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|year=2004
|year=2004
|author=Atwood IV KC
|author=Atwood IV KC
|accessdate=2008-08-02}}</ref> To demonstrate that ''H. pylori'' caused gastritis and was not merely a bystander, Marshall drank a beaker of ''H. pylori''. He became ill several days later with nausea and vomiting. An [[endoscopy]] ten days after inoculation revealed signs of gastritis and the presence of ''H. pylori''. These results proved that ''H. pylori'' was the causative agent of gastritis. Marshall and Warren went on to show that antibiotics are effective in the treatment of many cases of gastritis. In 1987 the Sydney [[Gastroenterology|gastroenterologist]] [[Thomas Borody]] invented the first triple therapy for the treatment of duodenal ulcers.<ref name=Borody_1989>{{cite journal
|accessdate=2008-08-02}}</ref> To demonstrate that ''H. pylori'' caused gastritis and was not merely a bystander, Marshall drank a beaker of ''H. pylori''. He became ill several days later with nausea and vomiting. An [[endoscopy]] ten days after inoculation revealed signs of gastritis and the presence of ''H. pylori''. These results suggested that ''H. pylori'' was the causative agent of gastritis. Marshall and Warren went on to show that antibiotics are effective in the treatment of many cases of gastritis. In 1987 the Sydney [[Gastroenterology|gastroenterologist]] [[Thomas Borody]] invented the first triple therapy for the treatment of duodenal ulcers.<ref name=Borody_1989>{{cite journal
|author=Borody TJ, Cole P, Noonan S, ''et al''
|author=Borody TJ, Cole P, Noonan S, ''et al''
|title=Recurrence of duodenal ulcer and ''Campylobacter pylori'' infection after eradication
|title=Recurrence of duodenal ulcer and ''Campylobacter pylori'' infection after eradication

Revision as of 06:51, 14 April 2009

Helicobacter pylori
Scientific classification
Kingdom:
Bacteria
Phylum:
Proteobacteria
Class:
Epsilon Proteobacteria
Order:
Campylobacterales
Family:
Helicobacteraceae
Genus:
Helicobacter
Species:
H. pylori
Binomial name
Helicobacter pylori
Helicobacter pylori

Helicobacter pylori (Template:Pron-en) is a Gram-negative, microaerophilic bacterium that inhabits various areas of the stomach and duodenum. It causes a chronic low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric ulcers and stomach cancer. Over 80% of individuals infected with the bacterium are asymptomatic.

The bacterium was initially named Campylobacter pyloridis, then renamed C. pylori to correct a Latin grammar error. When 16S rRNA gene sequencing and other research showed in 1989 that the bacterium did not belong in the genus Campylobacter, it was placed in its own genus, Helicobacter. The genus derived from the Ancient Greek hělix/έλιξ "spiral" or "coil".[1] The specific epithet pylōri means "of the pylorus" or pyloric valve (the circular opening leading from the stomach into the duodenum), from the Ancient Greek word πυλωρός, which means gatekeeper.[1]

More than 50% of the world's population harbour H. pylori in their upper gastrointestinal tract. Infection is more prevalent in developing countries. The route of transmission is unknown, although individuals become infected in childhood. H. pylori's helix shape (from which the generic name is derived) is thought to have evolved to penetrate the mucoid lining of the stomach.[2][3]

Microbiology

Scanning electron micrograph of H. pylori

H. pylori is a helix-shaped Gram-negative bacterium, about 3 micrometres long with a diameter of about 0.5 micrometres. It is microaerophilic; it requires oxygen although at lower concentration than is found in the atmosphere. It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) that is produced by intestinal bacteria.[4] It produces oxidase, catalase, and urease. It is capable of forming biofilms[5] and can convert from spiral to a possibly viable but nonculturable coccoid form,[6] both likely to favor its survival and be factors in the epidemiology of the bacterium. The coccoid form can adhere to gastric epithelial cells in vitro.[7]

H. pylori possesses five major outer membrane protein (OMP) families.[8] The largest family includes known and putative adhesins. The other four families include porins, iron transporters, flagellum-associated proteins, and proteins of unknown function. Like other typical Gram-negative bacteria, the outer membrane of H. pylori consists of phospholipids and lipopolysaccharide (LPS). The O antigen of LPS may be fucosylated and mimic Lewis blood group antigens found on the gastric epithelium.[8] The outer membrane also contains cholesterol glucosides, which is found in few other bacteria.[8] H. pylori has 4–6 flagella; all gastric and enterohepatic Helicobacter species are highly motile due to flagella.[9] The characteristic sheathed flagellar filaments of helicobacters are composed of two copolymerized flagellins, FlaA and FlaB.[10]

Genome

H. pylori consists of a large diversity of strains, and the genomes of three have been completely sequenced.[11][12][13][14][15] The genome of the strain "26695" consists of about 1.7 million base pairs, with some 1,550 genes. The two sequenced strains show large genetic differences, with up to 6% of the nucleotides differing.[13]

Study of the H. pylori genome is centered on attempts to understand pathogenesis, the ability of this organism to cause disease. Approximately 29% of the loci are in the "pathogenesis" category of the genome database. Both sequenced strains have an approximately 40 kb-long Cag pathogenicity island (a common gene sequence believed responsible for pathogenesis) that contains over 40 genes. This pathogenicity island is usually absent from H. pylori strains isolated from humans who are carriers of H. pylori but remain asymptomatic.[16]

The cagA gene codes for one of the major H. pylori virulence proteins. Bacterial strains that have the cagA gene are associated with an ability to cause ulcers.[17] The cagA gene codes for a relatively long (1186 amino acid) protein. The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IV secretion system. The low GC content of the cag PAI relative to the rest of the helicobacter genome suggests that the island was acquired by horizontal transfer from another bacterial species.[11]

Pathophysiology

Molecular model of H. pylori urease enzyme

To colonize the stomach H. pylori must survive the acidic pH of the lumen and burrow into the mucus to reach its niche, close to the stomach's epithelial cell layer. The bacterium has flagella and moves through the stomach lumen and drills into the mucoid lining of the stomach.[18] Many bacteria can be found deep in the mucus, which is continuously secreted by mucous cells and removed on the luminal side. To avoid being carried into the lumen, H. pylori senses the pH gradient within the mucus layer by chemotaxis and swims away from the acidic contents of the lumen towards the more neutral pH environment of the epithelial cell surface.[19] H. pylori is also found on the inner surface of the stomach epithelial cells and occasionally inside epithelial cells.[20] It produces adhesins which bind to membrane-associated lipids and carbohydrates and help it adhere to epithelial cells. For example, the adhesin BabA binds to the Lewis b antigen displayed on the surface of stomach epithelial cells.[21] H. pylori produces large amounts of the enzyme urease, molecules of which are localized inside and outside of the bacterium. Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia (which neutralizes gastric acid). The survival of H. pylori in the acidic stomach is dependent on urease, and it would eventually die without the enzyme. The ammonia that is produced is toxic to the epithelial cells, and, along with the other products of H. pylori—including protease, vacuolating cytotoxin A (VacA), and certain phospholipases—damages those cells.[22]

Colonization of the stomach by H. pylori results in chronic gastritis, an inflammation of the stomach lining. The severity of the inflammation is likely to underlie H. pylori-related diseases.[23] Duodenal and stomach ulcers result when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm the mechanisms that protect the stomach and duodenal mucosa from these caustic substances. The type of ulcer that develops depends on the location of chronic gastritis, which occurs at the site of H. pylori colonization.[24] The acidity within the stomach lumen affects the colonization pattern of H. pylori and therefore ultimately determines whether a duodenal or gastric ulcer will form. In people producing large amounts of acid, H. pylori colonizes the antrum of the stomach to avoid the acid-secreting parietal cells located in the corpus (main body) of the stomach.[8] The inflammatory response to the bacteria induces G cells in the antrum to secrete the hormone gastrin, which travels through the bloodstream to the corpus.[25] Gastrin stimulates the parietal cells in the corpus to secrete even more acid into the stomach lumen. Chronically increased gastrin levels eventually cause the number of parietal cells to also increase, further escalating the amount of acid secreted.[26] The increased acid load damages the duodenum, and ulceration may eventually result. In contrast, gastric ulcers are often associated with normal or reduced gastric acid production, suggesting that the mechanisms that protect the gastric mucosa are defective.[26] In these patients H. pylori can also colonize the corpus of the stomach, where the acid-secreting parietal cells are located. However chronic inflammation induced by the bacteria causes further reduction of acid production and, eventually, atrophy of the stomach lining, which may lead to gastric ulcer and increases the risk for stomach cancer.[27]

About 50-70% of H. pylori strains in Western countries carry the cag pathogenicity island (cag PAI).[28] Western patients infected with strains carrying the cag PAI have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island.[8] Following attachment of H. pylori to stomach epithelial cells the type IV secretion system expressed by the cag PAI "injects" the inflammatory inducing agent peptidoglycan from their own cell wall into the epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic immune sensor Nod1, which then stimulates expression of cytokines that promote inflammation.[29]

The type IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach's epithelial cells, where it disrupts the cytoskeleton, adherence to adjacent cells, intracellular signaling, and other cellular activities.[30] Once inside the cell the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase. Pathogenic strains of H. pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a tyrosine kinase domain. Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis. It has also been suggested that a c-terminal region of the CagA protein (amino acids 873–1002) can regulate host cell gene transcription independent of protein tyrosine phosphorylation.[16][17]

Two related mechanisms by which H. pylori could promote cancer are under investigation. One mechanism involves the enhanced production of free radicals near H. pylori and an increased rate of host cell mutation. The other proposed mechanism has been called a "perigenetic pathway"[31] and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins such as adhesion proteins. It has been proposed that H. pylori induces inflammation and locally high levels of TNF-α and/or interleukin 6. According to the proposed perigenetic mechanism, inflammation-associated signaling molecules such as TNF-α can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes such as genes that code for cell adhesion proteins.[32]

Diagnosis

H. pylori colonized on the surface of regenerative epithelium (image from Warthin-Starry's silver stain)

Diagnosis of infection is usually made by checking for dyspeptic symptoms and by tests which can indicate H. pylori infection. One can test noninvasively for H. pylori infection with a blood antibody test, stool antigen test, or with the carbon urea breath test (in which the patient drinks 14C- or 13C-labelled urea, which the bacterium metabolizes, producing labelled carbon dioxide that can be detected in the breath).[33] However, the most reliable method for detecting H. pylori infection is a biopsy check during endoscopy with a rapid urease test, histological examination, and microbial culture. None of the test methods is completely failsafe. Even biopsy is dependent on the location of the biopsy. Blood antibody tests, for example, range from 76% to 84% sensitivity. Some drugs can affect H. pylori urease activity and give false negatives with the urea-based tests.[34]

Prevention

H. pylori is a major cause of diseases of the upper gastrointestinal tract. Eradication of the infection in individuals will improve symptoms including dyspepsia, gastritis and peptic ulcers, and may prevent gastric cancer. Rising antimicrobial resistance increases the need for a prevention strategy for the bacteria.[35] There have been extensive vaccine studies in mouse models, which have shown promising results.[36] Researchers are studying different adjuvants, antigens, and routes of immunization to ascertain the most appropriate system of immune protection, with most of the research only recently moving from animal to human trials.[37]

An intramuscular vaccine against H. pylori infection is undergoing Phase I clinical trials and has shown an antibody response against the bacterium. Its clinical usefulness requires further study.[38]

Treatment

Once H. pylori is detected in patients with a peptic ulcer, the normal procedure is to eradicate it and allow the ulcer to heal. The standard first-line therapy is a one week triple therapy consisting of the antibiotics amoxicillin and clarithromycin, and a proton pump inhibitor such as omeprazole.[39] Variations of the triple therapy have been developed over the years, such as using a different proton pump inhibitor, as with pantoprazole or rabeprazole, or replacing amoxicillin with metronidazole for people who are allergic to penicillin.[40] Such a therapy has revolutionized the treatment of peptic ulcers and has made a cure to the disease possible; previously the only option was symptom control using antacids, H2-antagonists or proton pump inhibitors alone.[41][42]

An increasing number of infected individuals are found to harbour antibiotic-resistant bacteria. This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies such as a quadruple therapy, which adds a bismuth colloid.[43][44][45] For the treatment of clarithromycin-resistant strains of H. pylori the use of levofloxacin as part of the therapy has been suggested.[46][47]

Prognosis

H. pylori colonizes the stomach and induces chronic gastritis, a long-lasting inflammation of the stomach. The bacterium persists in the stomach for decades in most people. Most individuals infected by H. pylori will never experience clinical symptoms despite having chronic gastritis. Approximately 10-20% of those colonized by H. pylori will ultimately develop gastric and duodenal ulcers.[8] H. pylori infection is also associated with a 1-2% lifetime risk of stomach cancer and a less than 1% risk of gastric MALT lymphoma.[8]

It is widely believed that in the absence of treatment, H. pylori infection—once established in its gastric niche—persists for life.[3] In the elderly, however, it is likely infection can disappear as the stomach's mucosa becomes increasingly atrophic and inhospitable to colonization. The proportion of acute infections that persist is not known, but several studies that followed the natural history in populations have reported apparent spontaneous elimination.[48][49]

While H. pylori has been disappearing from the stomach of humans, the incidence of the related disorders acid reflux disease, Barrett's esophagus, and esophageal cancer have been rising dramatically.[50] In 1996, Martin J. Blaser advanced the hypothesis that H. pylori has a beneficial effect: by regulating the acidity of the stomach contents, it lowers the impact of regurgitation of gastric acid into the esophagus.[50][25] The hypothesis is not universally accepted as several randomized controlled trials failed to demonstrate worsening of acid reflux disease symptoms following eradication of H. pylori.[51][52] Nevertheless, Blaser has refined his view to assert that H. pylori is a member of the normal flora of the stomach.[53] He postulates that the changes in gastric physiology caused by the loss of H. pylori account for the recent increase in incidence of several diseases, including type 2 diabetes, obesity, and asthma.[53][54] His group has recently shown that H. pylori colonization is associated with a lower incidence of childhood asthma.[55]

Epidemiology

At least half the world's population are infected by the bacterium, making it the most widespread infection in the world.[56] Actual infection rates vary from nation to nation; the Third World has much higher infection rates than the West (Western Europe, North America, Australasia), where rates are estimated to be around 25%.[56] Infections are usually acquired in early childhood in all countries.[8] However, the infection rate of children in developing nations is higher than in industrialized nations, probably due to poor sanitary conditions. In developed nations it is currently uncommon to find infected children, but the percentage of infected people increases with age, with about 50% infected for those over the age of 60 compared with around 10% between 18 and 30 years.[56] The higher prevalence among the elderly reflects higher infection rates when they were children rather than infection at later ages.[8] Prevalence appears to be higher in African-American and Hispanic populations, although this is likely related to socioeconomic rather than racial factors.[57][58] The lower rate of infection in the West is largely attributed to higher hygiene standards and widespread use of antibiotics. Despite high rates of infection in certain areas of the world, the overall frequency of H. pylori infection is declining.[59] However, antibiotic resistance is appearing in H. pylori; there are already many metronidazole- and clarithromycin-resistant strains in most parts of the world.[60]

H. pylori is contagious, although the exact route of transmission is not known.[61][62] Person-to-person transmission by either the oral-oral or fecal-oral route is most likely.[3] Consistent with these transmission routes, the bacteria have been isolated from feces, saliva and dental plaque of some infected people.[3] Transmission occurs mainly within families in developed nations yet can also be acquired from the community in developing countries.[63] H. pylori may also be transmitted orally by means of fecal matter through the ingestion of waste-tainted water, so a hygienic environment could help decrease the risk of H. pylori infection.[3]

History

See also: Timeline of peptic ulcer disease and Helicobacter pylori

German scientists found spiral-shaped bacteria in the lining of the human stomach in 1875, but they were unable to culture it and the results were eventually forgotten.[50] The Italian researcher Giulio Bizzozero described similarly shaped bacteria living in the acidic environment of the stomach of dogs in 1893.[64] Professor Walery Jaworski of the Jagiellonian University in Kraków investigated sediments of gastric washings obtained from humans in 1899. Among some rod-like bacteria, he also found bacteria with a characteristic spiral shape, which he called Vibrio rugula. He was the first to suggest a possible role of this organism in the pathogenesis of gastric diseases. This work was included in the Handbook of Gastric Diseases, but it had little impact as it was written in Polish.[65] Several small studies conducted in the early 1900s demonstrated the presence of curved rods in the stomach of many patients with peptic ulcers and stomach cancer.[66] However interest in the bacteria waned when an American study published in 1954 failed to observe the bacteria in 1180 stomach biopsies.[67]

Interest in understanding the role of bacteria in stomach diseases was rekindled in the 1970s with the visualization of bacteria in the stomach of gastric ulcer patients.[68] The bacterium had also been observed in 1979 by Australian pathologist Robin Warren, who did further research on it with Australian physician Barry Marshall beginning in 1981. After numerous unsuccessful attempts at culturing the bacteria from the stomach, they finally succeeded in visualizing colonies in 1982 when they unintentionally left their Petri dishes incubating for 5 days over the Easter weekend. In their original paper, Warren and Marshall contended that most stomach ulcers and gastritis were caused by infection by this bacterium and not by stress or spicy food as had been assumed before.[69]

Although there was some skepticism initially, within several years, numerous research groups verified the association of H. pylori with gastritis and to a lesser extent ulcers.[70] To demonstrate that H. pylori caused gastritis and was not merely a bystander, Marshall drank a beaker of H. pylori. He became ill several days later with nausea and vomiting. An endoscopy ten days after inoculation revealed signs of gastritis and the presence of H. pylori. These results suggested that H. pylori was the causative agent of gastritis. Marshall and Warren went on to show that antibiotics are effective in the treatment of many cases of gastritis. In 1987 the Sydney gastroenterologist Thomas Borody invented the first triple therapy for the treatment of duodenal ulcers.[71] In 1994, the National Institutes of Health (USA) published an opinion stating that most recurrent duodenal and gastric ulcers were caused by H. pylori and recommended that antibiotics be included in the treatment regimen.[72] Warren and Marshall were awarded the Nobel Prize in Medicine in 2005 for their work on H. pylori.[73]

Recent research states that genetic diversity in H. pylori decreases with geographic distance from East Africa, the birthplace of modern humans. Using the genetic diversity data, the researchers have created simulations that indicate the bacteria seems to have spread from East Africa around 58,000 years ago. Their results indicate modern humans were already infected by H. pylori before their migrations out of Africa, remaining associated with human hosts since that time.[74]

References

  1. ^ a b Liddell HG and Scott R (1966). A Lexicon: Abridged from Liddell and Scott's Greek-English Lexicon. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-910207-4.
  2. ^ Yamaoka, Yoshio (2008). Helicobacter pylori: Molecular Genetics and Cellular Biology. Caister Academic Pr. ISBN 1-904455-31-X.
  3. ^ a b c d e Brown LM (2000). "Helicobacter pylori: epidemiology and routes of transmission". Epidemiol Rev. 22 (2): 283–97. PMID 11218379.
  4. ^ Olson JW, Maier RJ (2002). "Molecular hydrogen as an energy source for Helicobacter pylori". Science. 298 (5599): 1788–90. doi:10.1126/science.1077123. PMID 12459589. {{cite journal}}: Unknown parameter |month= ignored (help)
  5. ^ Stark RM, Gerwig GJ, Pitman RS; et al. (1999). "Biofilm formation by Helicobacter pylori". Lett Appl Microbiol. 28 (2): 121–6. PMID 10063642. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Chan WY, Hui PK, Leung KM, Chow J, Kwok F, Ng CS (1994). "Coccoid forms of Helicobacter pylori in the human stomach". Am J Clin Pathol. 102 (4): 503–7. PMID 7524304. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Liu ZF, Chen CY, Tang W, Zhang JY, Gong YQ, Jia JH (2006). "Gene-expression profiles in gastric epithelial cells stimulated with spiral and coccoid Helicobacter pylori". J Med Microbiol. 55 (Pt 8): 1009–15. doi:10.1099/jmm.0.46456-0. PMID 16849720. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ a b c d e f g h i Kusters JG, van Vliet AH, Kuipers EJ (2006). "Pathogenesis of Helicobacter pylori infection". Clin Microbiol Rev. 19 (3): 449–90. doi:10.1128/CMR.00054-05. PMC 1539101. PMID 16847081. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Josenhans C, Eaton KA, Thevenot T, Suerbaum S (2000). "Switching of flagellar motility in Helicobacter pylori by reversible length variation of a short homopolymeric sequence repeat in fliP, a gene encoding a basal body protein". Infect Immun. 68 (8): 4598–603. PMC 98385. PMID 10899861. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Rust M, Schweinitzer T, Josenhans C (2008). "Helicobacter Flagella, Motility and Chemotaxis". In Yamaoka Y (ed.). Helicobacter pylori: Molecular Genetics and Cellular Biology. Caister Academic Press. ISBN 1-904455-31-X. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)CS1 maint: multiple names: authors list (link)
  11. ^ a b Tomb JF, White O, Kerlavage AR; et al. (1997). "The complete genome sequence of the gastric pathogen Helicobacter pylori". Nature. 388 (6642): 539–47. doi:10.1038/41483. PMID 9252185. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ "Genome information for the H. pylori 26695 and J99 strains". Institut Pasteur. 2002. Retrieved 2008-09-01.
  13. ^ a b "Helicobacter pylori 26695, complete genome". National Center for Biotechnology Information. Retrieved 2008-09-01.
  14. ^ "Helicobacter pylori J99, complete genome". National Center for Biotechnology Information. Retrieved 2008-09-01.
  15. ^ Oh JD, Kling-Bäckhed H, Giannakis M; et al. (2006). "The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: evolution during disease progression". Proc Natl Acad Sci U.S.A. 103 (26): 9999–10004. doi:10.1073/pnas.0603784103. PMC 1480403. PMID 16788065. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ a b Baldwin DN, Shepherd B, Kraemer P; et al. (2007). "Identification of Helicobacter pylori genes that contribute to stomach colonization". Infect Immun. 75 (2): 1005–16. doi:10.1128/IAI.01176-06. PMC 1828534. PMID 17101654. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ a b Broutet N, Marais A, Lamouliatte H; et al. (2001). "cagA Status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia". J Clin Microbiol. 39 (4): 1319–22. doi:10.1128/JCM.39.4.1319-1322.2001. PMC 87932. PMID 11283049. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ Ottemann KM, Lowenthal AC (2002). "Helicobacter pylori uses motility for initial colonization and to attain robust infection". Infect. Immun. 70 (4): 1984–90. PMC 127824. PMID 11895962. {{cite journal}}: Unknown parameter |month= ignored (help)
  19. ^ Schreiber S, Konradt M, Groll C; et al. (2004). "The spatial orientation of Helicobacter pylori in the gastric mucus". Proc. Natl. Acad. Sci. U.S.A. 101 (14): 5024–9. doi:10.1073/pnas.0308386101. PMC 387367. PMID 15044704. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Petersen AM, Krogfelt KA (2003). "Helicobacter pylori: an invading microorganism? A review". FEMS Immunol. Med. Microbiol. 36 (3): 117–26. PMID 12738380. {{cite journal}}: Unknown parameter |month= ignored (help)
  21. ^ Ilver D, Arnqvist A, Ogren J; et al. (1998). "Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging". Science (journal). 279 (5349): 373–7. PMID 9430586. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Smoot DT (1997). "How does Helicobacter pylori cause mucosal damage? Direct mechanisms". Gastroenterology. 113 (6 Suppl): S31–4, discussion S50. PMID 9394757. {{cite journal}}: Unknown parameter |month= ignored (help)
  23. ^ Shiotani A, Graham DY (2002). "Pathogenesis and therapy of gastric and duodenal ulcer disease". Med. Clin. North Am. 86 (6): 1447–66, viii. PMID 12510460. {{cite journal}}: Unknown parameter |month= ignored (help)
  24. ^ Dixon MF (2000). "Patterns of inflammation linked to ulcer disease". Baillieres Best Pract Res Clin Gastroenterol. 14 (1): 27–40. PMID 10749087. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ a b Blaser MJ, Atherton JC (2004). "Helicobacter pylori persistence: biology and disease". J. Clin. Invest. 113 (3): 321–33. doi:10.1172/JCI20925. PMC 324548. PMID 14755326. {{cite journal}}: Unknown parameter |month= ignored (help)
  26. ^ a b Schubert ML, Peura DA (2008). "Control of gastric acid secretion in health and disease". Gastroenterology. 134 (7): 1842–60. doi:10.1053/j.gastro.2008.05.021. PMID 18474247. {{cite journal}}: Unknown parameter |month= ignored (help)
  27. ^ Suerbaum S, Michetti P (2002). "Helicobacter pylori infection". N. Engl. J. Med. 347 (15): 1175–86. doi:10.1056/NEJMra020542. PMID 12374879. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ Peek RM, Crabtree JE (2006). "Helicobacter infection and gastric neoplasia". J. Pathol. 208 (2): 233–48. doi:10.1002/path.1868. PMID 16362989. {{cite journal}}: Unknown parameter |month= ignored (help)
  29. ^ Viala J, Chaput C, Boneca IG; et al. (2004). "Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island". Nat. Immunol. 5 (11): 1166–74. doi:10.1038/ni1131. PMID 15489856. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ Backert S, Selbach M (2008). "Role of type IV secretion in Helicobacter pylori pathogenesis". Cell. Microbiol. 10 (8): 1573–81. doi:10.1111/j.1462-5822.2008.01156.x. PMID 18410539. {{cite journal}}: Unknown parameter |month= ignored (help)
  31. ^ Tsuji S, Kawai N, Tsujii M, Kawano S, Hori M (2003). "Review article: inflammation-related promotion of gastrointestinal carcinogenesis--a perigenetic pathway". Aliment. Pharmacol. Ther. 18 Suppl 1: 82–9. PMID 12925144. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Suganuma M, Yamaguchi K, Ono Y; et al. (2008). "TNF-α-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells". Int. J. Cancer. 123 (1): 117–22. doi:10.1002/ijc.23484. PMID 18412243. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ Stenström B, Mendis A, Marshall B (2008). "Helicobacter pylori - The latest in diagnosis and treatment". Aust Fam Physician. 37 (8): 608–12. PMID 18704207. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Logan RP, Walker MM (2001). "ABC of the upper gastrointestinal tract: Epidemiology and diagnosis of Helicobacter pylori infection". BMJ. 323 (7318): 920–2. PMC 1121445. PMID 11668141. {{cite journal}}: Unknown parameter |month= ignored (help)
  35. ^ Selgrad M, Malfertheiner P (2008). "New strategies for Helicobacter pylori eradication". Curr Opin Pharmacol. doi:10.1016/j.coph.2008.04.010. PMID 18555746. {{cite journal}}: Unknown parameter |month= ignored (help)
  36. ^ Hoffelner H, Rieder G, Haas R (2008). "Helicobacter pylori vaccine development: optimisation of strategies and importance of challenging strain and animal model". Int. J. Med. Microbiol. 298 (1–2): 151–9. doi:10.1016/j.ijmm.2007.07.006. PMID 17714988. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  37. ^ Kabir S (2007). "The current status of Helicobacter pylori vaccines: a review". Helicobacter. 12 (2): 89–102. doi:10.1111/j.1523-5378.2007.00478.x. PMID 17309745. {{cite journal}}: Unknown parameter |month= ignored (help)
  38. ^ Malfertheiner P, Schultze V, Rosenkranz B; et al. (2008). "Safety and Immunogenicity of an Intramuscular Helicobacter pylori Vaccine in Noninfected Volunteers: A Phase I Study". Gastroenterology. doi:10.1053/j.gastro.2008.05.054. PMID 18619971. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  39. ^ Mirbagheri SA, Hasibi M, Abouzari M, Rashidi A (2006). "Triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H. pylori eradication: a comparative three-armed randomized clinical trial". World J. Gastroenterol. 12 (30): 4888–91. PMID 16937475. Retrieved 2008-09-02. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  40. ^ Malfertheiner P, Megraud F, O'Morain C; et al. (2007). "Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report". Gut. 56 (6): 772–81. doi:10.1136/gut.2006.101634. PMID 17170018. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  41. ^ Rauws EA, Tytgat GN (1990). "Cure of duodenal ulcer associated with eradication of Helicobacter pylori". Lancet. 335 (8700): 1233–5. PMID 1971318. {{cite journal}}: Unknown parameter |month= ignored (help)
  42. ^ Graham DY, Lew GM, Evans DG, Evans DJ, Klein PD (1991). "Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing. A randomized controlled trial". Ann. Intern. Med. 115 (4): 266–9. PMID 1854110. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  43. ^ Stenström B, Mendis A, Marshall B (2008). "Helicobacter pylori - The latest in diagnosis and treatment". Aust Fam Physician. 37 (8): 608–12. PMID 18704207. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  44. ^ Fischbach L, Evans EL (2007). "Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori". Aliment. Pharmacol. Ther. 26 (3): 343–57. doi:10.1111/j.1365-2036.2007.03386.x. PMID 17635369. {{cite journal}}: Unknown parameter |month= ignored (help)
  45. ^ Graham DY, Shiotani A (2008). "New concepts of resistance in the treatment of Helicobacter pylori infections". Nat Clin Pract Gastroenterol Hepatol. 5 (6): 321–31. doi:10.1038/ncpgasthep1138. PMID 18446147. {{cite journal}}: Unknown parameter |month= ignored (help)
  46. ^ Perna F, Zullo A, Ricci C, Hassan C, Morini S, Vaira D (2007). "Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance". Dig Liver Dis. 39 (11): 1001–5. doi:10.1016/j.dld.2007.06.016. PMID 17889627. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ Hsu PI, Wu DC, Chen A; et al. (2008). "Quadruple rescue therapy for Helicobacter pylori infection after two treatment failures". Eur. J. Clin. Invest. 38 (6): 404–9. doi:10.1111/j.1365-2362.2008.01951.x. PMID 18435764. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  48. ^ Goodman KJ, O'rourke K, Day RS; et al. (2005). "Dynamics of Helicobacter pylori infection in a US-Mexico cohort during the first two years of life". Int J Epidemiol. 34 (6): 1348–55. doi:10.1093/ije/dyi152. PMID 16076858. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  49. ^ Goodman KJ, Cockburn M (2001). "The role of epidemiology in understanding the health effects of Helicobacter pylori". Epidemiology. 12 (2): 266–71. PMID 11246592. {{cite journal}}: Unknown parameter |month= ignored (help)
  50. ^ a b c Blaser MJ (2005). "An endangered species in the stomach". Sci. Am. 292 (2): 38–45. PMID 15715390. {{cite journal}}: Unknown parameter |month= ignored (help)
  51. ^ Graham DY, Yamaoka Y, Malaty HM (2007). "Contemplating the future without Helicobacter pylori and the dire consequences hypothesis". Helicobacter. 12 Suppl 2: 64–8. doi:10.1111/j.1523-5378.2007.00566.x. PMID 17991179. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  52. ^ Delaney B, McColl K (2005). "Review article: Helicobacter pylori and gastro-oesophageal reflux disease". Aliment. Pharmacol. Ther. 22 Suppl 1: 32–40. doi:10.1111/j.1365-2036.2005.02607.x. PMID 16042657. {{cite journal}}: Unknown parameter |month= ignored (help)
  53. ^ a b Blaser MJ (2006). "Who are we? Indigenous microbes and the ecology of human diseases". EMBO reports. 7 (10): 956–60. doi:10.1038/sj.embor.7400812. PMC 1618379. PMID 17016449. {{cite journal}}: Unknown parameter |month= ignored (help)
  54. ^ Blaser MJ, Chen Y, Reibman J (2008). "Does Helicobacter pylori protect against asthma and allergy?". Gut. 57 (5): 561–7. doi:10.1136/gut.2007.133462. PMID 18194986. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  55. ^ Chen Y, Blaser MJ (2008). "Helicobacter pylori colonization is inversely associated with childhood asthma". J. Infect. Dis. 198 (4): 553–60. doi:10.1086/590158. PMID 18598192. {{cite journal}}: Unknown parameter |month= ignored (help)
  56. ^ a b c Pounder RE, Ng D (1995). "The prevalence of Helicobacter pylori infection in different countries". Aliment. Pharmacol. Ther. 9 Suppl 2: 33–9. PMID 8547526.
  57. ^ Smoak BL, Kelley PW, Taylor DN (1994). "Seroprevalence of Helicobacter pylori infections in a cohort of US Army recruits". Am. J. Epidemiol. 139 (5): 513–9. PMID 8154475. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  58. ^ Everhart JE, Kruszon-Moran D, Perez-Perez GI, Tralka TS, McQuillan G (2000). "Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States". J. Infect. Dis. 181 (4): 1359–63. PMID 10762567. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  59. ^ Malaty HM (2007). "Epidemiology of Helicobacter pylori infection". Best Pract Res Clin Gastroenterol. 21 (2): 205–14. doi:10.1016/j.bpg.2006.10.005. PMID 17382273.
  60. ^ Mégraud F (2004). "H pylori antibiotic resistance: prevalence, importance, and advances in testing". Gut. 53 (9): 1374–84. doi:10.1136/gut.2003.022111. PMC 1774187. PMID 15306603. {{cite journal}}: Unknown parameter |month= ignored (help)
  61. ^ Mégraud F (1995). "Transmission of Helicobacter pylori: faecal-oral versus oral-oral route". Aliment. Pharmacol. Ther. 9 Suppl 2: 85–91. PMID 8547533.
  62. ^ Cave DR (1996). "Transmission and epidemiology of Helicobacter pylori". Am. J. Med. 100 (5A): 12S–17S, discussion 17S–18S. PMID 8644777. {{cite journal}}: Unknown parameter |month= ignored (help)
  63. ^ Delport W, van der Merwe SW (2007). "The transmission of Helicobacter pylori: the effects of analysis method and study population on inference". Best Pract Res Clin Gastroenterol. 21 (2): 215–36. doi:10.1016/j.bpg.2006.10.001. PMID 17382274.
  64. ^ Bizzozero G (1893). "Ueber die schlauchförmigen Drüsen des Magendarmkanals und die Beziehungen ihres Epitheles zu dem Oberflächenepithel der Schleimhaut". Archiv für mikroskopische Anatomie. 42: 82–152.
  65. ^ Konturek JW (2003). "Discovery by Jaworski of Helicobacter pylori and its pathogenetic role in peptic ulcer, gastritis and gastric cancer" (PDF). J. Physiol. Pharmacol. 54 Suppl 3: 23–41. PMID 15075463. Retrieved 2008-08-25. {{cite journal}}: Unknown parameter |month= ignored (help)
  66. ^ Egan BJ, O'Morain CA (2007). "A historical perspective of Helicobacter gastroduodenitis and its complications". Best Pract Res Clin Gastroenterol. 21 (2): 335–46. doi:10.1016/j.bpg.2006.12.002. PMID 17382281.
  67. ^ Palmer ED (1954). "Investigation of the gastric mucosa spirochetes of the human". Gastroenterology. 27 (2): 218–20. PMID 13183283. {{cite journal}}: Unknown parameter |month= ignored (help)
  68. ^ Steer HW (1975). "Ultrastructure of cell migration through the gastric epithelium and its relationship to bacteria". J. Clin. Pathol. 28 (8): 639–46. PMC 475793. PMID 1184762. {{cite journal}}: Unknown parameter |month= ignored (help)
  69. ^ Marshall BJ, Warren JR (1984). "Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration". Lancet. 1 (8390): 1311–5. PMID 6145023. {{cite journal}}: Unknown parameter |month= ignored (help)
  70. ^ Atwood IV KC (2004). "Bacteria, Ulcers, and Ostracism? H. pylori and the making of a myth". Retrieved 2008-08-02.
  71. ^ Borody TJ, Cole P, Noonan S; et al. (1989). "Recurrence of duodenal ulcer and Campylobacter pylori infection after eradication". Med. J. Aust. 151 (8): 431–5. PMID 2687668. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  72. ^ "Helicobacter pylori in peptic ulcer disease". NIH Consensus Statement Online Jan 7–9;12(1):1–23. Retrieved 2004-12-21.
  73. ^ "The Nobel Prize in Physiology or Medicine 2005". Retrieved 2008-08-02.
  74. ^ Linz B, Balloux F, Moodley Y; et al. (2007). "An African origin for the intimate association between humans and Helicobacter pylori". Nature. 445 (7130): 915–8. doi:10.1038/nature05562. PMC 1847463. PMID 17287725. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

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