1. Volume 114, Issue 2, Pages 372-381 (February 1998)
Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats 
Kenji Kimura, Tooru Shimosegawa, Hironobu Sasano, Reishi Abe, Akihiko Satoh, Atsushi Masamune, Masaru Koizumi, Hiroshi Nagura, Takayoshi Toyota 
Gastroenterology 
Volume 114, Issue 2, Pages (February 1998)
DOI: /S (98)
Copyright © 1998 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Light- and electron-microscopic findings of the pancreas examined 12 hours after. (A) H&E-stained pancreatic tissue of an ADx rat. Many apoptotic cells are found in the peripheral portion of acini (arrows). These cells show shrunken and condensed cytoplasm with fragmented and condensed nuclei. Acinar cells that surround the apoptotic cells appear near intact. Inflammatory cells are scarcely observed. (B) TUNEL in the pancreatic tissue of an ADx rat. TUNEL-positive nuclei are found predominantly in the peripheral portions of acini. Only acinar nuclei are labeled, and nuclei of other cell types are negative. Inflammatory cells are scarcely observed. (C) Ultrastructures of acinar cells in the pancreas of an ADx rat. The arrow indicates an apoptotic acinar cell. In the nucleus, condensed chromatin aggregates close to the nuclear membrane and shows an appearance of crescent-like clumping. The polarity of zymogen granules in adjacent nonapoptotic acinar cells is preserved (original magnification: A, 132×; B, 66×; and C, 2000×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

3. Fig. 1
Light- and electron-microscopic findings of the pancreas examined 12 hours after. (A) H&E-stained pancreatic tissue of an ADx rat. Many apoptotic cells are found in the peripheral portion of acini (arrows). These cells show shrunken and condensed cytoplasm with fragmented and condensed nuclei. Acinar cells that surround the apoptotic cells appear near intact. Inflammatory cells are scarcely observed. (B) TUNEL in the pancreatic tissue of an ADx rat. TUNEL-positive nuclei are found predominantly in the peripheral portions of acini. Only acinar nuclei are labeled, and nuclei of other cell types are negative. Inflammatory cells are scarcely observed. (C) Ultrastructures of acinar cells in the pancreas of an ADx rat. The arrow indicates an apoptotic acinar cell. In the nucleus, condensed chromatin aggregates close to the nuclear membrane and shows an appearance of crescent-like clumping. The polarity of zymogen granules in adjacent nonapoptotic acinar cells is preserved (original magnification: A, 132×; B, 66×; and C, 2000×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

4. Fig. 1
Light- and electron-microscopic findings of the pancreas examined 12 hours after. (A) H&E-stained pancreatic tissue of an ADx rat. Many apoptotic cells are found in the peripheral portion of acini (arrows). These cells show shrunken and condensed cytoplasm with fragmented and condensed nuclei. Acinar cells that surround the apoptotic cells appear near intact. Inflammatory cells are scarcely observed. (B) TUNEL in the pancreatic tissue of an ADx rat. TUNEL-positive nuclei are found predominantly in the peripheral portions of acini. Only acinar nuclei are labeled, and nuclei of other cell types are negative. Inflammatory cells are scarcely observed. (C) Ultrastructures of acinar cells in the pancreas of an ADx rat. The arrow indicates an apoptotic acinar cell. In the nucleus, condensed chromatin aggregates close to the nuclear membrane and shows an appearance of crescent-like clumping. The polarity of zymogen granules in adjacent nonapoptotic acinar cells is preserved (original magnification: A, 132×; B, 66×; and C, 2000×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

5. Fig. 2
(A) Temporal changes of apoptotic index in the pancreas after ADx (•) and sham operation (○). The apoptotic index of ADx rats increased steeply with time after ADx and plateaued at longer than 8 hours after ADx, whereas that of sham rats did not change after the procedure. *P < 0.05; ***P < (B) The effect of HC replacement on the apoptosis of the ADx rat pancreas. By administering HC (15 mg/kg) at 6 hours after ADx, the elevation of apoptotic index was suppressed to the level of sham-operated rats. ***P <
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

6. Fig. 3
Light- and electron-microscopic findings of the pancreas of ADx/cerulein rats. (A) H&E-stained pancreatic tissue of an ADx/cerulein rat. Strong edema, infiltration of numerous neutrophils, and formation of vacuoles in acinar cells are observed. Many acinar nuclei are condensed, fragmented, and scattered in the shrunken cytoplasms (arrows). (B) TUNEL of the pancreatic tissue of an ADx/cerulein rat. Numerous acinar nuclei including fragmented ones are labeled strongly. (C) Ultrastructures of pancreatic acinar cells in an ADx/cerulein rat. The arrow indicates apoptotic acinar cell. In the nucleus, condensed chromatin with crescent-like clumping can be seen. Large vacuoles are formed within the cytoplasms of adjacent acinar cells (arrowhead) and the polarity of zymogen granules in these cells is disturbed (original magnification: A, 132×; B, 66X; and C, 2000×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

7. Fig. 3
Light- and electron-microscopic findings of the pancreas of ADx/cerulein rats. (A) H&E-stained pancreatic tissue of an ADx/cerulein rat. Strong edema, infiltration of numerous neutrophils, and formation of vacuoles in acinar cells are observed. Many acinar nuclei are condensed, fragmented, and scattered in the shrunken cytoplasms (arrows). (B) TUNEL of the pancreatic tissue of an ADx/cerulein rat. Numerous acinar nuclei including fragmented ones are labeled strongly. (C) Ultrastructures of pancreatic acinar cells in an ADx/cerulein rat. The arrow indicates apoptotic acinar cell. In the nucleus, condensed chromatin with crescent-like clumping can be seen. Large vacuoles are formed within the cytoplasms of adjacent acinar cells (arrowhead) and the polarity of zymogen granules in these cells is disturbed (original magnification: A, 132×; B, 66X; and C, 2000×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

8. Fig. 3
Light- and electron-microscopic findings of the pancreas of ADx/cerulein rats. (A) H&E-stained pancreatic tissue of an ADx/cerulein rat. Strong edema, infiltration of numerous neutrophils, and formation of vacuoles in acinar cells are observed. Many acinar nuclei are condensed, fragmented, and scattered in the shrunken cytoplasms (arrows). (B) TUNEL of the pancreatic tissue of an ADx/cerulein rat. Numerous acinar nuclei including fragmented ones are labeled strongly. (C) Ultrastructures of pancreatic acinar cells in an ADx/cerulein rat. The arrow indicates apoptotic acinar cell. In the nucleus, condensed chromatin with crescent-like clumping can be seen. Large vacuoles are formed within the cytoplasms of adjacent acinar cells (arrowhead) and the polarity of zymogen granules in these cells is disturbed (original magnification: A, 132×; B, 66X; and C, 2000×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

9. Fig. 4
Double staining by TUNEL with FITC-labeling and by DNA-staining with PI. (A) A section processed for TUNEL with FITC-labeling. The white arrows indicate FITC-labeled, TUNEL-positive acinar nuclei with condensed and fragmented appearance. (B) PI staining of the same section. The TUNEL-positive nuclei are stained intensely by PI (original magnification: A and B, 400×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

10. Fig. 5
(A) Temporal changes of apoptotic index of the rat pancreas during cerulein pancreatitis. The apoptotic index of the pancreas increased after starting cerulein infusion. Six hours later, the apoptotic index of ADx/cerulein rats reached ± 8.0, which was approximately fourfold greater than that of sham/cerulein rats. The apoptotic index of sham/cerulein rats increased slightly at 6 hours after starting cerulein. *P < 0.05; ***P < •, ADx/cerulein; ○, sham/cerulein. (B) Effects of HC replacement on the apoptotic index of ADx/cerulein rats. Administration of HC to the ADx/cerulein rats decreased the apoptotic index dose-dependently. When HC was given three times, the increase in apoptotic index of ADx/cerulein rats was suppressed to a level equivalent to that of sham/cerulein rats. ***P < compared with the apoptotic index of ADx/cerulein rats; +P < 0.05 compared with the apoptotic index of sham/cerulein rats; ++P < compared with the apoptotic index of sham/cerulein rats. N.S., not significant.
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

11. Fig. 6
Effects of RU38486 on the nuclear morphology of AR42J cells, examined by staining with PI. AR42J cells were cultured with or without 100 μmol/L of RU38486 for 18 hours at 37°C. (A) The nuclei of RU38486-treated cells are condensed, shrunken, and fragmented. (B) The nuclei of RU38486-untreated cells show normal configuration and DNA density. (C) Electrophoresis of genomic DNA extracted from RU38486-treated AR42J cells (treated with 10 or 100 μmol/L of RU38486 for 18 hours at 37°C). Lane 1, a size marker (HaeIII); lane 2, 0 μmol/L RU38486; lane 3, 10 μmol/L RU38486; lane 4, 100 μmol/L RU The characteristic ladder-like pattern is observed in lanes 3 and 4 but not in lane 2 (original magnification: A and B, 400×).
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions

12. Fig. 7
Effects of DEX on the viability of RU38486-treated AR42J cells. The cells were incubated for 18 hours with RU38486 at a dose of 25 (●), 50 (▨), or 100 (■) μmol/L plus various doses of DEX (0.001, 0.01, 0.1, 10, 100, or 200 μmol/L). 2, Control. After the incubation, the cells in each well were incubated at 37°C for 4 hours in the assay medium containing 0.5 mg/mL of MTT. The optical density value was measured by multiwell spectrophotometer (ELISA reader), using the test wavelength at 570 nm and the reference wavelength at 660 nm. The viability of AR42J cells was decreased dose-dependently by RU38486, but the decrease in the viability was blocked by DEX in a manner depending on the dose of DEX. *P < 0.05.
Gastroenterology  , DOI: ( /S (98) )
Copyright © 1998 American Gastroenterological Association Terms and Conditions