Effect of Helicobacter pylori infection and eradication on gastric epithelial cell proliferation and apoptosis.

OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS: both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.     

The pathological examinations of gastric mucosa in patients with Helicobacter pylori-positive and -negative pernicious anemia

Background. The basic histopathological finding in gastric mucosa is chronic atrophic gastritis in patients with pernicious anemia.
Materials and Methods. We evaluated the frequency of Helicobacter pylori and pathological examinations of gastric mucosa in pernicious anemia (n = 30) by endoscopical findings and biopsy. The results were compared with gastric mucosa specimens of patients with H. pylori –positive nonulcer dyspepsia (n = 36) and H. pylori –negative nonulcer dyspepsia (n = 21).
Results. H. pylori was diagnosed in 12 patients (40%) with pernicious anemia. Fundal biopsy examinations showed atrophic gastritis in 30 patients (100%), intestinal metaplasia in 13 patients (43.3%), lymphoid follicle in 15 patients (50%), and dysplasia in 6 patients (20%). Antral biopsy examinations showed atrophic gastritis in 8 patients (26.6%), intestinal metaplasia in 8 patients (26.6%), lymphoid follicle in 8 patients (26.6%), and dysplasia in 3 patients (10%). The frequency of fundal inflammation, atrophy, intestinal metaplasia, lymphoid follicle, and dysplasia and antral intestinal metaplasia and mild antral dysplasia were found to be higher in those in the pernicious anemia group than in the nonulcer dyspeptic patients. Antral inflammation, atrophy, and moderate and severe antral dysplasia were found to be higher in those in the nonulcer dyspeptic group.
Conclusions. Particularly, fundal precancerous lesions were found to be more frequent in patients with pernicious anemia independent of H. pylori.     

Molecular assessment of c-H-ras p21 expression in Helicobacter pylori-mediated gastric carcinogenesis

Helicobacter pylori (H. pylori) infection plays a significant role in causing gastric cancer; the exact molecular mechanisms of gastric carcinogenesis have not yet been fully determined. Therefore, this study was planned to examine the role of c-H-ras p21 expression in H. pylori infection at different stages of disease progression from precursor lesions to gastric carcinoma. This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status have been analysed. The expression of c-H-ras p21 was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of c-H-ras p21 was also studied semiquantitatively by immunohistochemistry. The RT-PCR and western blotting results of c-H-ras p21 mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia, and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of c-H-ras p21 in the similar way. Overexpression of c-H-ras p21 might be due to H-ras mutation at codon 12 of ras gene family in H. pylori infection. The rate of expression of ras p21 was higher in the H. pylori-infected precursor lesions, chronic gastritis 49/56 (87.5%), intestinal metaplasia 16/17 (94%), and dysplasia 9/11(82%) whereas in the case of H. pylori negative cases these groups, show 12.5, 5.9, and 18.2%, respectively. The data suggested that H. pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis.     

P53 protein and Ki-67 expression in chronic gastritis patients with positive Helicobacter pylori infection

The present study was carried out to assess the predictive value and expression of the proliferative activity of Ki-67 and the expression of p53 protein in Helicobacter pylori associated chronic gastritis. This study comprised archival blocks from 20 dyspeptic patients who at National Hepatology and Tropical Medicine Research Institute underwent a diagnostic oesophago-gastroduodenoscopy with multiple gastric antral endoscopic biopsies for histological examination. The blocks were cut at 5 nM thicknesses, stained by hematoxylin and eosin to score the inflammatory grade and subjected to Giemsa stain to assess H. pylori infection, and then immune–histochemical method was done to determine protein P53 and Ki-67. The obtained results indicated that there was no significant association between the expression of Ki67 and P53 in the studied cases. There was no significant association between Ki67 and P53 in the presence of intestinal atrophy, intestinal metaplasia, intestinal activity and intestinal inflammation. While, there was significant association between Ki67 and P53 in intestinal dysplasia, P = 0.015, 0.025, respectively. It could be concluded that the significant association of the proliferative marker Ki-67 and apoptotic marker p53 protein with intestinal dysplasia may be one of the main predictive values in the development of gastric carcinoma in patients with gastritis secondary to H. pylori infection.     

Different Expression of Helicobacter pylori Gastritis in Children: Evidence for a Specific Pediatric Disease?

Background Infection with Helicobacter pylori causes active chronic gastritis. Once the infection is acquired, gastritis will persist for almost the rest of one's life. To date, very few data are available on H. pylori gastritis in relation to age. Therefore, we attempted to inestigate whether H. pylori gastritis in children exhibits features different from H. pylori gastritis in adults of two different age groups. Materials and Methods. Fifty consecutive children with a median age of 11 years (range, 3–18 years) were compared with two groups of 50 adult patients, one group with a median age of 43 (range, 19–56 years) and another group with a median age of 70 years (range, 59–86 years). All patients had H. pylori gastritis unrelated to active peptic ulcer disease. Two biopsy specimens were taken from the antrum and two from the corpus, and the following gastritis parameters were evaluated: degree and activity of gastritis, H. pylori colonization, replacement of foveolar epithelium by regenerative epithelium, mucous depletion, presence of atrophic gastritis with intestinal metaplasia, and presence of lymphoid follicles. Results. Degree and activity of gastritis, extent of H. pylori colonization, degree of replacement by regenerative epithelium, extent of mucous depletion, degree of atrophic gastritis with intestinal metaplasia, and the presence of lymphoid follicles in the antrum, as well as the presence of lymphoid follicles in the corpus differed significantly (chi-square test: p < .05). All these differences—except the once frequent occurrence of atrophic gastritis with intestinal metaplasia in adults—were attributable to a higher expression of these gastritis parameters in children. Conclusions. We conclude that H. pylori gastritis, particularly in the antrum, is more severely expressed in childhood. One reason for this might be a child-specific immune response to an infection with H. pylori. Alternatively, infection may represent a pediatric disease characterized by a nonatrophic, highly expressed form of gastritis, which changes its appearance once the host becomes adapted over time.     

Functional Role of Metaplastic Paneth Cell Defensins in Helicobacter pylori-Infected Stomach

Background and Aims:  Chronic gastritis is caused by Helicobacter pylori infection, and gastritis is classified as inflammation, atrophy, and intestinal metaplasia. Detailed pathologic studies have shown that H. pylori settles on the surface of gastric mucosa, and that it is eliminated from metaplastic mucosa. However, its mechanism of natural protection is not well known.
Methods:  Antimicrobial human enteric defensin expression was determined in the RNA and protein levels. Recombinant enteric defensins were produced with a bacterial expression system and their anti- H. pylori activities were assessed by bactericidal assay.
Results:  Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. HD-5 protein was coexpressed with trypsin, which is considered to be an activating enzyme of HD-5. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. The recombinant defensins showed killing activity against H. pylori at a low concentration in vitro.
Conclusions:  The human defensins that are expressed in the metaplastic Paneth cells eliminate H. pylori . Metaplastic change may be a purposive development of the human stomach.     

Immunohistochemical study of the expression of trophoblastic beta-1-globulin in the gastric epithelium of man in stomach cancer]

The expression of specific-pregnancy beta 1-globulin (SP1) was studied in gastric mucosa with chronic gastritis. The expression of SP1 was revealed in focus of intestinal metaplasia, dysplasia as well as in cover epithelial cells.     

Pathophysiology and clinical relevance of Helicobacter pylori.

Considerable knowledge has recently accumulated on the mechanism by which Helicobacter pylori (H. pylori) induces chronic gastritis. Although H. pylori is not an invasive bacterium, soluble surface constituents can provoke pepsinogen release from gastric chief cells or trigger local inflammation in the underlying tissue. Urease appears to be one of the prime chemoattractants for recruitment and activation of inflammatory cells. Release of cytokines, such as tumor necrosis factor alpha, interleukin 1 and 6, and oxygen radicals, leads to a further tissue inflammation accompanied by a potent systemic IgA and IgG type of immune response. Chronic inflammation and antigens on glandular epithelial cells lead to a progressive destruction with loss of the epithelial barrier function. Within the gastric mucosa, patches of intestinal metaplasia develop, which may be a risk factor for subsequent development of gastric carcinoma. Hyperacidity in duodenal ulcer patients induces gastric metaplasia in the duodenal bulb, which represents a target for H. pylori colonization and ulcer formation. H. pylori can be detected in the majority of patients with peptic ulcers and, compared to age-matched healthy people, it is also found more often in patients with dyspepsia and gastric carcinoma. Although H. pylori can be detected in healthy people, the marked reduction of the ulcer recurrence rate by eradication of H. pylori (80 percent versus 20 percent relapse within one year) suggests that H. pylori is a major risk factor for duodenal ulcer formation. The potential role of H. pylori in non-ulcer dyspepsia and carcinogenesis is under investigation. Current regimens aimed at eradicating H. pylori use a combination of several drugs that are potentially toxic. Since the risk of complications may exceed the potential benefit in most patients, eradication treatment should be limited to clinical trials and to patients with aggressive ulcer disease. New drug regimens, e.g., the combination of proton pump inhibitors with one antibiotic, may provide less toxic alternatives. Beyond ulcer treatment, effective and well-tolerated eradication regimens may have a place in prophylaxis of gastric carcinoma.     

The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection

Gastric cancer is an important worldwide health problem and causes considerable morbidity and mortality. It represents the second leading cause of cancer-related death worldwide. A cascade of recognizable precursor lesions precedes most distal gastric carcinomas. In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia to gastric carcinoma. Detection and treatment of premalignant lesions may thus provide a basis for gastric cancer prevention. However, at present, premalignant changes of the gastric mucosa are frequently disregarded in clinical practice or result in widely varying follow-up frequency or treatment. This review provides an overview of current knowledge on detection, surveillance and treatment of patients with premalignant gastric lesions, and identifies the uncertainties that require further research.     

Helicobacter pylori infection‐induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications

Background

Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori‐induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication.

Materials and Methods

Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low‐grade intraepithelial neoplasia, high‐grade intraepithelial neoplasia, and intestinal‐type gastric cancer groups. Helicobacter pylori infection was determined by either ¹³C‐urea breath test or immunohistochemistry staining.

Results

In Helicobacter pylori‐negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low‐grade intraepithelial neoplasia, and declined in high‐grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori‐infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori‐negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori‐negative control. Labeling index of Ki67 in Helicobacter pylori‐negative groups was higher in gastric cancer than chronic atrophic gastritis and low‐grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori‐positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress.

Conclusions

These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori‐induced gastric cancer.     

Endoscopic review of patients who have had gastric surgery.

Seventy one patients who had had operations on their stomachs over 15 years previously were examined by endoscopy and multiple mucosal biopsy sampling. Sixty six had histologically proved gastritis (56 chronic atrophic gastritis, 10 superficial gastritis), 38 intestinal metaplasia, and 11 epithelial dysplasia. In three cases the epithelial dysplasia was severe (carcinoma in situ). One patient had an infiltrating carcinoma and another, whose biopsy appearances were reported as severe dysplasia, developed a carcinoma of the stomach eight months later. All patients having undergone gastric surgery more than five years previously should be screened endoscopically and any found to have moderate dysplasia subjected to regular endoscopic screening thereafter. Patients with severe dysplasia (carcinoma in situ) should be considered for radical surgery.     

Terminal alpha1,4-linked N-acetylglucosamine in Helicobacter pylori-associated intestinal metaplasia of the human stomach and gastric carcinoma cell lines.

Helicobacter pylori (Hp) infection is associated with the development of gastric lesions including gastritis, intestinal metaplasia (IM), and gastric carcinoma. In humans, Hp is found almost exclusively in the foveolar epithelium of the gastric mucosa and rarely colonizes the deeper portions where mucous cells of the glands produce mucins with terminal alpha1,4-GlcNAc O-glycans. This structure exerts antimicrobial activity against Hp. The development of IM in the stomach is characterized by Hp clearance from the metaplastic glands and by major alterations in the expression of mucins and mucin-carbohydrates. The present work evaluated whether terminal alpha1,4-GlcNAc and sialyl-Tn antigen are implicated in the process of Hp clearance from metaplastic glands by analyzing the expression of these antigens in different types of IM-complete (n=12) and incomplete (n=8)-and in gastric cell lines. Terminal alpha1,4-GlcNAc was not detected in IM except in a single foci of one case, indicating that this structure is not implicated in the clearance of Hp from IM, in contrast to what is observed in normal gastric mucosa. None of the gastric carcinoma cell lines studied showed terminal alpha1,4-GlcNAc, suggesting that they do not display a gastric gland mucous cell phenotype and therefore are useful models for in vitro Hp studies. Finally, sialyl-Tn antigen colocalizes with MUC2 mucin and is present in all cases of complete and incomplete IM, suggesting that either or both can be implicated in Hp clearance from IM.     

慢性胃炎肠化生CD_(44)、CD_(44V6)及Cyclin D_1、Cyclin E的表达和意义

目的探讨慢性胃炎胃粘膜肠化生CD44、CD44V6及cyclin D1、Cyclin E表达的意义。方法利用免疫细胞化学技术对39例伴有肠化生的慢性胃炎和5例正常人胃窦粘膜的活检组织进行检查。结果正常人胃窦粘膜上皮,腺上皮对CD44、CD44V6、Cyclin D1和Cyclin E均为阴性,但在有神经内分泌样细胞的粘膜,CD44V6和cyclin D1为阳性。慢性胃炎肠化生区和不典型增生区除CD44为阴性外,CD44V6、cyclin D1和cyclin E均呈现不同的阳性反应,但未见有阳性的神经内分泌样细胞。间质细胞大都呈阳性反应。结论CD44V6、cyclin D1和cyclin E可能是胃癌前状态的早期事件,而CD44可能为胃癌晚期的标志物。     

Inducible nitric oxide synthase expression before and after eradication of Helicobacter pylori in different forms of gastritis

An increased expression of inducible nitric oxide synthase (iNOS) has been observed in the inflamed human gastric mucosa as well as in some tumors. This observation suggests a pathobiological role of elevated NO production. The purpose of this study was to compare the immunohistochemical iNOS expression in the different kinds of gastritis before and after the eradication of Helicobacter pylori. We performed iNOS and H. pylori immunohistochemical staining and counted iNOS positive cells. We detected elevated expression of iNOS around sites infected with H. pylori. iNOS expression in chemical gastritis was strongly elevated in mucosal glands. After treatment, we found a significant difference in iNOS expression in patients with classical H. pylori-induced antrum predominant gastritis and in patients with active autoimmune gastritis. In the special case of progressed gastritis with intestinal metaplasia we found persistence of intestinal metaplasia, and we could not find a significant difference in the number of positive iNOS cells before and after treatment. The persistence of IM as a possibly precancerous lesion is probably at least in the antrum a source of continuous iNOS induction even after H. pylori eradication.     

Genetic host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms

Helicobacter Pylori is a gram negative rod shaped microaerophilic bacterium that colonizes the stomach of approximately half the world's population. Infection with c may cause chronic gastritis which via a quite well described process known as Correas cascade can progress through sequential development of atrophic gastritis, intestinal metaplasia and dysplasia to gastric cancer. H. pylori is currently the only bacterium that is classified as a class 1 carcinogen by the WHO, although the exact mechanisms by which this bacterium contributes to gastric carcinogenesis are still poorly understood. Only a minority of H. pylori-infected patients will eventually develop gastric cancer, suggesting that host factors may be important in determining the outcome of H. pylori infection. This is supported by a growing body of evidence suggesting that the host genetic background contributes to risk of H. pylori infection and gastric carcinogenesis. In particular single nucleotide polymorphisms in genes that influence bacterial handling via pattern recognition receptors appear to be involved, further strengthening the link between host risk factors, H. pylori incidence and cancer. Many of these genes influence cellular pathways leading to inflammatory signaling, inflammasome formation and autophagy. In this review we summarize known carcinogenic effects of H. pylori, and discuss recent findings that implicate host genetic pattern recognition pathways in the development of gastric cancer and their relation with H. pylori.     

Acid, helicobacter and immunity: a new paradigm for oesophagogastric cancer.

Epidemiological evidence has clearly shown a highly significant relationship between Helicobacter pylori infection and the development of duodenal ulcer and distal gastric adenocarcinoma. Despite H. pylori being a common aetiological factor for both disorders, the two disease phenotypes are virtually mutually exclusive. This indicates that the host response to infection has a pivotal role in determining outcome; these disease phenotypes relate to the effect of infection on gastric acid secretion, duodenal ulcer being closely related to sustained acid secretion whereas gastric cancer follows gastric atrophy and impaired gastric acid secretion. Cancer at the oesophageal junction and that associated with Barrett's oesophagus is now the most rapidly increasing tumour in the gastrointestinal tract. The challenge for the next millennium, therefore, is to try and develop methods for identifying patients at risk of developing oesophagogastric cancer. A common feature in the pathogenesis of both gastric and oesophageal adenocarcinoma is inflammation presenting clinically as gastritis and oesophagitis. The pathway from gastritis to gastric atrophy, dysplasia and carcinoma is thought to be a multi-step process, probably triggered by free radicals within the gastric epithelium and increased exposure to luminal carcinogens. However, it has been unclear as to which aspect of the host response determines whether an individual will move along the neoplasia pathway. Recent work has shown that qualitative aspects of the immune environment in the stomach may account for a substantial part of the phenotypic divergence following H. pylori infection. Interleukin-1 beta polymorphisms relate closely to the propensity for an individual to develop distal gastric cancer and maybe useful for predicting risk in family members. In Barrett's oesophagus, we have recently shown that the immune environment may also be important in determining whether an individual will develop cancer. Although we did not find that Barrett's oesophagus was a profoundly inflammatory condition (unlike esophagitis in the squamous epithelium), where there was evidence of inflammation it was qualitatively different from that of oesophagitis in that a Th-2 response with increased expression of IL-4 predominated in Barrett's, whereas a Th-1 proinflammatory response characterised oesophagitis in squamous epithelium. It seems likely that the specific immune environment within Barrett's metaplasia may be an important driver towards dysplasia and carcinoma. Thus, the immune environment in the stomach and esophagus may be critical in determining whether an individual is at risk of developing neoplastic complications of H. pylori infection and gastroesophageal reflux. Identification of the genetic factors which underpin these responses may ultimately result in development of methods to identify individuals at high risk.     

树突状细胞对胃癌前病变的免疫保护分析

摘要 目的：探究树突状细胞(Dendritic cells,DC)对胃癌的免疫保护作用。方法：选择2016年1月至2018年1月于我院接受治疗的145例胃癌、39例慢性萎缩性胃炎、21例不典型增生、27例肠上皮化生以及20例正常对照组患者为研究对象,分别采集其胃粘膜标本进行染色,记录和比较其胃粘膜中S100⁺、CD4⁺和CD8⁺细胞的数量、平均面积以及平均吸光度,并将胃癌患者分为中分化腺癌(49例)、低分化腺癌(53例)和未分化癌(43例)进行对比。结果：(1)胃癌组、慢性萎缩性胃炎组、不典型增生、肠上皮化生组的胃粘膜S100⁺阳性细胞计数明显高于正常对照组（P<0.05）,胃癌组平均吸光度低于对照组,其他3组平均吸光度显著高于对照组,(P<0.05);胃癌组平均面积与正常对照组相比无差异(P>0.05),其他三组平均面积显著高于对照组（P<0.05）;(2)慢性萎缩性胃炎组、肠上皮化生组、不典型增生组患者CD4⁺细胞数均低于对照组(P<0.05);胃癌组、慢性萎缩性胃炎组、肠上皮化生组患者平均面积均低于对照组(P<0.05);胃癌组、慢性萎缩性胃炎组、不典型增生、肠上皮化生组平均吸光度均低于对照组(P<0.05);(3)慢性萎缩性胃炎组、肠上皮化生组、不典型增生组患者CD8⁺细胞数明显高于对照组(P<0.05),胃癌组稍低于对照组(P>0.05);胃癌组患者平均面积低于对照组(P<0.05);胃癌组患者平均吸光值低于对照组,慢性萎缩性胃炎组、肠上皮化生组患者高于对照组(P均<0.05);(4)随着胃癌分化程度的降低,胃癌患者DC细胞数有降低趋势。结论：胃癌前病变患者胃粘膜中DC数量会显著增多,免疫功能加强,DC细胞数量会随胃癌分化程度的降低而减少,分析其原因与DC细胞能够抑制癌前病变有关。     

Histology of the postoperative stomach before and after diversion of bile.

Gastric biopsy specimens were taken in 33 patients before and after procedures to divert bile (construction of Roux loop in 19, closure of gastrojejunostomy in 14). Each biopsy specimen was assessed for dysplasia, intestinal metaplasia, atrophy, and gastritis, each variable being given a score ranging from 0 to 6. Patients were given preoperative and postoperative scores for each of these variables based on the average score of all preoperative or postoperative specimens. Comparison between preoperative and postoperative histology showed that there was no difference for gastritis, atrophy, or intestinal metaplasia. Patients who underwent closure of a gastrojejunostomy showed improvement in dysplasia that was not statistically significant. There was, however, a significant improvement in dysplasia in patients in whom a Roux loop was fashioned (p = 0.006) and in all patients taken together (p = 0.002). It was concluded that procedures that divert bile improve dysplasia but not other histological abnormalities in the stomach postoperatively.     

Infection with CagA-Positive Helicobacter Pylori Strain Containing Three EPIYA C Phosphorylation Sites is Associated with More Severe Gastric Lesions in Experimentally Infected Mongolian Gerbils (Meriones Unguiculatus)

Infection with Helicobacter pylori strains containing high number of EPIYA-C phosphorylation sites in the CagA is associated with significant gastritis and increased risk of developing pre-malignant gastric lesions and gastric carcinoma. However, these findings have not been reproduced in animal models yet. Therefore, we investigated the effect on the gastric mucosa of Mongolian gerbil (Meriones unguiculatus) infected with CagA-positive H. pylori strains exhibiting one or three EPIYA-C phosphorilation sites. Mongolian gerbils were inoculated with H. pylori clonal isolates containing one or three EPIYA-C phosphorylation sites. Control group was composed by uninfected animals challenged with Brucella broth alone. Gastric fragments were evaluated by the modified Sydney System and digital morphometry. Clonal relatedness between the isolates was considered by the identical RAPD-PCR profiles and sequencing of five housekeeping genes, vacA i/d region and of oipA. The other virulence markers were present in both isolates (vacA s1i1d1m1, iceA2, and intact dupA). CagA of both isolates was translocated and phosphorylated in AGS cells. After 45 days of infection, there was a significant increase in the number of inflammatory cells and in the area of the lamina propria in the infected animals, notably in those infected by the CagA-positive strain with three EPIYA-C phosphorylation sites. After six months of infection, a high number of EPIYA-C phosphorylation sites was associated with progressive increase in the intensity of gastritis and in the area of the lamina propria. Atrophy, intestinal metaplasia, and dysplasia were also observed more frequently in animals infected with the CagA-positive isolate with three EPIYA-C sites. We conclude that infection with H. pylori strain carrying a high number of CagA EPIYA-C phosphorylation sites is associated with more severe gastric lesions in an animal model of H. pylori infection.Key words: Gastritis, atrophy, intestinal metaplasia, dysplasia, Mongolian gerbil, cagA EPIYA C motif     

Expression of cyclooxygenase-2 and nitrotyrosine in human gastric mucosa before and after Helicobacter pylori eradication

To determine whether cure of Helicobacter pylori infection influences the expression of COX-2 and nitrotyrosine in the distal stomach of humans, biopsy specimens were examined immunohistochemically. H. pylori infection was determined using a rapid urease test, culture and histology. Positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells.There was a significant increase in COX-2/nitrotyrosine staining in H. pylori -positive subjects compared with H. pylori -negative subjects. Cure of the infection resulted in a significant decrease in both COX-2/nitrotyrosine staining in all patients (52.1+/-12.1% vs 15. 4+/-7.2%, P<0.001; and 57.3+/-13.6% vs 36.1+/-18.0%, P<0.01, respectively). However, immunoreactivity of COX-2/nitrotyrosine was observed in all cases with intestinal metaplasia even after the cure of H. pylori infection.Thus, cure of H. pylori infection may decrease the risk of gastric carcinogenesis due to COX-2 and NO-related compounds in gastric mucosa but not in those patients with intestinal metaplasia.