The Experts below are selected from a list of 88467 Experts worldwide ranked by ideXlab platform
Eneida Barros Santos De Araujo - One of the best experts on this subject based on the ideXlab platform.
-
Analise radiografica e histologica da evolução de lesões periapicais em cães normais e imunossuprimidos
[s.n.], 2018Co-Authors: Eneida Barros Santos De AraujoAbstract:Orientador: Francisco Jose de Souza FilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A influência da imunossupressão no desenvolvimento de lesões periapicais é pouco conhecida. Neste estudo, os canais radiculares de cães normais e imunossuprimidos foram expostos ao meio bucal para contaminação, após pulpectomia com e sem ampliação do forame apical, para promover o desenvolvimento de lesões periapicais. Foi observado através da análise radiográfica e histológica, que o esenvolvimento de lesões periapicais não apresentou alterações entre cães normais e imunossuprimidos, havendo um aumento linear no tamanho e aumento na intensidade do processo I inflamatório, de acordo com os períodos de 30, 60 e 90 dias. A ampliação do. forame apical exerceu influência na intensidade da reação inflamatória periapical, nos diversos períodos estudadosAbstract: The influence of the immunosuppresion on the development of periapical lesions is not well elucidated. In this study, the root canais of either normal or immunosupressed dogs were exposed to the oral environment afier pulpectomy with or without enlargement of the apical foramen in order to induce the development of periapical lesions. Histologjc and radiographic analyses showed that there is no significant association between the development of the lesions and the presence or not of Immunosuppression. However. there is a linear increase in the size and intensity of the inflammatory process on the I I 30th. 60th and 90th da~s in both groups. especiall~ afier the enlargement of the apical foramenMestradoEndodontiaMestre em Clínica Odontológic
-
Analise radiografica e histologica da evolução de lesões periapicais em cães normais e imunossuprimidos
2017Co-Authors: Eneida Barros Santos De AraujoAbstract:Resumo: A influência da imunossupressão no desenvolvimento de lesões periapicais é pouco conhecida. Neste estudo, os canais radiculares de cães normais e imunossuprimidos foram expostos ao meio bucal para contaminação, após pulpectomia com e sem ampliação do forame apical, para promover o desenvolvimento de lesões periapicais. Foi observado através da análise radiográfica e histológica, que o esenvolvimento de lesões periapicais não apresentou alterações entre cães normais e imunossuprimidos, havendo um aumento linear no tamanho e aumento na intensidade do processo I inflamatório, de acordo com os períodos de 30, 60 e 90 dias. A ampliação do. forame apical exerceu influência na intensidade da reação inflamatória periapical, nos diversos períodos estudadosAbstract: The influence of the immunosuppresion on the development of periapical lesions is not well elucidated. In this study, the root canais of either normal or immunosupressed dogs were exposed to the oral environment afier pulpectomy with or without enlargement of the apical foramen in order to induce the development of periapical lesions. Histologjc and radiographic analyses showed that there is no significant association between the development of the lesions and the presence or not of Immunosuppression. However. there is a linear increase in the size and intensity of the inflammatory process on the I I30th. 60th and 90th da~s in both groups. especiall~ afier the enlargement of the apical forame
Stephan Schlickeiser - One of the best experts on this subject based on the ideXlab platform.
-
feasibility long term safety and immune monitoring of regulatory t cell therapy in living donor kidney transplant recipients
American Journal of Transplantation, 2021Co-Authors: Paul N Harden, David Game, Birgit Sawitzki, Jeroen B Van Der Net, Joanna Hester, A Bushell, Fadi Issa, Matthew O Brook, Alaa Alzhrani, Stephan SchlickeiserAbstract:Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to Immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate Immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1-10 × 106 Treg per kg at Day +5 posttransplantation in lieu of induction Immunosuppression (Treg Therapy cohort). Nineteen patients received standard Immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard Immunosuppression. Treg therapy may provide an exciting opportunity to minimize Immunosuppression therapy and improve long-term outcomes.
Benjamin T Himes - One of the best experts on this subject based on the ideXlab platform.
-
brain cancer induces systemic Immunosuppression through release of non steroid soluble mediators
Brain, 2020Co-Authors: Katayoun Ayasoufi, Christian K Pfaller, Laura Evgin, Roman H Khadka, Zachariah P Tritz, Emma N Goddery, Cori E Fain, Lila T Yokanovich, Benjamin T HimesAbstract:Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This Immunosuppression is a critical barrier to the successful development of immunotherapies for glioblastoma. We recapitulated the Immunosuppression observed in glioblastoma patients in the C57BL/6 mouse and investigated the aetiology of low CD4 T-cell counts. We determined that thymic involution was a hallmark feature of Immunosuppression in three distinct models of brain cancer, including mice harbouring GL261 glioma, B16 melanoma, and in a spontaneous model of diffuse intrinsic pontine glioma. In addition to thymic involution, we determined that tumour growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC II expression on blood leucocytes, and a modest increase in bone marrow resident CD4 T cells. Using parabiosis we report that thymic involution, declines in peripheral T-cell counts, and reduced major histocompatibility complex class II expression levels were mediated through circulating blood-derived factors. Conversely, T-cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for Immunosuppression in serum is non-steroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the Immunosuppression was not unique to cancer itself, but rather occurs in response to brain injury. Non-cancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived Immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that brain cancers cause multifaceted Immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.
-
severe and multifaceted systemic Immunosuppression caused by experimental cancers of the central nervous system requires release of non steroid soluble mediators
bioRxiv, 2020Co-Authors: Katayoun Ayasoufi, Christian K Pfaller, Laura Evgin, Roman H Khadka, Zachariah P Tritz, Emma N Goddery, Cori E Fain, Lila T Yokanovich, Benjamin T HimesAbstract:Immunosuppression of unknown etiology is a hallmark feature of glioblastoma (GBM) and is characterized by decreased CD4 T cell counts and down regulation of MHC class II expression on peripheral blood monocytes in patients. This Immunosuppression is a critical barrier to the successful development of immunotherapies for GBM. We recapitulated the Immunosuppression observed in GBM patients in the C57BL/6 mouse and investigated the etiology of low CD4 T cell counts. We determined that thymic involution was a hallmark feature of Immunosuppression in three distinct models of CNS cancer, including mice harboring GL261 glioma, B16 melanoma, and in a spontaneous model of Diffuse Intrinsic Pontine Glioma (DIPG). In addition to thymic involution, we determined that tumor growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC class II expression on hematopoietic cells, and a modest increase in bone marrow resident CD4 T cells with a naive phenotype. Using parabiosis we report that thymic involution, declines in peripheral T cell counts, and reduced MHC class II expression levels were mediated through circulating blood-derived factors. Conversely, T cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for Immunosuppression in serum is nonsteroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the aforementioned Immunosuppression was not unique to cancer itself, but rather occurs in response to CNS injury. Noncancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived Immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that CNS cancers cause multifaceted Immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity. Short SummaryCNS cancers and other brain-injuries suppress immunity through release of non-steroid soluble factors that disrupt immune homeostasis and dampen responses of the peripheral immune system. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/006825v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@171ab31org.highwire.dtl.DTLVardef@19e48c3org.highwire.dtl.DTLVardef@bb20feorg.highwire.dtl.DTLVardef@173061f_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG
Christian K Pfaller - One of the best experts on this subject based on the ideXlab platform.
-
brain cancer induces systemic Immunosuppression through release of non steroid soluble mediators
Brain, 2020Co-Authors: Katayoun Ayasoufi, Christian K Pfaller, Laura Evgin, Roman H Khadka, Zachariah P Tritz, Emma N Goddery, Cori E Fain, Lila T Yokanovich, Benjamin T HimesAbstract:Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This Immunosuppression is a critical barrier to the successful development of immunotherapies for glioblastoma. We recapitulated the Immunosuppression observed in glioblastoma patients in the C57BL/6 mouse and investigated the aetiology of low CD4 T-cell counts. We determined that thymic involution was a hallmark feature of Immunosuppression in three distinct models of brain cancer, including mice harbouring GL261 glioma, B16 melanoma, and in a spontaneous model of diffuse intrinsic pontine glioma. In addition to thymic involution, we determined that tumour growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC II expression on blood leucocytes, and a modest increase in bone marrow resident CD4 T cells. Using parabiosis we report that thymic involution, declines in peripheral T-cell counts, and reduced major histocompatibility complex class II expression levels were mediated through circulating blood-derived factors. Conversely, T-cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for Immunosuppression in serum is non-steroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the Immunosuppression was not unique to cancer itself, but rather occurs in response to brain injury. Non-cancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived Immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that brain cancers cause multifaceted Immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.
-
severe and multifaceted systemic Immunosuppression caused by experimental cancers of the central nervous system requires release of non steroid soluble mediators
bioRxiv, 2020Co-Authors: Katayoun Ayasoufi, Christian K Pfaller, Laura Evgin, Roman H Khadka, Zachariah P Tritz, Emma N Goddery, Cori E Fain, Lila T Yokanovich, Benjamin T HimesAbstract:Immunosuppression of unknown etiology is a hallmark feature of glioblastoma (GBM) and is characterized by decreased CD4 T cell counts and down regulation of MHC class II expression on peripheral blood monocytes in patients. This Immunosuppression is a critical barrier to the successful development of immunotherapies for GBM. We recapitulated the Immunosuppression observed in GBM patients in the C57BL/6 mouse and investigated the etiology of low CD4 T cell counts. We determined that thymic involution was a hallmark feature of Immunosuppression in three distinct models of CNS cancer, including mice harboring GL261 glioma, B16 melanoma, and in a spontaneous model of Diffuse Intrinsic Pontine Glioma (DIPG). In addition to thymic involution, we determined that tumor growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC class II expression on hematopoietic cells, and a modest increase in bone marrow resident CD4 T cells with a naive phenotype. Using parabiosis we report that thymic involution, declines in peripheral T cell counts, and reduced MHC class II expression levels were mediated through circulating blood-derived factors. Conversely, T cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for Immunosuppression in serum is nonsteroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the aforementioned Immunosuppression was not unique to cancer itself, but rather occurs in response to CNS injury. Noncancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived Immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that CNS cancers cause multifaceted Immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity. Short SummaryCNS cancers and other brain-injuries suppress immunity through release of non-steroid soluble factors that disrupt immune homeostasis and dampen responses of the peripheral immune system. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/006825v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@171ab31org.highwire.dtl.DTLVardef@19e48c3org.highwire.dtl.DTLVardef@bb20feorg.highwire.dtl.DTLVardef@173061f_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG
Paul N Harden - One of the best experts on this subject based on the ideXlab platform.
-
feasibility long term safety and immune monitoring of regulatory t cell therapy in living donor kidney transplant recipients
American Journal of Transplantation, 2021Co-Authors: Paul N Harden, David Game, Birgit Sawitzki, Jeroen B Van Der Net, Joanna Hester, A Bushell, Fadi Issa, Matthew O Brook, Alaa Alzhrani, Stephan SchlickeiserAbstract:Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to Immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate Immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1-10 × 106 Treg per kg at Day +5 posttransplantation in lieu of induction Immunosuppression (Treg Therapy cohort). Nineteen patients received standard Immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard Immunosuppression. Treg therapy may provide an exciting opportunity to minimize Immunosuppression therapy and improve long-term outcomes.
