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Paul P. Van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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Cells from Fetuses with a Neural Tube Defect Do Not Deposit Collagen Type I Protein After TGF-b1 Stimulation In Vitro
2016Co-Authors: Human Amniotic, Fluid-derived Mesenchymal, Nynke A. Hosper, Ruud A. Bank, Paul P. Van Den BergAbstract:In spina bifida, the Neural Tube fails to close during the embryonic period. Exposure of the Neural Tube to the amniotic fluid during pregnancy causes additional Neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the Defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a Neural Tube Defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibro-blasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLCE), PCOLCE2, ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2), ADAMTS14]. This indicates that NTD-AFMCs have different characteristics compared with healthy AFMCs and might not be suitable for fetal therapy to close the Defect in spina bifida patients
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human amniotic fluid derived mesenchymal cells from fetuses with a Neural Tube Defect do not deposit collagen type i protein after tgf β1 stimulation in vitro
Stem Cells and Development, 2014Co-Authors: Nynke A. Hosper, Ruud A. Bank, Paul P. Van Den BergAbstract:In spina bifida, the Neural Tube fails to close during the embryonic period. Exposure of the Neural Tube to the amniotic fluid during pregnancy causes additional Neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the Defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a Neural Tube Defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibroblasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLC...
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human amniotic fluid derived mesenchymal cells from fetuses with a Neural Tube Defect do not deposit collagen type i protein after tgf β1 stimulation in vitro
Stem Cells and Development, 2014Co-Authors: Nynke A. Hosper, Ruud A. Bank, Paul P. Van Den BergAbstract:In spina bifida, the Neural Tube fails to close during the embryonic period. Exposure of the Neural Tube to the amniotic fluid during pregnancy causes additional Neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the Defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a Neural Tube Defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibroblasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLCE), PCOLCE2, ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2), ADAMTS14]. This indicates that NTD-AFMCs have different characteristics compared with healthy AFMCs and might not be suitable for fetal therapy to close the Defect in spina bifida patients.
Roger E Stevenson - One of the best experts on this subject based on the ideXlab platform.
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mutations in the planar cell polarity genes celsr1 and scrib are associated with the severe Neural Tube Defect craniorachischisis
Human Mutation, 2012Co-Authors: Alexis A Robinson, Roger E Stevenson, Sarah Escuin, K Doudney, Michel Vekemans, Nicholas D E Greene, Andrew J Copp, Philip StanierAbstract:Craniorachischisis (CRN) is a severe Neural Tube Defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal Neural Tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbor mutations in core members of the planar cell polarity (PCP) signaling pathway. Previous studies of humans with CRN failed to identify mutations in the core PCP genes, VANGL1 and VANGL2. Here, we analyzed other key PCP genes: CELSR1, PRICKLE1, PTK7, and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein-protein interactions as well as subcellular protein localization. While protein interactions were not affected, variants from five of the 36 patients exhibited a profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with Defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
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mutations in the planar cell polarity genes celsr1 and scrib are associated with the severe Neural Tube Defect craniorachischisis
Human Mutation, 2012Co-Authors: Alexis A Robinson, Roger E Stevenson, Sarah Escuin, K Doudney, Michel Vekemans, Nicholas D E Greene, Andrew J Copp, Philip StanierAbstract:Craniorachischisis (CRN) is a severe Neural Tube Defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal Neural Tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbor mutations in core members of the planar cell polarity (PCP) signaling pathway. Previous studies of humans with CRN failed to identify mutations in the core PCP genes, VANGL1 and VANGL2. Here, we analyzed other key PCP genes: CELSR1, PRICKLE1, PTK7, and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein–protein interactions as well as subcellular protein localization. While protein interactions were not affected, variants from five of the 36 patients exhibited a profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with Defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism. Hum Mutat 33:440–447, 2012. © 2011 Wiley Periodicals, Inc.
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economic evaluation of a Neural Tube Defect recurrence prevention program
American Journal of Preventive Medicine, 2008Co-Authors: Scott D Grosse, Julianne S Collins, Lijing Ouyang, Denise Green, Jane H Dean, Roger E StevensonAbstract:BACKGROUND: Women with a pregnancy affected by a Neural Tube Defect (NTD) are encouraged to take folic acid prior to a subsequent pregnancy, but it is unknown whether organized attempts to identify and counsel such women to prevent recurrent NTDs are cost effective. METHODS: Data from the South Carolina recurrence-prevention program for October 2001-September 2002 were analyzed between October 2002 and December 2003 to calculate costs. Cost-effectiveness modeling of the program during 1992-2006 was conducted during 2007. Results were calculated for three scenarios based on recurrence risk, supplement use, and the effectiveness of folic acid in preventing recurrences. For each scenario, quality-adjusted life years (QALYs) were calculated separately using prevented NTD-affected live births; prevented NTD-affected births (including fetal deaths); and all prevented NTD-affected pregnancies. RESULTS: The prevention program cost approximately $155,000 per year in 2003 dollars to protect 35 pregnancies and prevent approximately one NTD. The direct costs associated with an NTD depend on type and outcome, but are approximately $560,000 in 2003 dollars for a live birth with spina bifida. The base-case cost-effectiveness ratio was $39,600 per QALY gained from avoided NTD-affected live births and stillbirths, and $14,700 per QALY gained from the avoidance of all NTD-affected pregnancies. The baseline NTD recurrence risk and the use of folic acid supplements by women who are at high risk for an NTD-affected pregnancy were influential parameters. CONCLUSIONS: The South Carolina NTD recurrence-prevention program appears comparable in cost effectiveness to other preventive services. Other states might consider including NTD recurrence prevention in birth Defect-prevention programs.
Philip Stanier - One of the best experts on this subject based on the ideXlab platform.
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mutations in the planar cell polarity genes celsr1 and scrib are associated with the severe Neural Tube Defect craniorachischisis
Human Mutation, 2012Co-Authors: Alexis A Robinson, Roger E Stevenson, Sarah Escuin, K Doudney, Michel Vekemans, Nicholas D E Greene, Andrew J Copp, Philip StanierAbstract:Craniorachischisis (CRN) is a severe Neural Tube Defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal Neural Tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbor mutations in core members of the planar cell polarity (PCP) signaling pathway. Previous studies of humans with CRN failed to identify mutations in the core PCP genes, VANGL1 and VANGL2. Here, we analyzed other key PCP genes: CELSR1, PRICKLE1, PTK7, and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein–protein interactions as well as subcellular protein localization. While protein interactions were not affected, variants from five of the 36 patients exhibited a profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with Defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism. Hum Mutat 33:440–447, 2012. © 2011 Wiley Periodicals, Inc.
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mutations in the planar cell polarity genes celsr1 and scrib are associated with the severe Neural Tube Defect craniorachischisis
Human Mutation, 2012Co-Authors: Alexis A Robinson, Roger E Stevenson, Sarah Escuin, K Doudney, Michel Vekemans, Nicholas D E Greene, Andrew J Copp, Philip StanierAbstract:Craniorachischisis (CRN) is a severe Neural Tube Defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal Neural Tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbor mutations in core members of the planar cell polarity (PCP) signaling pathway. Previous studies of humans with CRN failed to identify mutations in the core PCP genes, VANGL1 and VANGL2. Here, we analyzed other key PCP genes: CELSR1, PRICKLE1, PTK7, and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein-protein interactions as well as subcellular protein localization. While protein interactions were not affected, variants from five of the 36 patients exhibited a profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with Defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
Nynke A. Hosper - One of the best experts on this subject based on the ideXlab platform.
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Cells from Fetuses with a Neural Tube Defect Do Not Deposit Collagen Type I Protein After TGF-b1 Stimulation In Vitro
2016Co-Authors: Human Amniotic, Fluid-derived Mesenchymal, Nynke A. Hosper, Ruud A. Bank, Paul P. Van Den BergAbstract:In spina bifida, the Neural Tube fails to close during the embryonic period. Exposure of the Neural Tube to the amniotic fluid during pregnancy causes additional Neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the Defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a Neural Tube Defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibro-blasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLCE), PCOLCE2, ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2), ADAMTS14]. This indicates that NTD-AFMCs have different characteristics compared with healthy AFMCs and might not be suitable for fetal therapy to close the Defect in spina bifida patients
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human amniotic fluid derived mesenchymal cells from fetuses with a Neural Tube Defect do not deposit collagen type i protein after tgf β1 stimulation in vitro
Stem Cells and Development, 2014Co-Authors: Nynke A. Hosper, Ruud A. Bank, Paul P. Van Den BergAbstract:In spina bifida, the Neural Tube fails to close during the embryonic period. Exposure of the Neural Tube to the amniotic fluid during pregnancy causes additional Neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the Defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a Neural Tube Defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibroblasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLC...
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human amniotic fluid derived mesenchymal cells from fetuses with a Neural Tube Defect do not deposit collagen type i protein after tgf β1 stimulation in vitro
Stem Cells and Development, 2014Co-Authors: Nynke A. Hosper, Ruud A. Bank, Paul P. Van Den BergAbstract:In spina bifida, the Neural Tube fails to close during the embryonic period. Exposure of the Neural Tube to the amniotic fluid during pregnancy causes additional Neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the Defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a Neural Tube Defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibroblasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLCE), PCOLCE2, ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2), ADAMTS14]. This indicates that NTD-AFMCs have different characteristics compared with healthy AFMCs and might not be suitable for fetal therapy to close the Defect in spina bifida patients.
Regine P M Steegerstheunissen - One of the best experts on this subject based on the ideXlab platform.
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correction epigenetic profiles in children with a Neural Tube Defect a case control study in two populations
PLOS ONE, 2014Co-Authors: Lisette Stolk, Marieke I Bouwlandboth, Michael M P J Verbiest, Paul H C Eilers, Huiping Zhu, Lucina Suarez, Andre G Uitterlinden, N H Van Mil, Regine P M SteegerstheunissenAbstract:The name of the third author was spelled incorrectly. The correct name is: N.H. van Mil. The correct Citation is: Stolk L, Bouwland-Both MI, van Mil NH, Verbiest MMPJ, Eilers PHC, et al. (2013) Epigenetic Profiles in Children with a Neural Tube Defect; A Case-Control Study in Two Populations. PLoS ONE 8(11): e78462. doi:10.1371/journal.pone.0078462.
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epigenetic profiles in children with a Neural Tube Defect a case control study in two populations
PLOS ONE, 2013Co-Authors: Lisette Stolk, Marieke I Bouwlandboth, Nina H Van Mill, Michael M P J Verbiest, Paul H C Eilers, Huiping Zhu, Lucina Suarez, Andre G Uitterlinden, Regine P M SteegerstheunissenAbstract:Folate deficiency is implicated in the causation of Neural Tube Defects (NTDs). The preventive effect of periconceptional folic acid supplement use is partially explained by the treatment of a deranged folate-dependent one carbon metabolism, which provides methyl groups for DNA-methylation as an epigenetic mechanism. Here, we hypothesize that variations in DNA-methylation of genes implicated in the development of NTDs and embryonic growth are part of the underlying mechanism. In 48 children with a Neural Tube Defect and 62 controls from a Dutch case-control study and 34 children with a Neural Tube Defect and 78 controls from a Texan case-control study, we measured the DNA-methylation levels of imprinted candidate genes (IGF2-DMR, H19, KCNQ1OT1) and non-imprinted genes (the LEKR/CCNL gene region associated with birth weight, and MTHFR and VANGL1 associated with NTD). We used the MassARRAY EpiTYPER assay from Sequenom for the assessment of DNA-methylation. Linear mixed model analysis was used to estimate associations between DNA-methylation levels of the genes and a Neural Tube Defect. In the Dutch study group, but not in the Texan study group we found a significant association between the risk of having an NTD and DNA methylation levels of MTHFR (absolute decrease in methylation of −0.33% in cases, P-value = 0.001), and LEKR/CCNL (absolute increase in methylation: 1.36% in cases, P-value = 0.048), and a borderline significant association for VANGL (absolute increase in methylation: 0.17% in cases, P-value = 0.063). Only the association between MTHFR and NTD-risk remained significant after multiple testing correction. The associations in the Dutch study were not replicated in the Texan study. We conclude that the associations between NTDs and the methylation of the MTHFR gene, and maybe VANGL and LEKKR/CNNL, are in line with previous studies showing polymorphisms in the same genes in association with NTDs and embryonic development, respectively.