The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform

Peter F. Nichol - One of the best experts on this subject based on the ideXlab platform.

  • haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2iiib mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    The etiology of intestinal Atresia remains undetermined. Atresias have been ascribed to a number of events, including in utero vascular accidents,1–3 mechanical compression,4 and disruptions in notochord development.5,6 In the case of the duodenum, Atresias have been hypothesized to result from a failure of the intestinal lumen to recanalize after a period of exuberant endodermal growth.7 Over the last decade, genetic animal models of intestinal Atresia have been developed. The best characterized of these genetic models result from homozygous mutation of either fibroblast growth factor 10 (Fgf10) or its cognate receptor, fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) in mice.8,9 The homozygous mutation of either of these genes results in nonviable progeny at embryonic day (E) 18.5, in which 100% of the embryos have colonic Atresias9,10 and 38% to 42% have duodenal Atresias.8,11 Approximately 92% of the duodenal Atresias observed in the Fgf10 mouse model are type III (gap in the intestine and mesentery), and 8% are type I (intestinal tube is intact externally but has a blockage in the lumen).8 In the Fgfr2IIIb model, the formation of colonic and duodenal Atresia is preceded by an increase level of apoptosis in the endoderm.12 Interestingly, unlike human duodenal development, normal development of the mouse duodenum proceeds without a solid core phase in the lumen.12 These results suggest that in the Fgfr2IIIb mouse model, the formation of duodenal and colonic Atresias result from the loss of endoderm during a critical phase in development, as opposed to a failure in recanalization of the lumen as proposed originally.7 We observed previously that retinaldehyde dehydrogenase 2 (Raldh2) is expressed in the duodenum during the temporal window of Atresia formation (E 11.0–E 13.5).13 This gene encodes for an enzyme that catalyzes the final step of vitamin A conversion to its active metabolite, which is retinoic acid. Recent work has shown that this gene is critical for normal development in the pancreatic–duodenal region because homozygous mutations in Raldh2 result in disruptions in pancreatic development. These embryos fail to progress beyond E 9.5 in development, suggesting that Raldh2 is a critical gene in the development of numerous systems during embryogenesis.14 We hypothesized that haploinsufficiency of Raldh2 would affect the severity of duodenal Atresias in the Fgfr2IIIb−/− model. In this model, 93% of the Atresias are type III defects; however, the penetrance ranges from 38% to 42%.8,12 Therefore, if haploinsufficiency of Raldh2 were to increase the severity of the defects, we would expect to see a significant increase in Atresia incidence. If haploinsufficiency of Raldh2 were to have the opposite effect, then we would expect both the severity and the incidence of Atresias to decrease. To test this, we generated compound mutants using the hypoxanthine-guanine phosphoribosyltransferase-Cre (Hprt-Cre) system with conditional alleles for both Fgfr2IIIb and Raldh2.11 We observed that haploinsufficiency of Raldh2 decreased both the severity and incidence of duodenal Atresia in comparison to mutant controls.

  • Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2IIIb−/− mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal Atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal Atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal Atresia formation. To test this, we rendered Fgfr2IIIb(-/-) embryos haploinsufficient for the Raldh2 and examined these embryos for the incidence and severity of duodenal Atresia. Control embryos, Fgfr2IIIb(-/-) mutants, and Fgfr2IIIb(-/-); Raldh2(+/-) mutants were harvested at embryonic day 18.5, genotyped, and fixed overnight. Intestinal tracts were isolated. The type and severity of duodenal Atresia was documented. A total of 97 Fgfr2IIIb(-/-) embryos were studied; 44 had duodenal Atresias, and 41 of these presented as type III. In the 70 Fgfr2IIIb(-/-); Raldh2(+/-) embryos studied, a lesser incidence of duodenal Atresia was seen (15 of 70; P = .0017; Fisher exact test). Atresia severity was also decreased; there were 12 embryos with type I Atresias, 3 with type II Atresias, and 0 with type III Atresias (P < 2.81E-013; Fisher exact test). Haploinsufficiency of Raldh2 decreases the incidence and severity of duodenal Atresia in the Fgfr2IIIb(-/-) model. The ability to alter defect severity through manipulation of a single gene in a specific genetic background has potentially important implications for understanding the mechanisms by which intestinal Atresias arise. Copyright © 2012 Mosby, Inc. All rights reserved.

Amy L. Reeder - One of the best experts on this subject based on the ideXlab platform.

  • haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2iiib mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    The etiology of intestinal Atresia remains undetermined. Atresias have been ascribed to a number of events, including in utero vascular accidents,1–3 mechanical compression,4 and disruptions in notochord development.5,6 In the case of the duodenum, Atresias have been hypothesized to result from a failure of the intestinal lumen to recanalize after a period of exuberant endodermal growth.7 Over the last decade, genetic animal models of intestinal Atresia have been developed. The best characterized of these genetic models result from homozygous mutation of either fibroblast growth factor 10 (Fgf10) or its cognate receptor, fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) in mice.8,9 The homozygous mutation of either of these genes results in nonviable progeny at embryonic day (E) 18.5, in which 100% of the embryos have colonic Atresias9,10 and 38% to 42% have duodenal Atresias.8,11 Approximately 92% of the duodenal Atresias observed in the Fgf10 mouse model are type III (gap in the intestine and mesentery), and 8% are type I (intestinal tube is intact externally but has a blockage in the lumen).8 In the Fgfr2IIIb model, the formation of colonic and duodenal Atresia is preceded by an increase level of apoptosis in the endoderm.12 Interestingly, unlike human duodenal development, normal development of the mouse duodenum proceeds without a solid core phase in the lumen.12 These results suggest that in the Fgfr2IIIb mouse model, the formation of duodenal and colonic Atresias result from the loss of endoderm during a critical phase in development, as opposed to a failure in recanalization of the lumen as proposed originally.7 We observed previously that retinaldehyde dehydrogenase 2 (Raldh2) is expressed in the duodenum during the temporal window of Atresia formation (E 11.0–E 13.5).13 This gene encodes for an enzyme that catalyzes the final step of vitamin A conversion to its active metabolite, which is retinoic acid. Recent work has shown that this gene is critical for normal development in the pancreatic–duodenal region because homozygous mutations in Raldh2 result in disruptions in pancreatic development. These embryos fail to progress beyond E 9.5 in development, suggesting that Raldh2 is a critical gene in the development of numerous systems during embryogenesis.14 We hypothesized that haploinsufficiency of Raldh2 would affect the severity of duodenal Atresias in the Fgfr2IIIb−/− model. In this model, 93% of the Atresias are type III defects; however, the penetrance ranges from 38% to 42%.8,12 Therefore, if haploinsufficiency of Raldh2 were to increase the severity of the defects, we would expect to see a significant increase in Atresia incidence. If haploinsufficiency of Raldh2 were to have the opposite effect, then we would expect both the severity and the incidence of Atresias to decrease. To test this, we generated compound mutants using the hypoxanthine-guanine phosphoribosyltransferase-Cre (Hprt-Cre) system with conditional alleles for both Fgfr2IIIb and Raldh2.11 We observed that haploinsufficiency of Raldh2 decreased both the severity and incidence of duodenal Atresia in comparison to mutant controls.

  • Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2IIIb−/− mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal Atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal Atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal Atresia formation. To test this, we rendered Fgfr2IIIb(-/-) embryos haploinsufficient for the Raldh2 and examined these embryos for the incidence and severity of duodenal Atresia. Control embryos, Fgfr2IIIb(-/-) mutants, and Fgfr2IIIb(-/-); Raldh2(+/-) mutants were harvested at embryonic day 18.5, genotyped, and fixed overnight. Intestinal tracts were isolated. The type and severity of duodenal Atresia was documented. A total of 97 Fgfr2IIIb(-/-) embryos were studied; 44 had duodenal Atresias, and 41 of these presented as type III. In the 70 Fgfr2IIIb(-/-); Raldh2(+/-) embryos studied, a lesser incidence of duodenal Atresia was seen (15 of 70; P = .0017; Fisher exact test). Atresia severity was also decreased; there were 12 embryos with type I Atresias, 3 with type II Atresias, and 0 with type III Atresias (P < 2.81E-013; Fisher exact test). Haploinsufficiency of Raldh2 decreases the incidence and severity of duodenal Atresia in the Fgfr2IIIb(-/-) model. The ability to alter defect severity through manipulation of a single gene in a specific genetic background has potentially important implications for understanding the mechanisms by which intestinal Atresias arise. Copyright © 2012 Mosby, Inc. All rights reserved.

Krzysztof M. Zaremba - One of the best experts on this subject based on the ideXlab platform.

  • haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2iiib mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    The etiology of intestinal Atresia remains undetermined. Atresias have been ascribed to a number of events, including in utero vascular accidents,1–3 mechanical compression,4 and disruptions in notochord development.5,6 In the case of the duodenum, Atresias have been hypothesized to result from a failure of the intestinal lumen to recanalize after a period of exuberant endodermal growth.7 Over the last decade, genetic animal models of intestinal Atresia have been developed. The best characterized of these genetic models result from homozygous mutation of either fibroblast growth factor 10 (Fgf10) or its cognate receptor, fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) in mice.8,9 The homozygous mutation of either of these genes results in nonviable progeny at embryonic day (E) 18.5, in which 100% of the embryos have colonic Atresias9,10 and 38% to 42% have duodenal Atresias.8,11 Approximately 92% of the duodenal Atresias observed in the Fgf10 mouse model are type III (gap in the intestine and mesentery), and 8% are type I (intestinal tube is intact externally but has a blockage in the lumen).8 In the Fgfr2IIIb model, the formation of colonic and duodenal Atresia is preceded by an increase level of apoptosis in the endoderm.12 Interestingly, unlike human duodenal development, normal development of the mouse duodenum proceeds without a solid core phase in the lumen.12 These results suggest that in the Fgfr2IIIb mouse model, the formation of duodenal and colonic Atresias result from the loss of endoderm during a critical phase in development, as opposed to a failure in recanalization of the lumen as proposed originally.7 We observed previously that retinaldehyde dehydrogenase 2 (Raldh2) is expressed in the duodenum during the temporal window of Atresia formation (E 11.0–E 13.5).13 This gene encodes for an enzyme that catalyzes the final step of vitamin A conversion to its active metabolite, which is retinoic acid. Recent work has shown that this gene is critical for normal development in the pancreatic–duodenal region because homozygous mutations in Raldh2 result in disruptions in pancreatic development. These embryos fail to progress beyond E 9.5 in development, suggesting that Raldh2 is a critical gene in the development of numerous systems during embryogenesis.14 We hypothesized that haploinsufficiency of Raldh2 would affect the severity of duodenal Atresias in the Fgfr2IIIb−/− model. In this model, 93% of the Atresias are type III defects; however, the penetrance ranges from 38% to 42%.8,12 Therefore, if haploinsufficiency of Raldh2 were to increase the severity of the defects, we would expect to see a significant increase in Atresia incidence. If haploinsufficiency of Raldh2 were to have the opposite effect, then we would expect both the severity and the incidence of Atresias to decrease. To test this, we generated compound mutants using the hypoxanthine-guanine phosphoribosyltransferase-Cre (Hprt-Cre) system with conditional alleles for both Fgfr2IIIb and Raldh2.11 We observed that haploinsufficiency of Raldh2 decreased both the severity and incidence of duodenal Atresia in comparison to mutant controls.

  • Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2IIIb−/− mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal Atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal Atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal Atresia formation. To test this, we rendered Fgfr2IIIb(-/-) embryos haploinsufficient for the Raldh2 and examined these embryos for the incidence and severity of duodenal Atresia. Control embryos, Fgfr2IIIb(-/-) mutants, and Fgfr2IIIb(-/-); Raldh2(+/-) mutants were harvested at embryonic day 18.5, genotyped, and fixed overnight. Intestinal tracts were isolated. The type and severity of duodenal Atresia was documented. A total of 97 Fgfr2IIIb(-/-) embryos were studied; 44 had duodenal Atresias, and 41 of these presented as type III. In the 70 Fgfr2IIIb(-/-); Raldh2(+/-) embryos studied, a lesser incidence of duodenal Atresia was seen (15 of 70; P = .0017; Fisher exact test). Atresia severity was also decreased; there were 12 embryos with type I Atresias, 3 with type II Atresias, and 0 with type III Atresias (P < 2.81E-013; Fisher exact test). Haploinsufficiency of Raldh2 decreases the incidence and severity of duodenal Atresia in the Fgfr2IIIb(-/-) model. The ability to alter defect severity through manipulation of a single gene in a specific genetic background has potentially important implications for understanding the mechanisms by which intestinal Atresias arise. Copyright © 2012 Mosby, Inc. All rights reserved.

Robert A. Botham - One of the best experts on this subject based on the ideXlab platform.

  • haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2iiib mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    The etiology of intestinal Atresia remains undetermined. Atresias have been ascribed to a number of events, including in utero vascular accidents,1–3 mechanical compression,4 and disruptions in notochord development.5,6 In the case of the duodenum, Atresias have been hypothesized to result from a failure of the intestinal lumen to recanalize after a period of exuberant endodermal growth.7 Over the last decade, genetic animal models of intestinal Atresia have been developed. The best characterized of these genetic models result from homozygous mutation of either fibroblast growth factor 10 (Fgf10) or its cognate receptor, fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) in mice.8,9 The homozygous mutation of either of these genes results in nonviable progeny at embryonic day (E) 18.5, in which 100% of the embryos have colonic Atresias9,10 and 38% to 42% have duodenal Atresias.8,11 Approximately 92% of the duodenal Atresias observed in the Fgf10 mouse model are type III (gap in the intestine and mesentery), and 8% are type I (intestinal tube is intact externally but has a blockage in the lumen).8 In the Fgfr2IIIb model, the formation of colonic and duodenal Atresia is preceded by an increase level of apoptosis in the endoderm.12 Interestingly, unlike human duodenal development, normal development of the mouse duodenum proceeds without a solid core phase in the lumen.12 These results suggest that in the Fgfr2IIIb mouse model, the formation of duodenal and colonic Atresias result from the loss of endoderm during a critical phase in development, as opposed to a failure in recanalization of the lumen as proposed originally.7 We observed previously that retinaldehyde dehydrogenase 2 (Raldh2) is expressed in the duodenum during the temporal window of Atresia formation (E 11.0–E 13.5).13 This gene encodes for an enzyme that catalyzes the final step of vitamin A conversion to its active metabolite, which is retinoic acid. Recent work has shown that this gene is critical for normal development in the pancreatic–duodenal region because homozygous mutations in Raldh2 result in disruptions in pancreatic development. These embryos fail to progress beyond E 9.5 in development, suggesting that Raldh2 is a critical gene in the development of numerous systems during embryogenesis.14 We hypothesized that haploinsufficiency of Raldh2 would affect the severity of duodenal Atresias in the Fgfr2IIIb−/− model. In this model, 93% of the Atresias are type III defects; however, the penetrance ranges from 38% to 42%.8,12 Therefore, if haploinsufficiency of Raldh2 were to increase the severity of the defects, we would expect to see a significant increase in Atresia incidence. If haploinsufficiency of Raldh2 were to have the opposite effect, then we would expect both the severity and the incidence of Atresias to decrease. To test this, we generated compound mutants using the hypoxanthine-guanine phosphoribosyltransferase-Cre (Hprt-Cre) system with conditional alleles for both Fgfr2IIIb and Raldh2.11 We observed that haploinsufficiency of Raldh2 decreased both the severity and incidence of duodenal Atresia in comparison to mutant controls.

  • Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal Atresia in the fibroblast growth factor receptor 2IIIb−/− mouse model
    Surgery, 2012
    Co-Authors: Amy L. Reeder, Robert A. Botham, Krzysztof M. Zaremba, Peter F. Nichol
    Abstract:

    Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal Atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal Atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal Atresia formation. To test this, we rendered Fgfr2IIIb(-/-) embryos haploinsufficient for the Raldh2 and examined these embryos for the incidence and severity of duodenal Atresia. Control embryos, Fgfr2IIIb(-/-) mutants, and Fgfr2IIIb(-/-); Raldh2(+/-) mutants were harvested at embryonic day 18.5, genotyped, and fixed overnight. Intestinal tracts were isolated. The type and severity of duodenal Atresia was documented. A total of 97 Fgfr2IIIb(-/-) embryos were studied; 44 had duodenal Atresias, and 41 of these presented as type III. In the 70 Fgfr2IIIb(-/-); Raldh2(+/-) embryos studied, a lesser incidence of duodenal Atresia was seen (15 of 70; P = .0017; Fisher exact test). Atresia severity was also decreased; there were 12 embryos with type I Atresias, 3 with type II Atresias, and 0 with type III Atresias (P < 2.81E-013; Fisher exact test). Haploinsufficiency of Raldh2 decreases the incidence and severity of duodenal Atresia in the Fgfr2IIIb(-/-) model. The ability to alter defect severity through manipulation of a single gene in a specific genetic background has potentially important implications for understanding the mechanisms by which intestinal Atresias arise. Copyright © 2012 Mosby, Inc. All rights reserved.

Dharamvir Mangal - One of the best experts on this subject based on the ideXlab platform.

  • Simple Technique of Bridging Wide Gap in Esophageal Atresia with Tracheoesophageal Fistula - "Surgical Innovation".
    Journal of Indian Association of Pediatric Surgeons, 2017
    Co-Authors: Ak Sharma, Dharamvir Mangal
    Abstract:

    The survival of the patients with esophageal Atresia an tracheo esophageal fistula is believed to be an epitome of the success of the neonatal surgery. Restoring the continuty of the food pipe by esophagus to esophagus anastomosis is the best option. Preservation of natural esophagus by delayed repair in a wide gap esophageal Atresia is a preferred technique worldwide, however such a management required prolonged hospitalization and dedicated nursing care, which is often not available in most of the centres in India. Esophageal substitutes in wide gap requires multiple operations and have long term problems, so remains the last option. I use the technique of oblique anastomosis which had distrinct advantage over circular anastomosis in the management of esophageal Atresia1.This techniqe helps in bridging wide gap to some extent & minimal stricture formation.

  • Simple technique of bridging wide gap in esophageal Atresia with tracheoesophageal fistula – “surgical innovation”
    Wolters Kluwer Medknow Publications, 2017
    Co-Authors: Ak Sharma, Dharamvir Mangal
    Abstract:

    The survival of the patients with esophageal Atresia an tracheo esophageal fistula is believed to be an epitome of the success of the neonatal surgery. Restoring the continuty of the food pipe by esophagus to esophagus anastomosis is the best option. Preservation of natural esophagus by delayed repair in a wide gap esophageal Atresia is a preferred technique worldwide, however such a management required prolonged hospitalization and dedicated nursing care, which is often not available in most of the centres in India. Esophageal substitutes in wide gap requires multiple operations and have long term problems, so remains the last option. I use the technique of oblique anastomosis which had distrinct advantage over circular anastomosis in the management of esophageal Atresia1.This techniqe helps in bridging wide gap to some extent & minimal stricture formation