Adherence

Adhesins are bacterial proteins, glycoconjugates, or lipids that are involved in the initial stages of colonization by mediating the interaction between the bacterium and the host cell surface (Table 1). Thus, adhesins are generally regarded as virulence factors for the bacterium. Host cell receptors are composed of lipids, proteins, glycolipids, or glycoproteins. Adherence of bacteria to host cell receptors triggers cellular changes that include signal transduction cascades, leading to infiltration of inflammatory cells (neutrophils and monocytes) and to persistence of the organism. Since the gastric epithelium and mucus are in continual turnover, and peristalsis ensures constant movement of food and cell debris, H. pylori has evolved adherence and colonization mechanisms to maintain itself specifically in the gastric mucosa. In this section, we describe the cellular changes associated with attachment of H. pylori to host cells, the bacterial adhesins themselves, and host cell receptors that have been reported to date.

Table 1

H. pylori adhesins and host cell receptors.

Despite extensive research on H. pylori adherence in vitro, there is little consensus on which H. pylori adhesins are most important in vivo, or even whether adhesins and receptors for the H. pylori-epithelial cell interactions are similar to the H. pylori-phagocytic cell interactions. Numerous problems hinder the unequivocal identification of adhesins and host cell receptors: (i) H. pylori adherence differences among strains; (ii) presence of numerous adhesins in H. pylori; (iii) variable expression of H. pylori adhesins under different culture conditions for a single strain; (iv) variable expression in the coccoid versus bacillary forms of H. pylori; (v) use of nongastric and nonphagocytic cell experimental systems to identify H. pylori adhesins; (vi) autolysis of H. pylori; (vii) variable expression of host cell receptors within a single host upon contact with H. pylori; and (viii) genetic variability in receptor expression in different hosts. Few studies have investigated the effect of H. pylori mutants in specific candidate genes on adherence, and surprisingly, no studies have yet addressed the role of adherence genes in vivo. This may be because H. pylori adhesin-mediated colonization is clearly multifactorial and no single adhesin may be crucial. Regardless, adherence of H. pylori to the gastric epithelium is a necessary early step in colonization and renders H. pylori 100 to 1,000 times more resistant to antibiotics than nonadherent bacteria (211). Furthermore, adherence protects bacteria from being washed away and from the adherence-blocking effects of mucin.

Cellular changes following attachment of H. pylori and role of the cag pathogenicity island

Upon encountering the gastric mucosa, H. pylori swims through the viscous gastric mucus, propelled by its polar flagella, and adheres to gastric epithelial cells. Only a small percentage of the total H. pylori population adheres to the gastric epithelium (<1%); the rest of the population resides in the gastric mucous layer or is cleared by peristalsis or other mechanisms (134, 333). During adherence, H. pylori has a predilection for intercellular junctions of gastric epithelial cells (26, 235). Entrance of H. pylori into gastric epithelial cells (26, 235) or into gastric epithelial cell lines (67) has generally been thought to be rare, although some controversy surrounds this subject (see "Does Invasion into Host Cells Occur?," below).

In the antrum of the human stomach, H. pylori adheres very specifically to mucus-secreting gastric epithelial cells on the luminal surface, the gastric pit surface, within gastric pit pockets, occasionally adjacent to parietal cells, and in between adjacent gastric epithelial cells (42, 62, 104, 274), where they disrupt intercellular tight junctions through the ammonia produced by urease (286) (Fig. 2). Adherence to other cell lineages in the antrum, such as chief, parietal, fibroblasts, or neck cells (104), or to epithelial cells in the duodenum, esophagous, or colon is rare (56, 310). Binding occurs more readily under acidic conditions in vitro (62, 150, 151). Acidity could be a signal for enhanced adhesin transcriptional or translational expression, or could simply favor adhesin-receptor interactions. Despite the specific tropism of H. pylori for the antral mucus-secreting epithelial cells in vivo, H. pylori adheres to a vast range of gastric and nongastric (human and nonhuman) cells in vitro (57). The reasons for this apparent discrepancy and for the specific in vivo tropism of H. pylori are not understood.

Figure 2

Overview of adherence phenotypes of H. pylori. H. pylori adheres to the host cell surface via bacterial adhesins interacting with host cell receptors (see Fig. 4). Following attachment, microvilli are denuded and tight junctions disrupted. Bacterial urease (more...)

H. pylori probably adheres first to microvilli-containing regions of gastric epithelial cells (Fig. 2); then, by an undetermined mechanism, the microvilli become denuded (6, 26, 28, 35, 57, 62, 84, 125, 136, 140, 174, 230, 235, 272, 274, 284, 310). Upon subsequent tighter adherence, cup-like projections and pedestals form, accompanied by actin polymerization and cytoskeletal rearrangements. Tighter adherence leads to an increase in sialic acid glycoproteins on the host cell surface, depletion of mucous granules within host cells, and cellular degeneration (apoptosis) possibly mediated by the H. pylori vacuolating cytotoxin (VacA). Tyrosine phosphorylation of host and bacterial proteins occurs during intimate attachment (2, 284, 285). Fibrillar or filamentous appendages (variously reported as fimbriae or afimbrial adhesins) at the point of contact between H. pylori and the host cell during adherence have been suggested (35, 98, 140). Many of these properties (microvilli denudement, pedestal formation, actin polymerization, cytoskeletal rearrangements, tyrosine phosphorylation of proteins, and occasional cellular degeneration) are reminiscent of host cellular changes caused by adherence of enteropathogenic E. coli (EPEC) (57, 173). However, the EPEC adhesin called intimin, encoded by the eae gene, has no homolog in the H. pylori genome (7, 84, 332). The bacterial and host genes responsible for pedestal formation with concomitant actin polymerization are unknown, but genes encoded in the cag pathogenicity island may be required (285).

The above observations regarding H. pylori adherence have been made with human and gnotobiotic piglet gastric biopsies, primary human gastric cells, and human gastric cell lines, all with similar general conclusions, with rare exceptions (84, 230). The observation that H. pylori is sometimes found adjacent to acid-secreting parietal cells, coupled with the observation that patients with H. pylori infection suffer achlorhydria, suggests that H. pylori directly disrupts parietal cell function. Recent evidence strongly supports this hypothesis (see below;128,321).

The "cytotoxin-associated gene," cagA, was originally thought to be necessary for VacA vacuolating activity or expression, due to the strong correlation in clinical isolates: cagA ⁺ (type I) strains were Tox⁺, whereas cagA mutant (type II) strains were Tox (63, 337, 363). However, using an isogenic cagA mutant, it has been shown that cagA is not required for expression or vacuolating activity of VacA (338, 363). During the adhesion of H. pylori to gastric epithelial cells, an intense inflammatory response is generated. The cytokine interleukin (IL)-8, a chemotactic factor for human neutrophils, is secreted by gastric epithelial cells (in both gastric biopsies and cell lines) in response to binding of cag⁺ H. pylori isolates (67, 148, 267). The bacterial factor responsible for IL-8 induction remains a mystery, but genes in the cag pathogenicity island (PAI) are clearly required, based on observations that type I strains (cag⁺), but not type II strains (cag mutant), induce IL-8 expression and tyrosine phosphorylation of several proteins, including a 145-kDa protein (39, 285). Furthermore, isogenic mutants of numerous genes within the cag PAI abolish IL-8 induction and tyrosine phosphorylation (cagC, cagD, cagE [also known as picB], cagG, cagH, cagI, cagL, cagM, cagX, cagY, and cagβ) (39, 64, 190, 285, 339). Polar effects of one mutant on adjacent genes were not ruled out in these studies. This IL-8 induction is blocked by the protein tyrosine kinase inhibitor herbimycin A, indicating that a tyrosine kinase phosphorylates a protein (bacterial or host) necessary for IL-8 induction (190). Three mutants have no effect on IL-8 induction: cagA, cagF, and cagN (39, 69, 289). Type I strains bind to AGS cells better than type II strains, and the interaction of type I strains with AGS cells may up-regulate one or more host cell receptors triggered by interaction with the bacterium (317). Contact of live, intact H. pylori with gastric epithelial cells is a prerequisite for IL-8 induction (2, 267). IL-8 leads to infiltration of neutrophils and monocytes into the gastric mucosa, causing inflammation and mucosal damage (26, 125, 199). H. pylori adheres to and is phagocytosed by these neutrophils and monocytes in the absence of opsonins.

Further analysis of type I versus type II strains of H. pylori revealed that type I strains carry the 40-kb cag PAI, whereas type II strains do not (39). Nearly all isolates (88 to 100%) from patients with duodenal ulcers are cag⁺, whereas only 50 to 60% of isolates from patients with uncomplicated gastritis are cag⁺ (63, 66, 68). These findings indicate that type I (cag⁺) strains are more virulent than type II (cag mutant) strains, yet the presence of the cag PAI alone is not sufficient to confer full virulence. The organization of the cag PAI from several H. pylori strains has been reported (3, 7, 39, 332). Some of the cag genes are orthologous to the ptl/vir genes encoding a type IV secretion apparatus (e.g., cagE is orthologous to the gene encoding the membrane-associated ATPase, virB4, the VirB4 protein is involved in T-DNA transfer from Agrobacterium tumefaciens to plant cells; reviewed in references 54, 64, 65).

Recent data from four laboratories have shown that CagA is translocated into gastric epithelial cells via the cag PAI-encoded type IV secretion system (18, 238, 283, 313; reviewed in reference 64). Following translocation, CagA (120 to 140 kDa in different strains) is tyrosine phosphorylated. Thus, the 145-kDa tyrosine phosphorylated protein previously observed in host cells and thought to be a host protein is, in fact, the bacterial protein CagA. The cellular tyrosine kinase involved in tyrosine phosphorylation of CagA has not yet been reported. It will be of great interest to understand the role of phosphorylated CagA in perturbing host cell signaling pathways and elucidating the mechanism and signals responsible for translocation of CagA into host cells. Interestingly, a hemolysin mutant of H. pylori (specific gene not specified) cannot induce tyrosine phosphorylation of the 145-kDa protein (probably CagA), but still can induce IL-8 expression from a human gastric epithelial cell line, indicating that tyrosine phosphorylation and IL-8 induction are probably the result of separate signal transduction pathways (285). Part of this pathway may be activation of NF-κB and AP-1, which are known transcriptional activators of the IL-8 gene (2).

Chronic infection modulates the balance between gastric epithelial cell proliferation (cancer) and epithelial cell death (apoptosis) (224). Perturbation of this balance likely results from differences in factors produced by the bacterium, the host, or a combination of the two. H. pylori binds to class II major histocompatibility complex antigens on gastric epithelial cells, and a signal transduction cascade ensues, leading to apoptosis (107). Several groups have shown that the apoptosis cascade utilizes the Fas ligand/antigen pathway (CD95) (146, 163, 273), which fosters down-regulation of Bcl-2 (anti-apoptotic) and up-regulation of Bax (apoptotic) (178). The transcription factor NF-κB, activated by tumor necrosis factor (TNF)-α-mediated phosphorylation of IκB, activates transcription of the genes encoding IL-8, nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Several laboratories have recently shown that H. pylori induces iNOS and COX-2 expression in vitro and in vivo (114, 208, 271, 279, 358). It is unclear whether H. pylori-mediated induction of iNOS and COX-2 tilts the balance toward apoptosis or to increased proliferation of gastric epithelial cells leading to metaplasia and cancer. Both lipopolysaccharide (LPS)-dependent and LPS-independent (urease, VacA, cag-mediated protein secretion) H. pylori factors have been implicated (163, 175, 273, 305–308, 358).

The above studies clearly implicate the cag PAI in at least some of the cellular changes occurring immediately after H. pylori adheres to gastric epithelial cells. It will be of great interest to further discern the mechanism of how the cag PAI triggers these host cell signaling events and determine whether the PAI plays a role in apoptosis or proliferation of gastric epithelial cells.

Bacterial Adhesins and Receptors

Interactions of H. pylori with Mucin

Mucins are a family of high molecular weight oligomeric proteins (>2 million molecular weight) that are sulfated and heavily glycosylated (carbohydrate >80%) and represent a major component of mucus. These glycoproteins serve as host mucosal defenses by preventing colonization of microbes, as well as by protecting the epithelial cells from injury. Mucin contains a wide array of structurally distinct carbohydrate side chains, such as sulfated or nonsulfated sugar moieties, Lewis a, b, X, and/or Y moieties, and sialic acid residues. Because of its lifestyle as a mucosal pathogen, H. pylori has evolved a number of mechanisms to overcome the nonspecific host defenses due to mucin (Fig. 3). First, H. pylori has the ability to bind to gastric and salivary mucin, and optimal binding requires that the mucin be sulfated and/or sialylated (141, 142, 213, 229, 257, 294, 340, 345, 350). Sulfated galactose or sulfated Lewis a within salivary mucin was the likely antigen bound by H. pylori (350), although sialic acids and Lewis b are also possible antigens (104, 213, 236). Mucin binding is elevated by exposure of H. pylori to low pH in vitro, and by the presence of divalent cations (especially nickel and zinc), and is mediated most likely by electrostatic interactions (236, 350). Gastric mucin blocks H. pylori from adhering to the gastric epithelial cells, presumably by competing with the cell surface for H. pylori adhesins (104, 142, 294, 340). Desulfation of mucin by the anti-ulcer compound sulglycotide results in loss of binding of H. pylori to mucin (141, 257), and sialidase treatment of mucin likewise decreases H. pylori binding to gastric mucin and hemagglutination to red blood cells (141, 142, 213, 340). An H. pylori protein that binds mucin has been recently identified as the 16-kDa neutrophil-activating protein (Nap), a protein that binds pleiotropically to sulfated oligosaccharides such as sulfo-Lewis a, sulfogalactose, and sulfo-N-acetylglucosamine found on mucin (229, 327). Nap also binds to Lewis X and sialylated glycoconjugates in vitro (229, 327) and causes enhanced adhesion to human neutrophils by an unknown mechanism (102).

Figure 3

Interactions of H. pylori with mucin. H. pylori chemotactically moves from a region of low concentration of mucin to a higher concentration and then binds to it. There may be competition between Nap binding to mucin (left pathway) and LPS interacting (more...)

Second, H. pylori possesses several mucinase activities (proteins not yet identified): one desulfates mucin and the other proteolytically cleaves the proteinaceous component of mucin (299, 300, 304). Degradation of mucin allows H. pylori to migrate to and adhere to the gastric epithelial cell surface more quickly. In another study, urease of H. pylori was suggested to disrupt the carbonate-bicarbonate buffer of the stomach through the production of ammonium from urea, thereby leading to breakdown of gastric mucin (293). This was suggested based on the finding that filtrates of H. pylori passaged only once in vitro from gastric biopsies failed to degrade mucin unless urea was present. Whether urease can more directly degrade mucin has not been reported.

Third, H. pylori displays chemotactic activity toward mucin (111; T. L. Testerman, D. J. McGee, and H. L. T. Mobley, unpublished observations), which requires a two-component signal transduction system CheA/Y (111).

Fourth, the H. pylori thioredoxin was shown to reduce mucin such that oligomers of mucin are potentially converted to monomers (359). Reduction of mucin to monomeric form may destroy the ability of mucin to interact with the mucin receptor. Thus, H. pylori may chemotactically move toward mucin, bind mucin, and degrade it. This would decrease the viscosity of the mucous gel and allow H. pylori to facilitate migration to the epithelial cell surface, an event that prevents clearance by peristalsis.

Fifth, H. pylori may occasionally enter the mucin-containing compartment of goblet cells at areas of intestinal metaplasia (a precursor of gastric carcinoma) (117). This could explain the clinical observations that, upon adherence of H. pylori to the gastric epithelium, depletion of the mucin-containing mucous granules occurs (26). The mechanism of depletion of mucin secretion by the glandular epithelium has been further explored in two studies. A study of human biopsies showed that H. pylori infection significantly lowers the amount of mucin contained in cells from antral biopsies, but little effect is seen in cells from gastric body biopsies (170). Rats fed 0.01% ammonia for 4 weeks develop a similar pattern of mucin depletion in antral cells, suggesting that the ammonia produced by H. pylori urease may be responsible for effects on mucin (170). Micots and colleagues used a mucin-secreting cell line to further study the effects of H. pylori on mucus secretion (215). They found that baseline mucin biosynthesis was not impaired over a 24-h period; however, secretion of mucin was impaired at 24 h. Secretion by H. pylori-infected cells was more strongly inhibited following stimulation by forskolin and ionophore A23187, agents that raise intracellular cAMP levels. These studies indicate that H. pylori perturbs the release of mucin, which would facilitate H. pylori adherence to the gastric epithelial cell layer and may contribute to ulcer formation in the antrum. All of these interactions of H. pylori with mucin may also explain the clinical observations that H. pylori is found both free in the mucous layer and attached to gastric epithelial cells and strongly suggest that more research is needed to understand the H. pylori genes involved in these mucin interactions. Also, given the potential for H. pylori LPS to interact with host cell glycoconjugates of the same structure (homotypic interactions) (92, 324), a future area of examination should be determination of whether LPS is involved in adherence of H. pylori to mucin as both LPS and mucin contain Lewis X.

Role of Flagellar Secretion Apparatus in Adherence

An isogenic nonmotile mutant in the flagellar secretion apparatus component FliQ results in 30% reduced adherence to AGS cells (112), presumably because the mutation decreases release of a protein involved in adherence that would normally be transported through the apparatus. Since another flagellar, nonmotile mutant (in the flhB gene) adhered similarly to wild type, flagella per se are probably not necessary for adherence (112). However, an open question that still needs to be addressed is whether the flagellar sheath, which contains proteins, including the adhesin HpaA, is involved in adherence. Some of the best studied adhesin-receptor interactions are shown in Fig. 4.

Figure 4

Interaction of H. pylori adhesins with host cell receptors. For simplicity, only the best studied H. pylori adhesin-receptor interactions are shown. The in vivo situation is likely much more complex, as described in the text, in that there may be dynamic (more...)

Adherence Antagonists

Adherence of H. pylori to the gastric epithelium is a crucial initial step in colonization, as nonadhering bacteria would be washed away during peristalsis-mediated flushing of the stomach. Therapeutic approaches to inhibit adherence may thus prevent colonization and disease through eradication of H. pylori. Many adherence antagonists have been tested, and some promising candidate adherence antagonists are briefly summarized (Table 2).

Table 2

H. pylori adherence antagonists.

First, administration of 3′-sialyllactose to persistently colonized rhesus monkeys cures or decreases H. pylori colonization in some monkeys (225). 3′-sialyllactose also significantly reduces gastric bacterial load in H. pylori-infected humans (D. Zopf, P. M. Simon, M. Hurley, E. McGuire, and S. Roth, unpublished observation). These data were obtained following promising in vitro studies showing that 3′-sialyllactose inhibits adherence of low-passage isolates of H. pylori to epithelial cells (294). The 3′-sialyllactose presumably binds to and saturates H. pylori sialic acid adhesins, such as HpaA, and prevents binding of these adhesins to host cell sialic acid receptors. This adherence antagonist is safe, is nonimmunogenic, and can potentially be used in combination with other therapeutic agents. Second, the anti-ulcer compound sofalcone inhibits H. pylori adhesion to mucin in a dose-dependent fashion (319), probably by inhibiting the chemotaxis of H. pylori toward mucin (370). Third, the anti-ulcer compounds sucralfate and sulglycotide inhibit adherence by blocking the interaction of H. pylori LPS with laminin, GM3 ganglioside, and lactosylceramide at the gastric epithelium surface (255, 258, 301, 305, 309). These compounds also decrease H. pylori mucinase activity by desulfating mucin (300, 304), and they also block the interaction of H. pylori LPS to the 97-kDa mucin receptor by 90% (256). These activities lead to increased availability of mucin to bind normally to the mucin receptor on the gastric epithelium surface. Fourth, pretreatment of H. pylori with the anti-ulcer compound ecabet sodium inhibits adhesion of H. pylori to gastric epithelial cell lines by increasing stability of mucin to pepsin degradation and also inhibits surface urease activity (133, 172, 291). Fifth, pretreatment of gastric epithelial cells lines MKN-28 and MKN45 with the anti-ulcer compound rebamipide, or derivatives thereof, inhibits adhesion of H. pylori by about 50% (131). Sixth, pretreatment of MKN45 gastric epithelial cells with the commonly used antacid co-magaldrox (Maalox) inhibits adherence of H. pylori by 75% and specifically interferes with IL-8 secretion from the epithelial cells, while reducing surface expression of H. pylori Hsp60 (168). Seventh, the proton pump inhibitor omeprazole inhibits adherence of H. pylori extracts to human neutrophils (320). Eighth, addition of Lactobacillus salivarius, indigenous flora of the mouth, to MKN45 and KatoIII gastric epithelial cells decreases H. pylori adherence by up to 90%, suggesting that lactobacilli could be used as a probiotic agent against H. pylori (166). Lactobacilli are also colonization antagonists in a gnotobiotic murine model (1, 166). Ninth, milk could serve as a potential adherence antagonist by blocking adherence of H. pylori to sulfatide and Lewis b and by preventing cell vacuolation (130). Indeed, human milk inhibits adherence of H. pylori to KatoIII cells by 50 to 70% (59). The inhibitory fraction of milk was shown not to be secretory IgA (59), but rather κ-casein, in a fucose-dependent fashion (315). There is also a casein-independent fraction of human milk that inhibits H. pylori adherence, which could perhaps be the mucin found in milk (59). Tenth, bile acids, such as chenodeoxycholic acid, are effective inhibitors of adherence of certain H. pylori strains by mechanisms that are unclear (205). Finally, fucoidan, a sulfated α1,3 fucan, inhibits both Lewis b and sulfatide-mediated adherence of H. pylori to MKN28 and KatoIII gastric epithelial cells (291). Seven to 10 fucoidan-binding proteins of H. pylori were detected but not identified.

Adherence antagonists are already being tested for efficacy in combination with antibiotic therapy regimens, such as omeprazole with amoxicillin. Another use for adherence antagonists is dissection of molecular mechanisms of adherence. For example, several adhesin-receptor interactions can be blocked so that still additional interactions may be explored (132).

Does Invasion into Host Cells Occur?

A long-standing question in H. pylori research is whether the bacterium can invade gastric epithelial cells and, if so, whether the organisms can persist as viable organisms intracellularly. The answers to these questions, however, are still controversial. The vast majority of researchers agree that invasion is rare (26, 30). However, rare invaders could still be important for intracellular persistence, resistance to antimicrobial therapy, and protection from the human immune response.

H. pylori is occasionally localized within endocytic vacuoles in gastric epithelial cells, on the basis of studies using human gastric biopsy specimens or various cell lines (26, 235, 274, 333, 361, 362). Invasion into parietal and chief cells was also observed in patient gastric biopsies in one study (362). Additionally, H. pylori can invade the lamina propria and gain access to the basement membrane (10), where laminin is present. Using a nongastric epithelial cell line (HEp-2) and a gentamicin protection assay, Evans and colleagues observed that invasion of H. pylori was rapid and dependent on the sialic acid adhesin HpaA (99). However, little replication of H. pylori occurred after 24 h, and numerous coccoid forms were observed, suggesting the H. pylori may have died following entry. Indeed, using the same cells and experimental protocol for assessing invasion, Megraud and colleagues failed to recover viable intracellular organisms (211). More recent experiments suggest that the gentamicin protection assay is not useful for accurately assessing invasion of H. pylori because the organism finds extracellular pockets that protect it from the antibiotic, leading to falsely elevated invasion levels (62). HEp-2 cells are also probably a poor model to assess invasion and adherence of H. pylori because it is a nongastric cell line, and since only some strains of H. pylori adhere to these cells (174).

An early elegant study by Bode and colleagues (26) demonstrated internalization of H. pylori into the cytoplasm of mucus-secreting duodenal epithelial cells. This occurred in 10% of the duodenal ulcer patient biopsies examined. This study was subsequently confirmed by Noach and colleagues (235), who used human gastric biopsies in their study and found six samples that were highly suggestive of invasion. H. pylori has also been found inside the mucin compartment of goblet cells in gastric biopsies (117). H. pylori has a predilection for association with intercellular tight junctions (26, 134, 330). Initial attachment of H. pylori to the cell surface may weaken tight junctions between adjacent host cells (26, 235). This weakening may allow deeper penetration of H. pylori between cells, with subsequent internalization (26, 235). However, that coccoid forms of the organism were observed in some of these transmission electron micrographs suggests that the invaders may have been nonviable. Evidence for invasion in the studies mentioned above were by electron microscopy or by gentamicin protection assays and thus "invasion artifacts" cannot unequivocally be ruled out. In contrast, other investigators were unable to show evidence for invasion in gastric biopsies (134, 330) or in cell lines (62, 263).

Whether internalized H. pylori is viable was still not clear until more recently, when invasion of H. pylori was confirmed by immunohistochemical staining for bacterial Hsp60, which was found intracellularly in gastric biopsy specimens (96). Treatment of patients with standard antimicrobial triple therapy for 2 weeks resulted in clearance of the bacteria by day 14, but 5 of the 10 patients in the study relapsed by one month posttherapy, providing the first suggestive evidence for antimicrobial therapy failure due to persistent (and thus, viable) intracellular H. pylori (96). If H. pylori lives in an intracellular environment, then poorly penetrating antibiotics, such as the widely used amoxicillin, would fail and may explain occasional clinical failures of antimicrobial regimens.

Using a tissue culture-based system, H. pylori was shown to invade AGS cells using a gentamicin protection assay (317). Type I (cag⁺) strains invaded better than type II strains (cag mutant). Invasion was blocked by cytochalasin D, which inhibits actin polymerization, or by a tyrosine phosphatase. Interestingly, a 125- to 130-kDa protein that is almost certainly CagA, based on more recent studies (18, 64, 238, 283, 313), was tyrosine phosphorylated. Invasion was markedly enhanced by transfection of AGS cells with the β1 integrin gene, suggesting that integrins might serve as receptors for H. pylori in this system (317).

A highly sensitive method of assessing invasion of 18 clinical isolates of H. pylori into HEp-2 cells was recently reported by Wilkinson and colleagues (355). In this study, acridine orange was used to stain microbes; intracellular viable microbes fluoresce green, whereas nonviable organisms fluoresce red. Fluorescence of extracellular microbes is quenched by a counterstain. This study showed H. pylori invasion frequencies that exceeded those for Shigella flexneri and paralleled those of Yersinia enterocolitica (355). Despite being mostly coccoid in shape, intracellular H. pylori remained viable for at least 6 h after entry, and no significant correlation was observed between invasion frequencies and clinical state from which the H. pylori was isolated (355). It will be of great interest to apply this sensitive method to more relevant cell lines such as KatoIII gastric epithelial cells and to fresh gastric biopsies. One potential problem with assessing H. pylori invasion is that VacA may contribute to cell lysis, leading to disruption of tissue culture monolayers. Thus use of a vacA mutant of H. pylori may help investigate invasion mechanisms more closely (355).

Except for possibly HpaA (in a nongastric cell model), H. pylori invasins have not yet been identified in any study and specific genes need to be disrupted to lend stronger support for the hypothesis that H. pylori can occasionally invade host cells.

Interations of H. pylori with Phagocytic Cells

H. pylori adheres to and enters human monocytes and neutrophils, phagocytic cells that infiltrate the gastric mucosa. Adherence to neutrophils leads to up-regulation of the integrin CD11b, independent of the H. pylori genes cagA, vacA, and cagE (129). Entry of H. pylori into human neutrophils (9, 26), monocytes, and macrophages (5, 9) is opsonin independent, suggesting that H. pylori adhesins are responsible for entry. Whether these phagocytosed organisms remain viable or are killed depends on the presence of the cag PAI. Type I strains have a delay in phagocytosis followed by homotypic phagosome fusion into "megasomes," whereas type II strains are rapidly phagocytosed and killed (5). The megasomes contained viable organisms (5). The reason for survival of type I strains inside phagosomes is unclear, but perhaps catalase and superoxide dismutase produced by the bacterium detoxify reactive oxygen intermediates inside of phagosomes (241, 312). Also of importance is whether strains possess sialic acid hemagglutinins. Those H. pylori strains containing sialic acid hemagglutinins are more resistant to phagocytosis by human neutrophils and monocytes, in contrast to those lacking sialic acid hemagglutinins (9, 46, 48). However, H. pylori adherence, which can be clearly distinguished from phagocytosis, does require sialic acids on the surface of human monocytes (51). Therefore, sialic acid hemagglutinating strains adhere better yet are more resistant to bactericidal killing and phagocytosis compared with nonhemagglutinating strains. Heparan sulfate significantly enhances phagocytosis of H. pylori by human neutrophils (46, 49).

H. pylori activates monocytes by both LPS-dependent and -independent mechanisms, resulting in the production of IL-1 and TNF-α and in expression of major histocompatibility (MHC) antigens and the IL-2 receptor (199). Monocytes could thus be crucial for ingestion of H. pylori and presentation of bacterial antigens on the cell surface in the context of MHC antigens for eventual humoral or cell-mediated immune response. The role of specific bacterial genes in the interaction of H. pylori with phagocytic cells is a largely unexplored area of research.

Colonization

Host Factors

Even before the discovery of H. pylori, researchers had found significant correlations between certain genetic markers and prevalence of ulcer disease (Table 3). Similar studies have been performed more recently, and there are early indications that some alleles of host genes may predispose one to become colonized in the first place, while others are associated with subsequent development of ulcers or cancer. This section will focus primarily on factors believed to increase susceptibility to infection, rather than disease outcome; however, the present state of knowledge scarcely allows differentiation between susceptibility and prognosis.

Table 3

Factors influencing colonization by H. pylori.

Numerous epidemiological studies have examined a range of populations and environmental factors to determine what constitutes a risk factor for development of chronic H. pylori infection and subsequent pathologies. Although the evidence is circumstantial, it appears that the H. pylori infection rate varies due to both exposure level and intrinsic susceptibility to colonization. Studies have revealed that nursing home patients, endoscopists, and individuals consuming food from street vendors may be more likely to become infected with H. pylori than the general population (24, 122, 207, 264). These studies point toward a higher risk of exposure to the organism. In other studies, however, it is more difficult to imagine why the exposure rates should differ. For instance, comparisons of H. pylori-specific IgG, indicating an established infection, and IgM, suggesting recent exposure, reveal that women are more than twice as likely to become infected with H. pylori while pregnant than nonpregnant controls (181). Since pregnancy is known to result in many immunological changes, it is possible that host immune status could render the host less able to combat the initial infection with H. pylori. Although numerous studies have shown that acquisition often occurs during childhood (93, 201), at least one study has also demonstrated a high rate of spontaneous clearance among children before age 11 (331). Thus, it is possible that children are both more likely to be exposed to H. pylori and more likely to clear the infection as their immune systems mature, whereas adults are less likely to clear an established infection but are infrequently exposed to the organism.

Many investigators have accumulated evidence that factors specific to an individual host influence colonization by H. pylori. Studies of twins revealed that monozygotic twins were 81% concordant for infection, compared with 63% concordance in dizygotic twins (200). That is, 81% of identical twins were either both infected or neither infected. There were few cases in which one twin was infected and the other twin was not. This difference was maintained regardless of whether the twins were reared together or apart. In a multiethnic Malaysian city, a study of 1,060 consecutive endoscopy patients revealed that, overall, the prevalence of H. pylori infection measured by rapid urease tests of biopsies was 49%; however, only 16.4% of ethnic Malay patients were infected, whereas 48.5% of Chinese and 61.8% of Indian patients were H. pylori positive (121). Another study in a multiethnic region also revealed differences in H. pylori positivity related to ethnicity. Even when socioeconomic status was accounted for, Europeans were significantly less likely to be seropositive than Maori or Pacific Islanders (113). Neither research group could rule out dietary factors or cultural practices that may increase risk of infection; however, Campbell and colleagues noted that Maori and Pacific Islander populations interact more frequently with Europeans than with each other (34). This group also found that strains isolated from Europeans were almost three times more likely to express a biologically inactive VacA cytotoxin than strains isolated from Polynesians. This could mean that VacA confers an advantage to H. pylori only in certain hosts, while it is detrimental for the bacterium in others. Specific host characteristics could therefore influence the ability of H. pylori to colonize in the first place, and subsequently exert adaptive pressure leading to measurable differences in the colonizing strain.

A single encounter with a given strain of H. pylori may not be sufficient for lifelong infection. Ethnic correlations among inhabitants of the same geographic region merit further investigation to determine whether identifiable host markers predispose certain individuals to infection. Polynesians are known to express the Lewis b antigen at a lower frequency than Europeans, but this has not yet been correlated to risk of infection or strain type likely to be present (138, 139). Data regarding the identities or mechanisms of such host factors influencing H. pylori growth are sparse, due to the inherent difficulties in conducting controlled studies. Nonetheless, one study performed in rhesus monkeys has yielded some interesting data regarding host specificity, and apparent changes in selective pressure that occur as colonization progresses. A group of four monkeys that had been previously cured of their natural H. pylori infections was inoculated with a mixture of seven fresh clinical isolates (81). By 10 months postinfection, randomly amplified polymorphic DNA (RAPD) fingerprinting revealed that clinical isolate J166 predominated in all four animals, even though this strain had been detected in only one animal at the earliest timepoint. Two other strains were found early in infection in all four animals, but both had nearly reached undetectable levels by 10 months. Although only a small number of animals were used, this study strongly suggests that either the gastric environment changes as infection becomes established, and that this change affects the relative survival of H. pylori strains, or that strains differ in their relative competence for infection and persistence. It is possible that, had only one strain been used as an inoculum, the monkeys would have been only transiently infected.

Thus far, little is known about specific host factors that influence H. pylori infection. The HLA types that appear to be correlated with susceptibility to helicobacter infection are HLA DR and HLA DQ*0301. HLA DQA1*0301 and HLA DQ5 are frequently associated with more severe disease but may not predispose an individual to becoming infected in the first place. HLA-DQA1*0102 appears to confer partial protection to H. pylori-related atrophic gastritis and intestinal-type gastric adenocarcinoma (21). The identification of additional host cell markers relevant to H. pylori may provide important clues for understanding H. pylori infection and developing treatment strategies.

Conclusions

We are only beginning to understand the complex mechanisms used by H. pylori to establish infection and to maintain colonization in the same host over a period of many years. Penetration of the mucous layer likely involves motility, phospholipase activity, and mucinase activity. H. pylori-mediated reduction of mucus synthesis or secretion may also assist the bacterium in gaining access to the epithelium and persisting at this location. Adherence allows the bacteria to anchor themselves to the epithelial layer, but bacteria that remain attached to epithelial cells will eventually be swept away as these cells die and are exfoliated. Thus, a proportion of the H. pylori population exists in the nonadherent state. H. pylori must also contend with antibodies and phagocytic cells as the host mounts an immune response.

Colonization by H. pylori has only been confirmed in the gastric mucosa. Limitation to this site could be due to competition by other organisms in the mouth and small intestine. Other Helicobacter spp. have been isolated from blood and deep tissues, but H. pylori has not. Perhaps the exquisite sensitivity of H. pylori to complement-mediated lysis (261, 265) renders it incapable of causing extragastric disease; however, circumstantial evidence suggests that H. pylori may be present in the liver (233, 259).

Preventing the establishment of long-term colonization, or even curing an established H. pylori infection, may be achieved either by killing all organisms or by antagonizing one or more of the persistence mechanisms and suppressing growth until the combination of host immune response, exfoliation, and movement of gastric contents purge the last bacterium from the stomach. Data in humans on prevention of colonization or spontaneous cure are sparse; however, there is some evidence for both phenomena (29, 115, 198, 202, 328, 372). Widespread treatment of H. pylori infection with multidrug regimens is problematic even in industrialized nations. Thus, until an effective vaccine is developed to prevent H. pylori infection, improved sanitation and public education may be the most practical means of limiting infection.

At present, dissecting the individual contributions of the factors discussed in this chapter is exceedingly difficult. The development of new research tools, such as the completed genome sequence and superior in vivo and in vitro models will no doubt facilitate future studies of H. pylori adherence and colonization.

References

1.

Alba Y., Suzuki N., Kabir A. M., Takagi A., Koga Y. Lactic acid-mediated suppression of Helicobacter pylori by the oral administration of Lactobacillus salivarius as a probiotic in a gnotobiotic murine model. Am. J. Gastroenterol. 1998;93:2097–2101. [PubMed: 9820379]

2.

Aihara M., Tsuchimoto D., Takizawa H., Azuma A., Wakebe H., Ohmoto Y., Imagawa K., Kikuchi M., Mukaida N., Matsushima K. Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect. Immun. 1997;65:3218–3224. [PMC free article: PMC175455] [PubMed: 9234778]

3.

Akopyants N. S., Clifton S. W., Kersulyte D., Crabtree J. E., Youree B. E., Reece C. A., Bukanov N. O., Drazek E. S., Roe B. A., Berg D. E. Analyses of the cag pathogenicity island of Helicobacter pylori. Mol. Microbiol. 1998;28:37–53. [PubMed: 9593295]

4.

Alkout A. M., Blackwell C. C., Weir D. M., Poxton I. R., Elton R. A., Luman W., Palmer K. Isolation of a cell surface component of Helicobacter pylori that binds H type 2, Lewis(a), and Lewis(b) antigens. Gastroenterology. 1997;112:1179–1187. [PubMed: 9098001]

5.

Allen L. A., Schlesinger L. S., Kang B. Virulent strains of Helicobacter pylori demonstrate delayed phagocytosis and stimulate homotypic phagosome fusion in macrophages. J. Exp. Med. 2000;191:115–128. [PMC free article: PMC2195807] [PubMed: 10620610]

6.

Allen L. A. H. Intracellular niches for extracellular bacteria: lessons from Helicobacter pylori. J. Leuk. Biol. 1999;66:753–756. [PubMed: 10577505]

7.

Alm R., Ling L. S., Moir D. T., King B. L., Brown E. D., Doig P. C., Smith D. R., Noonan B., Guild B. C., deJonge B. L., Carmel G., Tummino P. J., Caruso A., Uria-Nickelsen M., Mills D. M., Ives C., Gibson R., Merberg D., Mills S. D., Jiang Q., Taylor D. E., Vovis G. F., Trust T. J. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature. 1999;397:176–180. [PubMed: 9923682]

8.

Amado M., Carniero F., Seixas M., Clausen H., Sobrinho-Simones M. Dimeric sialyl/Le^x expression in gastric carcinoma correlates with venous invasion and poor outcome. Gastroenterology. 1998;114:462–470. [PubMed: 9496936]

9.

Andersen L. P., Blom J., Nielsen H. Survival and ultrastructural changes of Helicobacter pylori after phagocytosis by human polymorphonuclear leukocytes and monocytes. APMIS. 1993;101:61–72. [PubMed: 8457327]

10.

Andersen L. P., Holck S. Possible evidence of invasiveness of Helicobacter (Campylobacter) pylori. Eur. J. Clin. Microbiol. Infect. Dis. 1990;9:135–138. [PubMed: 2318218]

11.

Andersen R. N., Ganeshkumar N., Kolenbrander P. E. Helicobacter pylori adheres selectively to Fusobacterium spp. Oral Microbiol. Immunol. 1998;13:51–54. [PubMed: 9573823]

12.

Andrutis K. A., Fox J. G., Schauer D. B., Marini R. P., Murphy J. C., Yan L., Solnick J. V. Inability of an isogenic urease-negative mutant stain of Helicobacter mustelae to colonize the ferret stomach. Infect. Immun. 1995;63:3722–3725. [PMC free article: PMC173518] [PubMed: 7642314]

13.

Ångstrom J., Teneberg S., Milh M. A., Larsson T., Leonardsson I., Olsson B. M., Halvarsson M. O., Danielsson D., Näslund I., Ljungh Å., Wadström T., Karlsson K.-A. The lactosylceramide binding specificity of Helicobacter pylori. Glycobiology. 1998;8:297–309. [PubMed: 9499377]

14.

Ansorg R., Schmid E. N. Adhesion of Helicobacter pylori to yeast cells. Zentralbl. Bakteriol. 1998;288:501–508. [PubMed: 9987188]

15.

Appelmelk B. J., Shiberu B., Trinks C., Tapsi N., Zheng P. Y., Verboom T., Maaskant J., Hokke C. H., Schiphorst W. E., Blanchard D., Simoons-Smit I. M., van den Eijnden D. H., Vandenbroucke-Grauls C. M. Phase variation in Helicobacter pylori lipopolysaccharide. Infect. Immun. 1998;66:70–76. [PMC free article: PMC107860] [PubMed: 9423841]

16.

Appelmelk B. J., Simoons-Smit I., Negrini R., Moran A. P., Aspinall G. O., Forte J. G., deVries T., Quan H., Verboom T., Maaskant J. J., Ghiara P., Kuipers E. J., Bloemena E., Tadema T. M., Townsend R. R., Tyagarajan K., Crothers J. M., Monteiro M. A., Savio A., deGraaff J. J. Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in auto-immunity. Infect. Immun. 1996;64:2031–2040. [PMC free article: PMC174033] [PubMed: 8675304]

17.

Armstrong J. A., Cooper M., Goodwin C. S., Robinson J., Wee S. H., Burton M., Burke V. Influence of soluble haemagglutinins on adherence of Helicobacter pylori to HEp-2 cells. J. Med. Microbiol. 1991;34:181–187. [PubMed: 2010909]

18.

Asahi M., Azuma T., Ito S., Ito Y., Suto M., Nagai Y., Tsubokawa M., Tohyama Y., Maeda S., Omata M., Suzuki T., Sasakawa C. Helicobacter pylori CagA protein can be tyosine phosphorylated in gastric epithelial cells. J. Exp. Med. 2000;191:593–602. [PMC free article: PMC2195829] [PubMed: 10684851]

19.

Ascencio F., Franson L. A., Wadström T. Affinity of the gastric pathogen Helicobacter pylori for the N-sulphated glycosaminoglycan heparan sulphate. J. Med. Microbiol. 1993;38:240–244. [PubMed: 7682621]

20.

Asikainen S., Chen C., Slots J. Absence of Helicobacter pylori in subgingival samples determined by polymerase chain reaction. Oral Microbiol. Immunol. 1994;9:318–320. [PubMed: 7808777]

21.

Azuma T., Ito S., Sato F., Yamazaki Y., Miyaji H., Ito Y., Suto H., Kuriyama M., Kato T., Kohli Y. The role of the HLA-DQA1 gene in resistance to atrophic gastritis and gastric adenocarcinoma induced by Helicobacter pylori infection. Cancer. 1998;82:1013–1018. [PubMed: 9506344]

22.

Bagchi D., McGinn T. R., Ye X., Balmoori J., Bagchi M., Stohs S. J., Kuszynski C. A., Carryl O. R., Mitra S. Mechanism of gastroprotection by bismuth subsalicylate against chemically induced oxidative stress in cultured human gastric mucosal cells. Dig. Dis. Sci. 1999;44:2419–2428. [PubMed: 10630491]

23.

Baik S. C., Youn H. S., Chung M. H., Lee W. K., Cho M. J., Ko G. H., Park C. K., Kasai H., Rhee K. H. Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. Cancer Res. 1996;56:1279–1282. [PubMed: 8640814]

24.

Begue R. E., Gonzales J. L., Correa-Gracian H., Tang S. C. Dietary risk factors associated with the transmission of Helicobacter pylori in Lima, Peru. Am. J. Trop. Med. Hyg. 1998;59:637–640. [PubMed: 9790444]

25.

Bennedsen M., Wang X., Willen R., Wadstrom T., Andersen L. P. Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunol. Lett. 1999;70:185–189. [PubMed: 10656672]

26.

Bode G., Malfertheiner P., Ditschuneit H. Pathogenic implications of ultrastructural findings in Campylobacter pylori related gastroduodenal disease. Scand. J. Gastroenterol. 1988;142:25–39. [PubMed: 3166531]

27.

Bonvicini F. M., Maltarello C., Versura P., Bianchi D., Gasbarrini G., Laschi R. Correlative scanning electron microscopy in the study of human gastric mucosa. Scanning Electron Microsc. 1986;2:687–702. [PubMed: 3099375]

28.

Borén T., Falk P., Roth K. A., Larson G., Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science. 1993;262:1892–1895. [PubMed: 8018146]

29.

Brenner H., Berg G., Lappus N., Kliebsch U., Bode G., Boeing H. Alcohol consumption and Helicobacter pylori infection: results from the German National Health and Nutrition Survey. Epidemiology. 1999;10:214–218. [PubMed: 10230827]

30.

Buck G. E., Gourley W. K., Lee W. K., Subramanyam K., Latimer J. M., DiNuzzo A. R. Relationship of Campylobacter pyloridis to gastritis and peptic ulcer. J. Infect. Dis. 1986;153:664–669. [PubMed: 3950448]

31.

Buiatti E., Palli D., Decarli A., Amadori D., Avellini C., Bianchi S., Bonaguri C., Cipriani F., Cocco P., Giacosa A. A case-control study of gastric cancer and diet in Italy: II. Association with nutrients. Int. J. Cancer. 1990;45:896–901. [PubMed: 2335393]

32.

Buiatti E., Palli D., Decarli A., Amadori D., Avellini C., Bianchi S., Biserni R., Cipriani F., Cocco P., Giacosa A., Marubini E., Puntoni R., Vindigni C., Fraumeni J., Blot W. A case-control study of gastric cancer and diet in Italy. Int. J. Cancer. 1989;44:611–616. [PubMed: 2793233]

33.

Calam J. Helicobacter pylori, acid and gastrin. Eur. J. Gastroenterol. Hepatol. 1995;7:310–317. [PubMed: 7600135]

34.

Campbell S., Fraser A., Holliss B., Schmid J., O'Toole P. W. Evidence for ethnic tropism of Helicobacter pylori. Infect. Immun. 1997;65:3708–3712. [PMC free article: PMC175528] [PubMed: 9284141]

35.

Caselli M., Figura N., Trevisani L., Pazzi P., Guglielmetti P., Bovolenta M. R., Stabellini G. Patterns of physical modes of contact between Campylobacter pylori and gastric epithelium: implications about the bacterial pathogenicity. Am. J. Gastroenterol. 1989;84:511–513. [PubMed: 2719007]

36.

Çelik J., Su B., Tirén U., Finkel Y., Thoresson A.-C., Engstrand L., Sandstedt B., Berander S., Normark S. Virulence and colonization-associated properties of Helicobacter pylori isolated from children and adolescents. J. Infect. Dis. 1998;177:247–252. [PubMed: 9419200]

37.

Cellini L., Allocati N., Angelucci D., Lezzi T., Di Campli E., Marzio L., Dainelli B. Coccoid Helicobacter pylori not culturable in vitro reverts in mice. Microbiol. Immunol. 1994;38:843–850. [PubMed: 7898382]

38.

Cellini L., Di Campli E., Masulli M., Di Bartolomeo S., Allocati N. Inhibition of Helicobacter pylori by garlic extract (Allium sativum). FEMS Immunol. Med. Microbiol. 1996;13:273–277. [PubMed: 8739190]

39.

Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type-I-specific and disease-associated virulence factors. Proc. Natl. Acad. Sci. USA. 1996;93:14648–14653. [PMC free article: PMC26189] [PubMed: 8962108]

40.

Chan E. C., Chang C. C., Li Y. S., Chang C. A., Chiou C. C., Wu T. Z. Purification and characterization of neutral sphingomyelinase from Helicobacter pylori. Biochemistry. 2000;39:4838–4845. [PubMed: 10769141]

41.

Chen W., Shu D., Chadwick V. S. Helicobacter pylori infection in interleukin-4-deficient and transgenic mice. Scand. J. Gastroenterol. 1999;34:987–992. [PubMed: 10563668]

42.

Chen X. G., Correa P., Offerhaus J., Rodriguez E., Janney F., Hoffmann E., Fox J., Hunter F., Diavolitsis S. Ultrastructure of the gastric mucosa harboring Campylobacter-like organisms. Am. J. Clin. Pathol. 1986;86:575–582. [PubMed: 2430450]

43.

Chesney J. A., Eaton J. W., Mahoney, Jr J. R. Bacterial glutathione: a sacrificial defense against chlorine compounds. J. Bacteriol. 1996;178:2131–2135. [PMC free article: PMC177915] [PubMed: 8606194]

44.

Chevalier C., Thiberge J. M., Ferrero R. L., Labigne A. Essential role of Helicobacter pylori gamma-glutamyltranspeptidase for the colonization of the gastric mucosa of mice. Mol. Microbiol. 1999;31:1359–1372. [PubMed: 10200957]

45.

Chew B. P., Park J. S., Wong M. W., Wong T. S. A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res. 1999;19:1849–1853. [PubMed: 10470126]

46.

Chmiela M., Czkwianianc E., Wadström T., Rudnicka W. Role of Helicobacter pylori surface structures in bacterial interaction with macrophages. Gut. 1997;40:20–24. [PMC free article: PMC1027002] [PubMed: 9155570]

47.

Chmiela M., Lawnik M., Czkwianianc E., Rechcinski T., Planeta-Malecka I., Wadström T., Rudnicka W. Attachment of Helicobacter pylori strains to human epithelial cells. J. Physiol. Pharmacol. 1997;48:393–404. [PubMed: 9376622]

48.

Chmiela M., Lelwala-Guruge J., Wadström T. Interaction of cells of Helicobacter pylori with human polymorphonuclear leucocytes: possible role of haemagglutinins. FEMS Immunol. Med. Microbiol. 1994;9:41–48. [PubMed: 7522735]

49.

Chmiela M., Ljungh Å., Rudnicka W., Wadström T. Phagocytosis of Helicobacter pylori bacteria differing in the heparan sulfate binding by human polymorphonuclear leukocytes. Zentralbl. Bakteriol. 1996;283:346–350. [PubMed: 8861873]

50.

Chmiela M., Paziak-Domanska B., Rudnicka W., Wadström T. The role of heparan sulphate-binding activity of Helicobacter pylori bacteria in their adhesion to murine macrophages. APMIS. 1995;103:469–474. [PubMed: 7546650]

51.

Chmiela M., Paziak-Domanska B., Wadström T. Attachment, ingestion and intracellular killing of Helicobacter pylori by human peripheral blood mononuclear leucocytes and mouse peritoneal inflammatory macrophages. FEMS Immunol. Med. Microbiol. 1995;10:307–316. [PubMed: 7773248]

52.

Choe Y. H., Kim S. K., Son B. K., Lee D. H., Hong Y. C., Pai S. H. Randomized placebo-controlled trial of Helicobacter pylori eradication for iron-deficiency anemia in preadolescent children and adolescents. Helicobacter. 1999;4:135–139. [PubMed: 10382128]

53.

Chowers M. Y., Keller N., Tal R., Barshack I., Lang R., Bar-Meir S., Chowers Y. Human gastrin: a Helicobacter pylori-specific growth factor. Gastroenterology. 1999;117:1113–1118. [PubMed: 10535874]

54.

Christie P. J. The Agrobacterium tumefaciens T-complex transport apparatus: a paradigm for a new family of multifunctional transporters in eubacteria. J. Bacteriol. 1997;179:3085–3094. [PMC free article: PMC179082] [PubMed: 9150199]

55.

Chung J. G., Chen G. W., Wu L. T., Chang H. L., Lin J. G., Yeh C. C., Wang T. F. Effects of garlic compounds diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity in strains of Helicobacter pylori from peptic ulcer patients. Am. J. Chin. Med. 1998;26:353–364. [PubMed: 9862023]

56.

Clyne M., Drumm B. Adherence of Helicobacter pylori to primary human gastrointestinal cells. Infect. Immun. 1993;61:4051–4057. [PMC free article: PMC281123] [PubMed: 8406792]

57.

Clyne M., Drumm B. Cell envelope characteristics of Helicobacter pylori: their role in adherence to mucosal surfaces and virulence. FEMS Immunol. Med. Microbiol. 1996;16:141–155. [PubMed: 8988394]

58.

Clyne M., Drumm B. Absence of Lewis A and Lewis B expression on adherence of H. pylori to human gastric cells. Gastroenterology. 1997;113:72–80. [PubMed: 9207264]

59.

Clyne M., Thomas J., Weaver L., Drumm B. In vitro evaluation of the role of antibodies against Helicobacter pylori in inhibiting adherence of the organism to gastric cells. Gut. 1997;40:731–738. [PMC free article: PMC1027197] [PubMed: 9245926]

60.

Coconnier M. H., Lievin V., Hemery E., Servin A. L. Antagonistic activity against Helicobacter infection in vitro and in vivo by the human Lactobacillus acidophilus strain LB. Appl. Environ. Microbiol. 1998;64:4573–4580. [PMC free article: PMC106686] [PubMed: 9797324]

61.

Cole S. P., Cirillo D., Kagnoff M. F., Guiney D. G., Eckmann L. Coccoid and spiral Helicobacter pylori differ in their abilities to adhere to gastric epithelial cells and induce interleukin-8 secretion. Infect. Immun. 1997;65:843–846. [PMC free article: PMC176138] [PubMed: 9009355]

62.

Corthésy-Theulaz I., Porta N., Pringault E., Racine L., Bogdanova A., Kraehenbuhl J.-P., Blum A. L., Michetti P. Adhesion of Helicobacter pylori to polarized T84 human intestinal cell monolayers is pH dependent. Infect. Immun. 1996;64:3827–3832. [PMC free article: PMC174299] [PubMed: 8751935]

63.

Covacci A., Censini S., Bugnoli M., Petracca R., Burroni D., Macchia G., Massone A., Papini E., Xiang Z., Figura N., Rappuoli R. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc. Natl. Acad. Sci. USA. 1993;90:5791–5795. [PMC free article: PMC46808] [PubMed: 8516329]

64.

Covacci A., Rappuoli R. Tyrosine-phosphorylated bacterial proteins: Trojan horses for the host cell. J. Exp. Med. 2000;191:587–592. [PMC free article: PMC2195833] [PubMed: 10684850]

65.

Covacci A., Telford J. L., Del Giudice G., Parsonnet J., Rappuoli R. Helicobacter pylori, virulence and genetic geography. Science. 1999;284:1328–1333. [PubMed: 10334982]

66.

Cover T. L., Dooley C. P., Blaser M. J. Characterization of and human serologic response to proteins in Helicobacter pylori broth culture supernatants with vacuolizing cytotoxin activity. Infect. Immun. 1990;58:603–610. [PMC free article: PMC258508] [PubMed: 2307514]

67.

Crabtree J. E., Farmery S. M., Lindley I. J. D., Figura N., Peichl P., Tompkins D. S. CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J. Clin. Pathol. 1994;47:945–950. [PMC free article: PMC502181] [PubMed: 7962609]

68.

Crabtree J. E., Taylor J. D., Wyatt J. I., Heatley R. V., Shallcross T. M., Tompkins D. S., Rathbone B. J. Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. Lancet. 1991;338:332–335. [PubMed: 1677696]

69.

Crabtree J. E., Xiang Z., Lindley I. J., Tompkins D. S., Rappuoli R. Induction of interleukin-8 secretion from gastric epithelial cells by a cagA isogenic mutant of Helicobacter pylori. J. Clin. Pathol. 1995;48:967–969. [PMC free article: PMC502959] [PubMed: 8537502]

70.

Crichton R. R., Charloteaux-Wauters M. Iron transport and storage. Eur. J. Biochem. 1987;164:485–506. [PubMed: 3032619]

71.

Davies G. R., Banatvala N., Collins C. E., Sheaff M. T., Abdi Y., Clements L., Rampton D. S. Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa. Scand. J. Gastroenterol. 1994;29:419–424. [PubMed: 8036457]

72.

De Koster E., Buset M., Fernandes E., Deltenre M. Helicobacter pylori: the link with gastric cancer. Eur. J. Cancer Prev. 1994;3:247–257. [PubMed: 8061590]

73.

Desai M. A., Mutlu M., Vadgama P. A study of macromolecular diffusion through native porcine mucus. Experientia. 1992;48:22–26. [PubMed: 1737572]

74.

Dhaenens L., Szczebara F., Husson M. O. Identification, characterization, and immunogenicity of the lactoferrin-binding protein from Helicobacter pylori. Infect. Immun. 1997;65:514–518. [PMC free article: PMC176089] [PubMed: 9009306]

75.

Doig P., Austin J. W., Kostrzynska M., Trust T. J. Production of a conserved adhesin by the gastroduodenal pathogen Helicobacter pylori. J. Bacteriol. 1992;174:2539–2547. [PMC free article: PMC205892] [PubMed: 1556073]

76.

Doig P., Austin J. W., Trust T. J. The Helicobacter pylori 19.6-kilodalton protein is an iron-containing protein resembling ferritin. J. Bacteriol. 1993;175:557–560. [PMC free article: PMC196173] [PubMed: 8419304]

77.

Doig P., Exner M. M., Hancock R. E., Trust T. J. Isolation and characterization of a conserved porin protein from Helicobacter pylori. J. Bacteriol. 1995;177:5447–5452. [PMC free article: PMC177350] [PubMed: 7559328]

78.

Dorgan J. F., Schatzkin A. Antioxidant micronutrients in cancer prevention. Hematol. Oncol. Clin. North Am. 1991;5:43–68. [PubMed: 2026568]

79.

Dorrell N., Martino M. C., Stabler R. A., Ward S. J., Zhang Z. W., McColm A. A., Farthing M. J., Wren B. W. Characterization of Helicobacter pylori PldA, a phospholipase with a role in colonization of the gastric mucosa. Gastroenterology. 1999;117:1098–1104. [PubMed: 10535872]

80.

Drake I. M., Davies M. J., Mapstone N. P., Dixon M. F., Schorah C. J., White K. L., Chalmers D. M., Axon A. T. Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals. Carcinogenesis. 1999;17:559–562. [PubMed: 8631145]

81.

Dubois A., Berg D. E., Incecik E. T., Fiala N., Heman-Ackah L. M., Del Valle J., Yang M., Wirth H. P., Perez-Perez G. I., Blaser M. J. Host specificity of Helicobacter pylori strains and host responses in experimentally challenged nonhuman primates. Gastroenterology. 1999;116:90–96. [PubMed: 9869606]

82.

Duggan A. E., Atherton J. C., Cockayne A., Balsitis M., Evison S., Hale T., Hawkey C. J., Spiller R. C. Clarification of the link between polyunsaturated fatty acids and Helicobacter pylori-associated duodenal ulcer disease: a dietary intervention study. Br. J. Nutr. 1997;78:515–522. [PubMed: 9389880]

83.

Dwarakanath A. D., Tsai H. H., Sunderland D., Hart C. A., Figura N., Crabtree J. E., Rhodes J. M. The production of neuraminidase and fucosidase by Helicobacter pylori: their possible relationship to pathogenicity. FEMS Immunol. Med. Microbiol. 1995;12:213–216. [PubMed: 8745005]

84.

Dytoc M., Gold B., Louie M., Huesca M., Fedorko L., Crowe S., Lingwood C., Brunton J., Sherman P. Comparison of Helicobacter pylori and attaching-and-effacing Escherichia coli adhesion to eukaryotic cells. Infect. Immun. 1993;61:448–456. [PMC free article: PMC302749] [PubMed: 8380793]

85.

Eaton K. A., Brooks C. L., Morgan D. R., Krakowka S. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 1991;59:2470–2475. [PMC free article: PMC258033] [PubMed: 2050411]

86.

Eaton K. A., Catrenich C. E., Makin K. M., Krakowka S. Virulence of coccoid and bacillary forms of Helicobacter pylori in gnotobiotic piglets. J. Infect. Dis. 1995;171:459–462. [PubMed: 7844390]

87.

Eaton K. A., Cover T. L., Tummuru M. K. R., Blaser M. J., Krakowka S. Role of vacuolating cytotoxin in gastritis due to Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 1997;65:3462–3464. [PMC free article: PMC175490] [PubMed: 9234813]

88.

Eaton K. A., Krakowka S. Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori. Infect. Immun. 1994;62:3604–3607. [PMC free article: PMC303008] [PubMed: 8063376]

89.

Eaton K. A., Morgan D. R., Krakowka S. Campylobacter virulence factors in gnotobiotic piglets. Infect. Immun. 1989;57:1119–1125. [PMC free article: PMC313239] [PubMed: 2925243]

90.

Eaton K. A., Morgan D. R., Krakowka S. Motility as a factor in the colonization of gnotobiotic piglets by Helicobacter pylori. J. Med. Microbiol. 1992;37:123–127. [PubMed: 1629897]

91.

Eaton K. A., Suerbaum S., Josenhans C., Krakowka S. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect. Immun. 1996;64:2445–2448. [PMC free article: PMC174096] [PubMed: 8698465]

92.

Edwards N. J., Monteiro M. A., Faller G., Walsh E. J., Moran A. P., Roberts I. S., High N. J. Lewis X structures in the O antigen side-chain promote adhesion of Helicobacter pylori to the gastric epithelium. Mol. Microbiol. 2000;35:1530–1539. [PubMed: 10760152]

93.

Elitsur Y., Adkins L., Saeed D., Neace C. Helicobacter pylori antibody profile in household members of children with H. pylori infection. J. Clin. Gastroenterol. 1999;29:178–182. [PubMed: 10478881]

94.

El-Omar E., Penman I., Dorrian C. A., Ardill J. E., McColl K. E. Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer. Gut. 1993;34:1060–1065. [PMC free article: PMC1374354] [PubMed: 8174954]

95.

Emödy L., Carlsson Å., Ljungh Å., Wadström T. Mannose-resistant haemagglutinin by Campylobacter pylori. Scand. J. Infect. Dis. 1988;20:353–354. [PubMed: 3406678]

96.

Engstrand L., Graham D. Y., Scheynius A., Genta R. M., El-Zaatari F. Is the sanctuary where Helicobacter pylori avoids antibacterial treatment intracellular? Am. J. Clin. Pathol. 1997;108:504–509. [PubMed: 9353088]

97.

Exner M. M., Doig P., Trust T. J., Hancock R. E. Isolation and characterization of a family of porin proteins from Helicobacter pylori. Infect. Immun. 1995;63:1567–1572. [PMC free article: PMC173190] [PubMed: 7534278]

98.

Evans D. G., Evans D. J., Graham D. Y. Receptor-mediated adherence of Campylobacter pylori to mouse Y-1 adrenal cell monolayers. Infect. Immun. 1989;57:2272–2278. [PMC free article: PMC313441] [PubMed: 2473033]

99.

Evans D. G., Evans D. J., Graham D. Y. Adherence and internalization of Helicobacter pylori by HEp-2 cells. Gastroenterology. 1992;102:1557–1567. [PubMed: 1568565]

100.

Evans D. G., Evans D. J., Mould J. J., Graham D. Y. N-acetylneuraminyllactose-binding fibrillar hemagglutinin of Campylobacter pylori: a putative colonization factor antigen. Infect. Immun. 1988;56:2896–2906. [PMC free article: PMC259668] [PubMed: 2459065]

101.

Evans D. G., Karjalainen T. K., Evans D. J., Graham D. Y., Lee C.-H. Cloning, nucleotide sequence, and expression of a gene encoding an adhesin subunit protein of Helicobacter pylori. J. Bacteriol. 1993;175:674–683. [PMC free article: PMC196205] [PubMed: 7678592]

102.

Evans D. J., Evans D. G., Takemura T., Nakano H., Lampert H. C., Graham D. Y., Granger D. N., Kvietys P. R. Characterization of a Helicobacter pylori neutrophil-activating protein. Infect. Immun. 1995;63:2213–2220. [PMC free article: PMC173288] [PubMed: 7768601]

103.

Falk P. G., Bry L., Holgersson J., Gordon J. I. Expression of a human alpha-1,3/4-fucosyltransferase in the pit cell lineage of FVB/N mouse stomach results in production of Lewis b-containing glycoconjugates: a potential transgenic mouse model for studying Helicobacter pylori infection. Proc. Natl. Acad. Sci. USA. 1995;92:1515–1519. [PMC free article: PMC42550] [PubMed: 7878011]

104.

Falk P., Roth K. A., Borén T., Westblom T. U., Gordon J. I., Normark S. An in vitro adherence assay reveals that Helicobacter pylori exhibits cell lineage-specific tropism in the human gastric epithelium. Proc. Acad. Natl. Sci. USA. 1993;90:2035–2039. [PMC free article: PMC46015] [PubMed: 8383333]

105.

Falkow S. Bacterial entry into eukaryotic cells. Cell. 1991;65:1099–1102. [PubMed: 1905978]

106.

Falkow S. What is a pathogen? ASM News. 1997;63:359–365.

107.

Fan X., Crowe S. E., Behar S., Gunasena H., Ye G., Haeberle H., Van Houten N., Gourley W. K., Ernst P. B., Reyes V. E. The effect of class II major histocompatibility complex expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: a mechanism for T helper cell type I-mediated damage. J. Exp. Med. 1998;187:1659–1669. [PMC free article: PMC2212295] [PubMed: 9584144]

108.

Fauchère J.-L., Blaser M. J. Adherence of Helicobacter pylori cells and their surface components to HeLa cell membranes. Microb. Pathog. 1990;9:427–439. [PubMed: 2097496]

109.

Fine K. D., Lee E. L. Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis. Gastroenterology. 1998;114:29–36. [PubMed: 9428215]

110.

Fox J. G., Dangler C. A., Taylor N. S., King A., Koh T. J., Wang T. C. High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res. 1999;59:4823–4828. [PubMed: 10519391]

111.

Foynes S., N., Dorrell, Ward S. J., Stabler R. A., McColm A. A., Rycroft A. N., Wren B. W. Helicobacter pylori possesses two CheY response regulators and a histidine kinase sensor, CheA, which are essential for chemotaxis and colonization of the gastric mucosa. Infect. Immun. 2000;68:2016–2023. [PMC free article: PMC97381] [PubMed: 10722597]

112.

Foynes S., N., Dorrell, Ward S. J., Zhang Z. W., McColm A. A., Farthing M. J. G., Wren B. W. Functional analysis of the roles of FliQ and FlhB in flagellar expression in Helicobacter pylori. FEMS Microbiol. Lett. 1999;174:33–39. [PubMed: 10234819]

113.

Fraser A. G., Scragg R., Metcalf P., McCullough S., Yeates N. J. Prevalence of Helicobacter pylori infection in different ethnic groups in New Zealand children and adults. Aust. N. Z. J. Med. 1996;26:646–651. [PubMed: 8958359]

114.

Fu S., Ramaanujam K. S., Wong A., Fantry G. T., Drachenberg C. B., James S. J., Meltzer S. J., Wilson K. T. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology. 1999;116:1319–1329. [PubMed: 10348815]

115.

Ganga-Zandzou P. S., Michaud L., Vincent P., Husson M. O., Wizla-Derambure N., Delassalle E. M., Turck D., Gottrand F. Natural outcome of Helicobacter pylori infection in asymptomatic children: a two-year follow-up study. Pediatrics. 1999;104:216–221. [PubMed: 10428997]

116.

Geis G., Suerbaum S., Forsthoff B., Leying H., Opferkuch W. Ultrastructure and biochemical studies of the flagellar sheath of Helicobacter pylori. J. Med. Microbiol. 1993;38:371–377. [PubMed: 8487294]

117.

Genta R. M., Gürer I. E., Graham D. Y., Krishnan B., Segura A. M., Gutierrez O., Kim J. G., Burchette, Jr J. L. Adherence of Helicobacter pylori to areas of incomplete intestinal metaplasia in the gastric mucosa. Gastroenterology. 1996;111:1206–1211. [PubMed: 8898634]

118.

Gerhard M., Lehn N., Neumayer N., Borén T., Rad R., Schepp W., Miehlke S., Classen M., Prinz C. Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc. Natl. Acad. Sci. USA. 1999;96:12778–12783. [PMC free article: PMC23096] [PubMed: 10535999]

119.

Ghiara P., Marchetti M., Blaser M. J., Tummuru M. K., Cover T. L., Segal E. D., Tompkins L. S., Rappuoli R. Role of the Helicobacter pylori virulence factors vacuolating cytotoxin, CagA, and urease in a mouse model of disease. Infect. Immun. 1995;63:4154–4160. [PMC free article: PMC173584] [PubMed: 7558333]

120.

Ghiara P., Rossi M., Marchetti M., Di Tommaso A., Vindigni C., Ciampolini F., Covacci A., Telford J. L., De Magistris M. T., Pizza M., Rappuoli R., Del Giudice G. Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection. Infect. Immun. 1997;65:4996–5002. [PMC free article: PMC175721] [PubMed: 9393788]

121.

Goh K. L. Prevalence of and risk factors for Helicobacter pylori infection in a multi-racial dyspeptic Malaysian population undergoing endoscopy. J. Gastroenterol. Hepatol. 1997;12:S29–S35. [PubMed: 9195409]

122.

Goh K. L., Parasakthi N., Ong K. K. Prevalence of Helicobacter pylori infection in endoscopy and non-endoscopy personnel: results of field survey with serology and 14C-urea breath test. Am. J. Gastroenterol. 1996;91:268–270. [PubMed: 8607491]

123.

Gold B. D., Dytoc M., Huesca M., Philpott D., Kuksis A., Czinn S., Lingwood C. A., Sherman P. M. Comparison of Helicobacter mustelae and Helicobacter pylori adhesion to eukaryotic cells in vitro. Gastroenterology. 1995;109:692–700. [PubMed: 7657097]

124.

Gold B. D., Huesca M., Sherman P. M., Lingwood C. A. Helicobacter mustelae and Helicobacter pylori bind to common lipid receptors in vitro. Infect. Immun. 1993;61:2632–2638. [PMC free article: PMC280894] [PubMed: 8500901]

125.

Goodwin C. S., Armstrong J. A., Marshall B. J. Campylobacter pyloridis, gastritis, and peptic ulceration. J. Clin. Pathol. 1986;39:353–365. [PMC free article: PMC499829] [PubMed: 3517070]

126.

Graham D. Y., Anderson S. Y., Lang T. Garlic or jalapeno peppers for treatment of Helicobacter pylori infection. Am. J. Gastroenterol. 1999;94:1200–1202. [PubMed: 10235193]

127.

Graham D. Y., Opekun A., Lew G. M., Evans, Jr D. J., Klein P. D., Evans D. G. Ablation of exaggerated meal-stimulated gastrin release in duodenal ulcer patients after clearance of Helicobacter (Campylobacter) pylori infection. Am. J. Gastroenterol. 1990;85:394–398. [PubMed: 2327380]

128.

Guruge J. L., Falk P. G., Lorenz R. G., Dans M., Wirth H.-P., Blaser M. J., Berg D. E., Gordon J. I. Epithelial attachment alters the outcome of Helicobacter pylori infection. Proc. Natl. Acad. Sci. USA. 1998;95:3925–3930. [PMC free article: PMC19939] [PubMed: 9520469]

129.

Hansen P. S., Go M. F., Varming K., Andersen L. P., Graham D. Y., Nielsen H. Proinflammatory activation of neutrophils and monocytes by Helicobacter pylori is not associated with cagA, vacA or picB genotypes. APMIS. 1999;107:1117–1123. [PubMed: 10660142]

130.

Hata Y., Kita T., Murakami M. Bovine milk inhibits both adhesion of Helicobacter pylori to sulfatide and Helicobacter pylori-induced vacuolation of Vero cells. Dig. Dis. Sci. 1999;44:1696–1702. [PubMed: 10492155]

131.

Hayashi S., Sugiyama T., Amano K.-I., Isogai H., Isogai E., Alhara M., Kikuchi M., Asaka M., Yokota K., Oguma K., Fugii N., Hirai Y. Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells. Antimicrob. Agents Chemother. 1998;42:1895–1899. [PMC free article: PMC105706] [PubMed: 9687380]

132.

Hayashi S., Sugiyama T., Asaka M., Yokota K., Oguma K., Hirai Y. Modification of Helicobacter pylori adhesion to human gastric epithelial cells by antiadhesion agents. Dig. Dis. Sci. 1998;43(Suppl.):56S–60S. [PubMed: 9753227]

133.

Hayashi S., Sugiyama T., Yachi A., Yokota K., Hirai Y., Oguma K., Fugii N. Effect of ecabet sodium on Helicobacter pylori adhesion to gastric epithelial cells. J. Gastroenterol. 1997;32:593–597. [PubMed: 9349983]

134.

Hazell S. L., Lee A., Brady L., Hennessy W. Campylobacter pyloridis and gastritis: association with intracellular spaces and adaptation to an environment of mucus as important factors in colonization of the gastric epithelium. J. Infect. Dis. 1986;153:658–663. [PubMed: 3950447]

135.

Hegarty J. P., Dowd M. T., Baker K. H. Occurrence of Helicobacter pylori in surface water in the United States. J. Appl. Microbiol. 1999;87:697–701. [PubMed: 10594710]

136.

Hemalatha S. G., Drumm B., Sherman P. Adherence of Helicobacter pylori to human gastric epithelial cells in vitro. J. Med. Microbiol. 1991;35:197–202. [PubMed: 1941988]

137.

Heneghan M. A., McCarthy C. F., Moran A. P. Relationship of blood group determinants on Helicobacter pylori lipopolysaccharide with host Lewis phenotype and inflammatory response. Infect. Immun. 2000;68:937–941. [PMC free article: PMC97226] [PubMed: 10639467]

138.

Henry S. M., Benny A. G., Woodfield D. G. Investigation of Lewis phenotypes in Polynesians: evidence of a weak secretor phenotype. Vox Sang. 1990;58:61–66. [PubMed: 2316213]

139.

Henry S. M., Woodfield D. G., Samuelsson B. E., Oriol R. Plasma and red-cell glycolipid patterns of Le(a + b +) and Le(a + b −) Polynesians as further evidence of the weak secretor gene Se(w). Vox Sang. 1993;65:62–69. [PubMed: 8362517]

140.

Hessey S. J., Spencer J., Wyatt J. I., Sobala G., Rathbone B. J., Axon A. T., Dixon M. F. Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis. Gut. 1990;31:134–138. [PMC free article: PMC1378366] [PubMed: 2311970]

141.

Hirmo S., Artursson E., Puu G., Wadström T., Nilsson B. Helicobacter pylori interactions with human gastric mucin studied with a resonant mirror biosensor. J. Microbiol. Methods. 1999;37:177–182. [PubMed: 10445316]

142.

Hirmo S., Kelm S., Iwersen M., Hotta K., Goso Y., Ishihara K., Suguri T., Morita M., Wadström T. Inhibition of Helicobacter pylori sialic acid-specific haemagglutination by human gastrointestinal mucins and milk glycoproteins. FEMS Immunol. Med. Microbiol. 1998;20:275–281. [PMC free article: PMC7135180] [PubMed: 9626932]

143.

Hirmo S., Kelm S., Wadström T., Schauer R. Lack of evidence for sialdase activity in Helicobacter pylori. FEMS Immunol. Med. Microbiol. 1997;17:67–72. [PubMed: 9061351]

144.

Hirmo S., Utt M., Ringner M., Wadström T. Inhibition of heparan sulphate and other glycosaminoglycans binding to Helicobacter pylori by various polysulphated carbohydrates. FEMS Immunol Med. Microbiol. 1995;10:301–306. [PubMed: 7539671]

145.

Hopkins R. J., Morris J. G., Papadimitriou J. C., Drachenberg C., Smoot D. T., James S. P., Panigrahi P. Loss of Helicobacter pylori hemagglutination with serial laboratory passage and correlation of hemagglutination with gastric epithelial cell adherence. Pathobiology. 1996;64:247–254. [PubMed: 9068007]

146.

Houghton J., Korah R. M., Condon M. R., Kim K. H. Apoptosis in Helicobacter pylori-associated gastric and duodenal ulcer disease is mediated via the Fas antigen pathway. Dig. Dis. Sci. 1999;44:465–473. [PubMed: 10080136]

147.

Huang J., Keeling P. W. N., Smith C. J. Identification of erythrocyte-binding antigens in Helicobacter pylori. J. Gen. Microbiol. 1992;138:1503–1513. [PubMed: 1512579]

148.

Huang J., O'Toole P. W., Doig P., Trust T. J. Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori. Infect. Immun. 1995;63:1732–1738. [PMC free article: PMC173217] [PubMed: 7729879]

149.

Huang J., Smyth C. J., Kennedy N. P., Arbuthnott J. P., Keeling P. W. N. Haemagglutinating activity of Campylobacter pylori. FEMS Microbiol. Lett. 1988;56:109–112.

150.

Huesca M., Borgia S., Hoffman P., Lingwood C. A. Acidic pH changes receptor binding specificity of Helicobacter pylori: a binary adhesion model in which surface heat shock (stress) proteins mediate sulfatide recognition in gastric colonization. Infect. Immun. 1996;64:2643–2648. [PMC free article: PMC174121] [PubMed: 8698490]

151.

Huesca M., Goodwin A., Bhagwansingh A., Hoffman P., Lingwood C. A. Characterization of an acidic-pH-inducible stress protein (hsp70), a putative sulfatide binding adhesin, from Helicobacter pylori. Infect. Immun. 1998;66:4061–4067. [PMC free article: PMC108486] [PubMed: 9712748]

152.

Hulten K., Han S. W., Enroth H., Klein P. D., Opekun A. R., Gilman R. H., Evans D. G., Engstrand L., Graham D. Y., El-Zaatari F. A. Helicobacter pylori in the drinking water in Peru. Gastroenterology. 1996;110:1031–1035. [PubMed: 8612990]

153.

Husson M. O., Legrand D., Spik G., Leclerc H. Iron acquisition by Helicobacter pylori: importance of human lactoferrin. Infect Immun. 1993;61:2694–2697. [PMC free article: PMC280902] [PubMed: 8500909]

154.

Ilver, D., A. Arnqvist, J. Ögren, and T. Borén. 1997. Adherence of Helicobacter pylori: mechanisms and relevance to pathogenesis, p. 16–27. In A. P. Moran and C. A. O'Morain (ed.), Pathogenesis and Host Response in Helicobacter pylori Infections. Normed Verlag, Englewood, N.J.

155.

Ilver D., Arnqvist A., Ögren J., Frick I.-M., Kersulyte D., Incecik E. T., Berg D. E., Covacci A., Engstrand L., Borén T. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998;279:373–377. [PubMed: 9430586]

156.

Isogai H., Isogai E., Hayashi S., Kimura K., Kubota T., Fujii N., Oguma K. Experimental Helicobacter pylori infection in association with other bacteria. Microbiol. Immunol. 1997;41:361–365. [PubMed: 9159411]

157.

Ito Y., Hongo A., Kinoshita M., Tamaki H. Mechanism of antiurease action by the anti-ulcer drug ecabet sodium. Biol. Pharm. Bull. 1995;18:850–853. [PubMed: 7550119]

158.

Ito Y., Shibata K., Hongo A., Kinoshita M. Ecabet sodium, a locally acting antiulcer drug, inhibits urease activity of Helicobacter pylori. Eur. J. Pharmacol. 1998;345:193–198. [PubMed: 9600637]

159.

Jack R. W., Tagg J. R., Ray B. Bacteriocins of gram-positive bacteria. Microbiol. Rev. 1995;59:171–200. [PMC free article: PMC239359] [PubMed: 7603408]

160.

Johansson L., Johansson P., Miller-Podraza H. Neu5Ac—3Gal is part of the Helicobacter pylori binding epitope in polyglycosylceramides of human erythrocytes. Eur. J. Biochem. 1999;266:559–565. [PubMed: 10561598]

161.

Johansson L., Karlsson K.-A. Selective binding by Helicobacter pylori of leucocyte gangliosides with 3-linked sialic acid, as identified by a new approach of linkage analysis. Glycoconj. J. 1998;15:713–721. [PubMed: 9881777]

162.

Jones A. C., Logan R. P. H., Foynes S., Cockayne A., Wren B. W., Penn C. W. A flagellar sheath protein of Helicobacter pylori is identical to HpaA, a putative N-acetyl-neuraminyllactose-binding hemagglutinin, but is not an adhesin for AGS cells. J. Bacteriol. 1997;179:5643–5647. [PMC free article: PMC179448] [PubMed: 9287032]

163.

Jones N. L., Day A. S., Jennings H. A., Sherman P. M. Helicobacter pylori induces gastric epithelial cell apoptosis in association with increased Fas receptor expression. Infect. Immun. 1999;67:4237–4242. [PMC free article: PMC96730] [PubMed: 10417197]

164.

Jonkers D., van den Broek E., van Dooren I., Thijs C., Dorant E., Hageman G., Stobberingh E. Antibacterial effect of garlic and omeprazole on Helicobacter pylori. J. Antimicrob. Chemother. 1999;43:837–839. [PubMed: 10404325]

165.

Jyonouchi H., Sun S., Mizokami M., Gross M. D. Effects of various carotenoids on cloned, effector-stage T-helper cell activity. Nutr. Cancer. 1996;26:313–324. [PubMed: 8910913]

166.

Kabir A. M. A., Aiba Y., Takagi A., Kamiya S., Miwa T., Koga Y. Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model. Gut. 1997;41:49–55. [PMC free article: PMC1027227] [PubMed: 9274471]

167.

Kamisago S., Iwamori M., Tai T., Mitamura K., Yazaki Y., Sugano K. Role of sulfatides in adhesion of Helicobacter pylori to gastric cancer cells. Infect. Immun. 1996;64:624–628. [PMC free article: PMC173811] [PubMed: 8550217]

168.

Kamiya S., Yamaguchi H., Osaki T., Taguchi H., Fukuda M., Kawakami H., Hirano H. Effect of an aluminum hydroxide-magnesium hydroxide combination drug on adhesion, IL-8 inducibility, and expression of Hsp60 by Helicobacter pylori. Scand. J. Gastroenterol. 1999;34:663–670. [PubMed: 10466876]

169.

Karita M., Li Q., Cantero D., Okita K. Establishment of a small animal model for human Helicobacter pylori infection using germ-free mouse. Am. J. Gastroenterol. 1994;89:208–213. [PubMed: 8304305]

170.

Kawano S., Tsujii M., Nagano K., Ogihara T., Tanimura H., Hayashi N., Ito T., Sato N., Kamada T., Tamura K., Tanaka M. Different effect of Helicobacter pylori on the human gastric antral and body mucosal intracellular mucin. Scand. J. Gastroenterol. 1990;25:997–1003. [PubMed: 1702231]

171.

Kelly S. M., Pitcher M. C., Farmery S. M., Gibson G. R. Isolation of Helicobacter pylori from feces of patients with dyspepsia in the United Kingdom. Gastroenterology. 1994;107:1671–1674. [PubMed: 7958677]

172.

Kinoshita M., Endo M., Yasoshima A., Saito N., Yamasaki K., Chishima S., Narita H. Ecabet sodium, a novel locally-acting anti-ulcer agent, protects the integrity of the gastric mucosal gel layer from pepsin-induced disruption in the rat. Aliment. Pharmacol. Ther. 1999;13:687–694. [PubMed: 10233194]

173.

Knutton S., Lloyd D. R., McNeish A. S. Adhesion of enteropathogenic E. coli to human intestinal epithelial enterocytes and cultured human intestinal mucosa. Infect. Immun. 1987;55:67–69. [PMC free article: PMC260281] [PubMed: 3539808]

174.

Kobayashi Y., Okazaki K.-I., Murakami K. Adhesion of Helicobacter pylori to gastric epithelial cells in primary cultures obtained from stomachs of various animals. Infect. Immun. 1993;61:4058–4063. [PMC free article: PMC281124] [PubMed: 7691743]

175.

Kohda K., Tanaka K., Aiba Y., Yasuda M., Miwa T., Koga Y. Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer. Gut. 1999;44:456–462. [PMC free article: PMC1727459] [PubMed: 10075950]

176.

Kono S., Hirohata T. Nutrition and stomach cancer. Cancer Causes Control. 1996;7:41–55. [PubMed: 8850434]

177.

Konturek J. W., Gillessen A., Konturek S. J., Domschke W. Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on postprandial gastrin release in duodenal ulcer patients. Gut. 1995;37:482–487. [PMC free article: PMC1382897] [PubMed: 7489932]

178.

Konturek P. C., Pierzchalski P., Konturek S. J., Meixner H., Faller G., Kirchner T., Hahn E. G. Helicobacter pylori induces apoptosis in gastric mucosa through an up regulation of Bax expression in humans. Scand. J. Gastroenterol. 1999;34:375–383. [PubMed: 10365897]

179.

Kostrzynska M., Betts J. D., Austin J. W., Trust T. J. Identification, characterization, and spatial localization of two flagellin species in Helicobacter pylori flagella. J. Bacteriol. 1991;173:937–946. [PMC free article: PMC207209] [PubMed: 1704004]

180.

Lambert J. R. Pharmacology of bismuth-containing compounds. Rev. Infect. Dis. 1991;13:S691–S695. [PubMed: 1925310]

181.

Lanciers S., Despinasse B., Mehta D. I., Blecker U. Increased susceptibility to Helicobacter pylori infection in pregnancy. Infect. Dis. Obstet. Gynecol. 1999;7:195–198. [PMC free article: PMC1784742] [PubMed: 10449268]

182.

Langton S. R., Cesareo S. D. Helicobacter pylori associated phospholipase A2 activity: a factor in peptic ulcer production? J. Clin. Pathol. 1992;45:221–224. [PMC free article: PMC495476] [PubMed: 1556229]

183.

Lee A., Dixon M. F., Danon S. J., Kuipers E., Megraud F., Larsson H., Mellgard B. Local acid production and Helicobacter pylori: a unifying hypothesis of gastroduodenal disease. Eur. J. Gastroenterol. 1995;7:461–465. [PubMed: 7614109]

184.

Lelwala-Guruge J., Ascencio F., Kreger A. S., Ljungh Å., Wadström T. Isolation of a sialic acid-specific surface haemagglutinin of Helicobacter pylori strain NCTC 11637. Zentralbl. Bakteriol. 1993;280:93–106. [PubMed: 7506596]

185.

Lelwala-Guruge J., Ascencio F., Ljungh Å., Wadström T. Rapid detection and characterization of sialic acid-specific lectings of Helicobacter pylori. APMIS. 1993;101:695–702. [PubMed: 7694599]

186.

Lelwala-Guruge J., Ljungh Å., Wadström T. Haemagglutination patterns of Helicobacter pylori. APMIS. 1992;100:908–913. [PubMed: 1445697]

187.

Leung W. K., Siu K. L., Kwok C. K., Chan S. Y., Sung R., Sung J. J. Isolation of Helicobacter pylori from vomitus in children and its implication in gastro-oral transmission. Am. J. Gastroenterol. 1999;94:2881–2884. [PubMed: 10520837]

188.

Leying H., Suerbaum S., Geis G., Haas R. Cloning and genetic characterization of Helicobacter pylori flagellin gene. Mol. Microbiol. 1992;6:2863–2874. [PubMed: 1435261]

189.

Li C., Ha T., Ferguson, Jr D. A., Chi D. S., Zhao R., Patel N. R., Krishnaswamy G., Thomas E. A newly developed PCR assay of H. pylori in gastric biopsy, saliva, and feces. Evidence of high prevalence of H. pylori in saliva supports oral transmission. Dig. Dis. Sci. 1996;41:2142–2149. [PubMed: 8943965]

190.

Li S. D., Kersulyte D., Lindley I. J. D., Neelam B., Berg D. E., Crabtree J. E. Multiple genes in the left half of the cag pathogenicity island of Helicobacter pylori are required for tyrosine kinase-dependent transcription of interleukin-8 in gastric epithelial cells. Infect. Immun. 1999;67:3893–3899. [PMC free article: PMC96669] [PubMed: 10417153]

191.

Lingwood C. A., Huesca M., Kuksis A. The glycerolipid receptor for Helicobacter pylori (and Exoenzyme S) is phosphatidylethanolamine. Infect. Immun. 1992;60:2470–2474. [PMC free article: PMC257183] [PubMed: 1587616]

192.

Lingwood C. A., Pellizzari A., Law H., Sherman P., Drumm B. Gastric glycerolipid as a receptor for Campylobacter pylori. Lancet. 1989;2:238–240. [PubMed: 2569053]

193.

Lingwood C. A., Wasfy G., Han H., Huesca M. Receptor affinity purification of a lipid-binding adhesin from Helicobacter pylori. Infect. Immun. 1993;61:2474–2478. [PMC free article: PMC280871] [PubMed: 8500882]

194.

Logan R. P. H., Robins A., Turner G. A., Cockayne A., Borriello S. P., Hawkey C. J. A novel flow cytometric assay for quantitating adherence of Helicobacter pylori to gastric epithelial cells. J. Immunol. Methods. 1998;213:19–30. [PubMed: 9671122]

195.

Luke C. J., Penn C. W. Identification of a 29 kDa flagellar sheath protein in Helicobacter pylori using a murine monoclonal antibody. Microbiology. 1995;141:597–604. [PubMed: 7711897]

196.

Macartney J. C. Lectin histochemistry of galactose and N-acetyl-galactosamine glycoconjugates in normal gastric mucosa and gastric cancer and the relationship with ABO and secretor status. J. Pathol. 1986;150:135–144. [PubMed: 3794866]

197.

Magnani J. L., Nilsson B., Brockhaus M., Zopf D., Steplewski Z., Koprowski H., Ginsburg V. A monoclonal antibody-defined antigen associated with gastrointestinal cancer in a ganglioside containing sialylated lacto-N-fuco-pentaose. J. Biol. Chem. 1982;257:14365–14369. [PubMed: 7142214]

198.

Mahalanabis D., Rahman M. M., Sarker S. A., Bardhan P. K., Hildebrand P., Beglinger C., Gyr K. Helicobacter pylori infection in the young in Bangladesh: prevalence, socioeconomic and nutritional aspects. Int. J. Epidemiol. 1996;25:894–898. [PubMed: 8921472]

199.

Mai U. E. H., Perez-Perez G. I., Wahl L. M., Wahl S. M., Blaser M. J., Smith P. D. Soluble surface proteins from Helicobacter pylori activate monocytes/macrophages by lipopolysaccharide-independent mechanism. J. Clin. Invest. 1991;87:894–900. [PMC free article: PMC329879] [PubMed: 1847939]

200.

Malaty H. M., Engstrand L., Pedersen N. L., Graham D. Y. Helicobacter pylori infection: genetic and environmental influences. A study of twins. Ann. Intern. Med. 1994;120:982–986. [PubMed: 8185146]

201.

Malaty H. M., Graham D. Y., Klein P. D., Evans D. G., Adam E., Evans D. J. Transmission of Helicobacter pylori infection. Studies in families of healthy individuals. Scand. J. Gastroenterol. 1991;26:927–932. [PubMed: 1947784]

202.

Manes G., Dominguez-Munoz J. E., Uomo G., Labenz J., Hackelsberger A., Malfertheiner P. Increased risk for Helicobacter pylori recurrence by continuous acid suppression: a randomized controlled study. Ital. J. Gastroenterol. Hepatol. 1998;30:28–33. [PubMed: 9615260]

203.

Mankoski R., Hoepf T., Krakowka S., Eaton K. A. flaA mRNA transcription level correlates with Helicobacter pylori colonisation efficiency in gnotobiotic piglets. J. Med. Microbiol. 1999;48:395–399. [PubMed: 10509483]

204.

Mannick E. E., Bravo L. E., Zarama G., Realpe J. L., Zhang X. J., Ruiz B., Fontham E. T., Mera R., Miller M. J., Correa P. Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res. 1996;56:3238–3243. [PubMed: 8764115]

205.

Mathai E., Arora A., Cafferkey M., Keane C. T., O'Morain C. The effect of bile acids on the growth and adherence of Helicobacter pylori. Aliment. Pharmacol. Ther. 1991;5:653–658. [PubMed: 1782308]

206.

Matysiak-Budnik T., Karkkainen P., Methuen T., Roine R. P., Salaspuro M. Inhibition of gastric cell proliferation by acetaldehyde. J. Pathol. 1995;177:317–322. [PubMed: 8551395]

207.

Matysiak-Budnik T., Megraud F. Epidemiology of Helicobacter pylori infection with special reference to professional risk. J. Physiol. Pharmacol. 1997;48(Suppl. 4):3–17. [PubMed: 9440051]

208.

McCarthy C. J., Crofford L. J., Greeneson J., Scheiman J. M. Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection. Am. J. Gastroenterol. 1999;94:1218–1223. [PubMed: 10235197]

209.

McColl, K. L. E., E. El-Omar, and D. Gillen. 1997. Helicobacter pylori-induced alterations in gastric acid secretion, p. 119–127. In A. P. Moran and C. A. O'Morain (ed.), Pathogenesis and Host Response in Helicobacter pylori Infections. Normed Verlag, Englewood, N.J.

210.

McGee D. J., Radcliff F. J., Mendz G. L., Ferrero R. L., Mobley H. L. Helicobacter pylori rocF is required for arginase activity and acid protection in vitro but is not essential for colonization of mice or for urease activity. J. Bacteriol. 1999;181:7314–7322. [PMC free article: PMC103695] [PubMed: 10572136]

211.

Mégraud F., Trimoulet P., Lamouliatte H., Boyanova L. Bactericidal effect of amoxicillin on Helicobacter pylori in an in vitro model using epithelial cells. Antimicrob. Agents Chemother. 1991;35:869–872. [PMC free article: PMC245121] [PubMed: 1854168]

212.

Mendz G. L., Hazell S. L. Amino acid utilization by Helicobacter pylori. Int. J. Biochem. Cell Biol. 1995;27:1085–1093. [PubMed: 7496998]

213.

Mentis A., Tzouvelekis L., Spiliadis C., Blackwell C. C., Weir D. M. Inhibition of Helicobacter pylori haemagglutination activity by human salivary mucins. FEMS Microbiol. Immunol. 1990;64:125–128. [PubMed: 2257167]

214.

Michetti P., Dorta G., Wiesel P. H., Brassart D., Verdu E., Herranz M., Felley C., Porta N., Rouvet M., Blum A. L., Corthesy-Theulaz I. Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans. Digestion. 1999;60:203–209. [PubMed: 10343133]

215.

Micots I., Augeron C., Laboisse C. L., Muzeau F., Mégraud F. Mucin exocytosis: a major target for Helicobacter pylori. J. Clin. Pathol. 1993;46:241–245. [PMC free article: PMC501178] [PubMed: 8463418]

216.

Miller-Podraza H., Bergström J., Milh M. A., Karlsson K.-A. Recognition of glycoconjugates by Helicobacter pylori. Comparison of two sialic acid-dependent specificities based on haemmagglutination and binding to human erythrocyte glycoconjugates. Glycoconj. J. 1997;14:467–471. [PubMed: 9249144]

217.

Miller-Podraza H., Bergström J., Teneberg S., Milh M. A., Longard M., Olsson B.-M., Uggla L., Karlsson K.-A. Helicobacter pylori and neutrophils: sialic-acid dependent binding to various isolated glycoconjugates. Infect. Immun. 1999;67:6309–6313. [PMC free article: PMC97034] [PubMed: 10569742]

218.

Miller-Podraza H., Milh M. A., Bergström J., Karlsson K.-A. Recognition of glycoconjugates by Helicobacter pylori: an apparently high-affinity binding of human polyglycosylceramides, a second sialic acid-based specificity. Glycoconj. J. 1996;13:453–460. [PubMed: 8781976]

219.

Mizoguchi H., Fujioka T., Kishi K., Nishizono A., Kodama R., Nasu M. Diversity in protein synthesis and viability of Helicobacter pylori coccoid forms in response to various stimuli. Infect. Immun. 1998;66:5555–5560. [PMC free article: PMC108699] [PubMed: 9784573]

220.

Mizoguchi H., Fujioka T., Nasu M. Evidence for viability of coccoid forms of Helicobacter pylori. J. Gastroenterol. 1999;34(Suppl. 11):32–36. [PubMed: 10616763]

221.

Mohammadi M., Nedrud J., Redline R., Lycke N., Czinn S. J. Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load. Gastroenterology. 1997;113:1848–1857. [PubMed: 9394724]

222.

Monteiro M. A., Chan K. H., Rasko D. A., Taylor D. E., Zheng P. Y., Appelmelk B. J., Wirth H.-P., Yang M., Blaser M. J., Hynes S. O., Moran A. P., Perry M. B. Simultaneous expression of type 1 and type 2 Lewis blood group antigens by Helicobacter pylori lipopolysaccharides. Molecular mimicry between H. pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. J. Biol. Chem. 1998;273:11533–11543. [PubMed: 9565568]

223.

Moran A. P., Kuusela P., Kosunen T. U. Interaction of Helicobacter pylori with extracellular matrix proteins. J. Appl. Bacteriol. 1993;57:187–189.

224.

Moss S. F. Helicobacter pylori and apoptosis. Yale J. Biol. Med. 1998;71:53–61. [PMC free article: PMC2578891] [PubMed: 10378350]

225.

Mysore J. V., Wigginton T., Simon P. M., Zopf D., Heman-Ackah L. M., Dubois A. Treatment of Helicobacter pylori infection in rhesus monkeys using a novel anti-adhesion compound. Gastroenterology. 1999;117:1316–1325. [PubMed: 10579973]

226.

Nakamura H., Yoshiyama H., Takeuchi H., Mizote T., Okita K., Nakazawa T. Urease plays an important role in the chemotactic motility of Helicobacter pylori in a viscous environment. Infect. Immun. 1998;66:4832–4837. [PMC free article: PMC108597] [PubMed: 9746586]

227.

Nakayama R., Kumagai H., Tochikura T. Leakage of glutathione from bacterial cells caused by inhibition of gamma-glutamyltranspeptidase. Appl. Environ. Microbiol. 1984;47:653–657. [PMC free article: PMC239743] [PubMed: 6144289]

228.

Nakazawa T., Ishibashi M., Konishi H., Takemoto T., Shigeeda M., Kochiyama T. Hemagglutinating activity of Campylobacter pylori. Infect. Immun. 1989;57:989–991. [PMC free article: PMC313210] [PubMed: 2917797]

229.

Namavar F., Sparrius M., Veerman E. C. I., Appelmelk B. J., Vandenbroucke-Grauls C. M. J. E. Neutrophil-activating protein mediates adhesion of Helicobacter pylori to sulfated carbohydrates on high-molecular-weight salivary mucin. Infect. Immun. 1998;66:444–447. [PMC free article: PMC107925] [PubMed: 9453593]

230.

Neman-Simha V., Mégraud F. In vitro model for Campylobacter pylori adherence properties. Infect. Immun. 1988;56:3329–3333. [PMC free article: PMC259747] [PubMed: 3182085]

231.

Nilius M., Bode G., Lehnhardt G., Malfertheiner P. In vitro inhibition of Helicobacter pylori urease: biochemical and ultrastructural analysis. Eur. J. Clin. Invest. 1991;21:551–557. [PubMed: 1752295]

232.

Nilius M., Malfertheiner P. Helicobacter pylori enzymes. Aliment. Pharmacol. Ther. 1996;10(Suppl. 1):65–71. [PubMed: 8730261]

233.

Nilsson H. O., Taneera J., Castedal M., Glatz E., Olsson R., Wadstrom T. Identification of Helicobacter pylori and other helicobacter species by PCR, hybridization, and partial DNA sequencing in human liver samples from patients with primary sclerosing cholangitis or primary biliary cirrhosis. J. Clin. Microbiol. 2000;38:1072–1076. [PMC free article: PMC86342] [PubMed: 10698999]

234.

Nishihara K., Nozawa Y., Nomura S., Kitazato K., Miyake H. Analysis of Helicobacter pylori binding site on HEp-2 cells and three cell lines from gastric carcinoma. Fundam. Clin. Pharmacol. 1999;13:555–561. [PubMed: 10520728]

235.

Noach L. A., Rolf T. M., Tytgat G. N. J. Electron microscopic study of association between Helicobacter pylori and gastric and duodenal mucosa. J. Clin. Pathol. 1994;47:699–704. [PMC free article: PMC502139] [PubMed: 7962619]

236.

Nordman H., Boren T., Davies J. R., Engstrand L., Carlstedt I. pH-dependent binding of Helicobacter pylori to pig gastric mucins. FEMS Immunol. Med. Microbiol. 1999;24:174–181. [PubMed: 10378417]

237.

Obst B., Wagner S., Sewing K. F., Beil W. Helicobacter pylori causes DNA damage in gastric epithelial cells. Carcinogenesis. 2000;21:1111–1115. [PubMed: 10836997]

238.

Odenbreit S., Püls J., Sedlmaier B., Gerland E., Fischer W., Haas R. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science. 2000;287:1497–1500. [PubMed: 10688800]

239.

Odenbreit S., Till M., Haas R. Optimized BlaM-transposon shuttle mutagenesis of Helicobacter pylori allows the identification of novel genetic loci involved in bacterial virulence. Mol. Microbiol. 1996;20:361–373. [PubMed: 8733234]

240.

Odenbreit S., Till M., Hofreuter D., Faller G., Haas R. Genetic and functional characterization of the alpAB gene locus essential for the adhesion of Helicobacter pylori to human gastric tissue. Mol. Microbiol. 1999;31:1537–1548. [PubMed: 10200971]

241.

Odenbreit S., Wieland B., Haas R. Cloning and genetic characterization of Helicobacter pylori catalase and construction of a catalase-deficient mutant strain. J. Bacteriol. 1996;178:6960–6967. [PMC free article: PMC178599] [PubMed: 8955320]

242.

O'Gara E. A., Hill D. J., Maslin D. J. Activities of garlic oil, garlic powder, and their diallyl constituents against Helicobacter pylori. Appl. Environ. Microbiol. 2000;66:2269–2273. [PMC free article: PMC101489] [PubMed: 10788416]

243.

Ohkusa T., Takashimizu I., Fujiki K., Araki A., Ariake K., Shimoi K., Honda K., Enomoto Y., Sakurazawa T., Horiuchi T., Suzuki S., Ishii K., Ishikura T. Prospective evaluation of a new anti-ulcer agent, ecabet sodium, for the treatment of Helicobacter pylori infection. Aliment. Pharmacol. Ther. 1998;12:457–461. [PubMed: 9663726]

244.

Osaki T., Yamagucki H., Taguchi H., Fukuda M., Kawakami H., Hirano H., Wantanabe S., Takagi A., Kamiya S. Establishment and characterisation of a monoclonal antibody to inhibit adhesion of Helicobacter pylori to gastric epithelial cells. J. Med. Microbiol. 1998;47:505–512. [PubMed: 9879969]

245.

Osaki T., Yamagucki H., Taguchi H., Fukuda M., Kumada J., Ogata S., Kamiya S. Studies on the relationship between adhesive activity and haemagglutination by Helicobacter pylori. J. Med. Microbiol. 1997;46:117–121. [PubMed: 9060870]

246.

O'Toole P. W., Janzon L., Doig P., Huang J., Kostrzynska M., Trust T. J. The putative neuraminyllactose-binding hemagglutinin HpaA of Helicobacter pylori CCUG 17874 is a lipoprotein. J. Bacteriol. 1995;177:6049–6057. [PMC free article: PMC177441] [PubMed: 7592366]

247.

Ottlecz A., Romero J. J., Hazell S. L., Graham D. Y., Lichtenberger L. M. Phospholipase activity of Helicobacter pylori and its inhibition by bismuth salts. Biochemical and biophysical studies. Dig. Dis. Sci. 1993;38:2071–2080. [PubMed: 8223083]

248.

Ottlecz A., Romero J. J., Lichtenberger L. M. Effect of ranitidine bismuth citrate on the phospholipase A2 activity of Naja naja venom and Helicobacter pylori: a biochemical analysis. Aliment. Pharmacol. Ther. 1999;13:875–881. [PubMed: 10383521]

249.

Paradies, H. H. 1990. Bismuth—from the element to the tablet: the general chemistry of bismuth with relevance to pharmacy and medicine, p. 409–426. In P. Malfertheiner and H. Ditsehuneit (ed.), Helicobacter pylori, Gastritis, and Peptic Ulcer. Springer-Verlag, New York, N.Y.

250.

Parsonnet J., Shmuely H., Haggerty T. Fecal and oral shedding of Helicobacter pylori from healthy infected adults. JAMA. 1999;282:2240–2245. [PubMed: 10605976]

251.

Pasquler M. C., Vatier J., Poitevin C., Vallot T., Mignon M. Assessment of mucus glycoprotein erosion by measurement of sialic acid in gastric secretions: pathophysiologic and therapeutic aspects. J. Clin. Gastroent. 1991;13(Suppl. 1):S22–S31. [PubMed: 1940193]

252.

Peach H. G., Bath N. E., Farish S. J. Helicobacter pylori infection: an added stressor on iron status of women in the community. Med. J. Aust. 1998;169:188–190. [PubMed: 9734575]

253.

Peck B., Ortkamp M., Diehl K. D., Hundt E., Knapp B. Conservation, localization and expression of HopZ, a protein involved in adhesion of Helicobacter pylori. Nucleic Acids Res. 1999;27:3325–3333. [PMC free article: PMC148566] [PubMed: 10454640]

254.

Petretti T., Schulze B., Schlag P. M., Kemmner W. Altered mRNA expression of glycosyltransferases in human gastric carcinomas. Biochim. Biophys. Acta. 1999;1428:209–218. [PubMed: 10434038]

255.

Piotrowski J., Czajkowski A., Yotsumoto F., Slomiany A., Slomiany B. L. Helicobacter pylori lipopolysaccharide inhibition of gastric mucosal laminin receptor: effect of sulglycotide. Gen. Pharmacol. 1993;24:1467–1472. [PubMed: 8112522]

256.

Piotrowski J., Majka J., Murty V. L. N., Czajkowski A., Slomiany A., Slomiany B. L. Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide: effect of sulglycotide. Gen. Pharmacol. 1994;25:969–976. [PubMed: 7835646]

257.

Piotrowski J., Slomainy A., Murty V. L. N., Fekete Z., Slomiany B. L. Inhibition of Helicobacter pylori colonization by sulfated gastric mucin. Biochem. Int. 1991;24:749–756. [PubMed: 1799374]

258.

Piotrowski J., Yamaki K., Slomiany A., Slomiany B. L. Inhibition of gastric mucosal laminin receptor by Helicobacter pylori lipopolysaccharide: effect of sucralfate. Am. J. Gastroenterol. 1991;86:1756–1760. [PubMed: 1835819]

259.

Ponzetto A., Pellicano R., Leone N., Cutufia M. A., Turrini F., Grigioni W. F., D'Errico A., Mortimer P., Rizzetto M., Silengo L. Helicobacter infection and cirrhosis in hepatitis C virus carriage: is it an innocent bystander or a troublemaker? Med. Hypotheses. 2000;54:275–277. [PubMed: 10790764]

260.

Pope A. J., Toseland C. D., Rushant B., Richardson S., McVey M., Hills J. Effect of potent urease inhibitor, fluorofamide, on Helicobacter sp. in vivo and in vitro. Dig. Dis. Sci. 1998;43:109–119. [PubMed: 9508511]

261.

Pruul H., Lee P. C., Goodwin C. S., McDonald P. J. Interaction of Campylobacter pyloridis with human immune defence mechanisms. J. Med. Microbiol. 1987;23:233–238. [PubMed: 3585959]

262.

Rasko D. A., Wilson T. J., Zopf D., Taylor D. E. Lewis antigen expression and stability in Helicobacter pylori isolated from serial gastric biopsies. J. Infect. Dis. 2000;181:1089–1095. [PubMed: 10720535]

263.

Rautelin H., Kihistrom E., Jurstrand M., Danielsson D. Adhesion to and invasion of HeLa cells by Helicobacter pylori. Int. J. Med. Microbiol. Virol. Parasitol. Infect. Dis. 1995;282:50–53. [PubMed: 7734829]

264.

Regev A., Fraser G. M., Braun M., Maoz E., Leibovici L., Niv Y. Seroprevalence of Helicobacter pylori and length of stay in a nursing home. Helicobacter. 1999;4:89–93. [PubMed: 10382121]

265.

Reina J., Alomar P. Campylobacter pylori's sensitivity to the bactericidal action of human serum. Enferm. Infecc. Microbiol. Clin. 1989;7:8–11. [PubMed: 2490652]

266.

Reinhard J., Basset C., Holton J., Binks M., Youinou P., Vaira D. Image analysis method to assess adhesion of Helicobacter pylori to gastric epithelium using confocal laser scanning microscopy. J. Microbiol. Meth. 2000;39:179–187. [PubMed: 10670764]

267.

Rieder G., Hatz R. A., Moran A. P., Walz A., Stolte M., Enders G. Role of adherence in interleukin-8 induction in Helicobacter pylori-associated gastritis. Infect. Immun. 1997;65:3622–3630. [PMC free article: PMC175515] [PubMed: 9284128]

268.

Ringnér M., Aleljung P., Wadström T. Adherence of haemagglutinating Helicobacter pylori to five cell lines. Zentralbl. Bakteriol. 1993;280:107–112. [PubMed: 8280930]

269.

Robinson J., Goodwin C. S., Cooper M., Burke V., Mee B. J. Soluble and cell-associated haemagglutinins of Helicobacter (Campylobacter) pylori. J. Med. Microbiol. 1990;33:277–284. [PubMed: 2258915]

270.

Roine R. P., Salmela K. S., Hook-Nikanne J., Kosunen T. U., Salaspuro M. Colloidal bismuth subcitrate and omeprazole inhibit alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori. Life Sci. 1992;51:L195–L200. [PubMed: 1435071]

271.

Romano M., Ricci V., Memoli A., Tuccillo C., Di Popolo A., Sommi P., Acquaviva A. M., Del Vecchio C. B., Bruni C. B., Zarrilli R. Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro. J. Biol. Chem. 1998;273:28560–28563. [PubMed: 9786845]

272.

Rosberg K., Berglingh T., Gustavsson S., Hübinette R., Rolfsen W. Adhesion of Helicobacter pylori to human gastric mucosal biopsy specimens cultivated in vitro. Scand. J. Gastroenterol. 1991;26:1179–1187. [PubMed: 1754854]

273.

Rudi J., Kuck D., Strand S., von Herbay A., Mariani S. M., Krammer P. H., Galle P. R., Stremmel W. Involvement of the CD95 (APO-1/Fas) receptor and ligand system, in Helicobacter pylori-induced gastric epithelial apoptosis. J. Clin. Invest. 1998;102:1506–1514. [PMC free article: PMC509000] [PubMed: 9788963]

274.

Rudmann D. G., Eaton K. A., Krakowka S. Ultrastructural study of Helicobacter pylori adherence properties in gnotobiotic piglets. Infect. Immun. 1992;60:2121–2124. [PMC free article: PMC257125] [PubMed: 1563801]

275.

Saitoh T., Natomi H., Zhao W., Okuzumi K., Sugano K., Iwamori M., Nagai Y. Identification of glycolipid receptors for Helicobacter pylori by TLC-immunostaining. FEBS Lett. 1991;282:385–387. [PubMed: 2037054]

276.

Sakamoto S., Watanabe T., Tokumaru T., Takagi H., Nakazoto H., Floyd K. O. Expression of Lewis^a, Lewis^b, Lewis^x, sialyl-Lewis^a, and sialyl-Lewis^x blood group antigens in human gastric carcinoma and in normal gastric tissue. Cancer Res. 1989;49:745–752. [PubMed: 2910493]

277.

Salaspuro M. Helicobacter pylori alcohol dehydrogenase. EXS. 1994;71:185–195. [PubMed: 8032149]

278.

Salmela K. S., Roine R. P., Hook-Nikanne J., Kosunen T. U., Salaspuro M. Acetaldehyde and ethanol production by Helicobacter pylori. Scand. J. Gastroenterol. 1994;29:309–312. [PubMed: 8047804]

279.

Sawaoka H., Kawano S., Tsuji S., Tsuiji M., Sun W., Gunawan E. S., Hori M. Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa. Prostaglandins Leukot. Essent. Fatty Acids. 1998;59:313–316. [PubMed: 9888205]

280.

Schorah C. J., Sobala G. M., Sanderson M., Collis N., Primrose J. N. Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis. Am. J. Clin. Nutr. 1991;53:287S–293S. [PubMed: 1985400]

281.

Schryvers A. B., Gonzalez G. C. Receptors for transferrin in pathogenic bacteria are specific for the host's protein. Can. J. Microbiol. 1990;36:145–147. [PubMed: 2110858]

282.

Schryvers A. B., Morris L. J. Identification and characterization of the human lactoferrin-binding protein from Neisseria meningitidis. Infect. Immun. 1988;56:1144–1149. [PMC free article: PMC259775] [PubMed: 3128478]

283.

Segal E. D., Cha J., Lo J., Falkow S., Tompkins L. S. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl. Acad. Sci. USA. 1999;96:14559–14564. [PMC free article: PMC24475] [PubMed: 10588744]

284.

Segal E. D., Falkow S., Tompkins L. S. Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc. Natl. Acad. Sci. USA. 1996;93:1259–1264. [PMC free article: PMC40067] [PubMed: 8577751]

285.

Segal E. D., Lange C., Covacci A., Tompkins L. S., Falkow S. Induction of host signal transduction pathways by Helicobacter pylori. Proc. Natl. Acad. Sci. USA. 1997;94:7595–7599. [PMC free article: PMC23867] [PubMed: 9207137]

286.

Segal E. D., Shon J., Tompkins L. S. Characterization of Helicobacter pylori urease mutants. Infect. Immun. 1992;60:1883–1889. [PMC free article: PMC257089] [PubMed: 1563778]

287.

Sekine H., Ohara S., Iijima K., Kato K. Recurrence rate of H. pylori after successful eradication and second eradication therapy after initial failure of treatment. Nippon Rinsho. 1999;57:116–120. [PubMed: 10036947]

288.

Shames B., Krajden S., Fuksa M., Babida C., Penner J. L. Evidence for the occurrence of the same strain of Campylobacter pylori in the stomach and dental plaque. J. Clin. Microbiol. 1989;12:2849–2850. [PMC free article: PMC267140] [PubMed: 2592545]

289.

Sharma S. A., Tummuru M. K., Miller G. G., Blaser M. J. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect. Immun. 1995;63:1681–1687. [PMC free article: PMC173210] [PubMed: 7729872]

290.

Shibata H., Kimura-Takagi I., Nagaoka M., Hashimoto S., Sawada H., Ueyama S., Yokokura T. Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells. J. Nutr. Sci. Vitaminol. 1999;45:325–336. [PubMed: 10524351]

291.

Shibata K., Ito Y., Hongo A., Yasoshima A., Endo T., Ohashi M. Bactericidal activity of a new antiulcer agent, ecabet sodium, against Helicobacter pylori under acidic conditions. Antimicrob. Agents Chemother. 1995;39:1295–1299. [PMC free article: PMC162730] [PubMed: 7574519]

292.

Shimoyama T., Fukuda Y., Fukuda S., Munakata A., Yoshida Y., Shimoyama T. Ecabet sodium eradicates Helicobacter pylori infection in gastric ulcer patients. J. Gastroenterol. 1996;31(Suppl. 9):59–62. [PubMed: 8959522]

293.

Sidebotham R. L., Batten J. J., Karim Q. N., Spencer J., Baron J. H. Breakdown of gastric mucus in presence of Helicobacter pylori. J. Clin. Pathol. 1991;44:52–57. [PMC free article: PMC497015] [PubMed: 1997534]

294.

Simon P. M., Goode P. L., Mobasseri A., Zopf D. Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides. Infect. Immun. 1997;65:750–757. [PMC free article: PMC176121] [PubMed: 9009338]

295.

Singh V. N., Gaby S. K. Premalignant lesions: role of antioxidant vitamins and beta-carotene in risk reduction and prevention of malignant transformation. Am. J. Clin. Nutr. 1991;53:386S–390S. [PubMed: 1985417]

296.

Sivam G. P., Lampe J. W., Ulness B., Swanzy S. R., Potter J. D. Helicobacter pylori—in vitro susceptibility to garlic (Allium sativum) extract. Nutr. Cancer. 1997;27:118–121. [PubMed: 9121937]

297.

Sjöstedt S. The upper gastrointestinal microflora in relation to gastric diseases and gastric surgery. Acta Chir. Scand. Suppl. 1989;551:1–57. [PubMed: 2741634]

298.

Skouloubris S., Labigne A., De Reuse H. Identification and characterization of an aliphatic amidase in Helicobacter pylori. Mol. Microbiol. 1997;25:989–998. [PubMed: 9364923]

299.

Slomiany B. L., Bilski J., Serosisk J., Murty V. L. N., Dworkin H., VanHorn K., Zielenski J., Slomiany A. Campylobacter pyloridis degrades mucin and undermines gastric mucosal integrity. Biochem. Biophys. Res. Commun. 1987;14:307–314. [PubMed: 3579908]

300.

Slomiany B. L., Murty V. L., Piotrowski J., Grabska M., Slomiany A. Glycosulfatase activity of H. pylori toward human gastric mucin: effect of sucralfate. Am. J. Gastroenterol. 1992;87:1132–1137. [PubMed: 1381553]

301.

Slomiany B. L., Murty V. L., Piotrowski J., Slomiany A. Gastroprotective agents in mucosal defense against Helicobacter pylori. Gen. Pharmacol. 1994;25:833–841. [PubMed: 7835626]

302.

Slomiany B. L., Piotrowski J., Samanta A., Van Horn K., Murty V. L. N., Slomiany A. Campylobacter pylori colonization factor shows specificity for lactosylceramide sulfate and GM3 ganglioside. Biochem. Int. 1989;19:929–936. [PubMed: 2619758]

303.

Slomiany B. L., Piotrowski J., Sengupts S., Slomiany A. Inhibition of gastric mucosal laminin receptor by Helicobacter pylori lipopolysaccharide. Biochem. Biophys. Res. Commun. 1991;175:963–970. [PubMed: 1827258]

304.

Slomiany B. L., Piotrowski J., Slomiany A. Effect of sucralfate on the degradation of human gastric mucus by Helicobacter pylori protease and lipases. Am. J. Gastroenterol. 1992;87:595–599. [PubMed: 1595646]

305.

Slomiany B. L., Piotrowski J., Slomiany A. Effect of sucralfate on gastric mucosal inflammatory responses induced by Helicobacter pylori lipopolysaccharide. Scand. J. Gastroenterol. 1998;33:916–922. [PubMed: 9759945]

306.

Slomiany B. L., Piotrowski J., Slomiany A. Induction of caspase-3 and nitric oxide synthase-2 during gastric mucosal inflammatory reaction to Helicobacter pylori lipopolysaccharide. Biochem. Mol. Biol. Int. 1998;46:1063–1070. [PubMed: 9861460]

307.

Slomiany B. L., Piotrowski J., Slomiany A. Gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide: down-regulation of nitric oxide synthase-2 and caspase-3 by sulglycotide. Biochem. Biophys. Res. Commun. 1999;261:15–20. [PubMed: 10405316]

308.

Slomiany B. L., Piotrowski J., Slomiany A. Involvement of endothelin-1 in up-regulation of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide. Biochem. Biophys. Res. Commun. 1999;258:17–20. [PubMed: 10222227]

309.

Slomiany B. L., Piotrowski J., Slomiany A. Suppression of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide by sulglycopeptide. Gen. Pharmacol. 1999;32:251–257. [PubMed: 10188628]

310.

Smoot D. T., Resau J. H., Naab T., Desborges B. C., Gilliam T., Henry K. B., Curry S. B., Nidiry J., Sewchand J., Mills-Robertson K., Frontin K., Abebe E., Dillon M., Chippendale G. R., Phelps P. C., Scott V. F., Mobley H. L. T. Adherence of Helicobacter pylori to cultured human gastric epithelial cells. Infect. Immun. 1993;61:350–355. [PMC free article: PMC302729] [PubMed: 8418061]

311.

Snepar R., Poporad G. A., Romano J. M., Kobasa W. D., Kaye D. Effect of cimetidine and antacid on gastric microbial flora. Infect. Immun. 1982;36:518–524. [PMC free article: PMC351258] [PubMed: 7085070]

312.

Spiegelhalder C., Gerstenecker B., Kersten A., Schlitz E., Kist M. Purification of Helicobacter pylori superoxide dismutase and sequencing of the gene. Infect. Immun. 1993;61:5315–5325. [PMC free article: PMC281317] [PubMed: 8225605]

313.

Stein M., Rappuoli R., Covacci A. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc. Natl. Acad. Sci. USA. 2000;97:1263–1268. [PMC free article: PMC15590] [PubMed: 10655519]

314.

Stratton C. W., Warner R. R., Coudron P. E., Lilly N. A. Bismuth-mediated disruption of the glycocalyx-cell wall of Helicobacter pylori: ultrastructural evidence for a mechanism of action for bismuth salts. J. Antimicrob. Chemother. 1999;43:659–666. [PubMed: 10382887]

315.

Stromqvist M., Falk P., Bergstrom S., Hansson L., Lonnerdal B., Normark S., Hernell O. Human milk-casein and inhibition of Helicobacter pylori adhesion to human gastric mucosa. J. Pediatr. Gastroenterol. 1995;21:288–296. [PubMed: 8523212]

316.

Su B., Hellström P. M., Rubio C., Çelik J., Granström M., Normark S. Type I Helicobacter pylori shows Lewis^b-independent adherence to gastric cells requiring de novo protein synthesis in both host and bacteria. J. Infect. Dis. 1998;178:1379–1390. [PubMed: 9780259]

317.

Su B., Johansson S., Fällman M., Patarroyo M., Granström M., Normark S. Signal transduction-mediated adherence and entry of Helicobacter pylori into cultured cells. Gastroenterology. 1999;117:595–604. [PubMed: 10464135]

318.

Suerbaum S., Josenhans C., Labigne A. Cloning and genetic characterization of the Helicobacter pylori and Helicobacter mustelae flaB flagellin genes and construction of H. pylori flaA- and flaB-negative mutants by electroporation-mediated allelic exchange. J. Bacteriol. 1993;175:3278–3288. [PMC free article: PMC204724] [PubMed: 8501031]

319.

Sunairi M., Watanabe K., Suzuki T., Tanaka N., Kuwayama H., Nakajima M. Effects of anti-ulcer agents on antibiotic activity against Helicobacter pylori. Eur. J. Gastroenterol. Hepatol. 1994;6:S121–S124. [PubMed: 7735928]

320.

Suzuki M., Mori M., Fukumura D., Suzuki H., Miura S., Ishii H. Omeprazole attenuates neutrophil-endothelial cell adhesive interaction induced by extracts of Helicobacter pylori. J. Gastroenterol. Hepatol. 1999;14:27–31. [PubMed: 10029274]

321.

Syder A. J., Guruge J. L., Li Q., Hu Y., Oleksiewicz C. M., Lorenz R. G., Karam S. M., Falk P. G., Gordon J. I. Helicobacter pylori attaches to NeuAc__2,3Gal__1,4glycoconjugates produced in the stomach of transgenic mice lacking parietal cells. Mol. Cell. 1999;3:263–274. [PubMed: 10198629]

322.

Takahashi S., Igarashi H., Nakamura K., Masubuchi N., Saito S., Aoyagi T., Itoh T., Hirata I. Helicobacter pylori and urease activity—comparative study between urease positive and negative mutant strains. Nippon Rinsho. 1993;51:3149–3153. [PubMed: 8283623]

323.

Tanaka T., Morishita Y., Suzui M., Kojima T., Okumura A., Mori H. Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. Carcinogenesis. 1994;15:15–19. [PubMed: 8293542]

324.

Taylor D. E., Rasko D. A., Sherburne R., Ho C., Jewell L. D. Lack of correlation between Lewis antigen expression by Helicobacter pylori and gastric epithelial cells in infected patients. Gastroenterology. 1998;115:1113–1122. [PubMed: 9797366]

325.

Taylor N. S., Hasubski A. T., Fox J. G., Lee A. Haemagglutination profiles of Helicobacter species that cause gastritis in man and animals. J. Med. Microbiol. 1992;37:299–303. [PubMed: 1279175]

326.

Teichmann R. K., Andress H. J., Leibich H., Seifert J., Brendel W. Possible role of la-positive cells in the antrum in gastrin secretion. Eur. Surg. Res. 1984;16:64–65.

327.

Teneberg S., Miller-Podraza H., Lampert H. C., Evans D. J., Evans D. G., Danielsson D., Karlsson K. A. Carbohydrate binding specificity of the neutrophil-activating protein of Helicobacter pylori. J. Biol. Chem. 1997;272:19067–19071. [PubMed: 9228091]

328.

Thomas J. E., Dale A., Harding M., Coward W. A., Cole T. J., Weaver L. T. Helicobacter pylori colonization in early life. Pediatr. Res. 1999;45:218–223. [PubMed: 10022593]

329.

Thomas J. E., Gibson G. R., Darboe M. K., Dale A., Weaver L. T. Isolation of Helicobacter pylori from human faeces. Lancet. 1992;340:1194–1195. [PubMed: 1359263]

330.

Thomsen L. L., Gavin J. B., Tasman-Jones C. Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum. Gut. 1990;31:1230–1236. [PMC free article: PMC1378690] [PubMed: 2253904]

331.

Tindberg Y., Blennow M., Granstrom M. Clinical symptoms and social factors in a cohort of children spontaneously clearing Helicobacter pylori infection. Acta Paediatr. 1999;88:631–635. [PubMed: 10419247]

332.

Tomb J.-F. O. White, Kerlavage A. R., Clayton R. A., Sutton G. G., Fleischmann R. D., Ketchum K. A., Klenk H. P., Gill S., Dougherty B. A., Nelson K., Quackenbush J., Zhou L., Kirkness E. F., Peterson S., Loftus B., Richardson D., Dodson R., Khalak H. G., Glodek A., McKenney K., Fitzgerald L. M., Lee N., Adams M. D., Hickey E. K., Berg D. E., Gocayne J. D., Utterback T. R., Peterson J. D., Kelley J. M., Cotton M. D., Weidman J. M., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W. S., Borodovsky M., Karp P. D., Smith H. O., Fraser C. M., Venter J. C. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997;388:539–547. [PubMed: 9252185]

333.

Tricottet V., Bruneval P., Vire O., Camilleri J. P. Campylobacter-like organisms and surface epithelium abnormalities in active, chronic gastritis in humans: an ultrastructural study. Ultrastruct. Pathol. 1986;10:113–122. [PubMed: 3961927]

334.

Trust T. J., Doig P., Emödy L., Kienle Z., Wadström T., O'Toole P. High-affinity binding of the basement membrane proteins collagen Type IV and laminin to the gastric pathogen Helicobacter pylori. Infect. Immun. 1991;59:4398–4404. [PMC free article: PMC259055] [PubMed: 1937798]

335.

Tsuda M., Karita M., Morshed M. G., Okita K., Nakazawa T. A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach. Infect. Immun. 1994;62:3586–3589. [PMC free article: PMC303000] [PubMed: 8039935]

336.

Tsugane S., Tei Y., Takahashi T., Watanabe S., Sugano K. Salty food intake and risk of Helicobacter pylori infection. Jpn. J. Cancer Res. 1994;85:474–478. [PMC free article: PMC5919501] [PubMed: 8014104]

337.

Tummuru M. K., Cover T. L., Blaser M. J. Cloning and expression of a high-molecular-mass antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect. Immun. 1993;61:1799–1809. [PMC free article: PMC280768] [PubMed: 8478069]

338.

Tummuru M. K., Cover T. L., Blaser M. J. Mutation of the cytotoxin-associated cagA gene does not affect vacuolating cytotoxin activity of Helicobacter pylori. Infect. Immun. 1994;62:2609–2613. [PMC free article: PMC186552] [PubMed: 8188385]

339.

Tummuru M. K., Sharma S. A., Blaser M. J. Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secreted protein, is required for induction of IL-8 in gastric epithelial cells. Mol. Microbiol. 1995;18:867–876. [PubMed: 8825091]

340.

Tzouvelekis L. S., Mentis A. F., Makris A. M., Spiliadis C., Blackwell C., Weir D. M. In vitro binding of Helicobacter pylori to human gastric mucin. Infect. Immun. 1991;59:4252–4254. [PMC free article: PMC259024] [PubMed: 1937781]

341.

Valkonen K. H., Ringner M., Ljungh Å., Wadström T. High-affinity binding of laminin by Helicobacter pylori: evidence for a lectin-like interaction. FEMS Immunol. Med. Microbiol. 1993;7:29–38. [PubMed: 8364520]

342.

Valkonen K. H., Wadström T., Moran A. P. Interaction of lipopolysaccharides of Helicobacter pylori with basement membrane protein laminin. Infect. Immun. 1994;62:3640–3648. [PMC free article: PMC303013] [PubMed: 8063380]

343.

Valkonen K. H., Wadström T., Moran A. P. Identification of the N-acetylneuraminyllactose-specific laminin-binding protein of Helicobacter pylori. Infect. Immun. 1997;65:916–923. [PMC free article: PMC175069] [PubMed: 9038297]

344.

Vandenbergh P. A. Lactic acid bacteria, their metabolic products and interference with microbial growth. FEMS Microbiol. Rev. 1993;12:221–238.

345.

Van den Brink G. R., Tytgat K. M., Van der Hulst R. W., Van der Loos C. M., Einerhand A. W., Buller H. A., Dekker J. H. pylori colocalises with MUC5AC in the human stomach. Gut. 2000;46:601–607. [PMC free article: PMC1727935] [PubMed: 10764701]

346.

Van Doorn N. E., Namavar F., Sparrius M., Stoof J., van Rees E. P., van Doorn L. J., Vandenbroucke-Grauls C. M. Helicobacter pylori-associated gastritis in mice is host and strain specific. Infect. Immun. 1999;67:3040–3046. [PMC free article: PMC96618] [PubMed: 10338517]

347.

Varis K., Taylor P. R., Sipponen P., Samloff I. M., Heinonen O. P., Albanes D., Harkonen M., Huttunen J. K., Laxen F., Virtamo J. Gastric cancer and premalignant lesions in atrophic gastritis: a controlled trial on the effect of supplementation with alpha-tocopherol and beta-carotene. The Helsinki Gastritis Study Group. Scand. J. Gastroenterol. 1998;33:294–300. [PubMed: 9548624]

348.

Vatier J., Poitevin C., Mignon M. Sialic acid content and proteolytic activity in gastric juice in humans. An approach for appreciating mucus glycoprotein erosion. Dig. Dis. Sci. 1988;33:144–151. [PubMed: 3123182]

349.

Vazquez-Torres A., Jones-Carson J., Baumler A. J., Falkow S., Valdivia R., Brown W., Le M., Berggren R., Parks W. T., Fang F. C. Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature. 1999;401:804–808. [PubMed: 10548107]

350.

Veerman E. C., Bank C. M., Namavar F., Appelmelk B. J., Bolscher J. G., Nieuw Amerongen A. V. Sulfated glycans on oral mucin as receptors for Helicobacter pylori. Glycobiology. 1997;7:737–743. [PubMed: 9376676]

351.

Wahlfors J., Meurman J. H., Toskala J., Korhonen A., Alakuijala P., Janatuinen E., Karkkkainen U. M., Nuutinen P., Janne J. Development of a rapid PCR method for identification of Helicobacter pylori in dental plaque and gastric biopsy specimens. Eur. J. Clin. Microbiol. Infect. Dis. 1995;14:780–786. [PubMed: 8536726]

352.

Watanabe H., Takahashi T., Okamoto T., Ogundigie P. O., Ito A. Effects of sodium chloride and ethanol on stomach tumorigenesis in ACI rats treated with N-methyl-N′-nitro-N-nitrosoguanidine: a quantitative morphometric approach. Jpn. J. Cancer Res. 1992;83:588–593. [PMC free article: PMC5918881] [PubMed: 1644663]

353.

Weigert N., Schaffer K., Schusdziarra V., Classen M., Schepp W. Gastrin secretion from primary cultures of rabbit antral G cells: stimulation by inflammatory cytokines. Gastroenterology. 1996;110:147–154. [PubMed: 8536851]

354.

Werther J. L. The gastric mucosal barrier. Mt. Sinai J. Med. 2000;67:41–53. [PubMed: 10677782]

355.

Wilkinson S. M., Uhl J. R., Kline B. C., Cockerill III F. R. Assessment of invasion frequencies of cultured Hep-2 cells by clinical isolates of Helicobacter pylori using an acridine orange assay. J. Clin. Pathol. 1998;51:127–133. [PMC free article: PMC500507] [PubMed: 9602686]

356.

Williams C. L., Preston T., Hossack M., Slater C., McColl K. E. Helicobacter pylori utilises urea for amino acid synthesis. FEMS Immunol. Med. Microbiol. 1996;13:87–94. [PubMed: 8821403]

357.

Willis P., Lynch D. A., Prescott R., Lamonby S. Cell proliferation in the post-surgical stomach, dietary salt, and the effect of H. pylori eradication. J. Clin. Pathol. 1999;52:665–669. [PMC free article: PMC501541] [PubMed: 10655987]

358.

Wilson K. T., Ramanujam K. S., Mobley H. L. T., Musselman R. F., James S. P., Meltzer S. J. Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line. Gastroenterology. 1996;111:1524–1533. [PubMed: 8942731]

359.

Windle H. J., Fox A., Ni Eidhin D., Kelleher D. The thioredoxin system of Helicobacter pylori. J. Biol. Chem. 2000;275:5081–5090. [PubMed: 10671551]

360.

Worku M. L., Sidebotham R. L., Karim Q. N. Effects of ranitidine bismuth citrate on Helicobacter pylori motility, morphology and survival. Aliment. Pharmacol. Ther. 1999;13:753–760. [PubMed: 10383504]

361.

Wyle F. A., Tarnawski A., Dabros W., Gergely H. Campylobacter pylori interactions with gastric cell tissue culture. J. Clin. Gastroenterol. 1990;12:S99–S103. [PubMed: 2212557]

362.

Wyle F. A., Tarnawski A., Schulman D., Dabros W. Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study. J. Clin. Gastroenterol. 1990;12:S92–S98. [PubMed: 2212556]

363.

Xiang Z., Censini S., Bayeli P. F., Telford J. L., Figura N., Rappuoli R., Covacci A. Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect. Immun. 1995;63:94–98. [PMC free article: PMC172962] [PubMed: 7806390]

364.

Yamaguchi H., Osaki T., Kurihara N., Taguchi H., Hanawa T., Yamamoto T., Kamiya S. Heat-shock protein 60 homologue of Helicobacter pylori is associated with adhesion of H. pylori to human gastric epithelial cells. J. Med. Microbiol. 1997;46:825–831. [PubMed: 9364138]

365.

Yamaguchi H., Osaki T., Taguchi H., Hanawa T., Yamamoto T., Kamiya S. Flow cytometric analysis of the heat shock protein 60 expressed on the cell surface of Helicobacter pylori. J. Med. Microbiol. 1996;45:270–277. [PubMed: 8849701]

366.

Yamaguchi H., Osaki T., Taguchi H., Hanawa T., Yamamoto T., Kamiya S. Induction and epitope analysis of Helicobacter pylori heat shock protein. J. Gastroenterol. 1996;31(Suppl. 9):12–15. [PubMed: 8959511]

367.

Yamaguchi H., Osaki T., Taguchi H., Hanawa T., Yamamoto T., Kamiya S. Relationship between expression of HSP60, urease activity, production of vacuolating cytotoxin, and adherence activity of Helicobacter pylori. J. Gastroenterol. 1998;33(Suppl. 10):6–9. [PubMed: 9840008]

368.

Yamamoto-Osaki T., Yamaguchi H., Taguchi H., Ogata S., Kamiya S. Adherence of Helicobacter pylori to cultured human gastric carcinoma cells. Eur. J. Gastroenterol. Hepatol. 1995;7:S89–S92. [PubMed: 8574746]

369.

Yoshiyama H., Nakamura H., Kimoto M., Okita K., Nakazawa T. Chemotaxis and motility of Helicobacter pylori in a viscous environment. J. Gastroenterol. 1999;34(Suppl. 11):18–23. [PubMed: 10616760]

370.

Yoshiyama H., Nakamura H., Okamoto T., Okita K., Nakazawa T. A novel in vitro effect of the mucosal protective agent sofalcone—inhibition of chemotactic motility in Helicobacter pylori. Aliment. Pharmacol. Ther. 2000;14(Suppl. 1):230–236. [PubMed: 10807429]

371.

Yoshiyama H., Nakazawa T. Unique mechanism of Helicobacter pylori for colonizing the gastric mucus. Microbes Infect. 2000;2:55–60. [PubMed: 10717541]

372.

You W. C., Zhang L., Gail M. H., Ma J. L., Chang Y. S., Blot W. J., Li J. Y., Zhao C. L., Liu W. D., Li H. Q., Hu Y. R., Bravo J. C., Correa P., Xu G. W., Fraumeni, Jr J. F. Helicobacter pylori infection, garlic intake and pre-cancerous lesions in a Chinese population at low risk of gastric cancer. Int. J. Epidemiol. 1998;27:941–944. [PubMed: 10024185]

373.

Zhang H. M., Wakisaka N., Maeda O., Yamamoto T. Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori. Cancer. 1997;80:1897–1903. [PubMed: 9366290]