Die Entwicklung von Immunoproteomics-Methoden am Beispiel der Identifizierung Magenkarzinom-assoziierter Helicobacter pylori AntigeneAlexander Krah1.101.1.1.1.1.111.1.2.121.2.1.2.1.131.2.2.141.2.3.15627#284161.2.4.171.3.1.3.1.1.3.2.181.4.1.4.1.1.4.1.1.191.4.1.2.615#160201.4.1.3.21605#4201.4.1.4.22570#3061.4.2.231.4.3.1.4.3.1.1.4.3.2.241.4.3.3.25261.5.27282.292.1.2.1.1.2.1.2.302.1.3.2.1.3.1.2.1.3.2.2.1.3.3.312.1.4.2.1.5.322.1.5.1.2.1.5.2.2.1.5.3.332.1.6.2.1.6.1.2.1.6.2.342.2.2.2.1.2.2.2.352.2.3.362.2.4.2.2.4.1.2.2.4.2.2.2.4.3.372.2.4.4.2.2.5.2.2.5.1.382.2.5.2.2.2.5.3.392.3.2.3.1.2.3.2.402.3.2.1.2.3.2.2.412.3.3.422.3.3.1.2.3.3.2.432.3.3.3.2.3.4.442.3.5.2.3.5.1.2.3.5.2.2.3.5.3.452.3.5.4.3.463.1.3.1.1.473.1.2.483.1.3.493.1.4.513.1.5.523.1.6.533.1.7.543.1.8.3.2.3.2.1.553.2.2.3.2.3.56573.2.4.5859603.2.5.3.2.5.1.61623.2.5.2.6364653.2.6.663.2.7.3.2.8.673.3.3.3.1.683.3.2.3.3.2.1.693.3.2.2.3.3.3.7071724.734.1.7475764.2.777879808182834.3.848586 Abkürzungen89 Referenzen87 Danksagung92 Publikationsliste9394ErklärungdeInhaltsverzeichnisHilfe Referenzen [1] Marshall, B. J. und Warren, J. R. (1984): Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration, Lancet 1 [8390], Seite 1311-1315. [2] Warren, J. R. und Marshall, B. J. (1983): Unidentified curved bacilli on gastric epithelium in active chronic gastritis, Lancet 1, Seite 1273-1275. [3] McNulty CAM (1999): The discovery of Campylobacter-like organisms., Westblom TU; Czinn SJ und Nedrud JG, Gastroduodenal Disease and Helicobacter pylori 241, Seite 1-9, Springer-Verlag,

Berlin Heidelberg

, 3-350-65084-9. [4] Tomb, J. F.; White, O.; 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.; Fitzegerald, L. M.; Lee, N.; Adams, M. D.; Venter, J. C. und . (1997): The complete genome sequence of the gastric pathogen Helicobacter pylori, Nature 388 [6642], Seite 539-547. [5] Mitchell HM (1999): The Epidemiology of Helicobacter pylori, Westblom TU; Czinn SJ und Nedrud JG, Gastroduodenal Disease and Helicobacter pylori 241, Seite 11-30, Springer-Verlag,

Berlin Heidelberg

, 3-350-65084-9. [6] Zevering, Y.; Jacob, L. und Meyer, T. F. (1999): Naturally acquired human immune responses against Helicobacter pylori and implications for vaccine development, Gut 45 [3], Seite 465-474. [7] Falush, D.; Wirth, T.; Linz, B.; Pritchard, J. K.; Stephens, M.; Kidd, M.; Blaser, M. J.; Graham, D. Y.; Vacher, S.; Perez-Perez, G. I.; Yamaoka, Y.; Megraud, F.; Otto, K.; Reichard, U.; Katzowitsch, E.; Wang, X.; Achtman, M. und Suerbaum, S. (2003): Traces of human migrations in Helicobacter pylori populations, Science 299 [5612], Seite 1582-1585. [8] Ernst, P. B. und Gold, B. D. (2000): The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer, Annu.Rev.Microbiol. 54, Seite 615-640. [9] El Omar, E. M. (2001): The importance of interleukin 1beta in Helicobacter pylori associated disease, Gut 48 [6], Seite 743-747. [10] Appelmelk, B. J.; Monteiro, M. A.; Martin, S. L.; Moran, A. P. und Vandenbroucke-Grauls, C. M. (2000): Why Helicobacter pylori has Lewis antigens, Trends Microbiol. 8 [12], Seite 565-570. [11] Rasko, D. A.; Keelan, M.; Wilson, T. J. und Taylor, D. E. (2001): Lewis antigen expression by Helicobacter pylori, J.Infect.Dis. 184 [3], Seite 315-321. [12] Labenz J.; Meining A.; Tillenburg B. und Stolte M. (1999): Helicobacteriose: Update 1999, Leber Magen Darm 29 [2], Seite 80-92. [13] Sutton, P. (2001): Progress in vaccination against Helicobacter pylori, Vaccine 19 [17-19], Seite 2286-2290. [14] Loffeld, R. J. und van der Hulst, R. W. (2002): Helicobacter pylori and gastro-oesophageal reflux disease: association and clinical implications. To treat or not to treat with anti-H. pylori therapy?, Scand.J.Gastroenterol.Suppl [236], Seite 15-18. [15] Peek, R. M., Jr. und Blaser, M. J. (2002): Helicobacter pylori and gastrointestinal tract adenocarcinomas, Nat.Rev.Cancer 2 [1], Seite 28-37. [16] Kotloff, K. L.; Sztein, M. B.; Wasserman, S. S.; Losonsky, G. A.; DiLorenzo, S. C. und Walker, R. I. (2001): Safety and immunogenicity of oral inactivated whole-cell Helicobacter pylori vaccine with adjuvant among volunteers with or without subclinical infection, Infect.Immun. 69 [6], Seite 3581-3590. [17] Aebischer, T.; Lucas, B.; Koesling, J.; Bumann, D. und Meyer, T. F. (2000): How CD4(+) T cells may eliminate extracellular gastric Helicobacter?, J.Biotechnol. 83 [1-2], Seite 77-84. [18] Bumann, D.; Holland, P.; Siejak, F.; Koesling, J.; Sabarth, N.; Lamer, S.; Zimny-Arndt, U.; Jungblut, P. R. und Meyer, T. F. (2002): A Comparison of Murine and Human Immunoproteomes of Helicobacter pylori Validates the Preclinical Murine Infection Model for Antigen Screening, Infect.Immun. 70 [11], Seite 6494-6498. [19] Jungblut, P. R. (2001): Proteome analysis of bacterial pathogens, Microbes.Infect. 3 [10], Seite 831-840. [20] Wasinger, V. C.; Cordwell, S. J.; Cerpa-Poljak, A.; Yan, J. X.; Gooley, A. A.; Wilkins, M. R.; Duncan, M. W.; Harris, R.; Williams, K. L. und Humphery-Smith, I. (1995): Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium, Electrophoresis 16 [7], Seite 1090-1094. [21] Rabilloud, T. (2002): Two-dimensional gel electrophoresis in proteomics: old, old fashioned, but it still climbs up the mountains, Proteomics. 2 [1], Seite 3-10. [22] Klose, J. (1975): Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. A novel approach to testing for induced point mutations in mammals, Humangenetik. 26 [3], Seite 231-243. [23] O'Farrell, P. H. (1975): High resolution two-dimensional electrophoresis of proteins, J.Biol.Chem. 250 [10], Seite 4007-4021. [24] Jungblut, P.; Thiede, B.; Zimny-Arndt, U.; Muller, E. C.; Scheler, C.; Wittmann-Liebold, B. und Otto, A. (1996): Resolution power of two-dimensional electrophoresis and identification of proteins from gels, Electrophoresis 17 [5], Seite 839-847. [25] Jungblut, P. R.; Bumann, D.; Haas, G.; Zimny-Arndt, U.; Holland, P.; Lamer, S.; Siejak, F.; Aebischer, A. und Meyer, T. F. (2000): Comparative proteome analysis of Helicobacter pylori, Mol.Microbiol. 36 [3], Seite 710-725. [26] Pleissner, K. P.; Eifert, T.; Buettner, S.; Schmidt, F.; Boehme, M.; Meyer, T. F.; Kaufmann, S. H. und Jungblut, P. R. (2004): Web-accessible proteome databases for microbial research, Proteomics. 4 [5], Seite 1305-1313. [27] Bumann, D.; Aksu, S.; Wendland, M.; Janek, K.; Zimny-Arndt, U.; Sabarth, N.; Meyer, T. F. und Jungblut, P. R. (2002): Proteome analysis of secreted proteins of the gastric pathogen Helicobacter pylori, Infect.Immun. 70 [7], Seite 3396-3403. [28] Sabarth, N.; Lamer, S.; Zimny-Arndt, U.; Jungblut, P. R.; Meyer, T. F. und Bumann, D. (2002): Identification of surface proteins of Helicobacter pylori by selective biotinylation, affinity purification, and two-dimensional gel electrophoresis, J.Biol.Chem. 277 [31], Seite 27896-27902. [29] Bumann, D.; Metzger, W. G.; Mansouri, E.; Palme, O.; Wendland, M.; Hurwitz, R.; Haas, G.; Aebischer, T.; von Specht, B. U. und Meyer, T. F. (2001): Safety and immunogenicity of live recombinant Salmonella enterica serovar Typhi Ty21a expressing urease A and B from Helicobacter pylori in human volunteers, Vaccine 20 [5-6], Seite 845-852. [30] Koesling, J.; Lucas, B.; Develioglou, L.; Aebischer, T. und Meyer, T. F. (2001): Vaccination of mice with live recombinant Salmonella typhimurium aroA against H. pylori: parameters associated with prophylactic and therapeutic vaccine efficacy, Vaccine 20 [3-4], Seite 413-420. [31] Rizos, K.; Lattemann, C. T.; Bumann, D.; Meyer, T. F. und Aebischer, T. (2003): Autodisplay: efficacious surface exposure of antigenic UreA fragments from Helicobacter pylori in Salmonella vaccine strains, Infect.Immun. 71 [11], Seite 6320-6328. [32] Metzger, W. G.; Mansouri, E.; Kronawitter, M.; Diescher, S.; Soerensen, M.; Hurwitz, R.; Bumann, D.; Aebischer, T.; von Specht, B. U. und Meyer, T. F. (2004): Impact of vector-priming on the immunogenicity of a live recombinant Salmonella enterica serovar typhi Ty21a vaccine expressing urease A and B from Helicobacter pylori in human volunteers, Vaccine 22 [17-18], Seite 2273-2277. [33] Rollenhagen, C.; Sorensen, M.; Rizos, K.; Hurvitz, R. und Bumann, D. (2004): Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen, Proc.Natl.Acad.Sci.U.S.A 101 [23], Seite 8739-8744. [34] Krah, A. und Jungblut, P. R. (2004): Immunoproteomics, Methods Mol.Med. 94, Seite 19-32. [35] McAtee, C. P.; Lim, M. Y.; Fung, K.; Velligan, M.; Fry, K.; Chow, T. und Berg, D. E. (1998): Identification of potential diagnostic and vaccine candidates of Helicobacter pylori by two-dimensional gel electrophoresis, sequence analysis, and serum profiling, Clin.Diagn.Lab Immunol., Seite 537-542. [36] Bumann, D.; Meyer, T. F. und Jungblut, P. R. (2001): Proteome analysis of the common human pathogen Helicobacter pylori, Proteomics. 1 [4], Seite 473-479. [37] Kimmel, B.; Bosserhoff, A.; Frank, R.; Gross, R.; Goebel, W. und Beier, D. (2000): Identification of immunodominant antigens from Helicobacter pylori and evaluation of their reactivities with sera from patients with different gastroduodenal pathologies, Infect.Immun. 68 [2], Seite 915-920. [38] Haas, G.; Karaali, G.; Ebermayer, K.; Metzger, W. G.; Lamer, S.; Zimny-Arndt, U.; Diescher, S.; Goebel, U. B.; Vogt, K.; Roznowski, A. B.; Wiedenmann, B. J.; Meyer, T. F.; Aebischer, T. und Jungblut, P. R. (2002): Immunoproteomics of Helicobacter pylori infection and relation to gastric disease, Proteomics. 2 [3], Seite 313-324. [39] Dunn, B. E.; Perez-Perez, G. I. und Blaser, M. J. (1989): Two-dimensional gel electrophoresis and immunoblotting of Campylobacter pylori proteins, Infect.Immun. 57 [6], Seite 1825-1833. [40] Lock, R. A.; Coombs, G. W.; McWilliams, T. M.; Pearman, J. W.; Grubb, W. B.; Melrose, G. J. und Forbes, G. M. (2002): Proteome analysis of highly immunoreactive proteins of Helicobacter pylori, Helicobacter. 7 [3], Seite 175-182. [41] McAtee, C. P.; Fry, K. E. und Berg, D. E. (1998): Identification of potential diagnostic and vaccine candidates of Helicobacter pylori by "proteome" technologies, Helicobacter. 3 [3], Seite 163-169. [42] Utt, M.; Nilsson, I.; Ljungh, A. und Wadstrom, T. (2002): Identification of novel immunogenic proteins of Helicobacter pylori by proteome technology, J.Immunol.Methods 259 [1-2], Seite 1-10. [43] Sabarth, N.; Hurwitz, R.; Meyer, T. F. und Bumann, D. (2002): Multiparameter Selection of Helicobacter pylori Antigens Identifies Two Novel Antigens with High Protective Efficacy, Infect.Immun. 70 [11], Seite 6499-6503. [44] Nilsson, C.; Sillen, A.; Eriksson, L.; Strand, M. L.; Enroth, H.; Normark, S.; Falk, P. und Engstrand, L. (2003): Correlation between cag pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease, Infect.Immun. 71 [11], Seite 6573-6581. [45] Graham, D. Y. und Yamaoka, Y. (2000): Disease-specific Helicobacter pylori virulence factors: the unfulfilled promise, Helicobacter. 5 Suppl 1, Seite S3-S9. [46] Farthing, M. J.; Fitzgerald, R. und Zhang, Z. W. (2001): Acid, helicobacter and immunity: a new paradigm for oesophagogastric cancer, J.Physiol Paris 95 [1-6], Seite 423-427. [47] McColl, K. E. und el Omar, E. (1996): Helicobacter pylori and disturbance of gastric function associated with duodenal ulcer disease and gastric cancer, Scand.J.Gastroenterol.Suppl 215, Seite 32-37. [48] Hansson, L. E.; Nyren, O.; Hsing, A. W.; Bergstrom, R.; Josefsson, S.; Chow, W. H.; Fraumeni, J. F., Jr. und Adami, H. O. (1996): The risk of stomach cancer in patients with gastric or duodenal ulcer disease, N.Engl.J.Med. 335 [4], Seite 242-249. [49] Graham, D. Y. (1997): Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model, Gastroenterology 113 [6], Seite 1983-1991. [50] Parsonnet, J.; Friedman, G. D.; Vandersteen, D. P.; Chang, Y.; Vogelman, J. H.; Orentreich, N. und Sibley, R. K. (1991): Helicobacter pylori infection and the risk of gastric carcinoma, N.Engl.J.Med. 325 [16], Seite 1127-1131. [51] Uemura, N.; Okamoto, S.; Yamamoto, S.; Matsumura, N.; Yamaguchi, S.; Yamakido, M.; Taniyama, K.; Sasaki, N. und Schlemper, R. J. (2001): Helicobacter pylori infection and the development of gastric cancer, N.Engl.J.Med. 345 [11], Seite 784-789. [52] Calam, J. und Baron, J. H. (2001): ABC of the upper gastrointestinal tract: Pathophysiology of duodenal and gastric ulcer and gastric cancer, BMJ 323 [7319], Seite 980-982. [53] El Omar, E. M.; Oien, K.; El Nujumi, A.; Gillen, D.; Wirz, A.; Dahill, S.; Williams, C.; Ardill, J. E. und McColl, K. E. (1997): Helicobacter pylori infection and chronic gastric acid hyposecretion, Gastroenterology 113 [1], Seite 15-24. [54] El Omar, E. M.; Carrington, M.; Chow, W. H.; McColl, K. E.; Bream, J. H.; Young, H. A.; Herrera, J.; Lissowska, J.; Yuan, C. C.; Rothman, N.; Lanyon, G.; Martin, M.; Fraumeni, J. F., Jr. und Rabkin, C. S. (2000): Interleukin-1 polymorphisms associated with increased risk of gastric cancer, Nature 404 [6776], Seite 398-402. [55] Furuta, T.; El Omar, E. M.; Xiao, F.; Shirai, N.; Takashima, M.; Sugimura, H. und Sugimurra, H. (2002): Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan, Gastroenterology 123 [1], Seite 92-105. [56] Alm, R. A.; 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. und Trust, T. J. (1999): Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori, Nature 397 [6715], Seite 176-180. [57] Ogura, K.; Maeda, S.; Nakao, M.; Watanabe, T.; Tada, M.; Kyutoku, T.; Yoshida, H.; Shiratori, Y. und Omata, M. (2000): Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil, J.Exp.Med. 192 [11], Seite 1601-1610. [58] Joyce, E. A.; Chan, K.; Salama, N. R. und Falkow, S. (2002): Redefining bacterial populations: a post-genomic reformation, Nat.Rev.Genet. 3 [6], Seite 462-473. [59] Schmidt, F.; Schmid, M.; Jungblut, P. R.; Mattow, J.; Facius, A. und Pleissner, K. P. (2003): Iterative data analysis is the key for exhaustive analysis of peptide mass fingerprints from proteins separated by two-dimensional electrophoresis, J.Am.Soc.Mass Spectrom. 14 [9], Seite 943-956. [60] Chang, J. W.; Young, D. A.; Coleman, P. D. und O'Banion, M. K. (2001): Two-dimensional gel analysis of secreted proteins induced by interleukin-1 beta in rat astrocytes, Neurochem.Int. 39 [5-6], Seite 349-359. [61] Houry, W. A.; Frishman, D.; Eckerskorn, C.; Lottspeich, F. und Hartl, F. U. (1999): Identification of in vivo substrates of the chaperonin GroEL, Nature 402 [6758], Seite 147-154. [62] Imam-Sghiouar, N.; Laude-Lemaire, I.; Labas, V.; Pflieger, D.; Le Caer, J. P.; Caron, M.; Nabias, D. K. und Joubert-Caron, R. (2002): Subproteomics analysis of phosphorylated proteins: application to the study of B-lymphoblasts from a patient with Scott syndrome, Proteomics. 2 [7], Seite 828-838. [63] Stancato, L. F. und Petricoin, E. F., III (2001): Fingerprinting of signal transduction pathways using a combination of anti-phosphotyrosine immunoprecipitations and two-dimensional polyacrylamide gel electrophoresis, Electrophoresis 22 [10], Seite 2120-2124. [64] Steinitz, M. und Tamir, S. (1995): An improved method to create nitrocellulose particles suitable for the immobilization of antigen and antibody, J.Immunol.Methods 187 [1], Seite 171-177. [65] Fenn, J. B. et. al.:Proc 36th Annual Conference, Am. Soc. for Mass Spectrom., 05.-10.06.1988, San Francisco. [66] Tanaka, K., Ido, Y., Akita, S., Yoshida, Y., and Yoshida, T.:Proc. Second Japan-China Joint Symposium on Mass Spectrometry 15.-18.09.1987 in Osaka, Japan. [67] Karas, M. und Hillenkamp, F. (1988): Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons, Anal.Chem. 60 [20], Seite 2299-2301. [68] Karas, M.; Gluckmann, M. und Schafer, J. (2000): Ionization in matrix-assisted laser desorption/ionization: singly charged molecular ions are the lucky survivors, J.Mass Spectrom. 35 [1], Seite 1-12. [69] Zolg, J. W. und Langen, H. (2004): How industry is approaching the search for new diagnostic markers and biomarkers, Mol.Cell Proteomics. 3 [4], Seite 345-354. [70] Mann M.:Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Applied Topics, Altana, GA. [71] Pleissner, K. P.; Regitz-Zagrosek, V.; Krudewagen, B.; Trenkner, J.; Hocher, B. und Fleck, E. (1998): Effects of renovascular hypertension on myocardial protein patterns: analysis by computer-assisted two-dimensional gel electrophoresis, Electrophoresis 19 [11], Seite 2043-2050. [72] Pun, T.; Hochstrasser, D. F.; Appel, R. D.; Funk, M.; Villars-Augsburger, V. und Pellegrini, C. (1988): Computerized classification of two-dimensional gel electrophoretograms by correspondence analysis and ascendant hierarchical clustering, Appl.Theor.Electrophor. 1 [1], Seite 3-9. [73] Schmid, H. R.; Schmitter, D.; Blum, P.; Miller, M. und Vonderschmitt, D. (1995): Lung tumor cells: a multivariate approach to cell classification using two-dimensional protein pattern, Electrophoresis 16 [10], Seite 1961-1968. [74] Krah, A.; Wessel, R. und Pleissner, K. P. (2004): Assessment of Protein Spot Components Applying Correspondence Analysis for Peptide Mass Fingerprint Data, Proteomics. in press. [75] Klade, C. S. (2002): Proteomics approaches towards antigen discovery and vaccine development, Curr.Opin.Mol.Ther. 4 [3], Seite 216-223. [76] Klose, J. und Kobalz, U. (1995): Two-dimensional electrophoresis of proteins: an updated protocol and implications for a functional analysis of the genome, Electrophoresis 16 [6], Seite 1034-1059. [77] Jungblut, P.; Eckerskorn, C.; Lottspeich, F. und Klose, J. (1990): Blotting efficiency investigated by using two-dimensional electrophoresis, hydrophobic membranes and proteins from different sources, Electrophoresis 11 [7], Seite 581-588. [78] Perkins, D. N.; Pappin, D. J.; Creasy, D. M. und Cottrell, J. S. (1999): Probability-based protein identification by searching sequence databases using mass spectrometry data, Electrophoresis 20 [18], Seite 3551-3567. [79] Barthel, M.; Hapfelmeier, S.; Quintanilla-Martinez, L.; Kremer, M.; Rohde, M.; Hogardt, M.; Pfeffer, K.; Russmann, H. und Hardt, W. D. (2003): Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host, Infect.Immun. 71 [5], Seite 2839-2858. [80] Jungblut, P. R. und Seifert, R. (1990): Analysis by high-resolution two-dimensional electrophoresis of differentiation-dependent alterations in cytosolic protein pattern of HL-60 leukemic cells, J.Biochem.Biophys.Methods 21 [1], Seite 47-58. [81] Iaquinto, G.; Todisco, A.; Giardullo, N.; D'Onofrio, V.; Pasquale, L.; De Luca, A.; Andriulli, A.; Perri, F.; Rega, C.; De Chiara, G.; Landi, M.; Taccone, W.; Leandro, G. und Figura, N. (2000): Antibody response to Helicobacter pylori CagA and heat-shock proteins in determining the risk of gastric cancer development, Dig.Liver Dis. 32 [5], Seite 378-383. [82] Keller, B. O. und Li, L. (2000): Discerning matrix-cluster peaks in matrix-assisted laser desorption/ionization time-of-flight mass spectra of dilute peptide mixtures, J.Am.Soc.Mass Spectrom. 11 [1], Seite 88-93. [83] Ding, Q.; Xiao, L.; Xiong, S.; Jia, Y.; Que, H.; Guo, Y. und Liu, S. (2003): Unmatched masses in peptide mass fingerprints caused by cross-contamination: An updated statistical result, Proteomics. 3 [7], Seite 1313-1317. [84] Harris, W. A.; Janecki, D. J. und Reilly, J. P. (2002): Use of matrix clusters and trypsin autolysis fragments as mass calibrants in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Rapid Commun.Mass Spectrom. 16 [18], Seite 1714-1722. [85] Krah, A.; Miehlke, S.; Pleissner, K. P.; Zimny-Arndt, U.; Kirsch, C.; Lehn, N.; Meyer, T. F.; Jungblut, P. R. und Aebischer, T. (2004): Identification of candidate antigens for serologic detection of Helicobacter pylori-infected patients with gastric carcinoma, Int.J.Cancer 108 [3], Seite 456-463. [86] Schmidt, F.; Lueking, A.; Nordhoff, E.; Gobom, J.; Klose, J.; Seitz, H.; Egelhofer, V.; Eickhoff, H.; Lehrach, H. und Cahill, D. J. (2002): Generation of minimal protein identifiers of proteins from two-dimensional gels and recombinant proteins, Electrophoresis 23 [4], Seite 621-625. [87] Krah, A.; Schmidt, F.; Becher, D.; Schmid, M.; Albrecht, D.; Rack, A.; Buttner, K. und Jungblut, P. R. (2003): Analysis of Automatically Generated Peptide Mass Fingerprints of Cellular Proteins and Antigens from Helicobacter pylori 26695 Separated by Two-dimensional Electrophoresis, Mol.Cell Proteomics. 2 [12], Seite 1271-1283. [88] Enroth, H.; Akerlund, T.; Sillen, A. und Engstrand, L. (2000): Clustering of clinical strains of Helicobacter pylori analyzed by two-dimensional gel electrophoresis, Clin.Diagn.Lab Immunol. 7 [2], Seite 301-306. [89] Yamaguchi, H.; Osaki, T.; Kai, M.; Taguchi, H. und Kamiya, S. (2000): Immune response against a cross-reactive epitope on the heat shock protein 60 homologue of Helicobacter pylori, Infect.Immun. 68 [6], Seite 3448-3454. [90] Gonzalez, C. A.; Sala, N. und Capella, G. (2002): Genetic susceptibility and gastric cancer risk, Int.J.Cancer 100 [3], Seite 249-260. [91] Kandror, O.; Busconi, L.; Sherman, M. und Goldberg, A. L. (1994): Rapid degradation of an abnormal protein in Escherichia coli involves the chaperones GroEL and GroES, J.Biol.Chem. 269 [38], Seite 23575-23582. [92] Wood, Z. A.; Poole, L. B.; Hantgan, R. R. und Karplus, P. A. (2002): Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins, Biochemistry 41 [17], Seite 5493-5504. [93] Shibayama, K.; Kamachi, K.; Nagata, N.; Yagi, T.; Nada, T.; Doi, Y.; Shibata, N.; Yokoyama, K.; Yamane, K.; Kato, H.; Iinuma, Y. und Arakawa, Y. (2003): A novel apoptosis-inducing protein from Helicobacter pylori, Mol.Microbiol. 47 [2], Seite 443-451. [94] McGovern, K. J.; Blanchard, T. G.; Gutierrez, J. A.; Czinn, S. J.; Krakowka, S. und Youngman, P. (2001): gamma-Glutamyltransferase is a Helicobacter pylori virulence factor but is not essential for colonization, Infect.Immun. 69 [6], Seite 4168-4173. [95] Wolf, K.; Fischer, E.; Mead, D.; Zhong, G.; Peeling, R.; Whitmire, B. und Caldwell, H. D. (2001): Chlamydia pneumoniae major outer membrane protein is a surface-exposed antigen that elicits antibodies primarily directed against conformation- dependent determinants, Infect.Immun. 69 [5], Seite 3082-3091.