Eosinophilic gastroenteritis due to cow's milk allergy presenting with acute pancreatitis.

Eosinophilic gastroenteritis (EGE) is characterized by eosinophilic infiltration of the digestive organs, most commonly of the stomach and the duodenum. Symptoms of EGE are nonspecific and include nausea, vomiting, abdominal pain, dyspepsia, malabsorption, ascites and weight loss. The various symptoms of EGE depend on its location and the depth of gastrointestinal eosinophil infiltration. We report a case presenting with acute pancreatitis caused by a milk allergy. The patient's symptoms rapidly improved after treatment with corticosteroids, and he remained symptom-free for more than 20 months by the elimination of cow's milk from his diet. Serum titers of pancreatic enzymes and total bilirubin simultaneously recovered and blood eosinophil counts normalized. The causative allergens of EGE are too various to detect; however, allergologic exams revealed that a cow's milk allergy had provoked EGE in our case. Adult-onset cow's milk allergies are rare; when seen, however, they may present severe complications such as anaphylaxis, gastroenteritis and pancreatitis. When unaccountable gastrointestinal symptoms are observed, EGE caused by food allergies should be included in the differential diagnosis.

Sporadic fundic gland polyp-related adenomas occurred in non-atrophic gastric mucosa without helicobacter pylori infection.

We report three cases of adenoma associated with sporadic fundic gland polyp (FGP) in the non-atrophic fundic gland mucosa without Helicobacter pylori (HP) infection, which was verified with both serological and histopathological examinations. Gastric tubular adenoma (flat adenoma) is common and focal cancers occurring in the hyperplastic polyp of foveolar cell type are also sometimes experienced. However, adenomas occurring in sporadic FGP are valuable, as they are very rare, in upper gastrointestinal endoscopy. Whether or not these adenoma lesions of three sporadic FGP cases may become the background of protruded gastric cancers without HP infection remains unclear. Therefore, we emphasize the importance of histological examination on fundic gland polyps that are > 5 mm in size to accumulate new similar cases. Follow-up studies of these lesions are also needed to evaluate their outcomes.

Ethanol impairs the assembly and disassembly of actin cytoskeleton and cell adhesion via the RhoA signaling pathway, catenin p120 and E-cadherin in CCK-stimulated pancreatic acini.

The purpose of the present study was to evaluate the effects of EtOH on RhoA, actin cytoskeleton, catenin p120 and E-cadherin and their interactions in CCK-stimulated rat pancreatic acini. In isolated rat pancreatic acinar cells, CCK stimulation enhanced protein expression and association of RhoA, G(α13), Vav-2, catenin p120 and E-cadherin. CCK induced translocation and activation of RhoA and actin-filamentous assembly and disassembly. RhoA was diffusely localized throughout the acinar cell in the resting state and redistributed to the apical site in response to submaximal CCK stimulation and to a lesser extent in response to supramaximal CCK stimulation. Ethanol and subsequent submaximal CCK stimulation mimicked the effect of supramaximal CCK stimulation in terms of amylase secretion and morphologic effects. However, inhibition of RhoA translocation and activation were observed only with ethanol pretreatment. Ethanol followed by supramaximal CCK stimulation disrupted the well-defined localization of catenin p120 and E-cadherin around the lateral plasma membrane. These data suggest that ethanol impaired the assembly and disassembly of actin cytoskeleton and impaired cell-cell adhesion via the RhoA signaling pathways, catenin p120 and E-cadherin in CCK-stimulated pancreatic acini.

Cholecystokinin stimulates the recruitment of the Src-RhoA-phosphoinositide 3-kinase pathway by Vav-2 downstream of G(alpha13) in pancreatic acini.

In isolated rat pancreatic acini, Src, RhoA, PI3-K, Vav-2, G(alpha12), and G(alpha13) were detected by immunoblotting. CCK enhanced the levels of these proteins, and the levels of Src and RhoA were reduced by the Src inhibitor herbimycin A and the Rho inhibitor pravastatin. The PI3-K inhibitor wortmannin reduced the level of PI3-K. These inhibitors also decreased amylase secretion in CCK-treated pancreatic acini without altering basal secretion. Immunoprecipitation studies indicated that CCK caused Src to associate with Vav-2, RhoA, and PI3-K and RhoA and Src to associate with Vav-2. Ras, RasGAP, and SOS did not coimmunoprecipitate with Vav-2, and RasGAP and SOS did not coimmunoprecipitate with RhoA. CCK also enhanced Vav-2 and RhoA to coimmunoprecipitate with G(alpha13). We conclude that CCK stimulates the recruitment of the Src-RhoA-PI3-K signaling pathway by Vav-2 downstream of G(alpha13) in pancreatic acini.

Receptor-operated Ca2+ influx and its association with the Src family in secretagogue-stimulated pancreatic acini.

We investigated signal transduction between receptor-operated Ca(2+) influx (ROCI) and Src-related nonreceptor protein tyrosine kinase (PTK) in rat pancreatic acini. CCK and the Ca(2+) ionophore enhanced the Src-related PTK activity, whereas the high-affinity CCK-A receptor agonists, fibroblast growth factor (FGF), and the protein kinase C (PKC) activator had no or little effect. This increase was abolished by eliminating [Ca(2+)](o), loading of the intracellular Ca(2+) chelator, and administering the PTK inhibitor genistein. While genistein inhibited extracellular Ca(2+) or Mn(2+) entry induced by CCK and carbachol, it did not affect intracellular Ca(2+) release and oscillations. CCK dose-dependently increased the Src phosphotransferase activity, which was abolished by inhibitors of G(q) protein, phospholipase C (PLC), and Src, but not by the calmodulin kinase (CaMK) inhibitor. Intensities of the Src band and amounts of tyrosine phosphorylated Src were enhanced by CCK stimulation. Thus, Src cascades appear to be coupled to the low-affinity CCK-A receptor and utilize G(q)-PLC pathways for their activation, independent of PKC and CaMK cascades. The low-affinity CCK-A receptor regulates ROCI via mediation of Src-related PTK and activates Src pathways to cause [Ca(2+)](o)-dependent pancreatic exocytosis.

Deactivation of ROCK-II by Y-27632 enhances basolateral pancreatic enzyme secretion and acute pancreatitis induced by CCK analogues.

In isolated rat pancreatic acini, protein expression of RhoA and Rho-associated kinase, ROCK-II, and the formation of immunocomplex of RhoA with ROCK-II were enhanced by CCK-8, carbachol, and the phorbol ester TPA. The ROCK-specific inhibitor, Y-27632, did not alter basal amylase secretion, whereas it potentiated CCK-stimulated pancreatic enzyme secretion in vitro. During caerulein-induced pancreatitis occurring in mice in vivo, Y-27632 enhanced serum amylase levels and the formation of interstitial edema and vacuolization at 12-18h after the first injection of caerulein. Y-27632 in turn inhibited the recovery of protein expression of ROCK-II at 18h after the first caerulein injection. These results suggest that RhoA and ROCK-II assemble normal CCK-stimulated pancreatic enzyme secretion and prevent caerulein-induced acute pancreatitis.