The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform
Kyoichi Takaori - One of the best experts on this subject based on the ideXlab platform.
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The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation.
Transplantation direct, 2020Co-Authors: Seiichiro Tada, Takero Shindo, Takayuki Anazawa, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi TakaoriAbstract:Background Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods Islets from fully Major Histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Results Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P
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the mek inhibitor trametinib suppresses Major Histocompatibility Antigen mismatched rejection following pancreatic islet transplantation
Transplantation direct, 2020Co-Authors: Seiichiro Tada, Takero Shindo, Takayuki Anazawa, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi TakaoriAbstract:Background Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods Islets from fully Major Histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Results Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P < 0.05). In addition, trametinib suppressed functional differentiation of naive CD4+ T cells in recipients. Expression of mRNA encoding inflammatory cytokines interleukin (IL)-2, tumor necrosis factor α, and interferon γ in recipients treated with trametinib was also inhibited (P < 0.001, P < 0.05, and P < 0.01, respectively). Trametinib also increased production of IL-4 and IL-10 (P < 0.05 and P = 0.20, respectively). In vitro, islets incubated with different concentrations of trametinib exhibited no harmful effects with respect to viability and function. Conclusions Trametinib delayed islet graft rejection by inhibiting functional differentiation of naive CD4+ T cells and regulating inflammatory cytokines. Trametinib might be a promising candidate for maintenance immunosuppressive therapy after allogeneic islet transplantation.
Seiichiro Tada - One of the best experts on this subject based on the ideXlab platform.
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The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation.
Transplantation direct, 2020Co-Authors: Seiichiro Tada, Takero Shindo, Takayuki Anazawa, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi TakaoriAbstract:Background Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods Islets from fully Major Histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Results Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P
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the mek inhibitor trametinib suppresses Major Histocompatibility Antigen mismatched rejection following pancreatic islet transplantation
Transplantation direct, 2020Co-Authors: Seiichiro Tada, Takero Shindo, Takayuki Anazawa, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi TakaoriAbstract:Background Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods Islets from fully Major Histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Results Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P < 0.05). In addition, trametinib suppressed functional differentiation of naive CD4+ T cells in recipients. Expression of mRNA encoding inflammatory cytokines interleukin (IL)-2, tumor necrosis factor α, and interferon γ in recipients treated with trametinib was also inhibited (P < 0.001, P < 0.05, and P < 0.01, respectively). Trametinib also increased production of IL-4 and IL-10 (P < 0.05 and P = 0.20, respectively). In vitro, islets incubated with different concentrations of trametinib exhibited no harmful effects with respect to viability and function. Conclusions Trametinib delayed islet graft rejection by inhibiting functional differentiation of naive CD4+ T cells and regulating inflammatory cytokines. Trametinib might be a promising candidate for maintenance immunosuppressive therapy after allogeneic islet transplantation.
Marti Jett - One of the best experts on this subject based on the ideXlab platform.
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SEB-induced host gene expression in peripheral blood mononuclear cells in vitro and in vivo in piglets
The FASEB Journal, 2006Co-Authors: Rasha Hammamieh, Roger Neill, Marti JettAbstract:Staphylococcal enterotoxins (SEs) constitute a family of proteins that bind to T-cell receptors and Major Histocompatibility Antigen complexes and induce massive activation of T cells in the host. ...
Yasutake Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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Major Histocompatibility Antigen-restricted cytotoxicity in inflammatory bowel disease.
Gastroenterology, 1993Co-Authors: Kazuichi Okazaki, Masanori Morita, Isao Nishimori, Shuichi Sano, Machi Toyonaga, Yoshihiko Nakazawa, Yasuro Yamamoto, Yasutake YamamotoAbstract:Abstract Background: The role of cytotoxicity mediated by peripheral blood mononuclear cells for colonic epithelial cells in inflammatory bowel disease (IBD) is still controversial. To clarify it, we studied Major Histocompatibility Antigen (MHC)-restricted T cell-mediated cytotoxicity (CTL). Methods: Cytotoxicity was measured by 51 Cr release from colonic cells after the 6-hour incubation with peripheral blood mononuclear cells in 11 IBD patients (6 with Crohn's disease and 5 with ulcerative colitis). Results: CTL activity (ET ratio=200:1 or 100:1) for autologous target cells was significantly increased (22%–40%) in 5 of 6 CD and 4 of 5 UC patients (22%–64%) compared with that for allogeneic target cells. The increase in CTL activity was mainly inhibited by anti-MHC class I and CD8 monoclonal antibodies (50 μg/mL), while it was partially inhibited by anti-MHC class II or CD 4 antibodies in some patients. Complement-mediated depletion of CD2 + cells also significantly decreased CTL activity. Conclusions: The results indicate that MHC-restricted T cell cytotoxicity may play a role in mucosal damage in some patients of IBD.
Toshihiko Masui - One of the best experts on this subject based on the ideXlab platform.
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The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation.
Transplantation direct, 2020Co-Authors: Seiichiro Tada, Takero Shindo, Takayuki Anazawa, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi TakaoriAbstract:Background Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods Islets from fully Major Histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Results Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P
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the mek inhibitor trametinib suppresses Major Histocompatibility Antigen mismatched rejection following pancreatic islet transplantation
Transplantation direct, 2020Co-Authors: Seiichiro Tada, Takero Shindo, Takayuki Anazawa, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi TakaoriAbstract:Background Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods Islets from fully Major Histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Results Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (P = 0.0007 and P = 0.005, respectively) when compared with vehicle. Histologic analyses revealed that cellular infiltration of the graft by lymphocytes was inhibited significantly on day 7 (P < 0.05). In addition, trametinib suppressed functional differentiation of naive CD4+ T cells in recipients. Expression of mRNA encoding inflammatory cytokines interleukin (IL)-2, tumor necrosis factor α, and interferon γ in recipients treated with trametinib was also inhibited (P < 0.001, P < 0.05, and P < 0.01, respectively). Trametinib also increased production of IL-4 and IL-10 (P < 0.05 and P = 0.20, respectively). In vitro, islets incubated with different concentrations of trametinib exhibited no harmful effects with respect to viability and function. Conclusions Trametinib delayed islet graft rejection by inhibiting functional differentiation of naive CD4+ T cells and regulating inflammatory cytokines. Trametinib might be a promising candidate for maintenance immunosuppressive therapy after allogeneic islet transplantation.
