Browsing by Subject "Pancreatic ducts"

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    Hepatocyte Growth Factor Signaling in Intrapancreatic Ductal Cells Drives Pancreatic Morphogenesis
    (Public Library of Science, 2013) Anderson, Ryan M.; Delous, Marion; Bosch, Justin A.; Ye, Lihua; Robertson, Morgan A.; Hesselson, Daniel; Stainier, Didier Y. R.; Pediatrics, School of Medicine
    In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908) , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF) tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.
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    T1 mapping for the diagnosis of early chronic pancreatitis: correlation with Cambridge classification system
    (British Institute of Radiology, 2021) Cheng, Monica; Gromski, Mark A.; Fogel, Evan L.; DeWitt, John M.; Patel, Aashish A.; Tirkes, Temel; Radiology and Imaging Sciences, School of Medicine
    Objective: This study aims to determine if T1 relaxation time of the pancreas can detect parenchymal changes in early chronic pancreatitis (CP). Methods: This study retrospectively analyzed 42 patients grouped as no CP (Cambridge 0; n = 21), equivocal (Cambridge 1; n = 12) or mild CP (Cambridge 2; n = 9) based on magnetic resonance cholangiopancreatography findings using the Cambridge classification as the reference standard. Unenhanced T1 maps were acquired using a three-dimensional dual flip-angle gradient-echo technique on the same 1.5 T scanner with the same imaging parameters. Results: There was no significant difference between the T1 relaxation times of Cambridge 0 and 1 group (p = 0.58). There was a significant difference (p = 0.0003) in the mean T1 relaxation times of the pancreas between the combined Cambridge 0 and 1 (mean = 639 msec, 95% CI: 617, 660) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692, 759). There was significant difference (p = 0.0009) in the mean T1 relaxation times of the pancreas between the Cambridge 0 (mean = 636 msec, 95% CI: 606, 666) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692,759) as well as between Cambridge 1 (mean = 643 msec, 95% CI: 608, 679) and Cambridge 2 groups (mean = 726 msec, 95% CI: 692,759) (p = 0.0017). Bland-Altman analysis showed measurements of one reader to be marginally higher than the other by 15.7 msec (2.4%, p = 0.04). Conclusion: T1 mapping is a practical method capable of quantitatively reflecting morphologic changes even in the early stages of chronic pancreatitis, and demonstrates promise for future implementation in routine clinical imaging protocols. Advances in knowledge: T1 mapping can distinguish subtle parenchymal changes seen in early stage CP, and demonstrates promise for implementation in routine imaging protocols for the diagnosis of CP.