Biomedical subjects

Kazuya Ise

Publications and source records attributed to Kazuya Ise.

4 recordsLinked to original sources

PubMed2005

[Islet transplantation program in Japan].

In Japan, pancreas donation had been possible from cadaveric donors, either heartbeating or non-heart beating (NHB) donors. Pancreas allografts were distributed on organ allocation system of Japan Organ Transplant Network. Meanwhile, islet transplantation is categorized as tissue transplantation, and is free from legal restraints. Thus, pancreases for islet isolation should be obtained from NHB donors. Here, we report the starting program and preliminary results of islet transplantation in Japan. Selection and listing criteria for transplantation include regional priority, ABO blood type, previous islet transplant who can be insulin-independent, and a longer waiting time. Five institutes in Japan (Fukushima, Chiba, Kyoto, Kobe, and Fukuoka) are ready to start programs.

Islets of Langerhans Transplantation↗

PubMed2004

Survival of mitomycin C-treated pancreatic islet xenografts is mediated by increased expression of transforming growth factor-beta.

BACKGROUND: Mitomycin C (MMC) can trigger various intracellular signals. The authors previously showed that pretreatment of highly immunogenic crude pancreatic islets with MMC improved their survival in a rat-to-mouse transplantation model. The aim of this study was to investigate the role of transforming growth factor (TGF)-beta in mediating MMC-induced survival of islet xenografts. METHODS: : Collagenase-digested islets obtained from WS rats (RT1k) were incubated for 30 min with 10 microg/mL MMC and then transplanted into streptozotocin-induced diabetic C57BL/6 (H-2b) mice after 20 hr of culture at 37 degrees C. RESULTS: Survival of xenografts was enhanced by pretreatment of islets with MMC. MMC-treated xenografts showed a mild inflammatory cell response and significantly minimal infiltration of macrophages, CD4 T cells, and CD8 T cells compared with untreated grafts. TGF-beta mRNA was increased at 20 hr after MMC treatment, and TGF-beta protein expression was also increased compared with untreated islet xenografts. TGF-beta concentration in blebs formed around the xenografts (but not in the serum) was higher in animals that underwent transplantation with MMC-treated islets than with untreated islets. Simultaneous transplantation of MMC-treated and untreated islets separately in each kidney of recipient mice showed that protection was only found in MMC-treated islets. Treatment of islets before transplantation by neutralizing anti-TGF-beta antibody suppressed the MMC-protective effects on graft survival, whereas no such effect was noted with isotype-matched immunoglobulin. CONCLUSIONS: : The authors' results indicate that MMC treatment effectively reduces local inflammatory response and that such effects are mediated by increase of TGF-beta during the early period of islet transplantation.

Animals↗

PubMed2003

Permanent acceptance of mitomycin C-treated islet allograft.

BACKGROUND: Mitomycin C (MMC) treatment produces genotoxic stress and exerts various biologic effects on cell function. This study determines the feasibility of MMC pretreatment of islet grafts as a sole immunomodulatory regimen to protect murine crude-digested islet allografts. METHODS: Collagenase-digested BALB/c (H-2d) islets were incubated for 30 min with MMC at different doses (0, 3.2, 10, 32, and 100 microg/mL; n=20, 15, 55, 15, 15, respectively), cultured for 20 hr, and transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (B6; H-2b) mice. RESULTS: All mice that received MMC-treated islets showed restoration of normoglycemia within 5 days postgrafting, which was maintained until rejection. All untreated islets were acutely rejected with a mean survival time of 15.1+/-3.5 days. Significant prolongation of graft survival was noted in mice undergoing transplantation with islets treated with 10 microg/mL MMC compared with untreated islets (58.9+/-37.7 days, P<0.01). Notably, the grafts of 24 of 55 animals (43%) that received islets treated with 10 microg/mL MMC survived more than 100 days without any other treatment. Furthermore, antigen-specific prolongation of graft survival of secondary untreated islets was observed in mice bearing long-term functioning islet grafts. CONCLUSIONS: Our results indicate that pretreatment of islets with MMC alone protects the graft against rejection and produces long-term graft survival with normal blood glucose levels, and that pretreatment with MMC offers a new strategy for allogeneic islet transplantation.

Animals↗

PubMed2002

Surgical management for intractable cholangitis in biliary atresia.

BACKGROUND/PURPOSE: The efficacy of antireflux surgical procedures involving the Roux-en-Y jejunal limb for cholangitis was evaluated retrospectively in patients with biliary atresia (BA). METHODS: From July 1993 to December 2001, 41 patients with BA underwent hepatic portojejunostomy with Roux-en-Y reconstruction. Of these patients, 11 had intractable cholangitis that was treated by creation of a value with or without lengthening of the Roux-en-Y limb. RESULTS: Among the 11 patients, the first episode of cholangitis occurred within 6 months after portojejunostomy in 10 patients and at the age of 4 years in one patient. Cholangitis developed at various intervals from once every week to once every 2 months requiring hospitalization each time. All patients underwent valve creation at 2 months to 5 years postoperatively, whereas 2 had an additional lengthening of the limb. Cholangitis resolved completely after surgery in all cases. Two patients underwent liver transplantation, and the third patient died of an unrelated cause. The 8 survivors with native livers are doing well after 1 to 8 years of follow-up. CONCLUSION: Early surgical intervention could control intractable cholangitis in all patients, both delaying the time of liver transplantation and improving the quality of life.

Anastomosis, Roux-en-Y↗