Gastric Pits Research Articles

Pathological features of Cryptosporidium andersoni-induced lesions in SCID mice

To assess the infectivity and the istopathological features of Cryptosporidium andersoni (C. andersoni) in laboratory animals, SCID mice were orally inoculated with oocysts of C. andersoni. Starting one week after inoculation, the SCID mice began shedding oocysts, and this continued for ten weeks. Histopathologically, myriads of C. andersoni were observed on the apical surface of the epithelium in the gastric pit of the glandular stomach. There were few lesions in the gastric epithelium except C. andersoni adhesion. In the lamina propria of the affected mucosa, minimum infiltration of inflammatory cells was observed. Immunohistochemically, C. andersoni demonstrated a positive reaction to a number of primary antibodies of Cryptosporidium parvum. In the experiment described here, few increases were seen in apoptotic epithelial cells in the affected mucosas of the SCID mice, and the nuclear augmentation was not enhanced. It was hypothesized that the absence of apoptosis and cell division were due to a lack of inflammatory cell reaction in the lamina propria.

Magnifying chromoendoscopy combined with immunohistochemical staining for early diagnosis of gastric cancer

To assess the diagnostic value of using magnifying chromoendoscopy combined with immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and p53 in the detection of gastric precancerous lesions. Ninety-five patients who were treated for abdominal discomfort, abdominal pain, bloating, and acid reflux at our hospital from January 2010 to December 2011 were included in the study. An ordinary gastroscopic procedure was initially performed to select the lesions. All subjects underwent magnifying chromoendoscopy to observe morphological changes of gastric pits. Biopsies were then taken from each area of interest and sent for pathological examination and detection of PCNA and p53 expression by immunohistochemistry. An immunoreactivity score for each lesion was calculated. Based on immunoreactivity scores, immunohistochemical staining was then considered. Compared to intestinal metaplasia, gastric pits were more diverse in size, more irregular in shape, and more disorderly in arrangement in moderate and severe dysplasia. PCNA and p53 expression was significantly higher in precancerous lesions (intestinal metaplasia and dysplasia) than in chronic gastritis. PCNA expression showed an upward trend in types A-F pits. The number of cases that showed strong PCNA positivity increased significantly with an increase in the severity of lesions. Rank sum test for independent samples showed that p53 expression was significantly higher in types E and F pits than in types A-D pits (H = 33.068, P = 0.000). Rank sum test for independent samples showed that PCNA expression was significantly higher in types E and F pits than in types A-D pits (H = 31.791, P = 0.001). The presence of types E and F pits, in which p53 and PCNA are highly expressed, is highly suggestive of the occurrence of early cancer, and patients developing these changes should be closely followed.

Clinical significance of white gastric crypt openings observedviamagnifying endoscopy

To evaluate the relationship between Helicobacter pylori (H. pylori)-induced gastritis and white gastric mucosal crypt openings (COs) in the gastric corpus. A total of 175 consecutive patients (including 69 patients with gastric cancer) were enrolled in this study. We used magnifying endoscopy (ME) to observe the mucosa microsurface of the lesser and greater curvature of the gastric corpus (350 areas in all). We focused on areas with a round pit microstructure (primarily observed in non-atrophied areas) and evaluated the white openings of these gastric pits. We classified the whiteness of the COs as the "white-edged dark spot" type (consisting of a dark spot bordered by white); the "white" type (pure white with no dark spot); and the "dense white pit (DWP)" type (dense white, resembling a snowball). Gastritis was also histologically evaluated according to the updated Sydney System. We detected round COs using ME in 246 of the 350 areas examined. The histological examination showed significantly more mononuclear cells and neutrophil infiltration in the "white" and "DWP" types than the "white-edged dark spot" type (P < 0.001). Furthermore, significantly high-grade inflammation and evidence of active H. pylori-induced gastritis was observed in the "DWP" type (P < 0.001). Significant differences were observed in the whiteness of COs between H. pylori-positive (n = 139) and negative (n = 36) patients (P < 0.001). The sensitivity and specificity of the "white" and "DWP" types for predicting H. pylori infection were 78.5% and 81.7%, respectively. Of the patients with gastric cancer, 22.5% (18/80) had "white-edged dark spots", 51.3% (41/80) had "white" COs, and 26.3% (21/80) had "DWP"-type COs. "DWPs" were frequently observed among patients with undifferentiated gastric cancer [45.7% (16/35)]. CO whiteness detected via ME was associated with histological evidence of gastritis and helps to predict the severity of inflammation and H. pylori-induced activity.

Gastric antisecretory and antiulcer activity of bovine hemoglobin

To investigate gastric antisecretory and gastroprotective activity of bovine hemoglobin (B-Hb) in rats. Adult Albino-Wistar rats were divided into groups of 6 animals each. B-Hb in doses of 100, 300 and 900 mg/kg body weight was tested for gastric acid secretion and antiulcer activity. Gastric secretions were measured 6 h after pylorus ligation in rats pretreated with B-Hb. The acidity was measured by titrating gastric contents against 0.01 mol/L NaOH to pH 7. Indomethacin ulcers were produced by oral administration of 30 mg/kg bw in the rats pretreated with B-Hb one hour before indomethacin. Six hours after indomethacin stomach removed and ulcer index was recorded. Ethanol ulcer were produced by 1 mL of ethanol in the rats pretreated with B-Hb 30 min before the ethanol. One hour after ethanol stomach were cut open to score ulcers. Histological examination and analysis of gastric wall mucus, non-protein sulfhydryl groups (NP-SH), and myeloperoxidase (MPO) were carried in gastric tissue following ethanol administration. In control rats pylorus ligation for 6 h resulted in the accumulation of 8.1 ± 0.61 mL of gastric secretion. The treatment of the rats with 100, 300 and 900 mg/kg of B-Hb produced a significant decrease in the volume of gastric secretion 5.6 ± 0.63, 5.5 ± 0.75 and 4.7 ± 0.58 mL respectively as compared to the control group [analysis of variance (ANOVA) F = 4.77, P < 0.05]. The lesion area in the control group was found to be 22.4 ± 3.2 mm(2) six hours after the administration of indomethacin. Treatment of rats with B-Hb at doses of 100 mg/kg (24.3 ± 3.29 mm(2)), 300 mg/kg (16.2 ± 1.45 mm(2)) and 900 mg/kg (12.6 ± 1.85 mm(2)) produced a dose dependent decreased the lesion scores (ANOVA F = 4.50, P < 0.05). The ulcer index following one hour after 1 mL ethanol was 7.1 ± 0.31. Pretreatment of rats with B-Hb at the doses of 100 mg/kg (2.5 ± 0.42), 300 mg/kg (2.1 ± 0.4) and 900 mg/kg (0.7 ± 0.21) significantly inhibited the formation of gastric lesions (ANOVA F = 63.26, P < 0.0001). Histological examination of gastric mucosa following ethanol showed significant lesions in the form of gastric pits with detachment of the surface epithelium; vacuolation of epithelial cells and elongation of microvessels. The changes were dose-dependently attenuated by B-Hb. The treatment of rats with ethanol significantly decreased the Alcian blue binding capacity of gastric wall mucus (480 ± 25.6 μg Alcian blue/g of tissue) as compared to control rats (667 ± 25.8 μg). Pretreatment of rats with B-Hb at the doses of 100 mg/kg (516 ± 31.6 μg/g), 300 mg/kg (558 ± 28.8 μg/g) and 900 mg/kg (654 ± 33.8 μg/g) significantly attenuated ethanol induced depletion of gastric wall mucus (ANOVA F = 8.05, P < 0.005). A significant and dose dependent increase of gastric mucosal NP-SH (ANOVA F = 19.62, P < 0.001) and decrease in MPO activity (ANOVA F = 3.1, P < 0.05) was observed in B-Hb treated rats. B-Hb possesses significant gastric antisecretory and gastroprotective activity against experimentally induced gastric lesion. The gastroprotective effects of B-Hb are accompanied by inhibition of neutrophils activity, reduction of oxidative stress and maintenance of mucosal integrity.

Histomorphometric and immunohistochemical study of the goat abomasum during prenatal development.

This study sought to chart the morphological changes taking place in the goat abomasum during prenatal development, using histomorphometric and immunohistochemical techniques. A total of 140 goat embryos and fetuses, from the first stages of prenatal life until birth. Differentiation of the abomasum as a separate compartment of the primitive gastric tube was observed at 35 days of prenatal life (CRL 3 cm, 23% gestation). Primitive abomasal folds were first observed at 38 days (CRL 4.3 cm, 25% gestation). The muscularis mucosae was visible by 64 days (CRL 13.5 cm, 43% gestation). Transformation of pseudostratified epithelium to simple cylindrical epithelium was also observed at this stage. Differentiation of gastric pits and glands first became apparent at 75 days (CRL 17.5 cm, 50% gestation) and 84 days (CRL 20 cm, 55% gestation), respectively. Neuroendocrine cells were detected by synaptophysin (SYP) at 64 days (CRL 13.5 cm, 43% gestation), while glial cell markers (glial fibrillary acidic protein - GFAP, and vimentin-VIM) were observed at 64 days (CRL 13.5 cm, 43% gestation) and 38 days (CRL 4.3 cm, 25% gestation), respectively. Neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were detected at 75 days (CRL 17.5 cm, 50% gestation). Gastrin-immunoreactive cells first appeared in the abomasum at 76 days (CRL 18 cm, 50% gestation). In conclusion, prenatal development of the abomasum appears to take place somewhat earlier in goats than in sheep or cattle, but at a similar rate to that reported in wild ruminants such as deer.

An Unusual Cause of Epigastric Pain

Question: A 64-year-old woman was hospitalized because of epigastric pain, back soreness, and poor appetite for 3 months. Her past and family histories were unremarkable. Physical examination showed epigastric tenderness without rebound pain and right axillary lymph node enlargement. Initial laboratory examination showed abnormalities as follows: Leukocyte count, 3.75 × 103/μL; hemoglobin level, 9.2 g/dL; platelet count, 148 × 103/μL; and aspartate aminotransferase, 92 U/L. Abdominal computed tomography demonstrated no significant changes. Upper gastrointestinal endoscopy identified elevated lesions with central ulcer on the greater curvature of stomach (Figure A) and in the duodenal bulb (Figure B). Magnified endoscopic observation with narrow band imaging was performed for the gastric lesion and revealed that it was surrounded by an elevation of gastric mucosa with normal gastric pits, indicating a submucosal tumor (Figure C). What is the most likely diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Excisional biopsies taken from gastric and duodenal lesions showed anaplastic large cell lymphoma (ALCL) characterized by the presence of large, anaplastic lymphoma cells around blood vessels (Figure D). Immunohistochemically, the tumor cells were positive for CD30 (Figure E) and Ki-67, but negative for ALK (anaplastic lymphoma kinase; Figure F), CD20, CD79a, and epithelial membrane antigen. The whole-body dual-modality 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images showed multiple increase of FDG uptake around the pons, cerebellum, C-, T-, L-spines, pelvic bones, humeral and femoral bones, mandibular bones, mediastinum, left supraclavicle, axillary, and gastrointestinal and abdominal lymph nodes (Figure G). CD30-positive ALCL is a distinctive malignant large-cell lymphoma of T-cell lineage, often presenting in lymph node or extranodal sites, such as the skin (the most common site), bone, lung, spleen, and gastrointestinal tract.1Lu Y. Zhao X. Wang E. et al.ALK-negative anaplastic large cell lymphoma with extensive peripheral blood and bone marrow involvements manifested as “leukemic phase”.Leuk Res. 2010; 34: 475-482Crossref PubMed Scopus (19) Google Scholar, 2Ross C.W. Hanson C.A. Schnitzer B. CD30 (Ki-1)-positive, anaplastic large cell lymphoma mimicking gastrointestinal carcinoma.Cancer. 1992; 70: 2517-2523Crossref PubMed Scopus (30) Google Scholar Our patient showed an extremely rare manifestation of ALK-negative ALCL with extensive involvement of multiple organs. The treatment regimens for primary systemic ALCL are the same as those used for diffuse large B-cell lymphoma.3Armitage J.O. Mauch P.M. Harris N.L. et al.DeVita Jr, V.T. Hellman S. Rosenberg S.A. Cancer: principles and practice of oncology. 6th ed. Lippincott, Philadelphia2001: 2297-2298Google Scholar Without receiving chemotherapy, our patient died of respiratory failure 1 month later.

ENDOSCOPIC EVALUATION AND BIOPSY COLLECTION OF THE GASTROINTESTINAL TRACT IN THE GREEN MORAY EEL (GYMNOTHORAX FUNEBRIS): APPLICATION IN A CASE OF CHRONIC REGURGITATION WITH GASTRIC MUCUS GLAND HYPERPLASIA

A green moray eel (Gymnothorax funebris) was evaluated for chronic regurgitation. By using flexible endoscopy, the gastrointestinal tract was evaluated and revealed multifocal proliferative gastric masses and an intestinal ulcer. Biopsy specimens revealed gastric mucus gland hyperplasia, intestinal nematodiasis, and mild enteritis. Esophagoscopy and gastroscopy were performed by using a larger endoscope (length, 200 cm). A smaller endoscope (length, 100 cm) facilitated entering the intestinal tract in normograde or retrograde directions. A control eel was also evaluated, and no gross or histologic abnormalities were detected. The case eel was treated with metoclopramide and fenbendazole, responded well to therapy, and regurgitation decreased. A year later, the animal died of unrelated causes. Necropsy revealed coelomic gastric adhesions. The gastric proliferative lesions were associated with degeneration and necrosis of gastric pit mucosa without significant inflammation; etiology was unknown. Gastrointestinal endoscopy proved a useful diagnostic tool for evaluation and biopsy collection in this eel species.

Changes of ultrastructure and downregulation of heat shock protein 70 and fibroblast growth factor 2 in gastric mucosa of rats with depressive-like behaviour.

To understand the underlying mechanism of gastric symptoms in patients with depressive disorder. This study tested in the rat depression model evoked with chronic mild stress whether the microstructure gastric mucosa is injured using scanning electronic microscopy and transmission electronic microscopy (TEM). In addition, the expression of heat shock protein 70 (HSP70) and fibroblast growth factor 2 (FGF2) proteins in the gastric mucosa were measured by Western blotting. We found that the gastric epithelial cells were ruptured and the gastric pits were widened in rats with depression. The amount of mucous granules was also reduced in the surface mucous cells. Moreover, parietal cells became active, and the secretory canaliculi were magnified. Expression of HSP70 and FGF2 was reduced in the gastric mucosa. These findings suggested that gastric symptoms in rats with depressive-like behaviour were caused by the injury of the gastric mucosa, AQ1 and HSP70 and FGF2 may be key molecules in the pathogenesis.

Characterization and regulation of the novel zinc transporter, ZIP11, in the murine gastrointestinal tract

ZIP11, a novel Zrt‐IRT‐like (ZIP) transporter is highly expressed in certain murine gastrointestinal (GI) tissues. We initiated research to characterize ZIP11 and to determine its regulation in a murine dietary model during low (&lt;1 mg Zn/kg), adequate (30 mg Zn/kg) or supplemental (180 mg Zn/kg) zinc intake. qPCR &amp; western blot analyses demonstrated that murine Zip11 expression is widely distributed among tissues. The highest relative expression of Zip11 mRNA was in the stomach, cecum, and colon of a C57BL/6 strain. ZIP11 protein was also confirmed in these tissues, along with the brain and kidney. Immunohistochemistry results revealed ZIP11 to be highly expressed in the lower region of the gastric pits, where chief cells reside and colonic epithelial cells. mRNA and protein data revealed an up‐regulation of ZIP11 in the stomach and colon during zinc deficiency. In contrast, administration of LPS reduced Zip11 expression in the stomach and had no effect in the jejunum, while Zip14 expression was increased throughout the small intestine. Our data reveals ZIP11 to be widely distributed among murine tissues, but the stomach and colon are of particular interest because of its unique tissue specificity and the response of the transporter during dietary studies. ZIP11 could be involved in the homeostatic control of zinc in mammals but may also provide tissue specific functions in the GI tract.

Synchrotron-radiation phase-contrast imaging of human stomach and gastric cancer:in vitrostudies

The electron density resolution of synchrotron-radiation phase-contrast imaging (SR-PCI) is 1000 times higher than that of conventional X-ray absorption imaging in light elements, through which high-resolution X-ray imaging of biological soft tissue can be achieved. For biological soft tissue, SR-PCI can give better imaging contrast than conventional X-ray absorption imaging. In this study, human resected stomach and gastric cancer were investigated using in-line holography and diffraction enhanced imaging at beamline 4W1A of the Beijing Synchrotron Radiation Facility. It was possible to depict gastric pits, measuring 50-70 µm, gastric grooves and tiny blood vessels in the submucosa layer by SR-PCI. The fine structure of a cancerous ulcer was displayed clearly on imaging the mucosa. The delamination of the gastric wall and infiltration of cancer in the submucosa layer were also demonstrated on cross-sectional imaging. In conclusion, SR-PCI can demonstrate the subtle structures of stomach and gastric cancer that cannot be detected by conventional X-ray absorption imaging, which prompt the X-ray diagnosis of gastric disease to the level of the gastric pit, and has the potential to provide new methods for the imageology of gastric cancer.

Recognition of changes in microvascular and microstructural patterns upon magnifying endoscopy predicted the presence of extranodal gastric MALToma

BACKGROUND AND OBJECTIVES: Gastric MALToma is difficult to recognize upon endoscopy. The aim of this study is to evaluate the application of microstructural and microvascular patterns in recognizing gastric MALToma on magnifying endoscopy. METHOD: All patients with diagnosis of gastric MALToma upon histology were recruited. They received magnifying endoscopy to observe for changes in microstructural and microvascular patterns. For patients with H pylori, eradication therapy would be given. For those without, appropriate treatments including gastrectomy or chemotherapy were commenced accordingly. Patients treated with H pylori eradication and non-operative treatments received follow-up magnifying endoscopy, and the same features were observed to predict the response to these treatments. RESULTS: From 2004 to 2007, nine patients presented to with epigastric pain, dyspepsia and belching. All patients were confirmed to have MALToma upon initial biopsy. Five patients had H pylori infection and received eradication. Two patients without H pylori were treated with Laparoscopic total gastrectomy. Two patients had pulmonary metastasis and treated with chemotherapy. Under magnifying endoscopy, all the lesions demonstrated either absence or irregular gastric pits. Moreover, there was consistently appearance of spider-shaped vascular pattern. Five patients with H pylori eradication had follow-up magnifying endoscopy, four of them showed resolution of abnormal vascular pattern and recovery of gastric pits. CONCLUSION: Abnormal spider like vasculature and disappearance of gastric pits are diagnostic features upon magnifying endoscopy for gastric MALToma. These features enhanced the diagnosis and assessment of extent of involvement during primary endoscopy, as well as follow-up surveillance for response to non-operative treatments.

Gut Peculiarities of Feed Deprived White Sturgeons (&amp;lt;i&amp;gt;Acipenser transmontanus&amp;lt;/i&amp;gt;, Richardson 1836)

In the White sturgeon fish farms, some individuals have difficulty in getting access to food: such sturgeons are called "runts", and they result in a slower growth rate than normally feeding fish. In this paper, we have studied the gut peculiarities of runt sturgeons. Utilizing in paralleling an analysis of diatom populations in both the fish gut tissues and the rearing tank waters, we hypothesized a causative relation between the occurrence of runt sturgeons and periodic diatom blooms. In fact, we have observed that the diatom species identified in the aquatic environment were also detected in organs (Fragilaria spp and Rhoicosfenia spp for both glandular body, mid-intestine) of the runt sturgeon's gut, but not in tissues of normally feeding individuals. Owing to their siliceous wall, diatoms can be responsible for areas of epithetlial detachment in the mucosal surfaces of the alimentary canal and a catharral inflammation in both the gastric pits and intestinal folds which may be the cause of secondary bacterial diseases. We suggest that diatom blooms may contribute to the occurrence of runt sturgeons in the studied Italian fish farm.

Morphological and histochemical investigation of the camel (Camelus dromedarius) abomasal mucous membrane by light and scanning electron microscopy (SEM)

Summary Morphological and histochemical study of the abomasal epithelium in camel (Camelus dromedarius) was carried out by light and scanning electron microscopes. The lining of the abomasum was divided into four regions, i.e. cardiac, pseudocardiac, fundic and pyloric. Our investigation revealed that the cardiac and pseudocardiac regions occupy a wide part of the abomasum in camel and it reaches approximately the thirdfourth of the abomasum. Our gross anatomical observation showed small diverticulae in the Fundic region, this part was covered with thick mucosal folds that have been separated by deep branching furrows. In the histological study we observed that, the mucosa has extensive gastric folds and small invaginations or gastric pits, which were in continuation with the gastric glands. The mucosal surface was covered with simple columnar epithelial. Our histochemical revealed that the surface epithelium in abomasum was negative to AB and positive to PAS staining, whereas in the gastric pit cells it was positive to AB and PAS staining, but gastric gland cells were negative to PAS and positive to AB staining. In the SEM study, after complete removal of mucin from the surface of the mucosa, simple columnar epithelial cells with a mean length of 20 µm were observed, and some epithelial cells have been arranged as flower body (FB). Also, we observed hexagonal structures on the surface of the abomasums that resembled honeycomb structure (HC). Mean diameter of these HC structures was 30-40 µm. For the first time our investigation revealed these FB and HC structures in the abomasal mucosa of camel.

Application of magnifying narrow-band imaging endoscopy for diagnosis of early gastric cancer and precancerous lesion

BackgroundGastric carcinoma is the second commonest cause of cancer deaths worldwide. Early detection and diagnosis of gastric cancer in the stomach is important for improving the prognosis of gastric cancer. This retrospective study was designed to investigate the value of magnifying narrow-band imaging (NBI) in the diagnosis of precancerous lesions and early gastric cancer.MethodsThis study included 122 patients who were diagnosed with early gastric cancer or precancerous gastric lesions by endoscopy. The patients underwent an examination with conventional endoscopy, magnifying NBI, and magnifying chromoendoscopy. Images resolution was evaluated, and the morphology, pit patterns and blood capillary forms of lesions were analyzed. The presence of gastric carcinoma and high grade intraepithelial neoplasia in the biopsy samples was considered as a positive pathological result, which is used to assess accuracy of endoscopic diagnosis.ResultsFor image resolution, magnifying NBI and magnifying chromoendoscopy were significantly superior to magnifying conventional endoscopy in morphology, pit pattern and blood capillary form (P < 0.01), and magnifying NBI was significantly superior to magnifying chromoendoscopy in blood capillary form (P < 0.01). IV, V1, and VI type of gastric pit pattern were detected in 14 cases, 43 cases, and 17 cases in patients with high grade intraepithelial neoplasia, respectively. V1 and VI type of gastric pit pattern were detected in 9 cases and 39 cases in patients with early gastric cancer, respectively. The presence of irregular minute vessels and variation in the caliber of vessels was found in 109 cases. The accuracy, sensitivity, specificity, false positive rate and false negative rate for diagnosis of early gastric cancer and precancerous gastric lesions were 68.9%, 95.1%, 63.1%, 24.5%, and 32.4% for conventional endoscopy, 93.6%, 92.7%, 94.5%, 5.7%, and 6.9% for magnifying NBI, and 91.3%, 88.6%, 93.2%, 13.2%, and 21.48% for magnifying chromoendoscopy, respectively.ConclusionsThis study demonstrates that magnifying NBI is superior to conventional endoscopy in the diagnosis of early gastric cancer and precancerous gastric lesions, and can be used for screening early malignancies of the stomach.

Complementary expression and repulsive signaling suggest that EphB receptors and ephrin-B ligands control cell positioning in the gastric epithelium

Eph receptors and ephrin ligands are membrane-bound cell-cell communication molecules with well-defined roles in development. However, their expression and functions in the gastric epithelium are virtually unknown. We detected several EphB receptors and ephrin-Bs in the gastric corpus mucosa of the adult rodent stomach by RT-PCR amplification. Immunostaining showed complementary expression patterns, with EphB receptors preferentially expressed in the deeper regions and ephrin-Bs in the superficial regions of the gastric units. EphB1, EphB2 and EphB3 are expressed in mucous neck, chief and parietal cells, respectively. In contrast, ephrin-B1 is in pit cells and proliferating cells of the isthmus. In a mouse ulcer model, EphB2 expression was upregulated in the regenerating epithelium and expanded into the isthmus. Thus, EphB/ephrin-B signaling likely occurs preferentially in the isthmus, where receptor-ligand overlap is highest. We show that EphB signaling in primary gastric epithelial cells promotes cell retraction and repulsion at least in part through RhoA activation. Based on these findings, we propose that the EphB-positive progeny of gastric stem cells migrates from the isthmus toward the bottom of the gastric glands due to repulsive signals arising from contact with ephrin-Bs, which are preferentially expressed in the more superficial regions of the isthmus and gastric pits.

Fuji intelligent color enhancement chromoendoscopy for diagnosis of early gastric cancer

Objective To evaluate Fuji intelligent color enhancement （FICE） chromoendoscopy for diagnosis of early gastric cancer. Methods From February 2010 to March 2011, a total of 67 patients with suspected gastric mucosal lesions were enrolled in this study. The lesions were observed with magnifying endoscopy, FICE, magnifying chromoendoscopy and indigo-carmine-magnifying-chromoendoscopy. Suspected gastric mucosal pit patterns and microvascular morphology were compared. Targeted biopsy was performed on suspected locations. Sensitivity, specificity and pathological consistency were compared be- tween the 3 procedures. Results Out of 67 patients, 17 were diagnosed as having early gastric cancer. There was no difference among magnifying endoscopy, FICE magnifying chromoendoscopy and indigo-carmine-magnifying-chromoendoscopy in pit pattern findings, however, FICE magnifying chromoendoscopy was superior to other 2 procedures in displaying capillary loop. The sensibility, specificity and pathological accordance rate of FICE magnifying chromoendoscopy were 94. 1% （16/17）, 98.0% （49/50）and 97.0% （65/67）, which were higher than those of the magnifying endoscopy [ 58.8% （10/17）, 84% （42/50） and 77.6% （52/67） ] （P 〈0. 05）, and were not different from those of indigo-carmine-magnifying-chromoendoscopy [ 88.2% （ 15/17）, 96% （48/50） and 94.0% （63/67） ] （P 〉 0. 05 ）. Conclusion FICE magnifying chromoendoscopy provides rather clear images of gastric mucosa and intrapapillary capillary, thereby improving the accuracy of endoscopic biopsy and then imporving the diagnosis rate of early gastric cancer. Key words: Magnifying endoscopy; Indigo-carmine-magnifying-chromoendoscopy; Early gastriccancer; Fuji intelligent color enhancement magnifying chromoendoscopy

The observation of the expression changes of protein gene product9.5 in neurons from the gastric walls of rats with gastritis

Objective To discuss the possible enteric nervous pathogenesis in gastritis related GI motor disorders on the expression changes of protein gene product9. 5 in neurons from the gastric walls of gastritis rat model. Methods 35 clean grade Wister rats were randomly divided into 3 groups, which included gastritis group A (n =10), gastritis group B(n =15) and control group(n =10). Rats in gastritis group A and B received gastric perfusion of HP and the mixture of 2% aspirin and 0. 6N hydrochloric acid respectively. The control group only received gastric perfusion of saline. All of the rats were killed and the gastric mucosal tissues were obtained for the pathological and HP examination. After immunohistochemical pretreatment, the tissues were stained with PGP9. 5 and at the same time the maximum diameter (Dmax, μm), mean area(μm2) and mean optical density (nm) of the neurons from the gastric walls were compared among the groups with Image-Pro Plus professional image analysis system. Results In gastric group A, HP could be found sparsely in the mucous layer or gastric pits, and all of the rapid urease tests were positive. In the other two groups, HP could not be found, and all of the rapid urease tests were negarive. In both gastric group A and B, different grades of inflammatory cell infiltration with active inflammation signs could be found in the deep layers of mucosa, while the control group was normal. The expression mean area, mean optical density of neurons from the gastric wall of rat in group A[(77. 10 ±48. 46) μm2, (53. 25 ±41.40) nm] or B [(73. 92 ± 39. 60) μm2, (45.33 ± 33.20) nm] was obvious lower than control group [(143.51 ± 29. 84) μm2, (85. 00 ± 14. 32) nm], while there was no significant difference between gastric group A and B (P ＞0. 05) (table 1). Conclusions Hp and NSAIDs might cause gastritis and decrease the PGP9. 5 expression of Neurous from gastric walls. The decrease of PGP9. 5 expression of neurons from the gastric wall might contribute to the pathogenesis of GI motor disorders or symptoms of functional dyspepsia. Key words: Gastritis/PA/ME; Parietal cells, gastric/ME; Nerve tissue proteins/BI; Neurons/ME; Stomach/IR

BabA-mediated Adherence Is a Potentiator of the Helicobacter pylori Type IV Secretion System Activity

Chronic infection of Helicobacter pylori in the stomach mucosa with translocation of the bacterial cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV secretion system (TFSS) into host epithelial cells are major risk factors for gastritis, gastric ulcers, and cancer. The blood group antigen-binding adhesin BabA mediates the adherence of H. pylori to ABO/Lewis b (Le(b)) blood group antigens in the gastric pit region of the human stomach mucosa. Here, we show both in vitro and in vivo that BabA-mediated binding of H. pylori to Le(b) on the epithelial surface augments TFSS-dependent H. pylori pathogenicity by triggering the production of proinflammatory cytokines and precancer-related factors. We successfully generated Le(b)-positive cell lineages by transfecting Le(b)-negative cells with several glycosyltransferase genes. Using these established cell lines, we found increased mRNA levels of proinflammatory cytokines (CCL5 and IL-8) as well as precancer-related factors (CDX2 and MUC2) after the infection of Le(b)-positive cells with WT H. pylori but not with babA or TFSS deletion mutants. This increased mRNA expression was abrogated when Le(b)-negative cells were infected with WT H. pylori. Thus, H. pylori can exploit BabA-Le(b) binding to trigger TFSS-dependent host cell signaling to induce the transcription of genes that enhance inflammation, development of intestinal metaplasia, and associated precancerous transformations.

Gastric Pit Dysplasia in Adjacent Gastric Mucosa in 414 Gastric Cancers

Despite wide acceptance of the chronic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence, especially for intestinal-type gastric adenocarcinoma, the precise nature of the subtle precursor lesions of gastric cancer remains to be delineated. For example, pit dysplasia with surface foveolar maturation is not well defined, nor is its prevalence and biological characteristics well characterized. We have evaluated the surrounding gastric mucosa of 414 gastric cancers for the presence of gastric pit dysplasia. We investigated its relationship with various clinicopathological and immunophenotypic features of gastric adenocarcinoma, as well as the severity and extent of any surrounding gastritis and intestinal metaplasia. p53 expression and Ki-67 proliferation index were also evaluated. We have found that 21.0% (n=87) of gastric cancer cases showed pit dysplasia in adjacent gastric mucosa. Gastric cancers with pit dysplasia were significantly associated with older age, male sex, body/fundic location, and intestinal histologic type (P<0.05). Interestingly, gastric mucin-containing intestinal metaplasia (incomplete intestinal metaplasia) was highly associated with adenocarcinoma with pit dysplasia (P=0.000). In addition, MUC6 expression in gastric adenocarcinoma was associated with pit dysplasia (P=0.036). p53 overexpression and increased Ki-67 proliferation index were more evident in gastric pit dysplasia compared with adjacent gastric mucosa. We suggest that gastric pit dysplasia is an important candidate precursor of gastric adenocarcinoma and may represent another morphologic step in the pathogenesis of gastric adenocarcinoma, especially of intestinal type. More detailed prospective studies are needed to determine the precise significance of these findings.

Abstract 5186: Lineage tracing of Cytokeratin 19 labels gastric, intestinal and colonic stem cells

Abstract Introduction: Tissue stem cells, characterized by multipotentiality and self renewing ability, are not readily distinguishable from other resident cells. Tissue stem cells are believed to be present in small numbers that may remain quiescent, or divide frequently as previously shown with Lgr-5+ cells. In the gastric antrum, intestine and colon, epithelial cells derived from the stem cells at the crypt base rapidly migrate up towards to the mucosal surface, whereas in the gastric corpus, stem cells located in the isthmus are believed to give rise to epithelial progenitors that undergo bipolar migration and differentiation into pit and oxyntic cell lineages. Cytokeratin 19 (K19) has been shown to be expressed in cells in the gastric isthmus and colonic and intestinal crypts. Therefore, we aimed to use the K19 gene promoter to drive Cre recombinase expression and to track the lineage of K19+ cells in an inducible fashion. Methods: In order to recapitulate the endogenous expression pattern of K19, we used a BAC strategy and generated a transgenic mouse with a Tamoxifen inducible Cre under the control of the K19 promoter (K19-BAC-Cre-ERTM). K19CreERT2 mice were crossed to ROSA26rLacZ (or GFP) reporter mice, treated the mice with tamoxifen (4 mg/ day p.o. for 3 days) and sacrificed at various time points (3 days, 7 days, 26 weeks and 52 weeks) following tamoxifen induction. Results: Treatment of K19CreERT2/Rosa26r mice with tamoxifen resulted in the selective marking of about 30% of gastric and intestinal glands. Following tamoxifen induction, in the corpus a few gastric pit cells near the isthmus were labeled at 3 days, whereas, all of pit cells within the labeled glands stained positively by 7 days. Consistent with the labeling of progenitor or stem cells, all pit cells within marked glands stained positively even up to 52 weeks following tamoxifen induction. In contrast, in the antrum, intestine and colon nearly all epithelial cells were labeled within 3 days following tamoxifen induction. Once again, lineage tracing of all the epithelial cells within marked glands was observed up to 52 weeks following tamoxifen induction, suggesting that K19 likely marks a common progenitor or stem cell in the antrum, intestine and colon. Interestingly, in the small intestine and antrum K19 positive cells do not overlap with Lgr5-GFP+ cells yet clearly demonstrate stem cell properties. Conclusions. Using K19CreERT2/Rosa26r mice, we show that K19 marks pit progenitors in the gastric corpus, as well as stem cells within the antrum, intestine and colon. These findings identify a novel population of stem cells for the lineage tracing of gastric pit cells following gastric injury or cancer, and for tracing epithelial cells in the development of intestinal or colonic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5186. doi:10.1158/1538-7445.AM2011-5186