Blood group-related antigen expression in normal and metaplastic human upper gastrointestinal mucosa.

Lewis antigen expression in upper gastrointestinal epithelium was studied using four monoclonal antibodies to determine the relationship between aberrant differentiation and antigen expression. Specific patterns of type 1 and type 2 Lewis blood group antigen expression were found in the surface and glands of the esophagus, gastric fundus, and duodenum. In biopsy specimens of Barrett's esophagus, gastric fundic-type columnar metaplasia expressed Lewis antigens indistinguishable from those in the normal stomach. In Barrett's junctional and specialized columnar metaplasia, Lewis a antigen was aberrantly expressed on the surface in secretors and in the glands independent of secretor state. Lewis x reactivity was markedly diminished in the glands of Barrett's junctional and specialized columnar epithelium irrespective of secretor state. There was no significant aberrancy observed in the expression of Lewis b and y antigens. The observed aberrant expression of Lewis antigens may be caused by an altered differentiation program in Barrett's metaplastic epithelium and may define a role for these glycoconjugates in the process of metaplasia and carcinogenesis in Barrett's epithelium.     

食管胃连接处疾病的病因学和形态学研究现状

食管胃连接处（EGJ）系指食管与胃的交界,其组织学具有特殊性。贲门部是连接远端食管与胃底黏膜的区域,贲门是否存在及其真实长度仍存有争议。EGJ所涉及的疾病主要有贲门炎、反流性食管炎（RE）和Barrett食管（BE）,三者间存在一定的联系.     

Gastric Electrical Stimulation With Parameters for Gastroparesis Enhances Gastric Accommodation and Alleviates Distention-Induced Symptoms in Dogs

Gastric electrical stimulation (GES) improves symptoms in patients with gastroparesis. We sought to determine if stimulation at fundus with parameters used for gastroparesis could affect gastric accommodation and distention-induced symptoms in dogs. Nine dogs were implanted with a gastric cannula at the anterior stomach and 1 pair of stimulation electrodes in the fundus. Assessment of gastric accommodation and a series of gastric distention were performed using a barostat. Stimulation parameters were of short pulse trains of 14 Hz, 5 mA, 0.3 ms, and 0.1 s on, 5 s off. GES at fundus significantly decreased fasting gastric tone. Fasting gastric volume was significantly increased from 56.3+/-10.4 mL at baseline to 102.4+/-23.1 mL with stimulation (P=.011). Postprandial gastric accommodation was significantly enhanced with stimulation. The extent of accommodation increased from 249.3+/-39.9 mL in the control session to 325.8+/-25.1 mL with stimulation (P=.011). Symptom scores induced by balloon distention of the stomach were significantly lower during stimulation in comparison with those of baseline (P=.016). In conclusion, GES with parameters for gastroparesis enhances postprandial gastric accommodation and reduces visceral perception in normal dogs. This effect, if seen also in humans, may explain in part the symptomatic improvement associated with GES therapy in patients with gastroparesis.     

Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach

Despite advances in treatment and the declining incidence, gastric cancer remains the second leading cause of cancer-related deaths in the world. Understanding the progression from inflammation to cancer in the stomach is crucial in the development of novel therapies and strategies for treating this disease. Chronic inflammation of the stomach is typically caused by Helicobacter pylori (H. pylori) and resulting lesions may lead to gastric cancer. During the progression from inflammation to cancer, the stomach epithelium changes with evidence of the disruption of normal epithelial cell differentiation and infiltrating inflammatory cells. Coincident with the development of atrophic gastritis and metaplasia, is the loss of the gastric morphogen Sonic Hedgehog (Shh). Given its critical role as a regulator of gastric tissue homeostasis, the disruption of Shh expression during inflammation correlates with the loss of normal epithelial cell differentiation, but this has only recently been rigorously tested in vivo using a unique mouse model of targeted gastric Shh deletion. While pre-neoplastic lesions such as atrophic gastritis and intestinal metaplasia are associated with the loss of Shh within the acid-secreting glands of the stomach, there is a clear link between elevated Shh and signaling to gastric cancers. The current review focuses on the effects of aberrant Shh expression and its role in the development of gastric cancer, specifically in response to H. pylori infection.     

Nesfatin-1对肥胖大鼠胃排空及胃平滑肌条收缩性的影响

目的:观察Nesfatin-1对正常及单纯性肥胖大鼠胃排空及离体胃平滑肌条收缩活性的影响.方法:高脂饲料喂养♂大鼠6wk,制作单纯性肥胖大鼠模型;正常及肥胖大鼠实验组中枢注入不同浓度Nesfatin-1(0.5μmol/L、5μmol/L、50μmol/L)后测胃排空率;生理记录仪记录大鼠胃底、胃体平滑肌条自发收缩及不同浓度Nesfatin-1(0.026μmol/L、0.26μmol/L、2.6μmol/L)作用下对乙酰胆碱(Ach)诱导的肌条收缩的影响.结果:Nesfatin-1可抑制正常及肥胖大鼠胃平滑肌条收缩,低、中、高浓度组与生理盐水对照组相比差异均有统计学意义(q=3.93-15.72,P<0.05-0.01).随Nesfatin-1浓度的增高,其抑制作用呈明显剂量依赖关系(q=3.45-5.69,P<0.05-0.01).低浓度Nesfatin-1抑制正常大鼠、肥胖大鼠胃底平滑肌条收缩作用无显著性差异(P>0.05),中、高浓度对正常大鼠胃底平滑肌条抑制作用强于肥胖大鼠(t=2.14,P<0.05;t=2.63,P<0.05).低、中浓度Nesfatin-1抑制正常大鼠、肥胖大鼠离体胃体平滑肌条收缩作用无显著性差异(P>0.05),但高浓度抑制正常大鼠离体胃体平滑肌条收缩作用显著强于肥胖大鼠(t=2.53,P<0.05).结论:Nesfatin-1可抑制正常及肥胖大鼠胃排空,胃排空率随Nesfatin-1浓度增加而降低.Nesfatin-1可抑制乙酰胆碱诱导的单纯性肥胖大鼠离体胃平滑肌条的收缩活动,其抑制作用随Nesfatin-1浓度增高而增强;相同Nesfatin-1浓度抑制正常大鼠离体平滑肌条收缩作用强于肥胖大鼠.     

Histochemical Study of Phosphorylase in Proliferating Cells of Intestinal Metaplasia and Carcinoma of the Human Stomach

A morphologic histochemical study of phosphorylase was carried out to investigate the relationship between gastric carcinoma and intestinal metaplasia. Intense phosphorylase activity was observed in the carcinoma cells, especially in well-differentiated adenocarcinoma, and in the proliferating cells of some intestinal metaplasias. Metaplastic epithelium other than the proliferating cells occasionally showed a positive reaction. Phosphorylase was negative in normal gastric epithelium, even in its proliferating cells. There was an apparent coincidence between the location of well-differentiated adenocarcinoma and the distribution of intestinal metaplasia, with the proliferating cells showing positive reaction for phosphorylase. These data suggest that the relationship between the proliferating cells of intestinal metaplasia showing phosphorylase activity and well-differentiated adenocarcinoma is apparently closer than the much-debated relationship between the epithelium of intestinal metaplasia and gastric carcinoma.     

SOLITARY PEDUNCULATED GASTRIC GLAND HETEROTOPIA TREATED BY ENDOSCOPIC POLYPECTOMY: REPORT OF A CASE

The patient, a 68‐year‐old woman with a long‐standing history of schizophrenia, was admitted to our hospital complaining of vomiting which had lasted approximately 3 weeks. Endoscopic examination of the stomach revealed a solitary pedunculated submucosal tumor, of approximately 2 cm in diameter, on the anterior wall of the upper body, close to the greater curvature. The lesion was endoscopically excised using a polypectomy snare without any complication. Microscopic examination was compatible with the diagnosis of gastric gland heterotopia showing submucosal proliferation of pseudopyloric glands, fundic glands and foveolar epithelium with fibromuscular stromal framework. The proliferating foveolar epithelium and fibromuscular stroma were in continuity with the overlaying gastric mucosa and muscularis mucosae, respectively. The lesion was entirely covered by normal gastric epithelium. No atypical cells were revealed in the lesion. The clinical significance of gastric gland heterotopia is unclear because of its controversial histogenesis and carcinogenetic potential. We herein report a rare case of solitary pedunculated gastric gland heterotopia with some review of scientific reports.     

Gene expression profile differences in gastric cancer, pencancerous epithelium and normal gastric mucosa by gene chip

AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonudeotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes, 530 were up-regulated (Signal Log Ratio [SLR]>2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64 genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35 were down-regulated (SLR<-2). CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.     

Gastric foregut cystic developmental malformation: Case series and literature review

Foregut cystic developmental malformation(FCDM) is a very rare lesion of the alimentary tract, especially in the stomach. We discuss the concepts of gastric duplication cyst, bronchogenic cysts, and FCDM. Nomenclature has been inconsistent and confusing, but, by some definitions, gastric duplication cysts involve gastric mucosa and submucosal glands, bronchogenic cysts involve respiratory mucosa with underlying cartilage and glands, and FCDM lacks gastric mucosa or underlying glands or cartilage but has pseudostratified ciliated columnar epithelium(PCCE). We searched our departmental case files from the past 15 years and identified 12 cases of FCDM in the alimentary tract. We summarize the features of these 12 cases including a report in detail on a 52-year-old man with a submucosal cyst lined with simple PCCE and irregular and stratified circular muscle layers that merged with gastric smooth muscle bundles near the lesser curvature of the gastric cardia. A literature review of cases with this histology yielded 25 cases. We propose the term gastric-FCDM for such cases. Our own series of 12 cases confirms that preoperative recognition of the entity is infrequent and problematic. The rarity of this developmental disorder, as well as a lack of understanding of its embryologic origins, may contribute to missing the diagnosis. Not appreciating the diagnosis preoperatively can lead to an inappropriate surgical approach. In contrast, presurgical recognition of the entity will contribute to a good outcome and reduced risk of complications.     

Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip

AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes, 530 were up-regulated (Signal Log Ratio (SLR) >2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64 genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35 were down-regulated (SLR<-2). CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.     

Expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inversely correlates with tumor progression in gastric adenomas and carcinomas

PURPOSE: The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), one of TGF-beta superfamily gene, is reported to be responsible for NSAID-induced apoptosis. We analyzed NAG-1 expression in gastric cancer and adenoma to find out its clinical implication. METHODS: Immunostaining was performed using standard procedures with antibody to NAG-1 on gastric tissue microarrays of tissue specimens obtained by gastrectomy. The immunoreactivity of normal and tumor tissues was graded as no, weak, moderate, and strong expression. RESULTS: The NAG-1 expression was stronger in intestinal metaplasia and adenoma than normal gastric epithelium. 47 (74.6%) of 63 normal gastric epithelium showed no or weak expression, but 33 (56.9%) of 58 and 13 (86.7%) of 15 intestinal metaplsia and adenoma showed moderate or strong expression. Only NAG-1 expression in diffuse type gastric cancer was weaker than in normal gastric tissue. Compared to intestinal metaplasia, both intestinal and diffuse type gastric cancer showed weaker expression. The intensity of NAG-1 expression inversely correlated with tumor differentiation and T and N stage status. While only 1 (2.2%) of 45 T1 stage cases lacked NAG-1 expression, 27 (45.8%) of 59 T3 stage cases lacked NAG-1 expression. Likewise, in N0 stage tumors only 10 (15.4%) of 65 cases lacked NAG-1 expression, but 17 (63.0%) of 27 N3 cases lacked NAG-1 expression. CONCLUSIONS: The NAG-1 was expressed strongly in intestinal metaplasia and adenoma, and inversely correlated to tumor stages. This interesting finding may provide new targets for chemoprevention and future development of drugs.     

Calcitonin in human gastric mucosa and carcinoma

Summary The localization of immunoreactive calcitonin (IR-CT) in the human gastric mucosa and tumor tissues was studied using an immunohistochemical peroxidase-antiperoxidase method. A small number of IR-CT-containing cells were observed in both infant and adult gastric antral mucosa and the ratio of IR-CT-containing cells to G cells was about 1:50-100. Moreover, tissue content of IR-CT in normal antral mucosa was 2.37±0.35 ng/g wet weight. IR-CT-containing cells and G cells decreased with the progress of chronic atrophic gastritis and were totally absent in intestinal metaplastic glands. IR-CT was detected in G cells, suggesting a paracrine relation between gastrin and CT. IR-CT was not found in tumor cells of 35 gastric adenomas and 40 well differentiated adenocarcinomas. On the other hand, it was demonstrated in a very small number of tumor cells in 4 of 46 poorly differentiated adenocarcinomas, and in a good number in 3 of 7 scirrhous argyrophil cell carcinomas. IR-CT in plasma could serve, therefore, as a tumor marker of scirrhous endocrine cell carcinoma, and its production in cancer cells was considered to be eutopic rather than ectopic.Supported in part by Grant-in Aid for Cancer Research from the Ministry of Education, Science and Culture (No. 59010074).     

HTRA1 gene expression in gastric epithelial cells

Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis.Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines.The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequeucing analysis.Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR.Results:HIC analysis indicated that HtrA1 was highly expressed in normal epithelium,but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues.HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to nontumorigenic counterparts.The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected.Total 14 CpGs in this region were all methylated in gastric cancer cells,whereas two normal cells.GES-1 and HFI-145,were having several unmethylated cytosines in this region.HtrA1 showed as~Mr 44,000,Expression of HtrA1 protein was not observed in any of the four gastric caucer cell lines.BGC-823.MKN-45.SGC-7901and MKN-28.HtrA1 expression was observed in the HF1-145and GES-1 cell lines.Conclusions:The epigenetic silencing for HtrA1gene expression could provide a possible strategy for re-activating Htrt1 gene expression in gastric cancer cells.thus facilitating further investigation of HtrA1's role in chemotherapy.     

Cellular localization of gastrone in gastroduodenal mucosa by immunofluorescence

In view of the previously demonstrated immunologic and biologic activity of a precipitating antibody to gastrone B, this antibody was used in immunofluorescence tests for cellular localization of gastrone in the gastroduodenal mucosa of man and dog. The antibody was raised in rabbits immunized with fraction 7 from the Sephadex G-100 gel filtration of anacid human gastric juices. In indirect Coons' test with the use of fluorescein-labeled antirabbit IgG and rabbit antigastrone B serum fluorescence appeared in the pyloric glands and surface epithelium of the antrum in man and dog and the villous epithelium and crypts of the duodenal bulb mucosa in the dog. These structures probably represent the main sites of cellular origin of gastrone B in these two species. No immunofluorescence was observed in the antrum of man or the antrum and duodenal bulb of the dog when normal rabbit or human serum was used in control tests. No immunofluorescence was detected, either, in the glandular structures of the fundal mucosa of man and dog. The surface epithelium of the fundus of the human and dog stomach gave a faint immunofluorescence both with antigastrone B and with normal rabbit sera, which could be nonspecific in nature.Supported by Research Grant #AM-07901 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, US Public Health Service.     

Nodular hyperplasia of Brunner''s glands

A clinical, endoscopic, and histological study of 206 cases of nodular hyperplasia of Brunner's glands was carried out. Firm nodules with a reddened surface due to hyperplastic Brunner's glands were limited mainly to the first part of the duodenum and affected almost exclusively male patients. Gastric acid secretion after pentagastrin stimulation was significantly increased compared to normal. In most cases, biopsies of the nodule center revealed spreading of Brunner's glands from within the lamina propria to the surface epithelium, whereas in biopsies performed between nodules, Brunner's glands were limited to the deeper part of the mucosa. Thirty-six nodules completely removed by diathermy were composed almost entirely of Brunner's glands. The frequent association with duodenal ulcer, chronic gastric erosions, and cobblestone pattern of the gastric body mucosa, as well as the significant hypersecretory state, suggest that hyperacidity plays a role in the pathogenesis of nodular hyperplasia of Brunner's glands.     

Squamous morules in gastric mucosa

An elderly white man undergoing evaluation for pyrosis was found to have multiple polyps in the fundus and body of the stomach by endoscopic examination. Histologic examination of the tissue removed for biopsy over a 2-year period showed fundic gland hyperplasia and hyperplastic polyps, the latter containing nests of immature squamous cells. These nests arose within superficial gastric glands and resembled squamous morules seen in benign endometrium. Previous reports of this type of squamous epithelium in gastric mucosa were not encountered in our literature review. This most probably represents a benign process since there is no evidence to support its relationship to the occurrence of either primary squamous cell carcinoma or adenosquamous carcinoma of the stomach.     

西甲硅油在内镜胃体胃底观察中的价值

目的 探讨西甲硅油在内镜胃体胃底观察中的应用价值。方法 对行胃镜检查的患者随机分成两组，检查前研究组予西甲硅油30ml＋利多卡因胶浆10ml口服，对照组予利多卡因胶浆10ml口服，根据内镜下视野清晰程度分成ABCD四级，并行统计学分析。结果 服用西甲硅油的研究组内镜下视野清晰程度明显高于对照组（P〈0．001）。结论 应用西甲硅油可明显提高胃镜视野清晰度，尤其对胃体胃底观察具有重要价值。     

Histological examination of gastric mucosal lesions induced by isolation in saline and cimetidine treated rat

It has been recently pointed out that the most reliable method of assessment of gastric mucosal injury is the microscopic examination of the tissue. The purpose of the present paper was, therefore, to study the histological features of gastric lesions induced by a six week isolation in rats. It has also been investigated whether a two week treatment, beginning four weeks after isolation, with cimetidine 80 and 160 mg kg-1 p.o. daily could protect the gastric mucosa. In saline treated rats, histological examination of haemorrhagic areas showed that both surface epithelium and gastric pits were damaged or even completely absent with a consequent surfacing of subepithelial vessels. Damage extended deeply into the gastric glands with evidence of necrotic cells in the corpus and fundus. Simultaneous occurrence of the process of restitution was evident. Cimetidine partially lessened the severity of damage and appeared to favour the restitution processes.     

M3受体在人胃和食管组织中的表达

目的研究发现石胆酰牛磺酸及其他一些胆汁酸是M3受体的部分激动剂，而胆汁反流到胃和食管又是一个普遍现象。本研究旨在探索胃、食管黏膜的M3受体表达情况。方法分别使用羊和兔抗人M3受体的多克隆IgG抗体A和B，采用免疫组化，在11例人胃和食管的不同部位黏膜对M3受体进行定位。结果使用抗体A发现胃泌酸腺表面黏液细胞、小凹细胞、颈部细胞和壁细胞，及食管鳞状上皮的棘层细胞表现为细胞质染色，使用抗体B发现除上述细胞的胞质染色外，人胃壁肌层平滑肌细胞表现为胞膜和胞质共同染色。结论研究揭示M3受体表达于人胃泌酸腺表面黏液细胞、小凹细胞、腺颈部细胞、壁细胞和食管鳞状上皮的棘层细胞。