Fumihiko Nozu

Hemodynamics in the colonic mucosa of rats with dextran sulfate-induced colitis in the early phase.

We investigated hemodynamics in the colonic mucosa of rats with experimental colitis induced by the administration of dextran sulfate sodium (DSS). As parameters of hemodynamics, we determined the indices of mucosal hemoglobin concentration (IHb) and mucosal oxygen saturation (ISO2), measured by reflectance spectrophotometry, and an index of colonic mucosal blood flow (Flow), measured by laser-Doppler flowmetry. In the ascending colon, each parameter was measured by a combination of these methods after 1, 3, 5, 7, and 10 days of DSS administration. Histopathological examination was also performed. IHb in the DSS group increased with time; on the 7th day, the value was 126.9±8.32, while that in the control group was 85.0±4.14, IHb in the DSS group being significantly increased (P<0.02). ISO2 in the DSS group was lower than that in the control group, and on the 7th day, was significantly lower in the DSS group (25.7±1.34) than in the control group (33.4±1.77) (P<0.01). No changes in Flow were observed in either the DSS or the control group during the administration period, and no significant difference in Flow was found between the two groups. On histopathological examination, we observed a time-dependent increase in the infiltration of inflammatory cells in the ascending colon of rats treated with DSS, but changes such as erosion and ulceration were not found in the superficial layer of the mucosa. No histopathological changes were found in the control animals. In the early phase of the experimental colitis, hemodynamic alterations in the colonic mucosa were already present at the time the slight histopathological changes developed. These observations seemed to indicate the involvement of hemodynamic alterations in the subsequent tissue injury.

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.

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.

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.

Malignant Paraganglioma of the Stomach

Abstract: We report a case of malignant paraganglioma of the stomach. A gastric endoscopic examination on a 67‐year‐old female, performed for follow‐up purposes, revealed an irregularly elevated lesion with a central ulcer on the lesser curvature of the lower body. The lesion showed characteristics of both an epithelial tumor and a submucosal tumor by endoscopy and radiography. The biopsy specimen suggested that the lesion was a malignant poorly differentiated tumor. On abdominal ultrasonography and computed tomography, several space occupying lesions were found in both lobes of the liver. Therefore, this case was diagnosed as having an advanced gastric cancer with liver metastases and underwent distal gastrectomy. Postoperatively, a final diagnosis of gastric paraganglioma was made by histological and immunohistochemical findings (positive for Grimelius, neuron specific enolase and other stains). These findings also revealed lymph node metastases. To date, only seven cases of gastric paraganglioma have been reported. Furthermore, two cases of malignant gastric paraganglioma have also been described in the literature. This is the first case of malignant gastric paraganglioma evaluated in detail by endoscopic and radiographic examinations.