The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Paul A Dawson - One of the best experts on this subject based on the ideXlab platform.
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FXR agonists and FGF15 reduce fecal Bile Acid excretion in a mouse model of Bile Acid Malabsorption
Journal of Lipid Research, 2007Co-Authors: Diana Jung, Robert D. Gerard, Steven A. Kliewer, David J. Mangelsdorf, Paul A Dawson, Takeshi Inagaki, Antonio MoschettaAbstract:Bile Acid Malabsorption, which in patients leads to excessive fecal Bile Acid excretion and diarrhea, is char- acterized by a vicious cycle in which the feedback regulation of Bile Acid synthesis is interrupted, resulting in additional Bile Acid production. Feedback regulation of Bile Acid syn- thesis is under the control of an endocrine pathway wherein activation of the nuclear Bile Acid receptor, farnesoid X re- ceptor (FXR), induces enteric expression of the hormone, fibroblast growth factor 15 (FGF15). In liver, FGF15 acts together with FXR-mediated expression of small hetero- dimer partner to repress Bile Acid synthesis. Here, we show that the FXR-FGF15 pathway is disrupted in mice lacking apical ileal Bile Acid transporter, a model of Bile Acid mal- absorption. Treatment of Asbt 2/2 mice with either a synthe- tic FXR agonist or FGF15 downregulates hepatic cholesterol 7a-hydroxylase mRNA levels, decreases Bile Acid pool size, and reduces fecal Bile Acid excretion. These findings suggest that FXR agonists or FGF15 could be used thera- peutically to interrupt the cycle of excessive Bile Acid produc- tion in patients with Bile Acid Malabsorption.—Jung, D., T. Inagaki, R. D. Gerard, P. A. Dawson, S. A. Kliewer, D. J. Mangelsdorf, and A. Moschetta. FXR agonists and FGF15 reduce fecal Bile Acid excretion in a mouse model of Bile Acid Malabsorption. J. Lipid Res. 2007. 48: 2693-2700.
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FXR agonists and FGF15 reduce fecal Bile Acid excretion in a mouse model of Bile Acid Malabsorption
Journal of lipid research, 2007Co-Authors: Diana Jung, Robert D. Gerard, Steven A. Kliewer, David J. Mangelsdorf, Paul A Dawson, Takeshi Inagaki, Antonio MoschettaAbstract:Bile Acid Malabsorption, which in patients leads to excessive fecal Bile Acid excretion and diarrhea, is characterized by a vicious cycle in which the feedback regulation of Bile Acid synthesis is interrupted, resulting in additional Bile Acid production. Feedback regulation of Bile Acid synthesis is under the control of an endocrine pathway wherein activation of the nuclear Bile Acid receptor, farnesoid X receptor (FXR), induces enteric expression of the hormone, fibroblast growth factor 15 (FGF15). In liver, FGF15 acts together with FXR-mediated expression of small heterodimer partner to repress Bile Acid synthesis. Here, we show that the FXR-FGF15 pathway is disrupted in mice lacking apical ileal Bile Acid transporter, a model of Bile Acid Malabsorption. Treatment of Asbt−/− mice with either a synthetic FXR agonist or FGF15 downregulates hepatic cholesterol 7α-hydroxylase mRNA levels, decreases Bile Acid pool size, and reduces fecal Bile Acid excretion. These findings suggest that FXR agonists or FGF15 could be used therapeutically to interrupt the cycle of excessive Bile Acid production in patients with Bile Acid Malabsorption.
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Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption.
World journal of gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
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analysis of ileal sodium Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
World Journal of Gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
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Absence of dysfunctional ileal sodium-Bile Acid cotransporter gene mutations in patients with adult-onset idiopathic Bile Acid Malabsorption.
Scandinavian journal of gastroenterology, 2001Co-Authors: Marco Montagnani, Paul A Dawson, P. Rössel, Martha W. Love, P. QvistAbstract:Background: A congenital form of idiopathic intestinal Bile Acid Malabsorption (IBAM) has been associated with dysfunctional mutations in the ileal apical sodium-dependent Bile Acid transporter (ASBT). The aim of this study was to determine whether mutations in the ASBT gene (SLC10A2) predispose to the development of adult-onset idiopathic Bile Acid Malabsorption and chronic watery diarrhea. Methods: Genomic DNA was obtained from 13 adult IBAM patients previously diagnosed on the basis of clinical data, response to cholestyramine, and abnormal 75Se-homocholic Acid taurine (SeHCAT) test values. The ASBT gene was screened for the presence of mutations or polymorphisms by single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. Results: ASBT gene polymorphisms were detected in 5 of the 13 adult IBAM patients. Four patients were heterozygous for a common polymorphism in exon 3, leading to an alanine to serine substitution at codon 171 (A171S). An additional subject was heterozygous for a ...
Marco Montagnani - One of the best experts on this subject based on the ideXlab platform.
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Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption.
World journal of gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
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analysis of ileal sodium Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
World Journal of Gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
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Absence of dysfunctional ileal sodium-Bile Acid cotransporter gene mutations in patients with adult-onset idiopathic Bile Acid Malabsorption.
Scandinavian journal of gastroenterology, 2001Co-Authors: Marco Montagnani, Paul A Dawson, P. Rössel, Martha W. Love, P. QvistAbstract:Background: A congenital form of idiopathic intestinal Bile Acid Malabsorption (IBAM) has been associated with dysfunctional mutations in the ileal apical sodium-dependent Bile Acid transporter (ASBT). The aim of this study was to determine whether mutations in the ASBT gene (SLC10A2) predispose to the development of adult-onset idiopathic Bile Acid Malabsorption and chronic watery diarrhea. Methods: Genomic DNA was obtained from 13 adult IBAM patients previously diagnosed on the basis of clinical data, response to cholestyramine, and abnormal 75Se-homocholic Acid taurine (SeHCAT) test values. The ASBT gene was screened for the presence of mutations or polymorphisms by single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. Results: ASBT gene polymorphisms were detected in 5 of the 13 adult IBAM patients. Four patients were heterozygous for a common polymorphism in exon 3, leading to an alanine to serine substitution at codon 171 (A171S). An additional subject was heterozygous for a ...
Matthias Stelzner - One of the best experts on this subject based on the ideXlab platform.
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Treatment of Bile Acid Malabsorption Using Ileal Stem Cell Transplantation
Journal of the American College of Surgeons, 2005Co-Authors: Jeffrey R. Avansino, David C. Chen, Vicki D. Hoagland, Jacob D. Woolman, W. Geoffrey Haigh, Matthias StelznerAbstract:Background We hypothesized that ileal stem cell clusters transplanted into a segment of jejunum can be used to treat Bile Acid Malabsorption. Study design In adult Lewis rats, a 15-cm segment of jejunum was isolated with its blood circulation left intact and partially stripped of enterocytes using luminal high-velocity perfusions with 3mmol/L ethylenediamine tetra-acetic Acid solutions. Continuity was restored by anastomosing the proximal and distal gut. Ileal stem cell clusters were harvested from neonatal Lewis rats and transplanted into the stripped segments to generate a "neoileum." After 4weeks, recipients underwent resection of the native ileum, and the isolated neoileum was anastomosed in its place. After an additional 4weeks, a 48-hour stool collection was performed. The engrafted segment was harvested for taurocholate uptake studies, ileal Bile Acid transporter (IBAT) protein by immunohistomorphometry, and IBAT mRNA quantitation by reverse transcription polymerease chain reaction. Data were analyzed by ANOVA/ t -test. Rats undergoing ileectomy, jejunectomy, or sham operations served as controls. Results Total Bile Acid loss in the stool was markedly lower in rats with a neoileum compared with rats with an ileectomy (p Conclusions Ileal stem cell clusters were used to establish a new zone of Bile Acid uptake and IBAT expression in a jejunal segment. This neoileum eliminated loss of Bile Acids in the stool after ileectomy. This is the first time that transplantation of intestinal stem cell clusters has been shown to correct a clinical Malabsorption syndrome.
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Treatment of Bile Acid Malabsorption using ileal stem cell transplantation
Journal of Surgical Research, 2003Co-Authors: Jeffrey R. Avansino, Vicki D. Hoagland, Jacob D. Woolman, W. Geoffrey Haigh, Matthias StelznerAbstract:Purpose: To determine if ileal stem cells transplanted into a segment of jejunum can be used to treat Bile Acid Malabsorption. Methods: In adult Lewis rats, a 15-cm segment of jejunum was isolated with its blood circulation left intact and partially stripped of enterocytes using luminal high-velocity perfusions with 3 mM EDTA solutions. Continuity was restored by anastomosing the proximal and distal gut. Ileal stem cell clusters were harvested from neo-natal Lewis rats and transplanted into these segments. After 4 weeks, rats underwent an ileectomy and the isolated segment was anastomosed in its place. After an additional 4 weeks, a 48 hour stool collection was performed. The engrafted segment was harvested for taurocholate uptake studies, ileal Bile Acid transporter (IBAT) protein (by immunohistomorphometry) and IBAT mRNA quantitation (by RT-PCR). Data was analyzed by ANOVA/t-test. Rats undergoing ileectomy, jejunectomy or sham operation served as controls. Results: Total Bile Acid loss in the stool was significantly lower in rats with a neo-ileum compared to rats with an ileectomy (p < 0.004; Fig. 1). Na+-dependent taurocholate uptake was significantly increased in the neo-ileum compared to the jejunum (p < 0.001). IBAT protein signal intensity was significantly higher in the neo-ileum compared to jejunum (p < 0.001). IBAT mRNA amounts were significantly higher (p < 0.004) than in the jejunum however comparable to the ileum. Conclusion: Ileal stem cells were used to establish a new zone of active Bile Acid uptake and IBAT expression in a jejunal segment. This neo-ileum eliminated loss of Bile Acids in the stool after ileectomy. This is the first time intestinal stem cell transplantation has been shown to correct a clinical Malabsorption syndrome. Download high-res image (132KB) Download full-size image
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Systemic effects of acute terminal ileitis on uninflamed gut aggravate Bile Acid Malabsorption.
The Journal of surgical research, 2001Co-Authors: Matthias Stelzner, Sivagurunathan Somasundaram, Temur KhakberdievAbstract:Abstract Background. Some patients with terminal ileitis suffer from significant Bile Acid Malabsorption even if the inflammation is locally limited. We hypothesized that inflammation in the terminal ileum may lead to changes in mucosal absorption in more proximal intestinal segments and aggravate Bile Acid Malabsorption. Methods. Five hamsters underwent laparotomy and localized instillation of 2,4,6-trinitrobenzenesulfonic Acid (TNBS) in 10% ethanol into the last 4 cm of ileum to create terminal ileitis. A control group (n = 5) underwent instillation of saline. Animals were sacrificed after 24 h. Active and passive transport of radiolabeled Bile Acids was measured in the proximal and terminal ileum and glucose absorption in the jejunum using an everted sleeve technique. Myeloperoxidase (MPO) activity and histomorphology were examined by standard methods. Results. In animals with ileitis, active Bile Acid uptake decreased by 84% in the terminal ileum (t test, P Conclusion. These data suggest that limited acute ileitis impairs active Bile Acid uptake in the terminal ileum. It also diminishes active Bile Acid and glucose absorption in more proximal segments of the small intestine, likely by a systemic effect. This systemic effect may aggravate Bile Acid Malabsorption in patients with limited ileitis.
Gösta Eggertsen - One of the best experts on this subject based on the ideXlab platform.
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Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption.
World journal of gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
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analysis of ileal sodium Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
World Journal of Gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
Elisa Ravaioli - One of the best experts on this subject based on the ideXlab platform.
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Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption.
World journal of gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
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analysis of ileal sodium Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption
World Journal of Gastroenterology, 2006Co-Authors: Marco Montagnani, Anna Abrahamsson, Cecilia Gälman, Gösta Eggertsen, Hanns-ulrich Marschall, Elisa Ravaioli, Curt Einarsson, Paul A DawsonAbstract:Analysis of ileal sodium/Bile Acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic Bile Acid Malabsorption