The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Toshihiko Hirano - One of the best experts on this subject based on the ideXlab platform.
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comparative study of the cellular pharmacodynamics of tacrolimus in renal Transplant recipients treated with and without basiliximab
Cell Transplantation, 2012Co-Authors: Kentaro Sugiyama, Kazuya Isogai, Satoshi Horisawa, Akira Toyama, Masayuki Tasaki, Kota Takahashi, Kazuhide Saito, Yuki Nakagawa, Hiroshi Satoh, Toshihiko HiranoAbstract:: Basiliximab is a recently developed immunosuppressive agent for the prevention of acute allograft rejection in renal Transplant recipients. The combination use of basiliximab and a calcineurin inhibitor was suggested to be more effective in comparison to immunosuppressive therapy using calcineurin inhibitor without basiliximab. Cyclosporine has been generally administered with basiliximab for renal Transplant recipients. However, in cases of tacrolimus-based immunosuppressive regimen, the clinical efficacy and safety of combined use of tacrolimus and basiliximab remains to be elucidated. This study evaluated the tacrolimus pharmacological efficacy using a lymphocyte immunosuppressant sensitivity test (LIST) with MTT assay Procedures in 16 cases of renal Transplant recipients treated by tacrolimus without basiliximab and in 13 cases treated by tacrolimus in combination with basiliximab. The rate of acute rejection episodes in the recipients treated with tacrolimus plus basiliximab was 1/13 (7.7%), whereas the rate in the recipients treated with tacrolimus without basiliximab was 6/16 (37.5%). The recipients were divided into two groups according to their peripheral blood mononuclear cell (PBMC) sensitivity to tacrolimus [i.e., including a tacrolimus high sensitivity group (IC(50) 1.0 ng/ml). In the recipients treated with tacrolimus without basiliximab, the rate of acute rejection episodes in the tacrolimus high sensitivity group was 1/10 (10.0%), which was significantly lower than the rate in the low sensitivity group of 5/6 (83.3%; p = 0.008). The incidence of cytomegalovirus infection was not significantly different between the tacrolimus high and the low sensitivity groups of the recipients treated with tacrolimus with and without basiliximab. Therefore, in the case of selected tacrolimus-based immunosuppressive therapy for renal Transplant recipients, the tacrolimus pharmacological efficacy should be evaluated using LIST at a time just before the Transplant Procedure in order to accurately predict allograft rejection. The data also suggested that low tacrolimus sensitivity recipients should be treated with tacrolimus-based immunosuppressive therapy in combination with basiliximab.
Hynek Mergental - One of the best experts on this subject based on the ideXlab platform.
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Transplantation of declined liver allografts following normothermic ex situ evaluation
American Journal of Transplantation, 2016Co-Authors: Hynek Mergental, M T P R Perera, Richard W Laing, Paolo Muiesan, J Isaac, Amanda Smith, Barney Stephenson, Hentie Cilliers, Desley NeilAbstract:The demand for liver Transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five Transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The Transplant Procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their Transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT.
Kentaro Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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comparative study of the cellular pharmacodynamics of tacrolimus in renal Transplant recipients treated with and without basiliximab
Cell Transplantation, 2012Co-Authors: Kentaro Sugiyama, Kazuya Isogai, Satoshi Horisawa, Akira Toyama, Masayuki Tasaki, Kota Takahashi, Kazuhide Saito, Yuki Nakagawa, Hiroshi Satoh, Toshihiko HiranoAbstract:: Basiliximab is a recently developed immunosuppressive agent for the prevention of acute allograft rejection in renal Transplant recipients. The combination use of basiliximab and a calcineurin inhibitor was suggested to be more effective in comparison to immunosuppressive therapy using calcineurin inhibitor without basiliximab. Cyclosporine has been generally administered with basiliximab for renal Transplant recipients. However, in cases of tacrolimus-based immunosuppressive regimen, the clinical efficacy and safety of combined use of tacrolimus and basiliximab remains to be elucidated. This study evaluated the tacrolimus pharmacological efficacy using a lymphocyte immunosuppressant sensitivity test (LIST) with MTT assay Procedures in 16 cases of renal Transplant recipients treated by tacrolimus without basiliximab and in 13 cases treated by tacrolimus in combination with basiliximab. The rate of acute rejection episodes in the recipients treated with tacrolimus plus basiliximab was 1/13 (7.7%), whereas the rate in the recipients treated with tacrolimus without basiliximab was 6/16 (37.5%). The recipients were divided into two groups according to their peripheral blood mononuclear cell (PBMC) sensitivity to tacrolimus [i.e., including a tacrolimus high sensitivity group (IC(50) 1.0 ng/ml). In the recipients treated with tacrolimus without basiliximab, the rate of acute rejection episodes in the tacrolimus high sensitivity group was 1/10 (10.0%), which was significantly lower than the rate in the low sensitivity group of 5/6 (83.3%; p = 0.008). The incidence of cytomegalovirus infection was not significantly different between the tacrolimus high and the low sensitivity groups of the recipients treated with tacrolimus with and without basiliximab. Therefore, in the case of selected tacrolimus-based immunosuppressive therapy for renal Transplant recipients, the tacrolimus pharmacological efficacy should be evaluated using LIST at a time just before the Transplant Procedure in order to accurately predict allograft rejection. The data also suggested that low tacrolimus sensitivity recipients should be treated with tacrolimus-based immunosuppressive therapy in combination with basiliximab.
Marieliesse Asselinlabat - One of the best experts on this subject based on the ideXlab platform.
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generation of a functional mammary gland from a single stem cell
Nature, 2006Co-Authors: Mark Shackleton, Francois Vaillant, Kaylene J Simpson, John Stingl, Gordon K Smyth, Marieliesse AsselinlabatAbstract:The existence of mammary stem cells has been inferred from genetic analysis of human breast tissue, and from the fact that mouse mammary gland can regenerate from tissue fragments. Two groups now report the isolation of mammary stem cells from mice. Shackleton et al. use a technique based on the introduction of a marker for stem-cell function. A single cell from this population then showed its potency by regenerating an entire mammary gland in vivo. This population of cells is expanded in a pre-malignant mammary tumour model, providing support for the concept of a mammary cancer stem cell. In a paper published online, Stingl et al. report the use of a powerful limiting dilution Transplant Procedure to purify to near homogeneity a rare subset of adult mouse mammary cells that can individually regenerate an entire mammary gland within six weeks. The existence of mammary stem cells (MaSCs) has been postulated from evidence that the mammary gland can be regenerated by Transplantation of epithelial fragments in mice1,2,3. Interest in MaSCs has been further stimulated by their potential role in breast tumorigenesis4. However, the identity and purification of MaSCs has proved elusive owing to the lack of defined markers. We isolated discrete populations of mouse mammary cells on the basis of cell-surface markers and identified a subpopulation (Lin-CD29hiCD24+) that is highly enriched for MaSCs by Transplantation. Here we show that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo. The Transplanted cell contributed to both the luminal and myoepithelial lineages and generated functional lobuloalveolar units during pregnancy. The self-renewing capacity of these cells was demonstrated by serial Transplantation of clonal outgrowths. In support of a potential role for MaSCs in breast cancer, the stem-cell-enriched subpopulation was expanded in premalignant mammary tissue from MMTV-wnt-1 mice and contained a higher number of MaSCs. Our data establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs.
Goran B Klintmalm - One of the best experts on this subject based on the ideXlab platform.
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a comparison of treatment with transjugular intrahepatic portosystemic shunt or distal splenorenal shunt in the management of variceal bleeding prior to liver Transplantation
Transplantation, 1995Co-Authors: Marwan S Abouljoud, Marlon F Levy, Chet R Rees, Norman G Diamond, David C Mulligan, Robert M Goldstein, B S Husberg, Thomas A Gonwa, Goran B KlintmalmAbstract:: Recurrent variceal bleeding in liver Transplant candidates with end-stage liver disease can complicate or even prohibit a subsequent Transplant Procedure (OLT). Endoscopic sclerotherapy and medical therapy are considered as first-line management with surgical shunts reserved for refractory situations. Surgical shunts can be associated with a high mortality in this population and may complicate subsequent OLT. The transjugular intrahepatic portosystemic shunt (TIPS) has been recommended in these patients as a bridge to OLT. This is a new modality that has not been compared with previously established therapies such as the distal splenorenal shunt (DSRS). In this study we report our experience with 35 liver Transplant recipients who had a previous TIPS (18 patients) or DSRS (17 patients) for variceal bleeding. The TIPS group had a significantly larger proportion of critically ill and Child-Pugh C patients. Mean operating time was more prolonged in the DSRS group (P = 0.014) but transfusion requirements were similar. Intraoperative portal vein blood flow measurements averaged 2132 +/- 725 ml/min in the TIPS group compared with 1120 +/- 351 ml/min in the DSRS group (P < 0.001). Arterial flows were similar. Mean ICU and hospital stays were similar. There were 3 hospital mortalities in the DSRS group and none in the TIPS group (P = 0.1). We conclude that TIPS is a valuable tool in the management of recurrent variceal bleeding prior to liver Transplantation. Intraoperative hemodynamic measurements suggest a theoretical advantage with TIPS. In a group of patients with advanced liver disease we report an outcome that is similar to patients treated with DSRS prior to liver Transplantation. The role of TIPS in the treatment of nonTransplant candidates remains to be clarified.
