Gastritis Lesions Research Articles

Genetic association of interleukin-1 haplotypes with gastritis and precancerous lesions in North Indians

We evaluated the association of functional variants of IL-1 genes with the development of gastritis and precancerous lesions, which are known to be influenced by inflammatory response against Helicobacter pylori. After upper gastrointestinal (GI) endoscopy, 120 patients with gastritis were tested for H. pylori infection using rapid urease test, modified Giemsa staining and IgG anti-CagA ELISA. All patients and 243 healthy controls were genotyped for IL-1B (-511 C/T) and IL-IRN (VNTR) genes using PCR-RFLP/PCR. IL-1B: (-511 C/T) genotype/allele were not associated with gastritis. IL-1RN 1/2 genotype carriers had susceptibility to gastritis (p=0.025, OR=1.7). Individuals with the IL-1RN 1/1 genotype (p=0.05, OR=0.65) and IL-1B -511*T-IL-1RN *1 haplotype were at low risk for gastritis (p=0.043, OR=0.72). High secretor haplotype combinations (C1-/T2+, C1-T1+ and T1+/T2+) did not influence neutrophilic infiltration, glandular atrophy or intestinal metaplasia. We identified that individuals with the IL-1RN 1/2 genotype had increased risk for gastritis. IL-1B -511*T-IL-1RN *1 (T1) haplotype carriers were at decreased risk for gastritis and no significant association was observed for precancerous lesions in North Indians.

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis

Chronic gastritis is frequently associated with infection of Helicobacter pylori and characterized by tissue infiltration of neutrophils, lymphocytes, and plasma cells. To address the mechanism of lymphocyte infiltration in chronic gastritis, we examined the expression of chemokines and their receptors using frozen sections of chronic gastritis, obtained from 23 patients who underwent gastrectomy for gastric cancer. By immunohistochemistry, lymphocytes in inflamed gastric mucosa expressed CCR5 abundantly, CXCR3 less frequently, and CCR4 sparsely. The numbers of CCR5+ cells, which were composed of mainly CD8+ and partly CD4+ T cells, were positively correlated with the degree of neutrophil infiltration, and decreased in areas with intestinal metaplasia or mucosal atrophy. RANTES/CCL5, one of the ligands of CCR5, was localized mainly in CD8+ and partly CD4+ T cells with a characteristic dotted pattern, and such lymphocytes were most densely distributed around the neck region of gastric glands. In situ hybridization confirmed the expression of CCL5 mRNA in these cells, and immunoelectron microscopy revealed localization of CCL5 in the membrane-bound granules, which most probably corresponded to the cytolytic granules of cytotoxic T cells. The numbers of CCL5+ lymphocytes showed a close correlation with the degree of neutrophil infiltration and markedly decreased in intestinal metaplasia. In conclusion, our data suggest that, together with neutrophils, CCL5+ T cells, presumably activated cytotoxic T cells, would play important roles in the active inflammatory process of chronic gastritis. Our data also suggest a self-recruiting mechanism involving CCR5 and CCL5 for tissue accumulation of such T cells.

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis

Chronic gastritis is frequently associated with infection of Helicobacter pylori and characterized by tissue infiltration of neutrophils, lymphocytes, and plasma cells. To address the mechanism of lymphocyte infiltration in chronic gastritis, we examined the expression of chemokines and their receptors using frozen sections of chronic gastritis, obtained from 23 patients who underwent gastrectomy for gastric cancer. By immunohistochemistry, lymphocytes in inflamed gastric mucosa expressed CCR5 abundantly, CXCR3 less frequently, and CCR4 sparsely. The numbers of CCR5+ cells, which were composed of mainly CD8+ and partly CD4+ T cells, were positively correlated with the degree of neutrophil infiltration, and decreased in areas with intestinal metaplasia or mucosal atrophy. RANTES/CCL5, one of the ligands of CCR5, was localized mainly in CD8+ and partly CD4+ T cells with a characteristic dotted pattern, and such lymphocytes were most densely distributed around the neck region of gastric glands. In situ hybridization confirmed the expression of CCL5 mRNA in these cells, and immunoelectron microscopy revealed localization of CCL5 in the membrane-bound granules, which most probably corresponded to the cytolytic granules of cytotoxic T cells. The numbers of CCL5+ lymphocytes showed a close correlation with the degree of neutrophil infiltration and markedly decreased in intestinal metaplasia. In conclusion, our data suggest that, together with neutrophils, CCL5+ T cells, presumably activated cytotoxic T cells, would play important roles in the active inflammatory process of chronic gastritis. Our data also suggest a self-recruiting mechanism involving CCR5 and CCL5 for tissue accumulation of such T cells.

Th1-biased tertiary lymphoid tissue supported by CXC chemokine ligand 13-producing stromal network in chronic lesions of autoimmune gastritis.

Secondary lymphoid tissue is developmentally programmed and characterized by well-ordered compartmentalization of lymphocyte subsets and specialized stromal cells supporting the tissue architecture. By contrast, tertiary lymphoid tissue is defined as that induced in ectopic sites by inflammation, although its immunological role is largely unknown. In this study, we characterize the lymphoid tissue induced in the chronic lesion of murine autoimmune gastritis (AIG). Within the lymphoid cluster in the gastric mucosa, there is a clear segregation of T and B cells. Follicle-like B cell areas are always located on the luminal side of the mucosa, while T cells are located in the basal part. A typical lymphoid reticular network and follicular dendritic cells support the structure. Importantly, complement receptor 1(+) follicular dendritic cells within the follicle express a B cell homing chemokine, CXC chemokine ligand 13. The number and size of the clusters correlate with the age of the mice and the serum autoantibody titer, suggesting the functional importance of the clusters in local Ab production, although involvement of the autoantibody in the disease progression is still unclear. AIG gastric lesions are known to constitute a Th1-biased, memory T cell-dependent immunomicroenvironment. The expression pattern of cytokines, including lymphotoxin-beta, and chemokines in the AIG stomach is consistent with this observation. Taken together, these facts suggest that, during the chronic phase of autoimmunity, long-lasting lymphocyte infiltration probably induces a unique tertiary lymphoid tissue that has a function distinct from that of regional lymph nodes. These neolymphoid tissues may maintain the local self reactivity supporting the vicious cycle of Th1-type reaction as well as autoantibody production.

A 12 years audit of upper gastrointestinal endoscopic procedures.

Evaluation of upper gastrointestinal (GI) endoscopy in terms of indications, diagnostic efficacy, and diseases diagnosed. Retrospective, observational case series. DHQ Teaching Hospital, Rawalpindi, from March 1990 to December 2001. Patients who underwent upper GI endoscopy in 12 years were included. Upper GI endoscopies were performed according to standard protocol. Endoscopic diagnoses were based on widely accepted criteria. Of the 8481 patients, 4935 (58.2%) were female and 3546 (41.8%) male. Mean patient age was 40.5 years. Dyspepsia (42.6%), upper GI bleed (32.8%), and evaluation of chronic liver disease (10.2%) were common indications of the procedure. An endoscopic diagnosis was possible in 82.6% patients. Varices, gastritis, duodenitis, and combined lesions were common endoscopic diagnosis. Gastritis and duodenitis were most frequent causes of upper GI bleed. We noted more gastric ulcers compared to duodenal ulcers. Females had significantly more normal endoscopies, p-value=0.02. Upper GI endoscopy is an effective procedure. Dyspepsia evaluation is commonest indication for upper GI endoscopy in our patients. Etiology of upper GI bleed, and incidence of duodenal ulcer compared to gastric ulcer in our patients are different than described in literature. Females have significantly more normal endoscopies.

Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features.

BackgroundThe growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized.MethodsThe expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China.ResultsThe positive immunostainig rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunosatining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining rate for p53, iNOS and VEGF was observed both in biopsy samples with CAG, IM and DYS from the symptom-free subjects and in gastric cancer tissue from the GC patients.ConclusionsThe present results indicated that p53 protein accumulation and increased expression of iNOS and VEGF might be responsible for gastric carcinogenesis and tumor aggressiveness of gastric cancer.

Selective accumulation of type 1 effector cells expressing P-selectin ligand and/or alpha(4)beta(7)-integrin at the lesions of autoimmune gastritis.

T(h)1 cells but not T(h)2 cells accumulate at the inflamed gastric mucosa (GM), while both subsets co-exist in the regional lymph node (RLN) in a murine experimental model for autoimmune gastritis (AIG). To understand the relationship between the immuno-microenvironment and effector localization in GM versus RLN of AIG-bearing mice, cells or tissue sections were stained with several mAb against adhesion molecules. The expression of RNA of various cytokines at these contrasting sites was also assessed. IFN-gamma-producing memory CD4(+) (T(h)1) and CD8(+) T cells as well as IL-12-producing mature macrophages which express P-selectin ligand and/or alpha(4)beta(7)-integrin selectively accumulated in the inflamed GM. Vessel endothelium at the site of infiltration expressed those counter-receptors, P-selectin and mucosal adressin cell adhesion molecule-1. Therefore, the tissue destruction of target tissue in autoimmune diseases might be promoted by a vicious circle between the selective accumulation of type 1 effectors mediated by multiple adhesion molecules and following an unusual type 1-biased microenvironment away from the type 2 response.

A 74 year patient with atrophic gastritis and multiple polypoid lesions in the stomach

A 74 year patient with atrophic gastritis and multiple polypoid lesions in the stomach

Clinical Study of Weishu capsule ("Equation missing" ) in treating precancerous lesions of chronic atrophic gastritis) in treating precancerous lesions of chronic atrophic gastritis

Objective: To explore the therapeutic effect and mechanism of Weishu capsule (WSC), Open image in new window in treating precancerous lesions of chronic atrophic gastritis (CAG).Methods: Seventy-five cases of precancerous lesions of CAG were distributed to two groups randomly, the WSC group (45 patients) treated with WSC taken orally and the Weining granule (WNG) group (30 patients) treated with Weining granule orally. The treatment course of both groups were 6 months. The clinical and pathological effects and the changes in scores of atrophy, intestinal metaplasia (IM) and its subgroups, dysplasia, carcinoembryonic antigen and proliferating cell nuclear antigen expression were observed before and after treatment.Results: The total effective rate was 91% and the effective rate of atrophy, IM, dysplasia in the WSC group were 64%, 67% and 65% respectively, and the respective scores were lowered significantly after treatment. Compared with the WNG group, the difference between the two groups was statistically significant (P < 0.01,P < 0.05). Immunohistochemical test showed that WSC could inhibit the subgroups of IM, circinoembryonic antigen and proliferating cell nuclear antigen expression significantly (P < 0.01).Conclusions: WSC could significantly improve the clinical and pathological changes in the precancerous lesions of CAG. The mechanism might be related to the inducing and promoting effect of WSC on the differentiation and maturity of IM cells and dysplasia cells. WSC could also inhibit and correct the abnormal proliferation of cells.

Collagenous gastritis revealed by severe anemia in a child

Collagenous gastritis is a rare histopathological disorder of unknown origin, characterized by a subepithelial collagen deposit greater than 10 μm thick, associated with an inflammatory infiltrate of the gastric mucosa. This report describes a second pediatric case of collagenous gastritis, revealed by severe anemia caused by gastric bleeding, as was the first case. Unlike the adult cases of collagenous gastritis, lesions were limited to the stomach, and remained unchanged on six series of biopsies taken during a 30 month follow-up, despite treatment with omeprazole, sucralfate and corticosteroids. An immunohistochemical study showed signs of local immune activation on all biopsy specimens, including overexpression of HLA-DR by epithelial cells, increased numbers of CD3+ intraepithelial lymphocytes, and CD25+ cells in the lamina propria. Although the cause of the disease remains unclear, our findings suggest that the histopathological lesions of collagenous gastritis may result from a local immune process.

How Should Helicobacter pylori Infection Be Diagnosed?

The ideal approach for the initial diagnosis of Helicobacter pylori infection is to perform an endoscopy to obtain biopsy specimens for histology and culture. Histology allows classification of any gastritis lesions present and may have prognostic value, and culture enables susceptibility testing of antimicrobial agents to direct proper treatment. Biopsy specimens must also be taken from the corpus if the patient was pretreated with proton pump inhibitors. The cost of these tests and the delay in receiving results limits their use in clinical practice. Therefore, the urease test, a quick and inexpensive test, is used to detect the presence of H. pylori and constitutes the basic invasive test for H. pylori. A new urease test based on a strip instead of an agar disk may be the test of choice in the future, because of its increased sensitivity and 2-hour delay (instead of 24 hours) in obtaining the result. In some countries, because of the cost, endoscopy will be used in selected patients only, either because of alarm symptoms or age > 45 years, which is considered a threshold for gastric cancer risk. In other patients, the noninvasive tests will be used. The cost of serology makes it more attractive compared with the urea breath test. Currently, there are accurate enzyme-linked immunosorbent assay tests that can be performed in any laboratory and that provide precise and quick diagnoses. In the event of a doubtful result, an immunoblot can be performed, as is the case for other infections. Patient follow-up after treatment provides a different situation because bacterial load is usually lower. A noninvasive test should be performed, and only the urea breath test can be used within the timing originally proposed to test eradication efficacy (i.e., 4-6 weeks after treatment). If the result is positive, susceptibility testing is required before administering a second course of treatment. The increasing use of antimicrobial agents to treat H. pylori is likely to result in antimicrobial resistance, requiring that bacteriologic surveillance programs be implemented. There are numerous research projects ongoing in this area, and one can expect that improved methods, such as colorimetric polymerase chain reaction (PCR) and improved antibody tests, will also be used in the future.

The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions.

The TPR-MET oncogenic rearrangement was originally observed in an in vitro transformed human osteosarcoma cell line. Recently, we detected the expression of this rearrangement at very low levels in several cell lines derived from human tumors of nonhematopoietic origin using a highly sensitive method based on polymerase chain reaction amplification of the transcript. We report here the results of analysis of TPR-MET expression in cell lines derived from human gastric tumors and 22 biopsy samples of human gastric mucosa showing cancer or precursor lesions. The rearranged RNA was expressed in all four cell lines as well as in biopsy samples from 12 of the 22 patients. Overexpression of TPR-MET RNA in superficial gastritis lesions with hyperplasia of glandular neck cells suggests the possible involvement of this oncogene at an early stage of gastric tumorigenesis. Analysis of gastric biopsy samples for RAS gene mutations showed base substitutions occurring in the codon 12 region of Ki- and Ha-RAS genes in four cases, including two precursor lesions.

Some Ultrastructural Aspects of Chronic Gastritis

Despite numerous observations and publications on the aethiology and pathogenesis of chronic gastritis many questions remain unanswered (1,2,3,4,6). Views on the aethiolcgy of chronic gastritis changed when in 1982 Campylobacter pyloridis (later named Campylobacter pylori CP) was first isolated in Western Australia from the stomach of patients with gastritis lesions and peptic ulceration (5).The aim of this study, carried out with cooperation with gastroenterologist, has been to investigate the ultrastructural changes in gastric surface epithelium and lamina propria in selected patients endoscopicaUy diagnosed gastritis.Observations have been carried out on 20 patients (10 men and 10 women). Biopsy material was obtained during endoscopy. In cases when the presence of bacteria has been confirmed further E M investigations have been introduced. Semithin sections for LM observations and ultrathin sections for EM were prepared according to routine EM technique.CP was found both on the airface of gastric epithelium cells, and what has not been reported so far, inside the lumen of the fundic glands (Fig. 1).

Low degree of relatedness betweenCampylobacter pyloridisand enteropathogenicCampylobacterspecies as revealed by DNA-DNA blot hybridization and immunoblot studies

Campylobacter pyloridis, an organism recently described in association with antrum gastritis and peptic lesions, shares a number of morphological and growth characteristics with other Campylobacter species such as C. jejuni or C. coli. The degree of relationship between these microorganisms was studied on molecular level using DNA-DNA blot hybridization and immunoblot techniques. SDS-PAGE protein profiles and immunoblot patterns of total lysates of C. pyloridis were fundamentally different from those of C. jejuni and C. coli. In accordance with those results positive hybridization signals between chromosomal DNA of the different species were not seen by the blot hybridization method. C. pyloridis isolates that differed in respect to urea hydrolysis and plasmid content, on the other hand, shared a number of major proteins and their blotted DNAs hybridized strongly. Some differences in protein patterns of different C. pyloridis strains became more apparent when studied by immunoblot analysis.

Epithelial cell proliferation in human fundic and antral mucosae. Influence of superselective vagotomy and relationship with gastritis.

Epithelial cell proliferation in the fundic and antral mucosae was studied in 19 duodenal ulcer patients, 11 patients having undergone fundic superselective vagotomy for duodenal ulcer, and 10 controls. This was achieved through in vitro incorporation of tritiated thymidine in mucosal biopsies and radioautography. Except for increased fundic mucosal height, duodenal ulcer patients did not differ from controls for all parameters studied. In vagotomized patients, as compared to the other two groups, the labeling index was significantly enhanced in the innervated antral mucosa where atrophic gastritis developed, but there was no change in the labeling index and no worsening of mucosal inflammation in the denervated fundic mucosa. The only abnormality in the latter was a striking expansion, towards the surface, of the proliferative area within the fundic pit. The labeling indices and the degree of gastritis in gastric mucosae are significantly correlated in control and duodenal ulcer patients. After superselective vagotomy, this correlation still existed in antral mucosa (r = 0.88, P less than 0.001) but not in fundic mucosa. If findings in antral mucosa, after superselective vagotomy, seemed related to gastritis lesions, those in fundic mucosa were not and may indicate an alteration due to the vagotomy per se.

Gastric acidity before and after development of gastric cancer: its etiologic, diagnostic and prognostic significance.

Excerpt Everyone knows that in gastric cancer the mean gastric secretory activity is subnormal, but to what extent is it subnormal? What factors influence gastric acidity in gastric cancer? Does ca...