Normal Gastric Antrum Research Articles

Unique EPIYT motif CagA gene Helicobacter pylori Bali 01 isolate as the cause of hematemesis in a male gastric ulcer patient in Wangaya General Teaching Hospital Denpasar Bali: a case report

Background: Helicobacter pylori (H. pylori) infection is related with a number of gastrointestinal disorders, including gastritis, peptic ulcer disease, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This case report aims to present an unique EPIYT motif CagA gene H. pylori Bali 01 isolate as the cause of hematemesis in a male gastric ulcer patient Case Presentation: A 70-year-old male Balinese patient came to the hospital due to hematemesis. Esophagogastroduodenoscopy was performed after stabilizing patient condition with prompt treatment and intravenous proton pump inhibitor. Esophagogastroduodenoscopy revealed a solitary giant ulcer in the gastric antrum. Gastric biopsy was performed and histopathology examination revealed a spherical-like organism, confirmed as H. pylori. Biopsy was sent to the Biomedical Laboratory at West Nusa Tenggara, Mataram, Lombok Island. Culture of biopsy and polymerase chain reaction revealed H. pylori, then named H. pylori Bali 01 isolate. Standard protocol of H. pylori eradication is conducted by administration of triple drug therapy consisting of omeprazole, amoxicillin, and clarithromycin for 14 days. Patient was discharged from hospital in stable condition. Helicobacter pylori was successfully eradicated and revealed completely normal gastric antrum in reperformance of esophagogastroduodenoscopy 3 months later. Conclusion: The EPIYA-ABD motif on this H. pylori Bali 01 isolate is distinctively unique from the EPIYT motif on the second EPIYA sequence.

S3354 Ménétrier’s Disease: A Rare Cause of Edema in Childhood

Introduction: Ménétrier’s disease (MD) is a rare protein-losing gastropathy characterized by enlarged gastric rugal folds. Adult MD is associated with a high degree of morbidity and mortality due to potential malignant transformation and need for gastrectomy. Pediatric MD, in contrast, is typically an acute, self-limited process, frequently associated with cytomegalovirus (CMV) infection of the stomach. Case Description/Methods: A previously healthy 2-year-old boy was admitted for generalized edema, which had been preceded by a week of diarrhea. Growth and development had been normal. Initial laboratory evaluation was notable for serum albumin of 1.3 g/dL. Other labs were largely unremarkable. Cardiac, renal, and liver etiologies were excluded. Esophagogastroduodenoscopy showed a normal gastric antrum, but the remainder of the stomach had enlarged rugae with areas of ulceration and nodularity. The duodenum and esophagus appeared normal. Histology was notable for hyperplastic gastric pits and foveolae. Immunohistochemistry for CMV and Helicobacter pylori were negative, and viral culture of a gastric sample was also negative for CMV. CMV serologies showed elevated IgM and IgG levels. Additionally, a viral enteric pathogens panel was positive for sapovirus. The patient received 2 doses of albumin and antisecretory agents during admission, but his edema and hypoalbuminemia improved without treatment of CMV. Discussion: In a toddler presenting with edema and hypoalbuminemia, it is necessary to consider protein-losing gastroenteropathies on the differential. Endoscopic evaluation with biopsy is essential for diagnosis of MD. Histology may show foveolar hyperplasia with cystic dilation of pits of the gastric body with relative sparing of the gastric antrum. Full-thickness biopsy may be required to detect classic histologic findings. Evaluation for infection should be done as one-third of pediatric cases are associated with CMV. Management of pediatric MD is primarily supportive due to the self-limited nature of the condition. Treatment with ganciclovir can be considered for severe or refractory cases associated with CMV.

SHP2/SPI1axis promotes glycolysis and the inflammatory response of macrophages in Helicobacter pylori-induced pediatric gastritis.

Macrophages, as innate immune cells, were reported to participate in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. However, the role and mechanism of macrophage dysfunction in H.pylori-associated pediatric gastritis remain unclear. An RNA-sequencing assay was used to examine the differential gene expression in normal gastric antrum, non-H.pylori-infected tissue, and H.pylori-infected pediatric gastritis tissue. qPCR assays were applied to verify the expression of target genes. HE staining was performed to identify the occurrence of inflammation in the normal gastric antrum, non-H.pylori-infected tissue, and H.pylori-infected pediatric gastritis tissue. Western blotting was used to measure the expression of SHP2 in pediatric gastritis tissue. The metabolic profile of macrophages was determined via Seahorse metabolic analysis. Flow cytometry analysis was used to examine the level of reactive oxygen species (ROS). We found that H.pylori -infected gastritis tissue exhibited many differentially expressed genes (DEGs) compared to gastritis tissue without H.pylori infection. Moreover, H.pylori -infected gastritis tissue showed many DEGs annotated with an overactive immune response. We identified that tyrosine-protein phosphatase nonreceptor type 11 (PTPN11), which encodes SHP2, was significantly increased in macrophages of H.pylori -infected gastritis tissue. Furthermore, we revealed that SHP2 could activate the glycolytic function of macrophages to promote H.pylori -induced inflammation. The transcription factor SPI1 , as the downstream molecule of SHP2, could be responsible for the regulation of metabolism-associated gene expression and inflammation. Our study illustrated the molecular landscape of H.pylori-infected gastritis tissue in children and suggested that the SHP2/SPI1axis could be a novel therapeutic target in H.pylori-induced pediatric gastritis.

In vivo and in vitro effects of Salsola collina on gastrointestinal motility in rats.

Objective(s): Salsola collina is widely distributed along the Bohai coast and consumed as an edible plant by native residents. We have found surprisingly that S. collina extracts promoted gastrointestinal motility in mice previously. In the present study, effects of S. collina on gastrointestinal motility in rats and its underlying mechanism were explored.Materials and Methods: In vivo, different fraction extracts from S. collina were prepared and the effects on gastric emptying and small intestinal propulsion in normal rats were measured. Plasma ghrelin (GRL), motilin (MTL), gastrin (GAS) and vasoactive intestinal peptide (VIP) and expressions of GRL receptor (GHSR), MTL receptor (MTLR), VIP receptor 2 (VIPR2) in the duodenum were also detected. In vitro, gastric antrum strips were prepared and activities of different extracts on gastric smooth muscle contractions were evaluated.Results:Results showed that the ethyl acetate extract (EAE) was the most effective fraction to promote gastric emptying and intestinal propulsion, showing a dose-dependent manner. EAE increased plasma GRL and GAS, elevated GHSR expression and restrained VIPR2 expression in the duodenum. In vitro, EAE promoted contraction of normal gastric antrum strips as well as relaxed strips induced by atropine.Conclusion:These data indicate that EAE has a significant prokinetic activity via a mechanism that mainly involves in modulating plasma GRL and GAS, expressions of GSHR and VIPR2 in the duodenum and activating M-cholinergic receptor. Our study provides a pharmacological basis for the use of S. collina extract in treating gastrointestinal motility disorders.

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1%). Histological examination revealed fundic type epithelium in 58.3% of cases, H. pylori was present in 50% and chronic inflammation in 66.7%. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7% of cases and Barrett's esophagus in 90% of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Gastrin Stimulates Cyclooxygenase-2 Expression in Intestinal Epithelial Cells through Multiple Signaling Pathways: EVIDENCE FOR INVOLVEMENT OF ERK5 KINASE AND TRANSACTIVATION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR

Gastrin is a hormone produced by G-cells in the normal gastric antrum. However, colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased expression of cholecystokinin B (CCK-B)/gastrin receptors. Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy. Thus, gastrin may act as an autocrine/paracrine or endocrine factor in the initiation and progression of colorectal carcinoma. The molecular mechanisms involved have not been elucidated. Hypergastrinemia induced by Helicobacter pylori infection is associated with increased cyclooxygenase-2 (COX-2) expression in gastric and colorectal tissues, suggesting the possibility that gastrin up-regulates COX-2 expression in these tissues; this has not been confirmed. We report here that gastrin significantly increases the expression of COX-2 mRNA and protein, the activity of the COX-2 promoter, and the release of prostaglandin E(2) from a rat intestinal epithelial cell line transfected with the CCK-B receptor. These actions were dependent upon the activation of multiple MAPK signal pathways, including ERK5 kinase; transactivation of the epidermal growth factor receptor; and the increased expression and activities of transcription factors ELK-1, activating transcription factor-2, c-Fos, c-Jun, activator protein-1, and myocyte enhancer factor-2. Thus, our findings identify the signaling pathways coupling the CCK-B receptor with up-regulation of COX-2 expression. This effect may contribute to this hormone-dependent gastrointestinal carcinogenesis, especially in the colon.

Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction.

It is currently unclear whether intestinal metaplasia at the esophagogastric junction and in the distal esophagus represent a continuum of the same underlying disease process, i.e., gastroesophageal reflux, or constitute different entities with a different pathogenesis. Biopsies below the Z line might show specialized epithelium in some patients and the question is whether this is another form of short segment Barrett's esophagus or whether it is related to a generalized atrophic process of the stomach. Data from recent studies regarding the expression of cytokeratin CK7 and CK20 in intestinal metaplasia (IM) found at the gastroesophageal junction are conflicting. Prompted by these data we undertook the present study: a) to evaluate the expression of CK7 and CK20 in IM of the gastric cardia and to compare the findings with those in patients with Barrett's esophagus and IM of the gastric corpus and antrum mucosa; and b) to evaluate the immunophenotype of non-intestinalized cardiac mucosa and to compare it with that of normal gastric epithelium. We studied the expression of CK7 and CK20 on biopsy specimens from patients with long-segment Barrett's esophagus (n=17) and surgical resection and biopsy specimens of gastric cardia (n=15), corpus (n=14) and antrum (n=22) from patients with histological evidence of IM. Eighty-four biopsy specimens from 42 patients (antrum n=15, corpus n=20, cardia n=7) without evidence of IM were studied as a control group. We observed an immunophenotype characterised by diffuse moderate to strong CK7 staining on the surface and crypt epithelium combined with strong CK20 staining on the surface and superficial part of the crypts in 94.1% (16/17) of the cases with long-segment Barrett's esophagus, but in none of the 36 cases with IM in distal stomach (antrum and corpus). IM in the gastric cardia expressed the immunophenotype seen in IM of the gastric mucosa in 93.3% (14/15) of the cases. On the other hand, normal cardiac epithelium expressed patchy strong CK7 staining on the surface epithelium and on both, superficial and deep parts of the pits combined with patchy strong CK20 staining on the surface epithelium and superficial pits, a feature permitting distinction of the normal cardiac epithelium from those of the normal gastric antrum and corpus epithelium. We conclude that the expression of cytokeratins 7 and 20 can be used to distinguish the origin of IM of the gastroesophageal junction. The CK7/20 immunophenotype of IM in the gastric cardia closely resembles that of the IM in the gastric antrum and corpus and is different from IM in long-segment Barrett's esophagus. In contrast, the CK7/20 immunophenotype of the cardiac epithelium is different from that of the gastric antrum and corpus mucosa, suggesting that cardiac epithelium might not be a native normal gastric epithelium but one that is acquired as a consequence of longstanding inflammation. Changing pattern of CK7 and CK20 expression from normal to intestinalized epithelium suggests that IM arising from cardiac epithelium might have distinctive features.

Phenotype of Barrett's esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction: an immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45 MI.

The pathogenesis of short segment Barrett's esophagus (SSBE) and intestinal metaplasia (IM) of the gastroesophageal junction (IMGEJ) are poorly understood. Also, these conditions are difficult to distinguish from one another based solely on endoscopic and pathologic criteria. Therefore, the aim of this study was to evaluate the immunophenotypic features of SSBE and IMGEJ and to compare the results with lesions of known etiologies: long segment BE (LSBE) caused by reflux disease and Helicobacter pylori-induced IM of the gastric antrum (IMGA). Routinely processed mucosal biopsy specimens from 11 patients with LSBE, 17 with SSBE, 10 with IMGEJ, 16 with IMGA, 17 with a normal nonmetaplastic GEJ, and 7 patients with a normal gastric antrum were immunohistochemically stained with monoclonal antibodies to: Das1, an antibody shown to react specifically with colonic goblet cells; 45M1, an antibody that recognizes the M1 gastric mucin antigen; and cytokeratin (CK) 7 and 20, antibodies that have previously been reported to show specific staining patterns in BE versus IMGA. Also evaluated was nonintestinalized mucinous epithelium from LSBE, SSBE, and also the normal GEJ and gastric antrum. LSBE, SSBE, and IMGEJ showed similar prevalences of Das1 (91% versus 88% versus 100%) and 45M1 reactivity (100% versus 100% versus 100%), and a similar pattern of CK7/20 reactivity (diffuse strong CK7 staining of the surface and crypt epithelium, and strong surface and superficial crypt CK20 staining) (91% versus 94% versus 90%). In contrast, although 45M1 reactivity in IMGA (93%) was similar to that of the other three groups, IMGA showed a significantly lower prevalence of Das positivity (13%, p < 0.001), and only a 14% prevalence of the CK7/20 staining pattern that was predominant in the other three groups (p < 0.001). Das1, 45M1, and CK7/20 staining were similar in nonintestinalized "cardia-type" mucinous epithelium from LSBE, SSBE, and the GEJ, but all were distinct from the normal gastric antrum. In summary, the immunophenotypic features of SSBE and IMGEJ are similar and closely resemble those seen in classic LSBE, but are distinct from IMGA. This may indicate that IM in LSBE, SSBE and at the GEJ have similar biologic properties. Based on our data, SSBE and IMGEJ cannot be distinguished on the basis of their immunophenotype.

Reduced gastric mucosal vascularity in patients with chronic gastritis.

Chronic inflammation is increasingly being linked to ischaemia, but the mechanism is poorly understood, and little is known about its effect on local gastric endothelial microvessels. We aimed at studying the number and surface area of gastric mucosal endothelial microstructures in the presence or absence of chronic gastritis. Immunohistochemical assessments were carried out on gastric antral and body biopsies taken from patients with chronic gastritis and others with normal histology. The primary antibody (QB-END/10) was raised against CD34 antigen within the endothelial cell membranes. A computer attached to a microscope was used to count the number and measure the surface area of mucosal endothelial entities. In patients with Helicobacter pylori gastritis (n = 19), the median number of endothelial microstructures per section was 43 in the antrum and 86 in the gastric body, compared with 205 (P = 0.00004) and 165 (P = 0.002), respectively, in subjects with normal gastric histology (n = 11). The median surface area of the endothelial microstructures was also reduced in patients with gastritis. The normal gastric antrum had more endothelial entities than the normal body (median of 205 vs 165; P = 0.007). Within the normal stomach, the antrum is more richly vascularized than the gastric body. However, active chronic gastritis is associated with reduction in both the number and surface area of mucosal endothelial microstructures, with the reduction being more marked in the antrum. This is different from acute inflammation, and is relevant to our understanding of the natural history of mucosal defence, particularly the greater susceptibility of the gastric antrum to ulceration, compared with the gastric body.

The endocrine cells of extratumoral mucosa in relation to the carcinoma in stomach

One hundred and sixty-one surgically resected gastric carcinomas and 5 stomachs obtained at necropsy were evaluated using anti chromogranin A (CgA). CgA-Positive cells were found in 55 of 161 gastric carcinoma. Endocrine cells (EC) of the 55 cases of tumors and extratumoral mucosa and 5 normal gastric mucosa were distinguished by immunoreastive gastrin (GAST) , somatostatin (SS) , serotonin (SERO) , calcitonin (CT) , ACTH, human chorionic gonadotropin (HCG) , glucagon (GLU) , pancreatic polypeptide (PP), bombesin (BOM). Each type EC in extratumoral mucosa was quantitated by image analyser. Two variants of changes of EC were identified on the basis of presence or absence of associated antral atrophy. In the group of antral atrophy, amount of G cells decreascs than normal control (58.7mm2,P<0. 001) ; D cells and BOM positive cell also decrease; GLU-positive cells distributing in glands of intestinal metaplasia increase (18.6/mm2,P<0.001) in antral mucosa. There is not obvious change in the average thickness of fundic mucosa (1. 42mm,P>0. 05). Intestinal type carcinoma was more found in this group. G cell hyperplasia was observed in nontrophic antral extratumoral mucosa (211/ mm2,P<C 0.001). G cell and D cell is in a ratio of about 14 to 1, however it is about 7. 6 to 1 in normal gastric antrum. BOM-positive cells are hyperplasia. The average thickness of fundic mucosa was found to be increased (1.92mm,P<0.05). Diffuse type carcinoma was more found in this group. PP, ACTH, HCG-positive cells were discovered in the two groups. It suggests that endocrine substances may act as promotors of tumor growth and that different kinds of hormones may play a effect on different type of gastric carcinoma.

Effects of nonsteroidal anti-inflammatory drugs and misoprostol on gastroduodenal epithelial proliferation in arthritis

In this study, quantitation of the epithelial proliferation status of gastric glands and duodenal crypts was performed using endoscopic biopsy specimens from patients with rheumatological conditions requiring long-term anti-inflammatory and analgesic therapy, testing the hypothesis that long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to enhanced epithelial cell proliferation in the stomach and duodenum. After a 1-week washout period from NSAID administration, specimens were taken from endoscopically normal gastric antrum and duodenum, and microdissection was used to quantitate mitoses in these sites. Endoscopy and biopsy were then repeated after 2 weeks of NSAID administration, during which patients received in addition either the prostaglandin E1 analogue misoprostol (10 patients) or a placebo (10 patients). Mitotic counts in gastric glands increased similarly and significantly in the two groups from (mean ± SEM) 4.45 ± 0.57 to 7.69 ± 1.08 (P < 0.001) in the NSAID + placebo-treated group and from 4.31 ± 0.53 to 7.68 ± 1.08 (P = 0.006) in the NSAID + misoprostol-treated group. Similar changes took place in the duodenal crypts, from 5.44 ± 0.68 to 8.60 ± 1.28 (P = 0.013) in the NSAID + placebo-treated group and from 4.68 ± 0.56 to 6.35 ± 0.63 (P = 0.011) in the NSAID + misoprostoltreated group. NSAIDs increased the proportion of glands and crypts with bifid or more complex architectural forms. In a small group of patients, misoprostol alone did not alter mitotic rate in glands or crypts over 4 weeks. Thus, NSAIDs increase the rate of proliferation in endoscopically normal gastric and duodenal epithelium of patients with arthritis. This may form one of the mechanisms underlying gastric and duodenal adaptation to NSAIDs.

Expression of human gastrin gene in normal and gastrinoma tissues

The complete sequence of the human gastrin gene is reported here. This gene consists of three exons. Nine Alu family sequences are found within the gene and in the surrounding region. S1 mapping study showed that the transcription of gastrin gene starts at 60, 57, or 55 bp upstream from the 3′ end of the first exon. The mechanism of mRNA synthesis in a gastrinoma tissue was studied to clarify the ectopic production of gastrin. It was found that mRNA synthesis starts from the same three transcriptional start points. Southern blotting profiles for normal gastric antrum and gastrinoma DNA were indistinguishable from each other within the 18-kb region containing the gastrin gene, showing that no genomic rearrangements are associated with the gastrinoma formation. Thus, the overproduction of gastrin in this tumor is likely to be due to an aberrant expression control system of the cell, rather than a change in the control region of the gastrin gene.

β-Endorphinlike immunoreactivity and somatostatinlike immunoreactivity in normal gastric mucosa, muscle layer, and adenocarcinoma

β-Endorphinlike immunoreactivity and somatostatinlike immunoreactivity were detected in the mucosa and muscle layer of normal gastric antrum and corpus and in moderately differentiated adenocarcinoma derived from the antral mucosa. The concentration of β-endorphinlike immunoreactivity in the normal gastric tissues was 4–15 pmol/g wet wt tissue; this value varied from 9.64 to 241.39 pmol/g wet wt tissue (81.38 ± 37.82 pmol/g wet wt tissue) in adenocarcinomas. The concentration of somatostatinlike immunoreactivity was 18–25 pmol/g wet wt tissue in normal gastric mucosa, whereas it was 1–2 pmol/g wet wt tissue in adenocarcinomas. Gel exclusion chromatography of β-endorphinlike immunoreactivity revealed two peaks corresponding to β-endorphin and β-lipotropin. In normal mucosa and in the whole layer of antrum, the major peak was eluted near the position of β-lipotropin, and the minor broad peak was eluted near the position of β-endorphin. In contrast, in adenocarcinoma, β-endorphinlike immunoreactivity was eluted broadly at the position of β-endorphin and the other smaller peak was at the position of β-lipotropin. Gel exclusion chromatography of somatostatinlike immunoreactivity also showed different patterns between antral mucosa and adenocarcinoma. This study revealed the presence of the opioid peptide, β-endorphinlike immunoreactivity, not only in normal gastric tissue but also in adenocarcinomas with highly increased concentration and different elution patterns in combination with decreased concentration of somatostatinlike immunoreactivity.