Takamasa Tokoro

Differentiation of acinar cells into acinoductular cells in regenerating rat pancreas

Background/Aims: Several lines of experimental data suggest that acinar cells have the potential to differentiate into ductular-like cells, and these newly formed acinoductular cells may act as (facultative) stem cells. The purpose of this study was to test this hypothesis in a model of pancreatic regeneration in rats. Methods: In the current study, using a 90% pancreatectomy as a rat model for pancreatic regeneration, we serially examined the pancreatic tissues in a time-dependent manner by conventional histology and immunostaining. Cell proliferation was assessed by in vivo bromodeoxyuridine (BrdU) labeling. Results: By 24 h after surgery, acini showed depleted granules with more dilated lumens (acinar ectasia). By day 2, focal regions of regeneration appeared which were separated by fibrosis and composed of ductular-like cells (tubular complexes) and acinar cells with dilated lumina. Double immunofluorescent staining revealed that both amylase and CK19 were positive in the same cells localized to the focus of regeneration from the animals on day 2, the phenotype of cells from those regions apparently reverted to acinar cells, and the regions completely disappeared by day 7. By 48 h after surgery, the number of BrdU-positive cells increased 4.3-fold in ductular cells, and 2.5-fold in acinar cells compared with control tissue. Conclusion: Acinar cells through acinoductular metaplasia may be a source of pancreatic regeneration.

Comparative study of antibody removal before pig-to-baboon and human ABO-incompatible renal transplantation

THE MECHANISM of rejection following pig-to-baboon xenotransplantation (XenoTx) has been compared with that following ABO-incompatible allotransplantation (ABO-Tx), because both involve natural antibody (Ab) against carbohydrate epitopes. Recently, ABO-Tx has shown excellent outcomes following pretreatment with double filtration plasmapheresis (DFPP). We compared changes in anti-donor Ab and histopathology of the renal graft between ABO-Tx and XenoTx. Before renal transplantation (Tx), DFPP was performed on days 26, 24, 22, and 21 in ABO-Tx (n 5 25) and on days 22 and 0 (immediately before reperfusion) in XenoTx (n 5 4). Cyclosporine (or tacrolimus), steroid, and cyclophosphamide were administered to both patients and baboons. Baboons were divided into two groups according to the extent of Ab removal: XenoTx Group I, Ab removal to the same extent as in ABO-Tx (n 5 2); XenoTx Group II, nearly total removal of Ab (n 5 2). Anti-A/B and anti-pig IgM (IgG) Abs were measured by flow cytometry. Twenty-five patients underwent ABO-Tx. All grafts remain functioning, except in two cases where the grafts were lost from recurrence of the original disease after 6 months and from chronic rejection after 5 years, although 3 had reversible humoral rejection. In pig-to-baboon renal transplantation without DFPP pretreatment, hyperacute rejection (HAR) was observed 60 and 90 minutes after transplantation. In XenoTx Group I, no HAR was observed. Grafts were rejected on days 6 and 7, and showed coagulative necrosis caused by vascular rejection; biopsies on days 1, 4, and 5 showed only minimal changes. In XenoTx Group II, the baboons could not tolerate the extra DFPP and died 4 hours and 2 days after transplantation. Immunohistochemical study of the grafts showed IgM, IgG, and C3 binding to endothelial cells within 1 hour post-Tx in XenoTx Group I, and IgM and C3 binding as early as 1 hour post-Tx in XenoTx Group II, while no Ab binding was detected at any time (1 hour to 2 years) after ABO-Tx. The same extent of Ab removal in XenoTx Group I as in ABO-Tx inhibited HAR but could not prevent delayed vascular rejection. Even when anti-pig Ab was depleted by 98% (XenoTx Group II), the small amount of remaining Ab still had the ability of binding to the pig graft within 1 hour. For successful xenografting, we suggest that the concentration of xenoantigen epitopes expressed on pig grafts may need to be reduced by genetic engineering to the level of the ABO antigens on human kidneys.

Cullen's sign in pancreatic trauma

Cullen’s sign (1) is named after Cullen, professor of gynecology at Johns Hopkins University, who in 1918 described the occurrence of the sign in a patient with a ruptured ectopic pregnancy. Now, it is more commonly observed in acute pancreatitis and rupture of an abdominal aortic aneurysm (2). This sign has also been described in other situations such as perforated duodenal ulcer (3), liver disease (4), and splenic rupture (5). However, to our knowledge, there has been no report of this sign associated with trauma. We report herein a rare case of Cullen’s sign following pancreatic blunt trauma.

Intraductal papillary mucinous tumor of the pancreas in a young man: report of a case.

Abstract.We report the rare case of an intraductal papillary mucinous tumor (IPMT) in a man younger than 30 years of age. The patient was admitted with upper abdominal pain and an elevated amylase level of 662u2009IU/l. Ultrasonography showed a cystic mass in the pancreatic body and endoscopic retrograde cholangiopancreatography (ERCP) revealed a dilated pancreatic duct with a filling defect communicating with the tumor. He was successfully treated by segmental resection, which seems to be the best surgical option for pancreatic body tumors since it results in long-term survival and preserves as much pancreatic parenchyma as possible. Nevertheless, it can only be done in the absence of additional nodules along the pancreatic duct. A pathological diagnosis of intraductal papillary adenocarcinoma of the noninvasive type was confirmed, and both stumps were free of tumor.

PSGBI Society News

s The abstracts of the 29th Annual Meeting, Southampton, November 20–21, 2003, are published as an online supplement to Pancreatology: www.karger.com/pan/2003/003/006/toc Pancreatic Society of Great Britain and Ireland

PREVENTION OF FREE RADICAL-INDUCED APOPTOSIS BY INDUCTION OF HUMAN RECOMBINANT Cu, Zn-SOD IN PIG ENDOTHELIAL CELLS.: Abstract# 936 Poster Board #-Session: P193-III

Vascular endothelial cells are the prime target in ischemia reperfusion injury. Growing evidence has shown that one of the main etiologies is considered to be reactive oxygen species (ROS) that induce endothelial-cell death either by necrosis or apoptosis. Cultured porcine endothelial cells were transfected with human copper, zinc-superoxide dismutase (h-Cu, Zn-SOD) to investigate whether these cells can prevent apoptosis from oxidative injury in vitro. The endothelial cells were cultured with SIN-1 (3-morpholinosydnonimine-N-ethylcarbanride) as a donor of peroxinitrite (ONOO(-)). The control cells without the gene transfection developed characteristic apoptotic changes both morphologically and biochemically when they were incubated with SIN-1 of 200 M. However, the cells showed necrosis predominantly when the concentration of SIN-1 was 1,000 M. On the other hand, the cells transfected with h-Cu, Zn-SOD showed significantly less evidence of apoptotic change after exposure to SIN-1. Nitric oxide (NO) did not significantly affect the viability of either the control cells or the transfected cells. One of the potent ROS, peroxinitrite, is considered to play a significant role in ischemia reperfusion injury. SIN-1 can produce peroxinitrite in vitro that induces endothelial-cell damage by apoptosis. This type of cytotoxicity can be successfully prevented by transfection of the h-Cu, Zn-SOD into the cells.