The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform
Rita Businaro - One of the best experts on this subject based on the ideXlab platform.
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Congenital diaphragmatic hernia after exposure to a triple retinoic acid antagonist during pregnancy.
Journal of cardiovascular medicine (Hagerstown Md.), 2017Co-Authors: Daria Cipollone, Denis A. Cozzi, Rita Businaro, Bruno MarinoAbstract:Aim To establish a mouse model for the study of congenital defects, using exposure of pregnant females to the teratogen BMS-189453, a multiple retinoic acid competitive antagonist. Aim We found not less than 60% of fetuses had transposition of the great arteries and l5% had other congenital heart defects such as double outlet right ventricle, tetralogy of Fallot, truncus and right aortic arch. Newborns exposed in utero to BMS-189453 were affected by Thymus Aplasia or hypoplasia, and severe congenital anomalies of the central nervous system due to neural tube defects. An anterior rotation of the right lung was also frequently present in our model. We also report a case of murine congenital diaphragmatic hernia associated with thymic Aplasia and transposition of the great arteries. Conclusion These findings support the hypothesis that the combination of diaphragmatic hernia and congenital heart defects may be related to an alteration of the retinoic acid signaling pathways.
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folic acid and methionine in the prevention of teratogen induced congenital defects in mice
Cardiovascular Pathology, 2009Co-Authors: Daria Cipollone, Bruno Marino, Rita Carsetti, Angela Tagliani, Maria Manuela Rosado, Paola Borgiani, Giuseppe Novelli, Giulia Damati, Lorenzo Fumagalli, Rita BusinaroAbstract:Abstract Introduction Periconceptional supplementation with multivitamins containing folic acid reduces the risk of congenital malformations. We have previously investigated the effect on the murine development of a multiple retinoic acid competitive antagonist, Bristol-Myers-Squibb 189453, showing that treated fetuses were affected with heart defects, Thymus Aplasia or hypoplasia, and severe anomalies of the central nervous system. Hereby, we analyzed the effects of nutritive therapy involving folic acid and methionine on teratogen-induced congenital defects in mice. Materials and methods A total of 132 outbred CD1 litters were studied. Pregnant mice were divided into four experimental groups, and an oral supplementation of H 2 O or folic acid, or methionine, or folic acid+methionine was administered from 0.5 days postcoitum until the end of pregnancy. At 7.5 days postcoitum, mice from all these groups were administered Bristol-Myers-Squibb 189453 to induce the teratogenic effect. At the end of pregnancy, fetuses were dissected and tissues were analyzed by histology and flow cytometric assays. Results Folic acid reduces congenital heart diseases from 81.3% to 64.8%, neural tube defects from 20.3% to 3.7%, and Thymus abnormalities from 98.4% to 27.8%, restoring a normal number of differentiated Thymus cells. Methionine is less effective in contrasting congenital heart diseases and neural tube defects, and induces Thymus cell proliferation but not differentiation. Folic acid+methionine weakly reduce congenital heart diseases and neural tube defects, but consistently reduce the incidence of fetuses affected with Thymus pathologies from 98.4% to 67.7%. Conclusions Our results suggest that folic acid and methionine periconceptional supplementations may influence the incidence of congenital defects and may probably induce negative selection of embryos presenting developmental anomalies.
Rui M M Victorino - One of the best experts on this subject based on the ideXlab platform.
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human foxn1 deficiency is associated with αβ double negative and foxp3 t cell expansions that are distinctly modulated upon thymic transplantation
PLOS ONE, 2012Co-Authors: Adriana S Albuquerque, Jose Goncalo Marques, Susana L Silva, Dario Ligeiro, Blythe H Devlin, Jacques Dutrieux, Remi Cheynier, Claudio Pignata, Rui M M VictorinoAbstract:Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and Thymus Aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of Thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.
Jacques Dutrieux - One of the best experts on this subject based on the ideXlab platform.
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human foxn1 deficiency is associated with αβ double negative and foxp3 t cell expansions that are distinctly modulated upon thymic transplantation
PLOS ONE, 2012Co-Authors: Adriana S Albuquerque, Jose Goncalo Marques, Susana L Silva, Dario Ligeiro, Blythe H Devlin, Jacques Dutrieux, Remi Cheynier, Claudio Pignata, Rui M M VictorinoAbstract:Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and Thymus Aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of Thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.
Daria Cipollone - One of the best experts on this subject based on the ideXlab platform.
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Congenital diaphragmatic hernia after exposure to a triple retinoic acid antagonist during pregnancy.
Journal of cardiovascular medicine (Hagerstown Md.), 2017Co-Authors: Daria Cipollone, Denis A. Cozzi, Rita Businaro, Bruno MarinoAbstract:Aim To establish a mouse model for the study of congenital defects, using exposure of pregnant females to the teratogen BMS-189453, a multiple retinoic acid competitive antagonist. Aim We found not less than 60% of fetuses had transposition of the great arteries and l5% had other congenital heart defects such as double outlet right ventricle, tetralogy of Fallot, truncus and right aortic arch. Newborns exposed in utero to BMS-189453 were affected by Thymus Aplasia or hypoplasia, and severe congenital anomalies of the central nervous system due to neural tube defects. An anterior rotation of the right lung was also frequently present in our model. We also report a case of murine congenital diaphragmatic hernia associated with thymic Aplasia and transposition of the great arteries. Conclusion These findings support the hypothesis that the combination of diaphragmatic hernia and congenital heart defects may be related to an alteration of the retinoic acid signaling pathways.
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folic acid and methionine in the prevention of teratogen induced congenital defects in mice
Cardiovascular Pathology, 2009Co-Authors: Daria Cipollone, Bruno Marino, Rita Carsetti, Angela Tagliani, Maria Manuela Rosado, Paola Borgiani, Giuseppe Novelli, Giulia Damati, Lorenzo Fumagalli, Rita BusinaroAbstract:Abstract Introduction Periconceptional supplementation with multivitamins containing folic acid reduces the risk of congenital malformations. We have previously investigated the effect on the murine development of a multiple retinoic acid competitive antagonist, Bristol-Myers-Squibb 189453, showing that treated fetuses were affected with heart defects, Thymus Aplasia or hypoplasia, and severe anomalies of the central nervous system. Hereby, we analyzed the effects of nutritive therapy involving folic acid and methionine on teratogen-induced congenital defects in mice. Materials and methods A total of 132 outbred CD1 litters were studied. Pregnant mice were divided into four experimental groups, and an oral supplementation of H 2 O or folic acid, or methionine, or folic acid+methionine was administered from 0.5 days postcoitum until the end of pregnancy. At 7.5 days postcoitum, mice from all these groups were administered Bristol-Myers-Squibb 189453 to induce the teratogenic effect. At the end of pregnancy, fetuses were dissected and tissues were analyzed by histology and flow cytometric assays. Results Folic acid reduces congenital heart diseases from 81.3% to 64.8%, neural tube defects from 20.3% to 3.7%, and Thymus abnormalities from 98.4% to 27.8%, restoring a normal number of differentiated Thymus cells. Methionine is less effective in contrasting congenital heart diseases and neural tube defects, and induces Thymus cell proliferation but not differentiation. Folic acid+methionine weakly reduce congenital heart diseases and neural tube defects, but consistently reduce the incidence of fetuses affected with Thymus pathologies from 98.4% to 67.7%. Conclusions Our results suggest that folic acid and methionine periconceptional supplementations may influence the incidence of congenital defects and may probably induce negative selection of embryos presenting developmental anomalies.
Adriana S Albuquerque - One of the best experts on this subject based on the ideXlab platform.
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human foxn1 deficiency is associated with αβ double negative and foxp3 t cell expansions that are distinctly modulated upon thymic transplantation
PLOS ONE, 2012Co-Authors: Adriana S Albuquerque, Jose Goncalo Marques, Susana L Silva, Dario Ligeiro, Blythe H Devlin, Jacques Dutrieux, Remi Cheynier, Claudio Pignata, Rui M M VictorinoAbstract:Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and Thymus Aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of Thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.