東北大学 · 医学
後藤正文教授の研究室は、主に生体適合性材料や生体分子の反応機構に注目し、特に臓器移植における急性炎症反応「IBMIR(インスタント血液媒介炎症反応)」のメカニズム解明と制御に取り組んでいます。特に、豚由来膵島細胞をヒトに移植する際の免疫応答を抑制する新規薬剤(LMW-DSやコンプレスタチン)の開発が目立ち、臨床応用に向けた基盤を構築しています。また、金属ローティン酵素阻害剤の開発や金属錯体の反応機構の解明にも貢献しており、医療応用に結びつく化学的知見の提供を目的としています。
Figures are computed from collected data and may differ slightly.
A standardized technique of islet isolation is presented applying novel means to improve enzymatic digestion and to meet cGMP standards.
The xenogeneic IBMIR in this non-human primate model is characterized by an immediate binding of antibodies that triggers deleterious complement activation and a subsequent clotting reaction that leads to further complement activation. The effectiveness of LMW-DS (in vivo and in vitro) and Compstatin (in vitro) in inhibiting this IBMIR provides the basis for a protocol that can be used to abrogate the IBMIR in pig-human clinical islet transplantation.
Given that LMW-DS has been used in clinical studies without serious adverse reactions, it has potential as a drug candidate that can control the strong innate immune response induced by pig islets when transplanted through the portal vein.
Low molecular weight thiol compounds have been found to be strong inhibitors of metallo-beta-lactamase (IMP-1) produced by Serratia marcescens TN9106, which was expressed by Echerichia coli JM109 cells. Mercaptoacetic acid and 2-mercaptopropionic acid strongly and competitively inhibited IMP-1 with Ki of 0.23 and 0.19 microM, respectively. 2-Mercaptoethanol reversibly inhibited IMP-1 but did not show simple competitive inhibition.
One of the main obstacles to successful intraportal islet transplantation is the instant blood-mediated inflammatory reaction (IBMIR) elicited by the isolated islets when exposed to fresh human blood. In the present study, we investigated whether intraportal transplantation of pig islets into diabetic athymic mice could be used as a small animal model to study xenogeneic IBMIR in vivo. Adult porcine islets (APIs) or rat islets were implanted into the portal vein or under the renal subcapsular sp
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStoichiometry and kinetics of base-promoted disproportionation with concomitant ligand oxidation of tetracyano(1,2-diamine)ferrate(III)Masafumi Goto, Michihiro Takeshita, Noriyuki Kanda, Tomoya Sakai, and Virgil L. GoedkenCite this: Inorg. Chem. 1985, 24, 4, 582–587Publication Date (Print):February 1, 1985Publication History Published online1 May 2002Published inissue 1 February 1985https://pubs.acs.org/doi/10.1021/ic00198a030https://doi.org/10.1021/ic
IgG Fc- cytotoxic cells found in the synovial fluid of patients with rheumatoid arthritis have natural killer (NK)-like characteristics but can kill NK-resistant cell lines as well. The phenotype of these cells was defined by complement-mediated lysis with monoclonal antibodies. The synovial fluid killer cell activity was significantly reduced by treatment with complement and OKT11 and 4F2, but the cytotoxic T cells did not express the NK-related antigens OKM1 and Leu-7, nor the cytotoxic T lymp
Tissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the islets have been identified as the main trigger of the instant blood-mediated inflammatory reaction (IBMIR) in islet transplantation. Because the key steps that directly induce TF and MCP-1 remain to be determined, we focused on the influence of brain death (BD) on TF and MCP-1 expression in the pancreatic tissues and isolated islets using a rodent model. TF and MCP-1 mRNA levels in the pancreatic tissues were sim
The present study demonstrates that tacrolimus inhibits the revascularization of isolated pancreatic islets without affecting the characteristics of the transplanted grafts. Further refinements of this immunosuppressive regimen, especially regarding the revascularization of islet grafts, could improve the outcome of islet allotransplantation.
The role(s) of collagenase G (ColG) and collagenase H (ColH) during pancreatic islet isolation remains controversial, possibly due to the enzyme blends used in the previous studies. We herein examined the role of ColG and ColH using highly pure enzyme blends of recombinant collagenase of each subtype. Rat pancreases were digested using thermolysin, together with ColG, ColH, or ColG/ColH (n = 9, respectively). No tryptic-like activity was detected in any components of the enzyme blends. The effic
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereochemical studies of metal chelates. III. Preparation and stereochemistry of cobalt(III) complexes with C-substituted triethylenetetramines at the central ethylenediamine bridgeMasafumi Goto, Masahiko Saburi, and Sadao YoshikawaCite this: Inorg. Chem. 1969, 8, 2, 358–366Publication Date (Print):February 1, 1969Publication History Published online1 May 2002Published inissue 1 February 1969https://pubs.acs.org/doi/10.1021/ic50072a034https://doi.org/
Clostripain had a strong synergistic effect with ChNP, but not with TL. Therefore, ChNP and CP, in combination with collagenase derived from the same bacteria, may effectively increase the isolation efficiency without affecting the quality of islets.
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