{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:25:29Z","timestamp":1791109529792,"version":"4.1.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,6,20]]},"abstract":"<jats:p>\n                    The complete genome sequence revealed a family of 32 outer membrane proteins (OMPs) in\n                    <jats:italic>Helicobacter pylori.<\/jats:italic>\n                    We examined the effect of four OMPs (HP0638, HP0796, HP1501, and\n                    <jats:italic>babA2<\/jats:italic>\n                    ) on the production of the proinflammatory cytokine, IL-8. Mutants of the four OMPs, as well as\n                    <jats:italic>cagE<\/jats:italic>\n                    and\n                    <jats:italic>galE<\/jats:italic>\n                    from\n                    <jats:italic>H. pylori<\/jats:italic>\n                    from the U.S. and Japan, were constructed by inserting a chloramphenicol-resistant cassette into the gene. Twenty-two pairs of parental and mutant\n                    <jats:italic>H. pylori<\/jats:italic>\n                    strains, as well as 160 clinical isolates (80 from Japanese and 80 from U.S.), were cocultured with gastric cancer cell lines. IL-8 production in the supernatant and adhesion was assayed by ELISA. HP0796, HP1501,\n                    <jats:italic>babA2<\/jats:italic>\n                    , and\n                    <jats:italic>galE<\/jats:italic>\n                    gene knockouts had no significant effect on IL-8 production. Knockout of the HP0638 gene in 81% of\n                    <jats:italic>cag<\/jats:italic>\n                    -positive strains reduced IL-8 production approximately 50%. The three\n                    <jats:italic>cag<\/jats:italic>\n                    -positive strains in which IL-8 levels were unchanged by HP0638 knockout had five or seven CT dinucleotide repeats in the 5\u2032 region, resulting in a frame shift and truncation. Strains with naturally inactive HP0638 gene were all from the U.S.; Japanese strains were always \u201con\u201d and thus, on average, may be more virulent. Although\n                    <jats:italic>cag<\/jats:italic>\n                    -negative isolates produced a limited IL-8 response,\n                    <jats:italic>cag<\/jats:italic>\n                    -negative strains that contained a functional HP0638 gene produced more than 3-fold greater IL-8 than\n                    <jats:italic>cag<\/jats:italic>\n                    -negative nonfunctional HP0638 strains. We hypothesize that functional HP0638 gene may be an important virulence factor in relation to the risk of clinically significant outcomes of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection. We denote HP0638 gene as outer inflammatory protein (\n                    <jats:italic>oipA<\/jats:italic>\n                    ).\n                  <\/jats:p>","DOI":"10.1073\/pnas.130079797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"7533-7538","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":337,"title":["A\n                    <i>M<\/i>\n                    <sub>r<\/sub>\n                    34,000 proinflammatory outer membrane protein (\n                    <i>oipA<\/i>\n                    ) of\n                    <i>Helicobacter pylori<\/i>"],"prefix":"10.1073","volume":"97","author":[{"given":"Yoshio","family":"Yamaoka","sequence":"first","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong H.","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Y.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Boulevard, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,6,13]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1053\/gast.1996.v110.pm8964399","volume":"110","author":"Yamaoka Y","year":"1996","unstructured":"Y Yamaoka, M Kita, T Kodama, N Sawai, J Imanishi Gastroenterology 110, 1744\u20131752 (1996).","journal-title":"Gastroenterology"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1136\/gut.45.6.804","volume":"45","author":"Yamaoka Y","year":"1999","unstructured":"Y Yamaoka, T Kodama, M Kita, J Imanishi, K Kashima, D Y Graham Gut 45, 804\u2013811 (1999).","journal-title":"Gut"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/1043-4666(89)91043-0","volume":"1","author":"Matsushima K","year":"1989","unstructured":"K Matsushima, J J Oppenheim Cytokine 1, 2\u201313 (1989).","journal-title":"Cytokine"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1136\/jcp.48.1.41","volume":"48","author":"Crabtree J E","year":"1995","unstructured":"J E Crabtree, A Covacci, S M Farmery, Z Xiang, D S Tompkins, S Perry, I J Lindley, R Rappuoli J Clin Pathol 48, 41\u201345 (1995).","journal-title":"J Clin Pathol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1128\/iai.63.5.1681-1687.1995","volume":"63","author":"Sharma S A","year":"1995","unstructured":"S A Sharma, M K Tummuru, G G Miller, M J Blaser Infect Immun 63, 1681\u20131687 (1995).","journal-title":"Infect Immun"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"14648","DOI":"10.1073\/pnas.93.25.14648","volume":"93","author":"Censini S","year":"1996","unstructured":"S Censini, C Lange, Z Xiang, J E Crabtree, P Ghiara, M Borodovsky, R Rappuoli, A Covacci Proc Natl Acad Sci USA 93, 14648\u201314653 (1996).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1126\/science.284.5418.1328","volume":"284","author":"Covacci A","year":"1999","unstructured":"A Covacci, J L Telford, G Del Giudice, J Parsonnet, R Rappuoli Science 284, 1328\u20131333 (1999).","journal-title":"Science"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/41483","volume":"388","author":"Tomb J F","year":"1997","unstructured":"J F Tomb, 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, et al. 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