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PubMed2001

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

Adult↗
PubMed1975

Isogeneic or allogeneic transplantation of duct-ligated pancreas in streptozotocin diabetic mice.

Recovery from hyperglycaemia was observed in three different mouse hybrids that were made diabetic with streptozotocin, and then transplanted with pancreas from isogeneic donors whose pancreatic ducts were ligated over 8 weeks earlier. Recovery did not occur in recipients of allografts indicating that islets in ligated pancreas cannot be successfully transplanted across a major histocompatibility barrier. However, in lethally irradiated mice injected with allogeneic bone marrow (allogeneic radiation chimeras), subsequent transplantation of ligated pancreas from either isogeneic donors or allogeneic donors of the same strain as the bone marrow donor decreased blood glucose of diabetic recipients. Thus, irradiation and allogeneic bone marrow therapy allow subsequent allogeneic transplantation of functional islet tissue in diabetic mice. Observations on diabetic mice transplanted isogeneically with ligated pancreas suggest that recovery from hyperglycaemia was more consistent when grafts were placed subcutaneously rather than intraperitoneally and when hosts received ligated pancreas from three donors rather than one. Thus, the site and amount of tissue transplanted are important considerations in the transplantation of ligated pancreas. Persistence of endocrine beta-cells in ligated pancreas was required for recovery in grafted mice since diabetic hosts failed to recover when grafted with ligated pancreas obtained from alloxan or streptozotocin-treated, diabetic donors.

Animals↗
PubMed1987

Pancreas transplantation: clinical considerations.

The number of pancreas transplants performed and the success rate have increased significantly since the first segmental pancreas transplant was performed in 1966. Since 1977, 716 pancreas transplants have been performed in 670 patients at 69 institutions. Currently 230 grafts (32 per cent) are listed as functioning (insulin independent). The present 1-year actuarial graft and survival rates at the University of Minnesota are 43 and 88 per cent, respectively. The indications for pancreas transplantation and the selection of recipients have undergone modification, and more nonuremic nonkidney transplant patients are now receiving pancreas allografts. A variety of techniques have been used for pancreas transplantation. Whole or segmental pancreas grafts have been used. Most centers drain the graft exocrine secretions into the gastrointestinal tract as a Roux-en-Y pancreaticojejunostomy or into the bladder as a pancreaticocystostomy. The most common complications requiring radiologic evaluation and treatment include vascular thromboses utilizing technetium flow studies and arteriography and intra-abdominal fluid collections and infections requiring ultrasonography and CT scans. Percutaneous aspiration of intra-abdominal fluid collections is important for diagnosis but has not been successful therapeutically. Intra-abdominal infections are most common in patients with enteric drainage of the pancreas graft, which carries a high risk of contamination at the site of anastomosis. Most intra-abdominal infections require surgical drainage and removal of the graft.

Cadaver↗
PubMed1990

Anatomy of the pancreas and Langerhans islets in snakes and lizards.

The pancreas of snakes (18 species) was comparatively examined and classified into five major types, based on structure of the lobes and ducts, spatial relationships with the spleen and the gall bladder, and the disposition of islet cells. These types trend toward fusion of the pancreatic lobes and compaction of the pancreas--a progression that coincides with the phylogeny of the snakes. The more primitive pancreas of lizards (17 species) also was surveyed; that of Varanus is of special interest because its structure is intermediate between the extended, tri-lobate pancreas of lizards and the compact pancreas of snakes and may represent a transitional link in the evolution of this organ. Islet tissue is always confined to the dorsal lobe and is concentrated in its distal region adjacent to the spleen. In primitive snakes and in Varanus, a large islet mass is sequestered within a distinct juxtasplenic "islet body" distanced from the dorsal lobe and connected to it by a slender stalk. In some of the most advanced snake species, numerous islets of endocrine cells are found within the spleen. The occurrence and formation of these intrasplenic islets is described in detail. The anatomic "affinity" between spleen and the islet region of the pancreas is discussed. A hypothesis for the development of the pancreas from embryonal placodes on the mid-gut is presented; it proposes that the exocrine and the endocrine components derive from different progenitor cells, and that the endocrine progenitors are located in the center of the dorsal placode. The hypothesis combines embryological and evolutionary views about the origin of the pancreas, and offers a rationale for differences in its structure and in the disposition of the islets.

Animals↗
PubMed2003

Anatomical study of the pancreas in the house musk shrew (Suncus murinus), with special reference to the blood supply and innervation.

To examine the macroscopic structure, blood supply, and innervation of the pancreas in the house musk shrew (Suncus murinus), we performed gross anatomical dissection and whole-mount immunostaining of the autonomic nerve of Suncus pancreases based on neurofilament protein (NFP) immunoreactivity. The adult Suncus pancreas is clearly separated into right and left lobes that are not fused. The right lobe of the Suncus pancreas is located in the dorsum of the duodenum and to the right of the common bile duct independently. The right lobe is supplied by branches of the superior mesenteric artery, and is innervated by branches that originate from the superior mesenteric plexus and run along the arterial branches of the superior mesenteric artery. The left lobe occupies 9/10 of the entire pancreas and is located to the left of the common bile duct. It is supplied mainly by branches of the splenic and common hepatic arteries, and is innervated by branches that originate from the celiac plexus and run along the splenic and common hepatic arteries. According to previous studies on the blood supply and innervation of the human pancreas, the right and left lobes of the Suncus pancreas correspond to the pancreatic parts derived from the ventral and dorsal pancreatic buds. The current results suggest that the Suncus pancreas is a suitable experimental model for studying the development of the human pancreas.

Animals↗
PubMed1996

Mycophenolate mofetil immunosuppression in rat pancreas allotransplantation.

Prolongation of pancreas allograft survival has been difficult to achieve in rodent models despite use of immunosuppression regimens that successfully increase graft survival of other organs. The purpose of this study was to evaluate a new immunosuppressive agent, mycophenolate mofetil (MM), for its ability to prevent rejection in a rat pancreas transplant model. In addition, using congenic strains of rats, the efficacy of MM in rat pancreas transplantation was treated in the context of isolated class I or class II major histocompatibility (MHC) differences. MM in doses of 12.5 to 37 mg/kg significantly prolonged BUF to LEW heart transplant survival beyond a 14-day course of therapy thereby demonstrating its immunosuppressive efficacy. In similar pancreas transplant experiments, however, most grafts were rejected during the period of MM administration. Combination therapy with MM and cyclosporine did not extend pancreas survival beyond that achieved with MM alone (Mean Survival Time of 13.8 +/- 2.7 vs 11.7 +/- 1.6 days, respectively). Conversely, combined therapy with MM and antilymphocyte serum achieved a mean survival for BUF to LEW pancreas transplants of 52.3 +/- 24.8 days, which was significantly longer than that observed for either MM (11.7 +/- 1.6) or ALS (18.0 +/- 7.6) alone. MM therapy doubled pancreas allograft survival when used in the face of class I MHC disparity and compared to controls (19.5 +/- 1.0 vs 10.0 +/- 1.9 days) but did not prolong grafts that were disparate at only the class II locus (12.6 +/- 1.5 vs 12.0 +/- 1.2 days, respectively, for MM vs control). These data indicate that MM may not be an effective single agent immunosuppressive for pancreas transplantation except when MHC disparity is limited to the class I locus.

Animals↗
PubMed1992

Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas.

In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit greater than guinea pig greater than or equal to pig and cat much greater than dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4 degrees C, but not at 37 degrees C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproducible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas.

Animals↗
PubMed1995

Ischemia reperfusion of the pancreas: a new in vivo model for acute pancreatitis in rats.

Based on the concept that ischemia is an important factor in the pathogenesis of acute pancreatitis, we developed a new model of complete ischemia/reperfusion of the pancreas in the rat. The aim of this study was to investigate the microcirculation of the pancreas after complete and reversible ischemia at different times after reperfusion by using intravital fluorescence microscopy. In addition, the effect of ischemia/reperfusion on the pancreas was assessed by means of light and electron microscopy and measurement of serum pancreas amylase concentration. In 35 adult Sprague-Dawley rats ischemia of the pancreas was induced by temporary occlusion of the four supplying arteries. Sham-operated animals served as controls (group A). After periods of 30 min (group B), 60 min (group C) or 120 min (group D) of ischemia the organ was reperfused. To exclude the influence of hypovolemia on microcirculation in group E (120 min ischemia) hydroxyethylstarch (HES) was given i.v. to maintain central venous pressure at baseline values. For intravital fluorescence microscopy the pancreas was exteriorized on a stage and quantitative analysis of microcirculation, including functional capillary density and leukocyte-endothelium interaction, was performed after 30 min, 1 h and 2 h of reperfusion. Serum pancreas-amylase was measured at control (prior ischemia) and at 2 h after reperfusion. Tissue samples for light and electron microscopy were taken 2 h after reperfusion. In sham-operated animals, functional capillary density (FCD) remained within baseline values (FCD 407.7 +/- 9 cm-1) during reperfusion. Dependent on the time of ischemia and time of reperfusion a gradual reduction in functional capillary density was observed; after 2 h of ischemia only 35% of capillaries were perfused (FCD 140.9 +/- 28.3 cm-1). Reduced functional capillary density was associated with an increase of perfusion heterogeneity to a maximum of 0.65 +/- 0.12, as against 0.13 +/- 0.02 in control animals. With a 2 h ischemia leukocyte-endothelium interaction was enhanced after 0.5 h of reperfusion (8-fold increase of adherent leukocytes in comparison to control) followed by a further significant increase until 2 h after the beginning of reperfusion. Amylase concentration after ischemia of 2 h (2967 +/- 289 U/l) was significantly higher as compared to controls (1857 +/- 99 U/l). Differences between group E and D were not observed. Pancreatic tissue injury was ascertained by histopathological studies. These results indicate that complete ischemia/reperfusion of the pancreas induces pancreatic microvascular failure. The severity of changes depends on duration of ischemia and duration of reperfusion. The morphological and biochemical changes suggest that ischemia/reperfusion causes an inflammatory reaction as observed in acute pancreatitis.

Animals↗
PubMed1991

Glutathione metabolism in the pancreas compared with that in the liver, kidney, and small intestine.

The pancreas plays a major role, along with the kidney, liver, small intestine, and several other organs, in glutathione (GSH) metabolism, as evidenced by the large concentration of GSH in the pancreas, its rapid turnover rate, and the presence, at significant levels, of various enzymes involved in GSH metabolism. The pancreas appears to obtain much of the cysteine that is required for both GSH and protein synthesis by hydrolyzing plasma GSH to its constituent amino acids and then transporting cysteine into the cells. GSH hydrolysis is accomplished by the ectoenzymes gamma-glutamyl transferase (GGTase) and aminopeptidase N, both of which are present in the pancreas. Only the kidney has a greater GGTase activity. Although pancreatic GSH synthesis has not been directly demonstrated, pancreatic secretory protein synthesis is substantial, and these proteins contain significant amounts of cysteine as disulfides. The pancreas also contains significant levels of protein disulfide isomerase, glutathione peroxidase, and NADPH:GSH oxidoreductase. Protein disulfide isomerase, using oxidized glutathione generated by glutathione peroxidase, is important in the formation of disulfide bonds in secretory proteins in the pancreas. No other organ has a higher specific activity of protein disulfide isomerase. By analogy with kidney and liver, the pancreas presumably exhibits a rapid apical secretion of GSH. The purpose of this apical secretion is unknown in the kidney. In the liver, it is important in bile secretion. The large GGTase activity of apical plasma membranes in the pancreas is likely to be instrumental in the hydrolysis, and subsequent recovery of the constituent amino acids of apically secreted GSH, as occurs in the kidney and liver.

Animals↗
PubMed1997

[Duodenum preserving resection of the head of the pancrease in therapy of pancreas divisum].

In 1-6% of the patients who are investigated by endoscopic retrograde cholangio-pancreatography a pancreas divisum can be found. In some patients pancreas divisum can lead to an acute relapsing and finally chronic pancreatitis (CP). Surgical intervention in these cases seems to offer a good chance of recovery. We report our experience with the duodenum-preserving resection of the head of the pancreas in 12 patients with pancreas divisum and CP. In all patients the preoperative evaluation showed clinical, functional or radiological signs of CP. The duodenum-preserving resection of the head of the pancreas was carried out in all patients without perioperative mortality. Ten postoperative versus eight preoperative patients showed a pathological exocrine function of the pancreas. Endocrine function, measured by the oral glucose tolerance test (OGTT), improved postoperatively in two patients. Eleven patients who were investigated after a mean follow-up time of 31 months (3-75 months) were completely pain free. No late mortality occurred. OGTT revealed a diabetic endocrine function in two patients. Disturbed exocrine pancreatic function had to be substituted in nine patients. One patient had to be reoperated by duct incision and renewal of the pancreatico-jejunostomy 10 months after the first operation. In conclusion, the duodenum-preserving resection of the head of the pancreas reduced pain in all patients with pancreas divisum and CP and may lead to an improvement of endocrine pancreatic function. Other, nonresecting procedures or endoscopic interventional therapy should be avoided in these patients.

Adult↗
PubMed1994

Combined analysis of islet cell antibodies which cross-react with mouse pancreas, antibodies to the M(r) 64,000 islet protein, and antibodies to glutamate decarboxylase in subjects at risk for IDDM.

With regard to progression to diabetes, ICA cross-reactive with mouse pancreas, antibodies to the M(r) 64,000 islet antigen (64K), antibodies immunotrapping brain GAD activity, and IAA were analysed in 53 ICA-positive first-degree relatives of IDDM patients and 18 ICA-positive schoolchildren without a family history of diabetes. Sera from 29 (55%) relatives did not bind to mouse pancreas, whereas 24 (45%) displayed cross-species reaction. ICA titres on human and mouse pancreas were weakly correlated in the overall population (p < 0.05) but more strongly (p < 0.01) in only those subjects who displayed antibodies on tissues from both species. GAD and 64K antibodies were detected in 31% and 35% of relatives. In schoolchildren, the frequencies of cross-species reactive ICA (22%), GAD antibodies (6%), 64K antibodies (22%), and IAA (6%), were lower (p < 0.05) than in relatives. A strong correlation (p < 0.0001) was observed between GAD and 64K antibodies. GAD or 64K antibodies were strongly correlated with ICA on human pancreas (p < 0.0001) but poorly with ICA on mouse pancreas (p = 0.05). After pre-incubation of sera with brain homogenate, ICA titres were unaffected on mouse pancreas but reduced on human pancreas. ICA-positive subjects who displayed neither cross-species reactive ICA nor GAD or 64K antibodies were more frequent (p < 0.05) among schoolchildren than relatives, whereas subjects who displayed all antibody specificities were more numerous (p < 0.04) in relatives. All relatives with ICA binding only to human pancreas, as well as all schoolchildren, permanently displayed an AIRG higher than the first control percentile and remained non-diabetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Pancreas organ transplantation. Short and long-term results in terms of diabetes control.

Diabetes mellitus is a very common and dreadful disease which cannot be cured by exogenous insulin substitution. Many of the patients suffer from recurrent, and sometimes rather dangerous, hypo- or hyperglycemias and, in the long term, from the well-known secondary diabetic complications. At the moment, pancreas transplantation is the only known therapy to reliably reestablish endogenous insulin secretion responsive to normal feed back controls. Within the last decade, pancreas transplantation has evolved as a clinically well-established procedure. Nevertheless, the perioperative risk after pancreas/kidney transplantation is still higher than after isolated kidney transplantation. However, the benefits of a functioning pancreas graft for the patients are enormous. Ten-year survival of type-I diabetic patients with combined pancreas/ kidney grafts is dramatically better than of those with an isolated kidney graft. Long-term function of the pancreas grafts is excellent, reaching more than 60% after 10 years. Contrary to kidney transplantation, chronic rejection does not seem to be a major problem. Blood glucose levels in the fasting state, after glucose challenge, and in the postprandial state are completely normalized. A significant peripheral hyperinsulinemia, however, is found when the pancreas graft is connected to the systemic venous circulation. Thus, portal venous drainage of the pancreas graft, which is already being performed by a few transplant centers routinely, might be the procedure of choice for the future. Beneficial effects on secondary diabetic lesions can only be expected after a rather long observation period. In addition, for all secondary diabetic complications, there is a point of no return. Nevertheless, significant improvement of diabetic polyneuropathy, diabetic nephropathy, and the disturbed microcirculation has been convincingly demonstrated. The effect on diabetic retinopathy, however, is still controversial. One of the most impressive effects for the pancreas graft recipients seems to be the enormous improvement in quality of life, which is reported unanimously by almost all patients. Thus, simultaneous pancreas/kidney transplantation can be regarded as the optimal and only causal therapy for type-I diabetic patients with end-stage renal disease.

Animals↗
PubMed2000

Frontiers of pancreas regeneration.

Recent advances in molecular biological techniques have made the search for the factors in pancreas regeneration more intensive. Many transcription factors and growth factors have been suggested to be involved in the proliferation, differentiation, and maintenance of endocrine and exocrine pancreas. Among the transcription factors, PDX-1 has been examined in a major pancreatectomy model and is suggested to play a role in beta-cell differentiation. Among the growth factors and related peptides, reg protein seems to be a promising candidate which can be applied to clinical practice. Our previous study showed that proton pump inhibitor-induced endogenous hypergastrinemia enhanced insulin secretion and pancreas regeneration. Our results and other studies have suggested that endogenous gastrin induces beta-cell differentiation. On the other hand, the role of classical gut hormones such as gastrin and cholecystokinin in pancreas regeneration has become less significant, as it has been shown that rodents deficient in the genes for these hormones form almost normal pancreas. Results in dogs have shown that pancreas regeneration occurs after major pancreatectomy. A preliminary experiment in primates also suggests latent developmental capacity in the adult primate pancreas. These results lead us to expect that regeneration of the remnant pancreas after subtotal pancreatectomy would be a good target of certain therapies to enhance pancreatic regeneration.

Adult↗
PubMed2006

Prevalence of pancreatic and biliary tract tumors in pancreas divisum.

BACKGROUND: The present study was undertaken to evaluate the prevalence of pancreatic and biliary tract tumors in pancreas divisum (PD). METHODS: A retrospective single-center study was performed, and a total of 118 cases of complete PD and 7850 cases of fused pancreas were identified among the 8537 consecutive new endoscopic retrograde cholangiopancreatography (ERCP) examinations performed between 1980 and 2002. The prevalence of pancreatic cancer (PCA), intraductal papillary mucinous neoplasms (IPMNs), other pancreatic tumors, and biliary tract cancer in the patients with PD and the patients with a fused pancreas were compared. RESULTS: The prevalence of the pancreatic tumors in the PD patients was: PCA, 10%; IPMN, 5.1%; other pancreatic tumors, 2.5%. The prevalence of pancreatic tumors in the patients with a fused pancreas was: PCA, 4.8%; IPMN, 2.6%; and other pancreatic tumors, 1.1%. The prevalence of PCA was significantly higher in the patients with PD than in those with a fused pancreas (P = 0.008; OR, 2.24). The percentages of PD patients with PCA who had pancreatic-type pain and a serum pancreatic enzyme elevation were significantly higher than among the PD patients without PCA. The prevalence of biliary tract cancer was 0.8% in the PD group and 5.3% in the fused pancreas group, and it was significantly lower in PD than in fused pancreas (P = 0.031). CONCLUSIONS: The results of this study showed a significantly higher prevalence of PCA in PD than in fused pancreas. We concluded that patients with PD, especially patients presenting with pancreatic-type pain and pancreatic enzyme elevation, should be carefully followed up because of the risk of developing PCA.

Adolescent↗
PubMed1998

Post-transplantation hypoglycaemia in type 1 diabetic pancreas allograft recipients.

Physiologic replacement of insulin in patients with type 1 (insulin-dependent) diabetes following pancreas allograft transplantation results in normoglycaemia during fasting and postprandial states. However, this is achieved at the expense of peripheral hyperinsulinaemia in the heterotopic pancreas allograft recipients with systemic insulin drainage. In addition, the pancreas allograft is denervated and thus devoid of autonomic nervous regulation of pancreatic beta-cell secretion. Recent reports of hypoglycaemia (symptomatic and asymptomatic), which can be fatal, have raised serious concerns regarding the aetiology of the hypoglycaemic epiphenomenon in type 1 diabetic pancreas allograft recipients. Although the prevalence of significant hypoglycaemia following pancreas transplantation remains unknown, it is important to conduct studies to determine the mechanisms, the natural history, predictors and treatment as well as the long-term prognosis (graft and patient survival rates) of type 1 diabetic patients who develop pancreas-allograft-associated hypoglycaemia. Indeed, predictors of hypoglycaemia following pancreas allograft could significantly impact on the selection of appropriate therapeutic options for pancreas allograft transplantation. Finally, whether postpancreas allograft transplantation-associated hypoglycaemia in type 1 diabetic patients carries greater morbidity and mortality when compared to those without hypoglycaemia deserves to be investigated.

Diabetes Mellitus, Type 1↗
PubMed1994

Novel expression of gastrin (CCK-B) receptors in pancreatic carcinomas and dysplastic pancreas from transgenic mice.

Transgenic mice bearing the elastase I promoter--SV40 T-antigen fusion gene (ELSV) develop pancreatic acinar cell carcinomas by 3 to 6 months of age. The purpose of the study was to determine if pancreatic carcinomas and dysplastic pancreas from the Tg (Ela-1, SV40E + Ela-1, neo) Bri19 strain of ELSV transgenic mice express gastrin (CCK-B) receptors. To accomplish this, we utilized iodine 125 (125I)-gastrin binding studies, reverse transcription-polymerase chain reaction (RT-PCR), and Southern blot analysis to examine pancreatic carcinomas from 26-week-old male ELSV transgenic mice, dysplastic pancreas from 8-week-old male ELSV transgenic mice, and normal pancreas from 30-week-old nontransgenic male mice (SJL/J) and from 8-week-old nontransgenic male mice (B6SJLF1/J). No saturable gastrin binding to normal nontransgenic mouse pancreas was found. In contrast, saturable gastrin binding was detected at pH 6.5, 22 degrees C, in 9 of 13 pancreatic carcinomas and all 5 dysplastic pancreata. Competitive inhibition 125I-gastrin binding assays showed gastrin bound to a single class of high-affinity receptors (receptor binding affinity [Kd] 0.11 +/- 0.02 nM, binding capacities ranging from 1 to 60 fmol/mg protein for pancreatic carcinomas; Kd: 0.15 +/- 0.04 nM, binding capacities ranging from 1 to 9 fmol/mg protein for dysplastic pancreas). RT-PCR and Southern blot analysis confirmed 125I-gastrin binding studies by demonstrating gastrin (CCK-B) receptor mRNA expression in pancreatic carcinomas and dysplastic pancreas but an absence of mRNA expression in normal nontransgenic mouse pancreas. In conclusion, pancreatic carcinomas and dysplastic pancreas in ELSV transgenic mice novelly express gastrin (CCK-B) receptors. This expression may provide a growth advantage to acinar cells as part of the multistage process of carcinogenesis.

Animals↗
PubMed1996

Isolation of tissue-type plasminogen activator, cathepsin H, and non-specific cross-reacting antigen from SK-PC-1 pancreas cancer cells using subtractive hybridization.

We have used subtractive hybridization to isolate cDNAs overexpressed in SK-PC-1 pancreas cancer cells. Forty-five independent clones corresponding to 11 genes were identified. Their expression in cultured pancreas cancer cells, normal pancreas tissue, and normal exocrine pancreas cultures was examined by Northern blotting. cDNA clones can be grouped into two broad categories: (1) those corresponding to genes expressed at high levels both in tumor cell lines and in primary cultures of normal pancreas, but not in normal tissue (i.e. thymosin beta4(3), cytokeratin 18, beta-actin, pyruvate kinase and mitochondrial genes); and (2) those corresponding to genes expressed at high levels in pancreas cancer cultures but not in normal pancreas tissue or cultured cells (i.e. tissue-type plasminogen activator and cathepsin H). The overexpression of these proteases in pancreas cancers suggests that they play a role in the aggressive biological behavior of this tumor.

Antigens, Neoplasm↗
PubMed1993

Peptide YY in the mammalian pancreas: immunocytochemical localization and immunochemical characterization.

Peptide YY (PYY) was demonstrated by immunochemical and/or immunocytochemical methods in endocrine cells in the pancreas of adult mice, rats, guinea-pigs, cats, dogs, pigs and cows. In the pancreas of mouse and rat, immunoreactive PYY was observed in a major subpopulation of the glucagon cells (splenic lobe of the pancreas); immunoreactive PYY also occurred in a subpopulation of the pancreatic polypeptide (PP) cells (duodenal lobe), and in a few extra-insular endocrine cells dispersed throughout the pancreatic parenchyma. In the pancreas of cat, dog and pig immunoreactive PYY was found to coexist with PP, but not with glucagon. Radioimmunoassay (RIA) revealed PYY-like material in extracts of pancreas (and colon) of all the species examined. The highest concentrations were found in the pancreas of cat and mouse; moderate amounts were found in the rat and only small amounts were detected in guinea-pig and pig. The concentrations in the pancreas were uniformly much lower than those in the colon. Analysis by high performance liquid chromatography (HPLC) showed that the PYY-immunoreactive material from pancreas (and rat colon) had an elution profile very similar to that of synthetic PYY, and distinct from that of PP and neuropeptide Y.

Amino Acid Sequence↗