浸漬して保存した.保存時間は同系間移植は6 時間,異系間移植は8 時間とした.保存後のグラフトをレシピエントラットに異所性に移植し,グラフトの再拍動までの時間を計測した.また,再灌流3時間後に心移植スコア,心筋傷害マーカー(CPK,troponin Ⅰ),炎症性メディエーター(IL-6,IL-1b,TNF-a,ICAM,iNOS)の発現量にてグラフトを評価し,比較を行った.同系間,異系間移植のどちらにおいても,hydrogen rich water bath で保存した場合のほうが再灌流後から再拍動までの時間は有意に短くなり,移植後3 時間でのグラフトの心移植スコアも有意な差があった.また,hydrogen rich water bath で保存した場合のほうが再灌流後3 時間での血中のCPK とtroponin Ⅰは有意に低下し,炎症性メディエーターの発現量も有意に低下していた.これらの結果から,hydrogen rich water bath で保存することによって,保存中のグラフトに持続的に水素を付加することができることがわかった.また,グラフトをhydrogen rich water bath で保存することにより移植後虚血再灌流障害を軽減できることがわかった.心移植において,移植後虚血再灌流障害に対するhydrogen rich water bath の有用性を確認できた.hydrogen rich water bath は移植グラフトの保存に有用であると考えられる.
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重水,水素,ヘリウムの生物活性
深井 原, 嶋村 剛, 武冨 紹信
2014 年 21 巻 2 号 p.
159-165
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Donor shortage has been an unresolved problem in clinical transplantation. It is difficult to enlarge donor pool to the expanded criteria donor(ECD)by simple cold storage, due to the severe ischemia and reperfusion injury (IRI). Resuscitation of the susceptible grafts by extracorporeal perfusion has been studied, but there has been no gold standard yet. In this review, we summarized the efficacy of novel medical gases, hydrogen and helium, for the use as an antioxidant and anti-inflammatory agents. Since hydrogen gas alone could not improve ATP content, cytoskeletal integrity, homeostasis of cytosolic ions including Na
+, K
+, and Ca
2+, possiblesupplemental actions of heavy water were briefly described.
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小原 弘道, 松野 直徒, 絵野沢 伸, 平野 俊彦, 水沼 博
2014 年 21 巻 2 号 p.
166-170
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Oxygenation condition during organ preservation is one of most important consideration issues to develop a machine perfusion system for transplantation. It is necessary to investigate the suitable preservation condition for the donor grafts from donors after cardiac death(DCD). However oxygen consumption during the machine preservation has not been explained yet in detail. In this report, the oxygen consumption of the DCD liver graft were discussed during the hypothermic machine perfusion(HMP)and the newly developed rewarming machine perfusion(RMP).
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尾崎 倫孝, 芳賀 早苗, 森田 直樹, 野田 なつみ, 小澤 岳昌
2014 年 21 巻 2 号 p.
171-176
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
In order to develop an effective organ/cell preservation method and to monitor/control post-transplant graft function continuously and non-invasively, an innovative optic technology to visualize/control cell/organ function seems to be useful. Recently, we have developed molecular probes to visualize redox states and cellular stresses, pH and cellular antigens in deeper lesions of the organ, and trying to activate intracellular key molecules by optical irradiation. In the hepatic ischemia/reperfusion model of mice, we successfully imaged liver oxidative stress and apoptosis by caspase-3 activity non-invasively and chronologically in a single mouse. We also developed a unique tool for visualizing intracellular pH and succeeded in imaging dynamic changes of pH in a mouse posterior limb ischemia/reperfusion model. Furthermore, we are now developing new tools to control intracellular molecules by blue light. We used plant-derived proteins to activate Akt/PKB molecule, essential for cell survival. By irradiating blue light, Akt in hepatocytes were phosphorylated(Ser and Thr)and activated. These tools will definitely provide a new avenue toward cell/organ transplantation in the future.
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特集2”平成24年度研究奨励賞受賞記念論文”に寄せて
剣持 敬
2014 年 21 巻 2 号 p.
178
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
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貝森 淳哉, 岩井 聡美, 小林 英司, 畑中 雅喜, 津田 秀年, 小尾 義嗣, 奥見 雅由, 矢澤 浩治, 市丸 直嗣, 楽木 宏美, ...
2014 年 21 巻 2 号 p.
179-181
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
We assessed cardiac death(CD)kidney tissue by BOLD(blood oxygenation-level dependency)MRI and diffusion MRI. BOLD and diffusion MRI successfully and non-invasively imaged and quantified red cell congestion and edema in CD grafts respectively. They can predict organ damage, and therefore the outcome, of transplanted CD kidney grafts.
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脱感作療法開始時および移植直前の免疫抑制薬感受性モニタリングから
杉山 健太郎, 笹原 浩康, 磯貝 和也, 塚口 真穂登, 外山 聡, 佐藤 博, 齋藤 和英, 中川 由紀, 高橋 公太, 田中 祥子, ...
2014 年 21 巻 2 号 p.
182-186
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
ABO incompatible renal transplant recipients were administered immunosuppressive agents from one month before operation as desensitization immunosuppressive therapy. Lymphocyte-immunosuppressant sensitivity test(LIST)can predict the pharmacological efficacy for renal transplant recipients at just before transplantation. However, in case of ABO incompatible renal transplantation, the evaluation point of LIST has been unclear either at the beginning of desensitization immunosuppressive therapy or just before renal transplantation. Therefore, we evaluated pharmacological efficacies of tacrolimus(Tac), cyclosporine(CyA), and mycophenolic acid(MPA)by LIST, as well as ATP amounts in peripheral blood mononuclear cells(PBMCs)of patient origin, at both the beginning of desensitization immunosuppressive therapy and just before renal transplant operation. The study includes patients treated by Tac without basiliximab(Bax) (n=8), patients treated by Tac with Bax(n=10), and patients treated by CyA with Bax(n=11) immunosuppressive therapy. In the recipients treated by Tac without Bax, the rate of acute rejection episodes of the Tac high sensitivity group was significantly higher than that of the low Tac sensitivity group at only just before operation(p=0.022). However, the rate of cytomegarovirus (CMV)infection did not significantly correlate with Tac sensitivity. The rate of acute rejection episode or CMV infection was not significantly different between the above two patient subgroups at the beginning of desensitization immunosuppressive therapy. From these observations, we concluded that LIST should be carried out for the evaluation of Tac pharmacological efficacy at just before operation to predict occurrence of acute rejection episodes in renal transplantation.
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渡邉 龍秋, 岡田 克典, 石橋 直也, 三友 英紀, 野田 雅史, 星川 康, 近藤 丘
2014 年 21 巻 2 号 p.
187-190
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Mesenchymal stem cells(MSCs)are known to possess anti-inflammatory effect. We investigated whether intratracheal administration of MSCs ameliorate ischemia-reperfusion injury of prolonged cold ischemia in a mouse model. The mouse lungs were perfused with low-potassium dextran glucose solution and preserved at 4℃ for 18 hours prior to transplantation. Cultured MSCs isolated from healthy human were administered into the left bronchus of the lung graft. Orthotopic left lung transplantation was performed. The recipient mice were euthanatized 6 hours after transplantation. Bronchoalveolar lavage fluid(BALF)from the left lung was collected and the total protein concentration, cell counts and the concentrations of pro-inflammatory cytokines were measured. The other lung grafts were histologically examined. The results indicated that intratracheal administration of MSCs ameliorated ischemia-reperfusion injury.
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八木 洋, 北川 雄光
2014 年 21 巻 2 号 p.
192-198
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
劇症肝炎や,慢性肝炎に伴う肝硬変,肝切除後などを含むさまざまな病態が引き起こす肝不全に対して,現在唯一の根治的治療は臓器移植に頼らざるをえない現状であるが,慢性的なドナー不足によって移植医療を享受できる患者数は必要とする数の3 割にも満たないと考えられている.したがって,肝臓をいかに再生し臓器移植に代わる新たな治療法として発展させるかという肝再生医療開発へのニーズは,iPS 細胞などの幹細胞技術の発展とともに急速に高まっている.このなかで再生医療の発展に非常に重要な基盤として,近年つぎつぎと新たな技術開発がなされている組織工学的手法に大きな注目が集まっている.これまで未知の部分の多かった組織再生の理解を深めるとともに,再生細胞や組織を実際の臨床応用へ押し進めるにあたり大きな役割を担ってきた.なかでも生体内組織の微細環境を再現するためにさまざまな方法が開発されてきたが,特に筆者らは臓器を対象として近年改めて発表された脱細胞化技術を世界に先駆けて肝臓に適応し,その有用性を示した1).本手法は組織再生を理解する基盤技術として有効であるのみならず,これまでの組織工学的手法と比較し臨床応用に向けたいくつかの特徴的利点を有している.しかしながら,一方で今後解決すべきいくつかの課題も明らかにされてきている.本稿では,脱細胞化技術の持つ特徴と今後の再生医療における役割について,筆者らの研究成果を踏まえて現在の知見を述べたい.
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福嶌 五月, 宮川 繁, 川村 匡, 戸田 宏一, 澤 芳樹
2014 年 21 巻 2 号 p.
199-205
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Regeneration therapy using derivatives of induced pluripotent stem cells(iPSCs)is a promising treatment for advanced cardiac failure. We herein document our studies for allogeneic transplantation therapy using iPSCs-derived cardiac myocytes(CMs), which were prepared as a scaffold-free cell-sheet form, for treating chronic cardiac failure in a large animal model. Cardiomyogenic differentiation was induced in iPSCs of human origin in vitro, showing that more than 80% of the cells were positive for cardiac specific markers. Scaffold-free cell-sheets of the iPSC-CMs, which were prepared by thermoresponsive culture dish, were then transplanted into the cardiac surfac e of the immune-suppressed pigs which were subjected to myocardial infarction 4 weeks prior to the treatment.As a result, global and regional cardiac function was significantly improved until 8 weeks after the treatment, as assessed by echocardiography and multi-slice CT scanning, without generating arrhythmia or tumor. The transplanted cells expressing cardiacspecific contractile proteins remained in the heart for 8 weeks.In conclusion, transplantation of the iPSC-CM cell-sheets into the pig chronic myocardial infarction model was feasible, safe and effective. Although pre-clinical proof-of-concept established, this treatment needs to be developed by further basic studies to ensure safety and enhance therapeutic efficacy to launch clinical study.
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合川 公康, 宮澤 光男, 岡田 克也, 渡邉 幸博, 岡本 光順, 小山 勇
2014 年 21 巻 2 号 p.
206-211
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
肝胆膵領域の外科手術において胆道の再建が必要となる場合には,一般的に胆管―腸吻合により胆道を再建する.しかし,この再建法においては,必ず十二指腸乳頭部(ファーター乳頭部)の逆流防止機能が廃絶されることとなり,少なからず逆行性胆管炎が起こる.さらには,長期経過において狭窄やがんの発生が報告されており,この再建法は理想的とはいえない.筆者らは,これらの問題点を考慮し,可能な限りファーター乳頭部の逆流防止機能を温存する手術法を検討している.本稿においては,筆者らの検討している生体吸収性材料を用いたtissue engineering による胆道再生療法を紹介し,臨床応用への今後の展望を述べたい.
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重田 孝信, 絵野沢 伸, 金澤 寛之, 福田 晃也, 阪本 靖介, 笠原 群生
2014 年 21 巻 2 号 p.
212-214
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Hepatocyte transplantation (HCT) is a promising option for the non-invasive treatment of acute liver failure and urea cycle disorder. A problem to solve in HCT is the limited availability of cell donor. Here, we review the possibility of use of remnant liver of hyper reduced left lateral segment(HRLLS)graft from living donor liver transplantation as the cell source. Because liver transplantation for low body weight infants often needs reduction of an adult liver of which quality is assured to be compatible to transplantation. Thus, the remnant liver tissues provide the best opportunity of hepatocytes banking. In Japan, the research use of organs from brain dead donor is not allowed legally and the remnant liver of HRLLS graft of living donor is only invaluable resource. Indeed, the quality of cells isolated by ourselves showed comparable to that reported by oversea researchers. We propose that the remnant liver of HRLLS graft from living donor could be an important cell source for HCT.
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CD90high 脂肪由来間葉系幹細胞亜分画の有効性
川本 弘一, 今野雅允 , 石井秀始 , 富丸慶人 , 濱 直樹, 和田 浩志, 小林 省吾, 江口 英利, 種村 匡弘, 伊藤 壽記, 土 ...
2014 年 21 巻 2 号 p.
215-220
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Mesenchymal stem cells (MSCs), including adipose tissue-derived mesenchymal stem cells(ADSC), are multipotent and can differentiate into various cell types possessing unique immunomodulatory features. Several clinical trials have demonstrated the safety and possible efficacy of MSCs in organ transplantation. Thus, stem cell therapy is promising for tolerance induction. In this study, we assessed the reprogramming capacity of murine ADSCs and found that CD90(Thy-1), originally discovered as a thymocyte antigen, could be a useful marker for cell therapy. Murine ADSCs were isolated from B6 mice, sorted by selection of CD90Hi or CD90Lo, and then transduced with four standard factors (Oct4, Sox2, Klf4, and c-Myc). Among unsorted, CD90Hi-, and CD90Lo- murine ADSCs, reprogrammed CD90Hi ADSCs showed increased numbers of alkaline phosphatase-positive colonies compared with reprogrammed CD90Lo ADSCs. The relative reprogramming efficiencies of unsorted, CD90Hi-sorted, and CD90Lo-sorted ADSCs were 100%, 116.5%, and 74.7%, respectively. CD90Hi cells were more responsive to reprogramming. CD90Hi ADSCs had greater reprogramming capacity than CD90Lo ADSCs, suggesting that ADSCs have heterogeneous subpopulations. Thus, CD90Hi selection presents an effective strategy to isolate a highly suppressive subpopulation for stem cell-based tolerance induction therapy.
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テーラーメード免疫抑制療法確立を目指して
村上 徹, 岩藤 和広, 三木 克幸, 小川 勇一, 甲斐 耕太郎, 三宮 彰仁, 小山 一郎, 北島 久視子, 中島 一朗, 渕之上 昌平
2014 年 21 巻 2 号 p.
222-226
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Short-term outcome of renal transplantation has dramatically improved due to advance in immunosuppressive agents. However effective treatments for chronic renal graft injury have not been established, and long-term outcome remained unsatisfactory. Transplanted kidney toxicity of side-effect of calcineurin inhibitors, and antibody-mediated rejection by anti-HLA antibodies are major factors hindering the long-term graft survival. To overcome chronic renal graft injury, we currently underway to establish tailor-made immunosuppressive therapy in renal transplantation, by grouping renal transplant recipients with immunological and non-immunological risk factors. Here we report our protocol and short-term results.
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髙橋 禎暢, 武部 貴則, 谷口 英樹
2014 年 21 巻 2 号 p.
228-236
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Pancreatic islet transplantation is performed as a curative treatment of type 1 diabetes mellitus, however, this approach is significantly limited due to the critical shortage of islet source. Recently, a number of publications have developed protocols for directed β-cell differentiation of pluripotent cells such as embryonic stem(ES), or induced pluripotent stem(iPS) cells. By recapitulating the molecular developmental cues, decades of studies reported the modified protocols with improved efficiency by combining various growth factors and small molecules. In many cases, the differentiated pancreaticβ-cells have been shown to rescue experimentally induced diabetes animal models in vivo, however, the final step of directed differentiation into functional, mature pancreatic β-cells with sufficient quantities has yet to be achieved in vitro. Here, we summarize recent progress in the directed differentiation into the pancreaticβ-cells with a focus on two-dimensional (2D) and three-dimensional (3D) differentiation settings. We also discuss the limitations of current methods with the use of stem cells for diabetes therapy, and predict the future directions of pancreaticβ-cells differentiation.
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湯川 博, 馬場 嘉信
2014 年 21 巻 2 号 p.
237-240
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
In this study, we herein examined the effects of the exosomes secreted from a stable hepatocellular carcinoma (HCC) cell line (HCC-exosomes) on the lumen formation of human umbilical vein endothelial cells(HUVECs). The uptake of HCC-exosomes by HUVECs and lumen formation by the HUVECs that included the exosomes were observed. The degree of lumen formation of HUVECs was dependent on the number of the HCC-exosomes. HCC-exosomes expressed a stress-induced heat shock protein associated with angiogenesis through the vascular endothelial growth factor(VEGF)receptor. In addition, the exosomes contained several microRNAs (miRNAs)reported to exist in the serum of HCC patients. The changes in the expression levels of miRNAs associated with angiogenesis were detected in the HUVECs treated with HCC-exosomes. Moreover, the abilities of the exosomes maintained after the treatment of cryopreservation. These results suggest that the HCC-exosomes play an important role in the angiogenesis. Further studies on the function of HCC-exosomes may provide a new target for HCC treatment.
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ゲノム情報の臨床的意義
高橋 晴美, 大原 みなみ, 小野 塚秋子
2014 年 21 巻 2 号 p.
241-246
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
The clinical utility of pharmacogenetic information during warfarin induction therapy was assessed in Asians. A prospective randomized trial in Chinese patients was performed to compare responses of warfarin between genotype-guided vs. standard dosing groups. Population pharmacokinetic-pharmacodynamic(PK-PD)analyses were conducted in an attempt to predict the time-courses of the plasma S-warfarin concentration, Cp(S), the normal prothrombin concentration (NPT)as a coagulation marker and anticoagulation response(INR). We estimated the clearance of S-warfarin, CL(S), IC50 in the relationship between Cp(S)and NPT and the non-linear indexλin the relationship between NPT and INR. Population analyses accurately predicted the time-courses of Cp(S), NPT and INR. Multivariate analyses revealed that CYP2C9 *3 mutation and body surface area were covariates of CL(S), that VKORC1 and CYP4F2 polymorphisms were covariates of IC50, and that baseline NPT was a covariate of λ. To clarify PK-PD factors associated with the overanticoagulation response, obtained PK-PD parameters were compared between the patient groups with and without INRB4. CL(S)andλwere significantly lower in patients with INRB4 than in those with INR<4 (P<0.01). These results indicate that factors associated with the reduced metabolic activity of warfarin represented by CL(S), might be critical determinants of the overanticoagulation response during warfarin initiation in Asians.
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家入 一郎
2014 年 21 巻 2 号 p.
247-253
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Genetic information, which is useful for understanding and describing large interindividual differences in the pharmacokinetics and pharmacodynamics of clinically useful drugs, is continuously increasing. Genetic polymorphism in drug metabolizing enzymes and drug transporters has been focused on currently, especially for cytochrome P-450s (CYPs, such as CYP2C9, CYP2C19, and CYP2D6), and organic anion transporting polypeptides 1B1(OATP1B1)and pglycoprotein, respectively, are available in various clinical situations. Currently in Japan, pharmacogenomic(PGx)observations are incorporated into drug labels(for various types of drugs such as proton pump inhibitors(PPIs), anti-cancer drugs and NSAIDs), highly advanced medical technology(e. g., CYP2C19 genotyping for eradication of H. pylori by PPIs), and national healthcare insurance for the genotyping test(e. g., UGT1A1 genotyping in irinotecan therapy). Nevertheless, the clinical uptake of PGx knowledge has been limited. Concise and reproducible evidences, the genotyping cost, and education of PGx utility for medical staffs should be considered for the future medicine.
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小田邉 浩二, 関矢 一郎, 宗田 大
2014 年 21 巻 2 号 p.
254-259
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Cartilage tissue is characterized by its limited regenerative potential because of the poor cellularity and perfusion by blood vessels. Replenishing cellular constituents can be one of the promising strategies for regeneration of defective cartilage. Synovial mesenchymal stem cells are superior as a cell source for cartilage regeneration to those from other tissues due to its higher colony formation rate, proliferative potential with autologous serum, and in vitro/vivo chondrogenic potentials. Approximately 60% of synovial mesenchymal stem cells placed on cartilage defects attached to the defect within 10 minute, and the addition of magnesium further enhanced the ratio of attached cells and resulted in better regeneration. Based on the accumulated evidences from basic researches, we have started clinical study for cartilage defect by transplantation of synovial stem cells arthroscopically. No problematic adverse events have been confirmed so far, and both regeneration of cartilage defect and improvement of the symptom have been recognized in most patients.
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塚口 真穂登, 笹原 浩康, 杉山 健太郎, 磯貝 和也, 外山 聡, 佐藤 博, 齋藤 和英, 中川 由紀, 高橋 公太, 田中 祥子, ...
2014 年 21 巻 2 号 p.
260-264
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Lymphocyte immunosuppressant-sensitivity test (LIST) is useful to predict the pharmacological efficacy for renal transplant recipients just before transplantation. Generally, IC50 rate and bottom levels based on peripheral blood mononuclear cells(PBMCs)blastogenesis are used for evaluation of the efficacy of immunosuppressants. Kuzuya et al. reported the strong positive correlation bottom level of both cyclosporine(CyA)and tacrolimus(Tac)by flow cytometry method. In our institute, we have used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)method for LIST to date. In this study, we have evaluated the relationship between IC50 level and bottom level of CyA and Tac by MTT method in 21 healthy volunteers. All the participantsʼ CyA bottom levels were below 0%, so we thought 2-sigmoid curve pattern(blastogenesis and killing cells). On the other hands, Tac bottom levels were over 0%, so we thought 1-sigmoid curve pattern(blastogenesis). We made IC50 rate and bottom levels by least squares method. We have found statistically significant correlation between CyA-Tac bottom levels(r=0.48, p=0.027), however, there were no positive correlation were indicated in any other combinations. In order to evaluate the immuno-compromised status, in accordance with patientsʼ clinical courses, we have compared cytomegalovirus(CMV)reactivation/infection status and these pharmacological parameters. CMV reactivation/infection was diagnosed by CMV antigenemia method. However, there was neither positive correlation between IC50 levels nor bottom levels and CMV reactivation status after kidney transplantation〔CyA(CMV+: n=11, CMV−: n=2)IC50: p=0.344, CyA bottom: p=0.927, Tac (CMV+: n=9, CMV−: n=6) IC50: p=0.141 bottom: p=0.629〕. In CMV+patient, CyAʼs average trough were 144.81±60.00 ng/mL(n=11), and Tacʼs average trough were 4.58±1.16 ng/mL(n=9). In future, we would like to examine what kind of phrarmacological parameter is useful for evaluating adequate immunosuppression status after kidney transplantation.
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杉山 健太郎, 石澤 瞳, 中村 友利恵, 恩田 健二, 田中 祥子, 平野 俊彦
2014 年 21 巻 2 号 p.
265-270
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Certain kinds of antibiotics were known to have biological activities other than their original antimicrobial activity. However, precise action mechanisms of these antibiotics on immune cells of human origin have not been well-understood. In this study, we examined inhibitory effects of valinomycin, azithromycin and nigericin on the production of several cytokines from T cell mitogen-stimulated peripheral blood mononuclear cells(PBMCs)obtained from healthy subjects. Concentrations of interferonγ(IFN-γ), tumor necrosis factorα(TNF-α), interleukin(IL)-2, IL-4, IL-6, IL-10 and IL-17 in the culture supernatant of concanavalin A-stimulated PBMCs were determined with cytometric bead array procedures. Valinomycin and nigericin at 0.01-100μmol/L significantly decreased the production of these cytokines. Azithromycin also decreased the cytokine production, while its effects were weaker than that of valinomycin or nigericin. Immunosuppressive antibiotics may have benefits for prevention of acute rejection and opportunistic infection in organ transplant recipients. Thus, our present data valuate further study for the efficacies of valinomycin, azithromycin, and nigericin as immunosuppressive agents.
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肝疾患に対する新規治療法の開発
村田 聡一郎, 大河内 信弘
2014 年 21 巻 2 号 p.
271-273
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
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Marginal Donors
剣持 敬
2014 年 21 巻 2 号 p.
274-275
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
Part ⅠHistory of Marginal Donors in the World/Part ⅡManagement of Extended Criteria Donors/Part Ⅲ Heart Transplantation/Part Ⅳ Lung Transplantation/Part Ⅴ Liver Transplantation/Part Ⅵ Kidney Transplantation/Part Ⅶ Pancreas Transplantation/Part Ⅷ Islet Transplantation/Part Ⅸ Small Intestine Transplantation/Part Ⅹ ABO-Incompatible Donor
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2014 年 21 巻 2 号 p.
276
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー
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絵野沢 伸
2014 年 21 巻 2 号 p.
280
発行日: 2014/07/10
公開日: 2014/11/10
ジャーナル
フリー