Helicobacter pylori

Andre Dubois; Anthony Welch; Douglas E. Berg; Martin J. Blaser

doi:10.1128/9781555818104.ch13

Chapter 13 : Helicobacter pylori

Authors: Andre Dubois¹, Anthony Welch², Douglas E. Berg³, Martin J. Blaser⁴

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Affiliations: 1: Laboratory of Gastrointestinal and Liver Studies, Digestive Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md; 2: Laboratory of Gastrointestinal and Liver Studies, Digestive Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, and Bioqual Inc., Rockville, Md; 3: Departments of Molecular Microbiology and of Genetics, Washington University Medical School, St. Louis, Mo; 4: Departments of Medicine and Microbiology, New York University School of Medicine, and New York Harbor VA Medical Center, New York, NY

Content Type: Monograph

Publication Year: 2000

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818104

Chapter DOI: 10.1128/9781555818104.ch13

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Abstract:

Helicobacter pylori is extraordinary among bacteria in its ability to colonize the stomachs of more than half of all people worldwide and often to persist for years or decades once it has become established. H. pylori can be detected and analyzed by a variety of different methods. Seroepidemiological studies performed in the United States and abroad have demonstrated the worldwide presence of H. pylori in a large majority of individuals from low socioeconomic groups and also in many people of higher socioeconomic status. The recent observation that H. pylori can be isolated from cats and that cats can be colonized by H. pylori following inoculation suggests that transmission from pets to humans (or humans to pets) is also possible. The presence of H. pylori can be diagnosed from gastric-biopsy specimens harvested at endoscopy. Long-term gastric colonization is associated with intense humoral and cellular immune responses. However, these responses are usually unable to eradicate H. pylori and they may, in fact, play a role in the persistence of the bacterium and/or in the production of disease. Interestingly, vaccination can reduce the severity of antral gastritis in mice, ferrets, and monkeys. However, immunization can eliminate colonization by H. pylori in mice and ferrets but not in monkeys or humans. The immune response to colonization by H. pylori has been proposed as being responsible in part for the production of peptic ulcer disease (PUD).

Citation: Dubois A, Welch A, Berg D, Blaser M. 2000. Helicobacter pylori, p 263-280. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch13

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Helicobacter pylori

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/content/10.1128/9781555818104.chap13.fig13-1

FIGURE 1

Schematic representation of the flow of particles within the stomach lumen (arrows indicate direction of peristaltic waves or flow).

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10.1128/9781555818104/fig13-1.gif

FIGURE 1

Schematic representation of the flow of particles within the stomach lumen (arrows indicate direction of peristaltic waves or flow).

/content/10.1128/9781555818104.chap13.fig13-2

FIGURE 2

Time course of antral gastritis score (●) and plasma IgG (▽) before and after transient or unsuccessful colonization. Absence of the organism is indicated by ○, and positivity for H. pylori by culture and/or histology is indicated by +. Animal 9A5 was not colonized in trial 1 but developed transient colonization during trials 2 and 3. Animal 8V5 was not colonized during trials 1 and 2 but developed transient colonization during trial 3. Animal E0E was included only in trial 2 and did not become colonized with H. pylori ( 34 ).

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FIGURE 2

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FIGURE 3

Time course of antral gastritis score (●) and plasma IgG (▽) before and after successful colonization. Absence of the organism is indicated by ○, and positivity for H. pylori by culture and/or histology is indicated by +. Animal 8RC became persistently colonized in trial 2, and the plasma IgG and gastritis scores increased after a 3-month delay. Animal KJ2 did not become colonized in trial 2 but was colonized by one of the human strains from a patient with gastric ulcer used in trial 3 ( 34 ).

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FIGURE 3

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FIGURE 4

Effect of administration of rUre plus LT or placebo plus LT on conversion in specific antiurease serum and saliva IgG and IgA at 1 week after the fourth immunization. The H. pylori + or − designation reflects the status at endoscopy 11.5 months after immunization. The dotted line represents 100% of the initial immunoglobulin level. *, P < 0.05 ( 36 ). SE, standard error.

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FIGURE 4

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FIGURE 5

Time course of serum anti-urease IgG. Following administration of rUre plus LT, mean IgG initially increased (○ and +). IgG subsequently decreased in animals that were H. pylori-negative at the endoscopy performed at 11.5 months (○; n = 8), whereas it did not change significantly in those who were H. pylori positive at 11.5 months (+ ; n = 18). In animals given placebo plus LT, IgG initially did not change and then increased progressively in the animals that were H. pylori positive at the endoscopy performed at 11.5 months (♦; n = 27). IgG remained low in the two animals that had received placebo plus LT and remained H. pylori negative (data not illustrated). *, P < 0.05 versus placebo plus LT and H. pylori positive at 11.5 months. SE, standard error. (Adapted from reference 36 .)

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FIGURE 5

References

/content/book/10.1128/9781555818104.chap13

1. Akopyants, N. S.,, S. W. Clifton,, D. Kersulyte,, J. E. Crabtree,, B. E. Youree,, C. A Reece,, B. A. Roe,, N. O. Bukanov,, E. S. Drazek,, and D. E. Berg. 1998. The cag pathogenicity island of Helicobacter pylori. Mol. Microbiol. 28:37–54.

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

3.Anonymous. 1994. Helicobacter pylori in peptic ulcer disease. NIH Consensus Conference. JAMA 272:65–69.

4. Atherton, J. C.,, R. M. Peek, Jr.,, K. T. Tham,, T. L. Cover,, and M. J. Blaser. 1997. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 112:92–99.

5. Atherton, J. C.,, and R. C. Spiller. 1999. The urea breath test for Helicobacter pylori. Gut 35:723–725.

6. Azuma, T.,, S. Ito,, F. Sato,, Y. Yamazaki,, H. Miyaji,, Y. Ito,, H. Suto,, M. Kuriyama,, T. Kato,, and Y. Kohli. 1998. The role of the HLADQA1 gene in resistance to atrophic gastritis and gastric adenocarcinoma induced by Helicobacter pylori infection. Cancer 82:1013–1018.

7. Azuma, T.,, J. Konishi,, Y. Ito,, M. Hirai,, Y. Tanaka,, S. Ito,, T. Kato,, and Y. Kohli. 1995. Genetic differences between duodenal ulcer patients who were positive or negative for Helicobacter pylori. J. Clin. Gastroenterol. 21:S1514.

8. Bamford, K. B.,, X. Fan,, S. E. Crowe,, J. F Leary,, W. K. Gourley,, G. K. Luthra,, E. G Brooks,, D. Y. Graham,, V. E. Reyes,, and P. B. Ernst. 1998. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology 114:482–492.

9. Beachey, E. H. 1981. Bacterial adherence: adhesin- receptor interactions mediating the attachment o f bacteria to mucosal surfaces. J. Infect. Dis 143:325–345.

10. Blaser, M. J. 1998. Helicobacters are indigenous to the human stomach: duodenal ulceration is due to changes in gastric microecology in the modern era. Gut 43:721–727.

11. Blaser, M. J. 1999. The changing relationship of Helicobacter pylori and humans: implications for health and disease. J. Infect. Dis. 179:1523–1530.

12. Blaser, M. J.,, and D. Kirschner. 1999. Dynamics o f Helicobacter pylori colonization in relation to the host response. Proc. Natl. Acad. Sci. USA 96:8359–8364.

13. Blaser, M. J.,, and J. Parsonnet. 1994. Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J. Clin. Investig. 94:4–8.

14. Boren, T.,, P. Falk,, K. A. Roth,, G. Larson,, and S. Normark. 1993. Attachment of Helicobacter pylori to human gastric epithehum mediated by blood group antigens. Science 262:1892–1895.

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

16. Cover, T. L. 1996. The vacuolating cytotoxin of Helicobacter pylori. Mol. Microbiol 20:241–246.

17. Cover, T. L.,, P. Cao,, U. K. Murth,, M. S Sipple,, and M. J. Blaser. 1992. Serum neutralizing antibody response to the vacuolating cytotoxin of Helicobacter pylori. J. Clin. Investig. 90:913–918.

18. Cover, T.L.,, C. P. Dooley,, and M. J. Blaser 1990. Characterization of a human serologicresponse to proteins in Helicobacter pylori broth culture supernatant withvacuolizing cytotoxin activity. Infect. Immun. 58:603–610.

19. Crabtree, J.E.,, D. Kersulyte,, S. D. Li,, I. J. D. Lindley,, and D. E. Berg. 1999. Modulation of Helicobacter pylori-induced IL-8 synthesis in gastric epithelial cells mediated by cag PAI-encoded VirD4 homologue. J. Clin. Pathol 52:653–657.

20. Crabtree, J. E.,, P. Peichl,, J. I. Wyatt,, U. Stachl,, and I. J. Lindley. 1993. Gastric interleukin-8 and IgA 11-8 autoantibodies in Helicobacter pylori infection. Scand. J. Immunol 37:65–70.

21. Crabtree, J. E.,, J. D. Taylor,, J. I. Wyatt,, R. V. Heatley,, T. M. Shalicross,, D. S. Tompkins,, and B. J. Rathbone. 1991. Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. Lancet 338:335

22. Crabtree, J. E.,, J. I. Wyatt,, L. K. Trejdosiewicz,, P. Peichl,, P. H. Nichols,, N. Ramsay,, J. N. Primrose,, and I. J. D. Lindley. 1994 Interleukin-8 expression in Helicobacter pylori-infected, normal, and neoplastic gastroduodenal mucosa. J. Clin. Pathol 47:61–66.

23. Crowe, S.E.,, L. Alvarez,, P. M. Sherman,, Y. Jin,, M. Dytoc,, R. H. Hunt,, H. Patel,, M. J. Muller,, and P. B. Ernst. 1995. Expression of interleukin 8 and CD54 by human gastric epithehum after H. pylori infection in vitro. Gastroenterology 108:65–74.

24. Cuenca, R.,, T. G. Blanchard,, S. J. Czinn,, J. G. Nedrud,, T. P. Monath,, C. K. Lee,, and R. W. Redline. 1996. Therapeutic immunization against Helicobacter mustelae in naturally infected ferrets. Gastroenterology 110:1170–1175.

25. Cullen, D.J.,, B. J. Collins,, B. J. Christiansen,, J. R. Warren,, R. Surveyor,, and K. J. Cullen 1993. When is Helicobacter pylori infection acquired? Gut 34:1681–1682.

26. Czinn, S. J.,, A. Cai,, and J. G. Nedrud. 1993 Protection of germ-free mice from infection by Helicobacter felis after active oral or passive IgA immunization Vaccine 11:637–642.

27. Darwin, P. E.,, M. B. Sztein,, Q. X. Zheng,, S. P. James,, and G. T. Fantry. 1996. Immune evasion by Helicobacter pylori: gastric spiral bacteria lack surface immunoglobulin deposition and reactivity with homologous antibodies. Helicobacter 1:20–27.

28. D'Elios, M. M.,, M. Manghetti,, F. Almerigogn,, E. Arnedel,, F. Costa,, D. Burroni,, C. T. Baldari,, S. Romagnani,, J. L. Telford,, and G. Del Prete. 1997. Different cytokine profile and antigens specificity repertoire in Helicobacter pylori specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer. Eur. J. Immunol 27:1751–1755.

29. D'Elios, M. M.,, M. Manghetti,, M. De Carli,, F. Costa,, C. T. Baldari,, D. Burroni,, J. L. Telford,, S. Romagnani,, and G. Del Prete. 1997 T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum o f patients with peptic ulcer disease. J. Immunol 158:962–967.

30. Doig, P. C.,, and T. J. Trust. 1994. Identification of surface exposed outer membrane antigens of Helicobacter pylori. Infect. Immun. 62:4526–4533.

31. Drumm, B.,, G. I. Perez-Perez,, M. J. Blaser,, and P. M. Sherman. 1990. Intrafamilial clustering of Helicobacter pylori infection. N. Engl J. Med 322:359–363.

32. Dubois, A., 1989. Functional causes ofdisturbed gastric function, p.143–170. In W. P. Snape (ed.), Pathogenesis of Functional Bowel Disease. Plenum Medical Book Company, New York, N.Y.

33. Dubois, A. 1995. Spiral bacteria in the human stomach: the gastric helicobacters. Emerg. Infect Dis. 1:79–85.

34. Dubois, A.,, D. E. Berg,, E. T. Incecik,, N. Fiala,, L. M. Heman-Ackah,, G. I. Perez-Perez,, and M. J. Blaser. 1996. Transient and persistent experimental infection of nonhuman primates with Helicobacter pylori: implications for human disease. Infect. Immun. 64:2885–2891.

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

36. Dubois, A.,, C. P. Lee,, P. T. Mehlman,, N. Fiala,, H. Kleanthous,, and T. Monath. 1998 Immunization against natural Helicobacter pylori infection in rhesus monkeys. Infect. Immun. 66: 4340–4346.

37. Dunn, B. E.,, C. C. Sung,, N. S. Taylor,, and J. G. Fox. 1991. Purification and characterization of Helicobacter mustelae urease. Infect. Immun. 59: 3343–3345.

38. Eaton, K.,, D. R. Morgan,, C. L. Brooks,, and S. Krakowka. 1991. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 59: 2470–2475.

39. Ermak, T. H.,, P. J. Giannasca,, R. Nichols,, G. A. Myers,, J. Nedrud,, R. Weltzin,, C. K Lee,, H. Kleanthous,, and T. P. Monath. 1998 Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence o f antibodies and is mediated by MHC class II-restricted responses. J. Exp. Med. 188: 2277–2288.

40. Ernst, P.B.,, S. E. Crowe,, and V. E. Reyes 1995. The immunopathogenesis of gastroduodenaldisease associated with Helicobacter pylori infection Curr.Opin. Gastroenterol. 11:512–518.

41. Ernst, P.B.,, S. E. Crowe,, and V. E. Reyes 1997. How does Helicobacterpylori cause mucosal damage? The inflammatory response. Gastroenterology 113:S35–S42.

42. Evans, D. G.,, D. J. Evans,, H. C. Lampert,, and D. Y. Graham. 1995. Restriction fragment length polymorphism in the adhesin gene hpaA of Helicobacter pylori. Am. J. Gastroenterol. 90: 1282–1288.

43. Evans, D. G.,, D. J. Evans,, J. J. Moulds,, and D. Y. Graham. 1988. N-acetylneuraminyllactose-binding fibrillar hemagglutinin of Campylobacter pylori: a putative colonization factor antigen Infect. Immun. 56:2896–2906.

44. Falk, P.,, K. A. Roth,, T. Boren,, T. U. Westblom,, J. I. Gordon,, and S. Normark. 1993. An in vitro adherence assay reveals that Helicobacter pylori exhibits cell lineage-specific tropism in the human gastric epithelium. Proc. Natl. Acad. Sci USA 90:2035–2039.

45. Fan, X. G.,, J. Yakoob,, X. J. Fan,, and P. W N. Keeling. 1996. Enhanced T helper 2 lymphocyte responses: immune mechanism of Helicobacter pylori infection. Ir.J. Med. Sci. 165:37–39.

46. Fan, X. J.,, A. Chua,, C. N. Shahi,, J. McDevitt,, P. W. N. Keeling,, and D. Kelleher. 1994. Gastric T lymphocyte responses to Helicobacter pylori in patients with H. pylori colonization. Gut 35: 1379–1384.

47. Fauchere, J.,, and M. J. Blaser. 1990. Adherence of Helicobacter pylori cells and their surface components to HeLa cell membranes. Microb. Pathog 9:427–439.

48. Ferguson, D. A.,, C. Li,, N. R. Patel,, W. R Mayberry,, D. S. Chi,, and E. Thomas. 1993 Isolation of Helicobacter pylori from saliva. J. Clin Microbiol. 31:2802–2804.

49. Ferrero, R.L.,, J.-M. Thiberge,, and A. Labigne 1997. Local immunoglobuhn G antibodies inthe stomach may contribute to immunity against Helicobacter infection inmice. Gastroenterology 113: 185–194.

50. Ferrero, R. L.,, J. M. Thiberge,, I. Kansau,, N. Wuscher,, M. Huerre,, and A. Labigne. 1995 The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice. Proc. Natl. Acad. Sci. USA 92:6499–6503.

51. Genta, R. M.,, G. O. Robason,, and D. Y Graham. 1994. Simultaneous visualization of Helicobacter pylori and gastric morphology: a new stain. Hum. Pathol. 25:221–226.

52. Granstrom, M.,, Y. Tindberg,, and M. Blennow. 1997. Seroepidemiology of Helicobacter pylori infection in a cohort of children monitored from 6 months to 11 years o f age. J. Clin. Microbiol 35:468–470.

53. Handt, L. K.,, J. G. Fox,, F. E. Dewhirst,, G. J. Fraser,, B. J. Paster,, L. L. Yan,, H. R ozmiarek,, R. Rufo,, and I. H. Stalis. 1994. Helicobacter pylori isolated from the domestic cat: public health implications. Infect. Immun. 62:2367–2374.

54. Handt, L. K.,, M. Kubin,, K. B. Bamford,, R. Carofalo,, D. Y. Graham,, F. El-Zaatari,, S. E. Kartunen,, S. E. Crowe,, V. E. Reyes,, and P. B. Ernst. 1997. Differential stimulation of interleukin 12 (IL-12) and IL-10 by live and killed Helicobacter pylori in vitro and association of IL-12 production with gamma interferon-producing T cells in the human gastric mucosa. Infect. Immun 65:4229–4235.

55. Hemalatha, S.G.,, B. Drumm,, and P. J. Sherman 1991. Adherence of Helicobacterpylori to human gastric epithelial cells in vitro. Med.Microbiol 35:197–202.

56. Ilver, D.,, A. Arnqvist,, J. Ogren,, I. M. Frick,, D. Kersulyte,, E. T. Incecik,, D. E. Berg,, A Covacci,, L. Engstrand,, and T. Boren. 1998 Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging Science 279:373–377.

57. Karttunen, R.,, T. Karttunen,, H.-P. T. Ekre,, and T. T. MacDonald. 1995. Interferon gamma and interleukin 4 secreting cells in the gastric antrum in Helicobacter pylori positive and negative gastritis Gut 36:341–345.

58. Kazi, J. L.,, R. Sinniah,, N. A. Jaffirey,, S. M. Alam,, V. Z man,, S. J. Zuberi,, and A. M. Kazi. 1989. Cellular and humoral immune responses in Campylobacter pylori-associated chronic gastritis. J. Pathol. 159:231–237.

59. Keates, S.,, Y. S. Hitti,, M. Upton,, and C. P Kelly. 1997. Helicobacter pylori infection activates NF-κB in gastric epithelial cells. Gastroenterology 113:1099–1109.

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

61. Keranen, A. 1975. Gangliosides of the human gastrointestinal mucosa. Biochim. Biophys. Acta 409:320–328.

62. Kirkland, T.,, S. Viriyakosol,, G. I. Perez-Perez,, and M. J. Blaser. 1997. Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14. Infect. Immun. 65:604–608.

63. Klein, P.D.,, R. H. Gilman,, R. Leon-Barua,, F. Diaz,, E. O. Smith,, and D. Y. Graham 1994. The epidemiology of Helicobacter pylori in Peruvian children between 6 and 30 months of age. Am. J. Gastroenterol. 89:2196–2200.

64. Klein, P. D.,, D. Y. Graham,, A. Gaillour,, A. R. Opekun,, and E. O. Smith. 1991. Gastrointestinal Physiology Working Group. Water source as risk factor for Helicobacter pylori infection in Peruvian children. Lancet 337:1503–1506.

65. Lee, A. 1996. Therapeuticimmunization against Helicobacter infection. Gastroenterology 110:2003–2006.

66. Lee, C. K.,, R. Weltzin,, W. D. Thomas, Jr.,, H. Kleanthous,, T. H. Ermak,, G. Soman,, J. E. Hill,, S. K. Ackerman,, and T. P. Monath 1995. Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis. J. Infect. Dis. 172:161–172.

67. Lee, J. E.,, A. M. Lowy,, W. A. Thompson,, M. Lu,, P. T. Loflin,, J. M. Skibber,, D. B Evans,, S. A. Curley,, P. F. Mansfield,, and J D. Reveille. 1996. Association of gastric adenocarcinoma with the HLA class II gene DQB10301. Gastroenterology 111:426–432.

68. Levenstein, S.,, S. Ackerman,, J. K. Kiecolt-Glaser,, and A. Dubois. 1999. Stress and peptic ulcer disease. JAMA 281:10–11.

69. Lewala-Guruge, J.,, A. Ljungh,, and T. Wadstrom 1992. Haemagglutination patterns of Helicobacter pylori. Frequency of sialic acid-specific and nonsialic acid-specifichaemagglutinins. APMIS 100:908–913.

70. Leying, H.,, S. Suerbaum,, G. Geis, and R Haas. 1992. Cloning and genetic characterization of a Helicobacter pylori flagellin gene. Mol. Microbiol 6:2863–2874.

71. Li, S. D.,, D. Kersulyte,, I. J. Lindley,, B. Neelam,, D. E. Berg,, and J. E. Crabtree. 1999 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 67:3893–3899.

72. Malaty, H. M.,, L. Engstrand,, N. L. Pedersen,, and D. Y. Graham. 1994. Helicobacter pylori infection: genetic and environmental influences Ann. Intern. Med. 120:982–986.

73. Marshall, B. J.,, J. A. Armstrong,, D. B McGechie,, and R. J. Glancy. 1985. Attempt to fulfill Koch's postulate for pyloric Campylobacter Med. J. Aust. 142:436–439.

74. Michetti, P.,, I. E. Corthesy-Theulaz,, C. Davin,, R. Haas,, A.-C. Vaney,, M. Heitz,, J. Bille,, J.-P. Krahenbuhl,, E. Saraga,, and A. L. Blum. 1994. Immunization of BALB/c mice against Helicobacter felis infection with Helicobacter pylori urease. Gastroenterology 107:1002–1011.

75. Michetti, P.,, C. Kreiss,, K. L. Kotloff,, N. Porta,, J.-L. Blanco,, D. Bachmann,, M. Herranz,, P. F. Saldinger,, I. E. Corthesy-Theulaz,, G. Lozonsky,, R. Nichols,, M. Stolte,, S. Ackerman,, T. P. Monath,, and A. L. Blum 1999. Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults. Gastroenterology 116:804–812.

76. Miller-Podraza, H.,, M. A. Mihl,, S. Teneberg,, and K. A. Karlsson. 1997. Binding of Helicobacter pylori to sialic acid-containing glycolipids of various origins separated by thin-layer chromatograms Infect. Immun. 65:2480–2482.

77. Miyaji, H.,, Y. Kohli,, T. Azuma,, Y. Ito,, M. Hirai,, T. Kato,, M. Kuriyama,, and Y. Abe 1995. Endoscopic cross-infection with Helicobacter pylori. Lancet 345:464.

78. Moriai, T.,, and N. Hirahara. 1999. Clinical course of acute gastric mucosal lesions caused by acute infection with Helicobacter pylori. N. Engl. J Med. 341:456–458.

79. Morris, A. J.,, M. R. Ali,, G. I. Nicholson,, G. I. Perez-Perez,, and M. J. Blaser. 1991. Long term follow-up of voluntary ingestion of Helicobacter pylori. Ann. Intern. Med. 114:662–663.

80. Muraoka, H.,, I. Kobayashi,, M. Hasegawa,, T. Saika,, H. Toda,, M. Nishida,, J. Suzuki,, T. Mine,, and T. Fujita. 1997. Urease-negative Helicobacter pylori isolates from gastrointestinal mucosa of patients with peptic ulcer. Kansenshogaku Zasshi 71:1216–1220.

81. Mutiola, A.,, I. M. Helander,, L. Pyhala,, T. U. Kosunen,, and A. P. Moran. 1992. Low biological activity of Helicobacter pylori lipopolysaccharide Infect. Immun. 60:1714–1716.

82. Mysore, J. V.,, P. M. Simon,, D. Zopf,, L. M Heman-Ackah,, and A. Dubois. 1999. Treatment of Helicobacter pylori infection in rhesus monkeys using a novel antiadhesive compound. Gastroenterology 117:1316–1325.

83. Neman-Simba, V.,, and F. Megraud. 1988 In vitro model for Campylobacter pylori adherence properties. Infect. Immun. 56:3329–3333.

84. Newell, D.G.,, and A. R. Staccy,. 1994. B cell responses in H. pylori infection, p.309–320. In R. H. Hunt, and G. N. Tytgat (ed.), H. pylori: Basic Mechanisms to Clinical Cure. Kluwer Academic Publishers, Amsterdam, The Netherlands.

85. Nomura, A.,, G. N. Stemmermann,, P. H. Chyou,, I. Kato,, G. I. Perez-Perez,, and M. J. Blaser. 1994. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii Ann. Intern. Med. 120:977–981.

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

87. Pappo, J.,, W. D. J. Thomas,, Z. Kabok,, N. S. Taylor,, J. C. Murphy,, and J. G. Fox. 1995 Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis. Infect Immun. 63:1246–1252.

88. Parsonnet, J.,, S. Hansen,, L. Rodriguez,, A. B. Gelb,, R. A. Warnke,, E. Jellum,, N. Orentreich,, J. H. Vogelman,, and G. D. 1994. Helicobacter pylori infection and gastric lymphoma N. Engl. J. Med. 330:1267–1271.

89. Peek, R. M.,, S. Thompson,, J. P. Donahue,, K. T. Tham,, J. C. Atherton,, M. J. Blaser,, and G. G. Miller. 1998. Adherence to epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Am. Assoc. Physicians 110:531–544.

90. Perez-Perez, G. I.,, B. M. Dworkin,, J. E. Chodos,, and M. J. Blaser. 1988. Campylobacter pylori antibodies in humans. Ann. Intern. Med 109:11–17.

91. Perez-Perez, G. I.,, A. Z. Olivares,, T. L Cover,, and M. J. Blaser. 1992. Characteristics of Helicobacter pylori variants selected for urease deficiency. Infect. Immun. 60:3658–3663.

92. Perez-Perez, G. I.,, V. L. Shepherd,, J. D Morrow,, and M. J. Blaser. 1999. Activation of human THP-1 cells and rat bone marrowderived macrophages by Helicobacter pylori lipopolysaccharide Infect. Immun. 63:1183–1187.

93. Perez-Perez, G. I.,, S. M. Thiberge,, A. Labigne,, and M. J. Blaser. 1996. Relationship of immune response to heatshock protein A and characteristics of Helicobacter pylori infected patients. J. Infect. Dis. 174:1050.

94. Perkins, S. E.,, J. G. Fox,, R. P. Marini,, Z. Shen,, C. A. Dangler,, and Z. Ge. 1998. Experimental infection in cats with a cagA+ human isolate of Helicobacter pylori. Helicobacter 3: 225–235.

95. Robbins, J. B.,, R. Schneerson,, and S. C. Szu. 1995. Perspective: hypothesis: Serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating inoculum. J Infect. Dis. 171:1387–1398.

96. Saitoh, T.,, H. Natomi,, W. Zhao,, K. Okuzumi,, K. Sugano,, M. Iwamori,, and Y. Nagai. 1991. Identification of gjycolipid receptors for Helicobacter pylori by TLC-immunostaining FEBS Lett. 282:385–387.

97. Sharma, S. A.,, M. K. Tummuru,, M. J Blaser,, and L. D. Kerr. 1998. Activation of IL8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor KB in gastric epithelial cells. J. Immunol. 160: 2401–2407.

98. Sharma, S. A.,, M. K. Tummuru,, G. G Miller,, and M. J. Blaser. 1995. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect. Immun 63:1681–1687.

99. Simon, P. M.,, P. L. Goode,, A. Mobasseri,, and D. Zopf. 1997. Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides. Infect Immun. 65:750–757.

100. Taylor, D. N.,, and M. J. Blaser. 1991. The epidemiology of Helicobacter pylori infection. Epidemiol Rev. 13:42–59.

101. Thomas, J. E.,, G. R. Gibson,, M. K. Darboe,, A. Dale,, and L. T. Weaver. 1992. Isolation of H. pylori from human faeces. Lancet 340:1194–1195.

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

103. Tosi, M. F.,, and S. J. Czinn. 1990. Opsonic activity o f specific human IgG against Helicobacter pylori. J. Infect. Dis. 162:156–162.

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

105. Van Doom, L. J.,, C. Figueiredo,, R. Sanna,, A. Plaisier,, P. Schneeberger,, W. De Boer,, and W. Quint. 1998. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 115:58–66.

106. Veldhuyzen van Zanten, S.,, D. Malatjalian,, R. Tanton,, D. Leddin,, R. H. Hunt,, and W. Blanchard. 1995. The effect of eradication of Helicobacter pylori (HP) on symptoms of non-ulcer dyspepia (NUD): randomized double-blind placebo controlled trial. Gastroenterology 108:A2050.

107. Wang, G.,, D. A. Rasko,, R. Sherbourne,, and D. E. Taylor. 1999. Molecular genetic basis for the variable expression of Lewis Y antigen in Helicobacter pylori: analysis o f the alpha (l, 2) fucosyltransferase gene. Mol Microbiol 31: 1265–1274.

108. Welch, A.,, L. Jones,, T. Wigginton,, R. Kampen,, A. Kirk,, and A. Dubois. 1999. Cytokine mRNA expression during experimental H. pylori infection in rhesus monkeys. Gut 45:A36.

109. Wirth, H. P.,, M. Yang,, A. Dubois,, D. E. Berg,, and M. J. Blaser. 1999. Host Lewis phenotype-dependent selection of H. pylori Lewis expression in rhesus monkeys. Gut 43(Suppl. 2): A26.

110. Wirth, H. P.,, M. Yang,, R. M. Peek,, K. T. Tham,, and M. J. Blaser. 1997. Helicobacter pylori Lewis expression is related to the host Lewis phenotype. Gastroenterology 113:1091–1098.

111. Wyatt, J. I.,, B. J. Rathbone,, and R. V. Heatley. 1986. Local immune response togastric Campylobacter in non-ulcer dyspepsia. J. Clin.Pathol. 863–870.

112. Zopf, D.,, and S. Roth. 1996. Oligosaccharide anti-infective agents. Lancet 347:1017–1021.