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Volume 128, Issue 3, Pages 717-727 (March 2005)
Transgenic expression of pancreatic secretory trypsin inhibitor-I ameliorates secretagogue-induced pancreatitis in mice Jaimie D. Nathan, Joelle Romac, Ruth Y. Peng, Michael Peyton, Raymond J. MacDonald, Rodger A. Liddle Gastroenterology Volume 128, Issue 3, Pages (March 2005) DOI: /j.gastro Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 1 Expression of PSTI-I in transgenic and nontransgenic mice. Western blot analysis of rat PSTI-I in 10 organs of a representative transgenic mouse (A) and nontransgenic mouse (B) is depicted. Recombinant PSTI-I (Rec PSTI-I) was run as a positive control, and membranes were reincubated with anti-α-tubulin antibody as a control for protein loading. PSTI-I was detected only in the pancreas of transgenic mice. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 2 Immunostaining of PSTI-I in pancreas. Histologic sections of pancreas from nontransgenic (A and B) and PSTI-I transgenic mice (C and D) with normal rabbit sera (A and C) or anti-PSTI-I sera (B and D) as the primary antibody (original magnification ×200). Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 3 Secretion of PSTI-I and amylase in vitro from isolated pancreatic acini of PSTI-I transgenic mice. The effects of CCK-8 on amylase release (A) and PSTI-I secretion (B) are shown. (A) Amylase release from PSTI mice are shown in solid circles compared with nontransgenic mice (open circles). Values are the means ± SEM of triplicate determinations. (B) Media collected from acini of PSTI-I transgenic mice following incubation with various concentrations of CCK-8 were analyzed by Western blot and densitometric scanning. Values are the average of 2 experiments. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 4 The effects of PSTI-I expression and caerulein on serum amylase concentration. Caerulein administration significantly increased the serum amylase concentration, but PSTI-I expression had no effect on this caerulein-induced elevation. Results are expressed as mean ± SEM (n = 8). *P < .001 vs. vehicle. NT, nontransgenic; PSTI-I, PSTI-I transgenic. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 5 The effects of PSTI-I expression and caerulein on pancreas wet weight-to-body weight ratio, as a measure of tissue edema. Caerulein administration increased the pancreas wet weight-to-body weight ratio, and this effect was significantly inhibited in mice expressing PSTI-I. Results are expressed as mean ± SEM (n = 10). *P < .001 vs. NT, vehicle; †P < .001 vs. NT, caerulein. NT, nontransgenic; PSTI-I, PSTI-I transgenic. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 6 The effects of caerulein and PSTI-I expression on pancreatic histoarchitecture. Representative histologic sections of mouse pancreas stained with H&E from vehicle-treated nontransgenic (A), vehicle-treated PSTI-I transgenic (B), caerulein-treated nontransgenic (C), and caerulein-treated PSTI-I transgenic (D) mice. Caerulein administration caused pancreatic edema, neutrophil infiltration, and parenchymal injury and necrosis. PSTI-I expression inhibited the effects of caerulein on pancreatic histoarchitecture (original magnification ×250). Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 7 The effects of PSTI-I expression and caerulein on total histologic score of pancreatitis. Caerulein administration increased the total histologic severity score of pancreatitis in nontransgenic mice, and PSTI-I expression significantly inhibited this effect. Results are expressed as mean ± SEM (n = 10). *P < .001 vs. NT, vehicle; †P < .05 vs. NT, caerulein. NT, nontransgenic; PSTI-I, PSTI-I transgenic. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 8 Electron micrographs of pancreas from transgenic and nontransgenic mice. Representative electron micrographs of pancreas from vehicle-treated nontransgenic (A), vehicle-treated PSTI-I transgenic (B), caerulein-treated nontransgenic (C), and caerulein-treated PSTI-I transgenic (D) mice. The major distinguishing feature with caerulein treatment was that pyknotic cells were more abundant in nontransgenic mice compared with transgenic mice. Scale bar = 1 μm. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 9 The effects of PSTI-I expression and caerulein on pancreatic content of trypsinogen activation peptide (TAP). Caerulein administration increased the pancreatic content of TAP, and this increase was not affected by PSTI-I expression. Results are expressed as mean ± SEM (n = 4). *P < .01 vs. vehicle. NT, nontransgenic; PSTI-I, PSTI-I transgenic. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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Figure 10 The effects of PSTI-I expression and caerulein on pancreatic trypsin activity. Caerulein administration increased pancreatic trypsin activity in nontransgenic mice, and PSTI-I expression significantly reduced the quantity of pancreatic trypsin activity. Results are expressed as mean ± SEM (n = 5). *P < .001 vs. NT, vehicle; †P < .001 vs. NT, caerulein. NT, nontransgenic; PSTI-I, PSTI-I transgenic. Gastroenterology , DOI: ( /j.gastro ) Copyright © 2005 American Gastroenterological Association Terms and Conditions
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