Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.     

Peptides derived from collagen: new biochemical markers of bone metabolism]

OBJECTIVE: To study a possible association of the Helicobacter pylori seroprevalence with ABO(H) and Lewis (a,b) blood group phenotypes in blood donors. DESIGN: A cross-sectional study of blood donors using ABO(H) and Lewis (a,b) blood group phenotype as predictors. METHODS: ABO(H) and Lewis (a,b) blood group phenotyping was performed with monoclonal antibody. The H. pylori immunoglobulin G (IgG) antibody relative activity was evaluated by enzyme-linked immunosorbent assay (ELISA) using acid glycine extract from H. pylori. SUBJECTS: One hundred and fifty-nine randomly selected blood transfusion donors. RESULTS: The individuals with Lewis (a+b-)/non-secretor phenotype showed a significantly higher proportion of the H. pylori-seronegative subjects and a lower IgG immune response to H. pylori antigens as compared with the individuals of Lewis (a-b+)/secretor phenotype. CONCLUSION: The Lewis (a,b) histo-blood group antigens are implicated in the mechanisms of naturally occurring resistance to H. pylori infection.     

Trends in state laws and regulations affecting nurse-midwives: 1995-1997

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.     

Gastric mucosal hepatocyte growth factor in Helicobacter pylori gastritis and peptic ulcer disease

OBJECTIVES: Hepatocyte growth factor (HGF) is increasingly recognized for its role in a variety of hepatic and systemic diseases. Its relationship to gastritis has not been studied. We aimed at measuring gastric mucosal HGF levels in the presence or absence of Helicobacter pylori gastritis, in peptic ulcers, and in response to H. pylori eradication. METHODS: Fifty one patients were studied. Patients were not entered if they had liver disease, malignancy, or any systemic illness. HGF was measured in gastric antral incubates using an enzyme-linked immunosorbent assay. Assessments were repeated 6 wk after a 2-wk course of anti-H. pylori triple therapy in 12 patients. Code numbers were used for blinding. RESULTS: The median gastric mucosal HGF level was 36 ng/gm/tissue in patients with H. pylori gastritis (n = 33) compared with 19 ng/gm in 18 negative controls (p = 0.0024), 18 ng/gm after the eradication of H. pylori (p = 0.021), 23 ng/gm in all patients with ulcers (n = 10), and 26 ng/gm/tissue in H. pylori-positive ulcers (n = 7). CONCLUSIONS: Gastric mucosal HGF levels were elevated in H. pylori gastritis and reduced by its eradication. These results are relevant to our understanding of the increased gastric cell proliferation in patients with H. pylori-related gastritis.     

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy

BACKGROUND: Helicobacter pylori may interfere with gastroduodenal protective mechanisms. Such effects could be due to a direct interaction with gastric epithelial cells but also to the action of a wide range of secreted and membrane-bound virulence factors. Our aim was to study the acute effects of water extracts produced from H. pylori on gastric mucosal blood flow and acid secretion and to relate them to VacA and CagA activity. METHOD: Extracts were produced from strains 88-23 and A5, both wild type; A5VacA, an isogenic mutant lacking expression of the vacuolating cytotoxin (VacA) and the immunodominant antigen (CagA); and Escherichia coli strain ATCC-25922. Bacterial extracts were applied on the exteriorized gastric corporal mucosa in inactin-anaesthetized rats after removal of as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured by means of laser-Doppler flowmetry. RESULTS: All H. pylori extracts, including the extract from 88-23 heated to 100 degrees C for 30 min, significantly reduced blood flow by 15%-19%, whereas E. coli had no significant effect on blood flow. CONCLUSION: A factor or a combination of factors, other than VacA and CagA released from H. pylori, might compromise the natural defence of the gastric corporal mucosa by reducing mucosal blood flow. The factor is heat-stable and lacking or less potent in E. coli.     

Detection of Helicobacter pylori associated antigen and heat shock protein 60 on follicular dendritic cells in the germinal centres of low grade B cell lymphoma of gastric mucosa associated lymphoid tissue (MALT)

AIMS: To investigate the localisation of Helicobacter pylori antigens and the expression of human heat shock proteins (HSP) in stomachs affected by MALT lymphoma. METHODS: Surgically resected stomachs from 24 patients with MALT lymphoma were immunostained with anti-H pylori rabbit antibodies (ORP-1 and ORP-2) and anti-human HSP60 mouse monoclonal antibodies (mAb) (LK-1 and LK-2). RESULTS: Follicular dendritic cells of germinal centres in the stomachs affected by MALT lymphoma were immunostained with anti-H pylori polyclonal antibodies and with anti-human HSP60 mAb, as were the epithelial cells. None of the lymph node samples reacted. CONCLUSIONS: Human HSP60, which cross reacts with anti-H pylori polyclonal antibodies, is often expressed on follicular dendritic cells in gastric MALT lymphoma tissues and may be aetiologically relevant to lymphomagenesis of MALT lymphoma.     

The vascular effects of topical and intravenous alpha2-adrenoceptor agonist clonidine on canine pial microcirculation

Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.     

Chemical characterization and distribution of ABO blood group active glycoprotein in human erythrocyte membrane

Occurrence and distribution of glycoprotein H substances in blood type O human erythrocyte membrance were studied using an alpha N-acetylgalactosaminyltransferase (A-enzyme) purified from milk of blood type A women. Erythrocytes of blood group O, nonsecretors and secretors alike, contain H substances that serve as a substrate for this transferase, and the H determinants seem to occur in all three erythrocyte membrane glycoproteins (periodic acid-Schiff (PAS)-1, PAS-2, and PAS-3). Structural studies of the A glycoproteins obtained by the transferase action, suggested that all erythrocyte H glycoproteins contain only type 2 antigenic determinant.     

Promoter element spacing controls basal expression and light inducibility of the cyanobacterial secA gene

BACKGROUND & AIMS: Lewis antigens are expressed by both human gastric epithelial tissue and Helicobacter pylori. We examined Lewis antigens expressed by gastric epithelium and by H. pylori isolated from the corresponding biopsy tissue. METHODS: H. pylori Lewis expression was determined by enzyme immunoassays, and immunoelectron microscopy was used to confirm the Lewis antigens on some H. pylori cells and in some biopsy specimens. Histopathology using identical monoclonal antibodies specific for Lewis A, B, X, and Y antigens was used to detect these antigens in 24 gastric biopsy specimens. RESULTS: We identified Lewis Y in 100%, Lewis X and Lewis B in 95.8%, and Lewis A in 87.5% of biopsy specimens. In H. pylori, 87.5% expressed Lewis Y, 79.2% Lewis X, and 4.2% (one strain) Lewis B. No Lewis A was detected. Antibody specific for Lewis X labeled the bacteria and associated adhesion pedestal. The cagA gene was present in 92% of strains. CONCLUSIONS: There was no direct relationship between Lewis antigen expression by H. pylori and gastric epithelial cells in infected patients. Expression of Lewis X and Lewis Y by H. pylori suggests the possibility of their requirement for establishment and/or maintenance of infection. An immunoelectron micrograph of H. pylori interaction with the gastric epithelial adhesion pedestal suggests a tentative role for Lewis X in the adhesion process.     

Delayed healing of chronic gastric ulcer after Helicobacter pylori infection in mice

It has been suggested that there is a close relationship between Helicobacter pylori and the onset or recurrence of gastroduodenal disease. The aim of this study was to examine the effect of H. pylori on the healing of chronic gastric ulcers induced in mice. H. pylori administered to nude mice delayed the healing of experimental acetic acid-induced gastric ulcers. Histological examination showed the occurrence of high densities of H. pylori on the surface of epithelial cells and in the ulcerated area. Repeated administration of amoxicillin (10 mgkg(-1) daily for 5 days) eradicated H. pylori and increased the rate of healing of gastric ulcers in H. pylori-infected mice, but metronidazole, which also eradicated the organisms, did not significantly affect the rate of healing. In conclusion, H. pylori-infection delayed the healing of gastric ulcers induced by the serosal application of acetic acid in mice, possibly by aggravation or prolongation of the mucosal inflammation. Amoxicillin eradicated H. pylori and promoted gastric ulcer healing in mice infected with H. pylori.     

Factors influencing Helicobacter pylori eradication with 2 week combination therapy of lansoprazole and amoxycillin: intragastric distribution of colonization and gastric mucosal atrophy

In Japan, gastric ulcers are often accompanied by marked gastric mucosal atrophy. We evaluated the dual therapy of double-dose lansoprazole and amoxycillin for Helicobacter pylori eradication in Japanese ulcer patients and investigated the effects of intragastric distribution of H. pylori colonization and gastric mucosal atrophy on eradication with this combination therapy. Seventy-six H. pylori-positive ulcer patients received lansoprazole (30 mg) plus amoxycillin (500 mg) twice daily for 2 weeks (LA-60 group), lansoprazole (30 mg once daily) plus amoxycillin (500 mg twice daily) for 2 weeks (LA-30 group) or lansoprazole (30 mg once daily) for 6 or 8 weeks (LPZ group). Infection was evaluated by light microscopy, culture and biopsy urease tests. Helicobacter pylori colonization was classified as localized to the corpus (localized type) or involving the antrum and corpus (whole type). Fundic mucosal atrophy was graded according to endoscopic and histological features. Eradication was achieved in 67.6% in the LA-60 group, 31.6% in the LA-30 group, and 0% in the LPZ group, and moderate or severe histological gastritis was improved in the LA-60 group. Eradication was better in localized-type colonization (92%) than whole-type (56%), and better with fundic mucosal atrophy (84%) than without, but poor in both whole-type colonization and scanty mucosal atrophy (47%). The LA-60 therapy achieves better eradication in Japanese ulcer patients with localized H. pylori colonization and/or gastric mucosal atrophy, which are likely to be important predictors for the successful eradication with dual therapy.     

Hemagglutination inhibition studies of water soluble blood group substances recovered from the erythrocytes of classical Bombay Oh subjects

Using ethanol and acetone fractionation to isolate soluble blood group substances from red blood cells, 'Bombay' Oh bloods were found to contain variable amounts of concealed H substance. The IgG variety of anti-H in 'Bombay' bloods has a greater affinity for these substances than the IgM variety of anti-H. Group O parents of 'Bombay' Oh subjects were found to have normal levels of H substance, indicating that individuals heterozygous for a recessive suppressor gene 'x' synthesize it normally. In the 'Bombay' family studied, Lewis determinants were abnormally expressed in two members. Lewis activity was detected in the soluble extracts of their red blood cells but not by the direct agglutination test. Further tests using known Le(a-b-) types are necessary to determine whether these findings are linked to the 'Bombay' Oh phenomenon.     

Nurses'' and patients'' perceptions of most important caring behaviors in a long-term care setting

Helicobacter pylori lipopolysaccharide (LPS) expresses Lewis x and Lewis y blood group antigens that are identical to those occurring in the human gastric mucosa. During infection, antibodies against LPS, which bind to host Lewis antigens, may be induced. These consequently recognize gastric glycoprotein targets and cause autoimmune inflammation.     

Improvement of glucose/insulin metabolism reduces hypertension in insulin-dependent diabetes mellitus recipients of kidney-pancreas transplantation

OBJECTIVE: The current guidelines recommend 1-wk triple therapy regimens for eradicating H. pylori infection. Until now, shorter regimens have scarcely been investigated. Azithromycin is a new generation macrolide antibiotic with unusual and favorable pharmacokinetics, and seems to be a very promising agent for innovative anti-H. pylori regimens. We assessed the efficacy and tolerability of a new 4-day low dose triple therapy in comparison with a well established 1-wk triple therapy in the treatment of Helicobacter pylori infection. METHODS: One hundred-sixty consecutive patients with biopsy-proven H. pylori infection were randomized to receive lansoprazole 30 mg b.i.d. on days 1-4, azithromycin 500 mg u.i.d. on days 2-4, and tinidazole 2000 mg u.i.d. on day 3 (LAT group), or 7 days of triple therapy of omeprazole 20 mg u.i.d., clarithromycin 250 mg b.i.d., and tinidazole 500 mg b.i.d. (OCT group). Patients with gastric or duodenal active ulcer received proton pump inhibitors for an additional 4 wk. H. pylori eradication was defined as negative of both rapid urease test and histology on biopsies taken from the gastric body and antrum at least 1 month after the end of treatment. RESULTS: Seven patients in the LAT group and four in the OCT group were lost to follow-up. No significant difference in either efficacy or tolerability was observed between the two regimens. Active ulcers healed in 97.8% of cases with LAT and in 100% of cases with OCT. The eradication rate was 80.8% in the LAT group and 85.5% in the OCT group, considering the per-protocol results, and 73.3% and 81.2%, respectively, considering the intention-to-treat results. Side effects occurred in one LAzT patient and in two OCT patients; they were mild and did not interfere with compliance. CONCLUSION: The new proposed ultrashort triple therapy, including lansoprazole, low dose azithromycin for 3 days, and a single dose of tinidazole, appears to be a very effective anti-H. pylori regimen, a simpler, cheaper, well-tolerated, and equally effective alternative to 1-wk triple therapy.     

Immunochemical characterization of anti-H monoclonal antibodies obtained from a mouse immunized with human saliva

Three IgM class anti-H monoclonal antibodies (1E3, 1E5 and 3H1) were obtained from a BALB/c mouse immunized with human O type saliva. These antibodies were found to agglutinate red cells from O group and A and B subgroups but not from Bombay and para-Bombay individuals whose H antigen was barely detected by anti-H reagents. The agglutination reactions of these antibodies were inhibited by H antigens from human tissues. It was also demonstrated that both 1E3 and 3H1 reacted with H disaccharide (Fuc alpha 1-->2Gal beta), H type 1 (Fuc alpha 1-->2Gal beta 1-->3GlcNAc beta), H type 2 (Fuc alpha 1-->2Gal beta 1-->4GlcNAc beta), H type 3 (Fuc alpha 1-->2Gal beta 1-->3GalNAc alpha) and H type 4 (Fuc alpha 1-->2Gal beta 1-->3GalNAc beta) but not with Lea (Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), Leb (Fuc alpha 1-->2Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), X (Gal beta 1-->4[Fuc alpha-->3]GlcNAc beta) or Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta). On the other hand, 1E5 was found to react with H type 1, H type 2, Leb and Y. Because of the unique reactivities against various fucosyl linkages these monoclonal antibodies could be useful not only as anti-H reagents but also as reagents for the structural analysis of fucosylated glycoconjugates.     

Effect of hygiene measures, water sanitation and oral rehydration therapy on diarrhea in children less than five years old in the south of Ivory Coast

BACKGROUND: Gastric sucrose permeability is a noninvasive marker that reliably increases in association with gastrointestinal injury due to use of nonsteroidal antiinflammatory drugs. Despite the effect of Helicobacter pylori infection on the gastric mucosa, in a previous study we were unable to demonstrate that H. pylori infection was associated with abnormal gastric sucrose permeability. Our goal in this study was to explore further whether H. pylori infection changed gastric permeability; therefore, we evaluated the effect of treatment of H. pylori infection on gastric permeability to sucrose and the relation of sucrose permeability to density of polymorphonuclear leukocytes. MATERIALS AND METHODS: Five hundred milliliters of a solution containing 100 gm of sucrose was ingested by the subject at bedtime. Overnight urine was collected and assayed for sucrose by high-performance liquid chromatography. Sucrose permeability was assessed both before and approximately 4 weeks after anti-H. pylori therapy. RESULTS: Seventeen asymptomatic H. pylori-infected volunteers participated; 8 were cured. Sucrose permeability was in the range commonly found in normal controls both before and after anti-H. pylori therapy (mean excretion, 76.3 mg; range, 13-171 mg). Gastric sucrose permeability correlated with the density of polymorphonulcear cell infiltration of the mucosa. Cure of the H. pylori infection was associated with a small but significant decrease in sucrose permeability (98.8 +/- 18 mg to 51.7 +/- 9.8 mg (p = .01). Sucrose permeability was greater in those with a high density of mucosal polymorphonuclear cells compared to those with lower scores (119.5 +/- 4 vs 71.4 +/- 13 for those with scores > or = 5 compared to scores < or = 4; p = .023). Failed therapy resulted in an increase in the mucosal density of polymorphonuclear infiltration and sucrose permeability (56.4 +/- 13 mg-99.7 +/- 19 mg pretreatment vs posttreatment, respectively; p = .031). CONCLUSION: H. pylori gastritis causes a small but measurable increase in gastric permeability to sucrose that may reflect epithelial transmigration of neutrophils.     

Duodenal bicarbonate secretion: eradication of Helicobacter pylori and duodenal structure and function in humans

BACKGROUND & AIMS: Eradication of Helicobacter pylori expedites duodenal ulcer healing and prevents recurrences. Most patients with duodenal ulcers have impaired proximal duodenal mucosal bicarbonate secretion (DMBS). In patients with inactive, healed duodenal ulcers and normal subjects, the effect of H. pylori infection on DMBS and proximal duodenal secretory function and structure were examined. METHODS: DMBS was quantitated before and after eradication of H. pylori. Mucosal structure (duodenal bulb histopathology) and function (DMBS at rest and stimulated, effect of active vs. healed ulcer and of age) were determined in patients with duodenal ulcers and normal subjects. RESULTS: In patients with duodenal ulcers, H. pylori eradication normalized proximal DMBS. Histological examination of duodenal biopsy samples was comparable in patients with duodenal ulcers and normal subjects without apparent relationship between inflammation and DMBS. Significantly impaired DMBS occurred in response to all agonists tested (luminal acid, prostaglandin E2, and cephalic-vagal stimulation) in patients with duodenal ulcers, suggesting a generalized secretory defect. Neither the presence of active (vs.inactive) ulcer nor age significantly affected bicarbonate secretion. CONCLUSIONS: In patients with duodenal ulcers, eradication of H. pylori normalized proximal DMBS and may thereby reduce ulcer recurrences. Altered DMBS in patients with duodenal ulcers was unrelated to histopathologic abnormalities. Impaired bicarbonate secretion in patients with duodenal ulcers could be caused by a cellular and/or physiological regulatory transport defect possibly related to H. pylori.     

Peptic ulcer in Greenland Inuit: evidence for a low prevalence of duodenal ulcer

In an eight years period new peptic ulcer was diagnosed in 127 Inuit patients at the Central Hospital, Dronning Ingrids Hospital, Nuuk/Godth?b. The ratios: duodenal ulcers (DU): prepyloric ulcers (PPU): gastric ulcers (GU) were 17:22:88. The male:female ratio was 2:1. 46 of the patients were living permanently in Nuuk, 81 in The Districts. There were no significant differences in the type of ulcers among the two groups. The incidence of GU among the Nuuk population was comparable to the incidence in the Danish population (0.63/1000 inhabitants per year), whereas the mean age at the time of diagnosis was only 45 years, thus the patients were approximately 15 years younger than the Danish counterparts. The incidence of DU among the Inuits was 0.15/1000 inhabitants per year, significantly less than in the Danish population. The frequency of Helicobacter (H.) pylori infection among 56 Inuits with dyspeptic symptoms was: 0.61. Only 6/12 patients suffering from DU had a positive test for H. pylori infection. Conclusions: The incidence of duodenal ulcers in the Inuit population was only 10% of the incidence in a Danish population, whereas the incidence of gastric ulcers among the Inuits was comparable to the incidence among Danes. Only 50% of Inuit patients with proven DU had a positive test for H. pylori infection, whereas the frequency of H.pylori infection in a population with dyspeptic symptoms corresponded very well to the frequency reported from other populations.     

Subcorneal pustular dermatosis in a patient with hyperthyroidism

OBJECTIVES: Gastric carcinoma is the world's second most common cancer. Recent studies suggest an association between Helicobacter pylori and gastric carcinoma. The aim of this study was to address the effects of H. pylori infection on gastric antrum mucosal cell proliferation. METHODS: Forty patients undergoing upper endoscopy for standard indications were included in the study. A rapid urease test was used to determine the presence of H. pylori. Epithelial cell proliferation was determined by immunohistochemical techniques utilizing monoclonal antibody to bromodeoxyuridine. RESULTS: There were no significant differences in the number of labeled cells and in the proliferation fraction (p > 0.1) when patients with H. pylori were compared with those without, and when those over the age of 50 were compared to those under 50. The presence of ulcers similarly had no effect (p > 0.1). CONCLUSION: Helicobacter pylori infection does not increase gastric antrum mucosal cell proliferation.