{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T05:45:50Z","timestamp":1765691150483,"version":"3.48.0"},"reference-count":30,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1995,8]]},"abstract":"<jats:p>Duodenal ulcers are associated with gastric metaplasia in the duodenum, both at the ulcer margin and at more distant sites in the duodenal bulb. pS2 and human spasmolytic polypeptide (hSP) are secretory peptides expressed in gastric epithelial cells and in gastric metaplasia. As these peptides may be important in ulcer healing, this study investigated the possibility that the expression of pS2 and hSP is increased in gastric metaplasia at the margin of duodenal ulcers. Duodenal bulb biopsy specimens from 12 duodenal ulcer patients were assessed. Sections were immunostained with monoclonal antibodies for pS2 and hSP. Cytoplasmic stain intensities were measured by an image analysis system and expressed as integrated optical density (IOD) units, In situ hybridisation for pS2 and hSP mRNA was carried out on parallel sections. Duodenal sections were also stained with diatase periodic acid Schiff\/alcian blue to localise areas of gastric metaplasia. pS2 antigen staining in the duodenum was restricted to surface epithelial cells, and hSP to acinar and ductular components of Brunner's gland. mRNA localisation corresponded to immunostaining cells. In gastric metaplasia, pS2 expression was greater at the ulcer margin than away from the ulcer, as judged by the intensity of antibody staining (mean IOD units (SEM), 20.6 (3.3) v 9.5 (3.0); p &lt; 0.001). There was a trend towards greater hSP staining at the ulcer margin but this did not achieve statistical significance. These findings support the putative role of pS2 and possible hSP in mucosal healing and providy further evidence for an autocrine 'ulcer-gastric metaplasia-repair' loop involving these trefoil peptides.<\/jats:p>","DOI":"10.1136\/gut.37.2.205","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"205-209","source":"Crossref","is-referenced-by-count":22,"title":["Expression of trefoil peptides pS2 and human spasmolytic polypeptide in gastric metaplasia at the margin of duodenal ulcers."],"prefix":"10.1136","volume":"37","author":[{"given":"S","family":"Khulusi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A M","family":"Hanby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Marrero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A","family":"Mendall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Badve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Poulsom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Elia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N A","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T C","family":"Northfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1995,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0014-5793(89)80690-8","article-title":"A new family of growth factor-like peptides. 'Trefoil' disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins)","volume":"250","author":"Thim, L.","year":"1989","unstructured":"Thim L. A new family of growth factor-like peptides. 'Trefoil' disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins). FEBS Lett 1989; 250: 85-90.","journal-title":"FEBS Lett"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/path.1711620402","article-title":"Epidermal growth factor (EGF\/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues","volume":"162","author":"Wright, N.A.; Poulsom, R.; Stamp, G.W.; Hall, P.A.; Jeffery, R.E.; Longcroft, J.M.","year":"1990","unstructured":"Wright NA, Poulsom R, Stamp GW, Hall PA, Jeffery RE, Longcroft JM, et al. Epidermal growth factor (EGF\/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues. J Pathol 1990; 162: 279-84.","journal-title":"J Pathol"},{"key":"ref_3","first-page":"375","article-title":"Induction of pS2 and hSP genes as markers of mucosal ulceration","volume-title":"of the digestive tract. Gastroenterology 1991","volume":"100","author":"Rio, M.C.; Chenard, M.P.; Wolf, C.; Marcellin, L.; Tomasetto, C.; Lathe, R.","unstructured":"Rio MC, Chenard MP, Wolf C, Marcellin L, Tomasetto C, Lathe R, et al. Induction of pS2 and hSP genes as markers of mucosal ulceration of the digestive tract. Gastroenterology 1991; 100: 375-9."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/path.1711690313","article-title":"The expression of the trefoil peptides pS2 and human spasmolytic polypeptide (hSP) in 'gastric metaplasia' of the proximal duodenum: implications for the nature of 'gastric metaplasia'","volume":"169","author":"Hanby, A.M.; Poulsom, R.; Elia, G.; Singh, S.; Longcroft, J.M.; Wright, N.A.","year":"1993","unstructured":"Hanby AM, Poulsom R, Elia G, Singh S, Longcroft JM, Wright NA. The expression of the trefoil peptides pS2 and human spasmolytic polypeptide (hSP) in 'gastric metaplasia' of the proximal duodenum: implications for the nature of 'gastric metaplasia'. JPathol 1993; 169: 355-60.","journal-title":"JPathol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1126\/science.3041593","article-title":"Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa","volume":"241","author":"Rio, M.C.; Bellocq, J.P.; Daniel, J.Y.; Tomasetto, C.; Lathe, R.; Chenard, M.P.","year":"1988","unstructured":"Rio MC, Bellocq JP, Daniel JY, Tomasetto C, Lathe R, Chenard MP, et al. Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa. Science 1988; 241: 705-8.","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1093\/nar\/12.6.2861","article-title":"Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7","volume":"12","author":"Jakowlew, S.B.; Breathnach, R.; Jeltsch, J.M.; Masiakowski, P.; Chambon, P.","year":"1984","unstructured":"Jakowlew SB, Breathnach R, Jeltsch JM, Masiakowski P, Chambon P. Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7. NucleicAcids Res 1984; 12: 2861-78.","journal-title":"NucleicAcids Res"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1210\/endo-121-5-1759","article-title":"Characterization of the estrogen-induced pS2 protein secreted by the human breast cancer cell line MCF-7","volume":"5","author":"Nunez, A.M.","year":"1987","unstructured":"Nunez AM, Jakowlev 5, Briand JP, Gaire M, Krust A, Rio MC, et al. Characterization of the estrogen-induced pS2 protein secreted by the human breast cancer cell line MCF-7. Endocrinologzy 1987; 121: 1759-65.","journal-title":"Endocrinologzy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/j.1460-2075.1990.tb08125.x","article-title":"hSP, the domain-duplicated homologue of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma","volume":"9","author":"Tomasetto, C.; Rio, M.C.; Gautier, C.; Wolf, C.; Hareuveni, M.; Chambon, P.","year":"1990","unstructured":"Tomasetto C, Rio MC, Gautier C, Wolf C, Hareuveni M, Chambon P, et al. hSP, the domain-duplicated homologue of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. EMBO J 1990; 9: 407-14.","journal-title":"EMBO J"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0014-5793(93)80543-4","article-title":"Purification and characterization of the trefoil peptide human spasmolytic polypeptide (hSP) produced in yeast","volume":"318","author":"Thim, L.; Norris, K.; Norris, F.; Nielsen, P.F.; Bjom, S.E.; Christensen, M.","year":"1993","unstructured":"Thim L, Norris K, Norris F, Nielsen PF, Bjom SE, Christensen M, et al. Purification and characterization of the trefoil peptide human spasmolytic polypeptide (hSP) produced in yeast. FEBS Lett 1993; 318: 345-52.","journal-title":"FEBS Lett"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/0016-5085(95)90014-4","article-title":"Human spasmolytic polypeptide is a cytoprotective agent which stimulates cell migration","volume":"108","author":"Playford, R.; Marchbank, T.; Chinery, R.; Evison, R.; Pignatelli, M.; Bolton, R.","year":"1995","unstructured":"Playford R, Marchbank T, Chinery R, Evison R, Pignatelli M, Bolton R, et al. Human spasmolytic polypeptide is a cytoprotective agent which stimulates cell migration. Gastroenterology 1995; 108: 108-16.","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0014-5793(89)81357-2","article-title":"Growth stimulatory effect of pancreatic spasmolytic polypeptide on cultured colon and breast tumor cells","volume":"247","author":"Hoosein, N.M.; Thim, L.; Jorgensen, K.H.; Brattain, M.G.","year":"1989","unstructured":"Hoosein NM, Thim L, Jorgensen KH, Brattain MG. Growth stimulatory effect of pancreatic spasmolytic polypeptide on cultured colon and breast tumor cells. FEBS Lett 1989; 247: 303-6.","journal-title":"FEBS Lett"},{"key":"ref_12","first-page":"3832","article-title":"Prediction of relapse and survival in breast cancer patients by pS2 protein status","volume":"50","author":"Foekens, J.A.; Rio, M.C.; Seguin, P.; van PW; Fauque, J.; Nap, M.; Klijn, J.G.","year":"1990","unstructured":"Foekens JA, Rio MC, Seguin P, van PW, Fauque J, Nap M, Klijn JG, et al. Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res 1990; 50: 3832-7.","journal-title":"Cancer Res"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/j.1460-2075.1989.tb03443.x","article-title":"The 5' flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein","volume":"8","author":"Nunez, A.M.; Berry, M.; Imler, J.L.; Chambon, P.","year":"1989","unstructured":"Nunez AM, Berry M, Imler JL, Chambon P. The 5' flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein. EMBOJ_ 1989; 8: 823-9.","journal-title":"EMBOJ_"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1136\/gut.30.6.790","article-title":"Campylobacter pylori, duodenal ulcer, and gastric metaplasia: possible role of functional heterotopic tissue in ulcerogenesis","volume":"30","author":"Carrick, J.; Lee, A.; Hazell, S.; Ralston, M.; Daskalopoulos, G.","year":"1989","unstructured":"Carrick J, Lee A, Hazell S, Ralston M, Daskalopoulos G. Campylobacter pylori, duodenal ulcer, and gastric metaplasia: possible role of functional heterotopic tissue in ulcerogenesis. Gut 1989; 30: 790-7.","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1007\/BF01538072","article-title":"Gastric metaplasia in duodenal bulb and Campylobacter-like organisms in development of duodenal ulcer","volume":"34","author":"Caselli, M.; Trevisani, L.; Aleotti, A.; Bovolenta, M.R.; Stabellini, G.","year":"1989","unstructured":"Caselli M, Trevisani L, Aleotti A, Bovolenta MR, Stabellini G. Gastric metaplasia in duodenal bulb and Campylobacter-like organisms in development of duodenal ulcer. Dig Dis Sci 1989; 34: 1374-8.","journal-title":"Dig Dis Sci"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1136\/gut.5.5.454","article-title":"Experimental production of gastric epithelium in the duodenum","volume":"5","author":"Rhodes, J.","year":"1964","unstructured":"Rhodes J. Experimental production of gastric epithelium in the duodenum. Gut 1964; 5: 454-60.","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1136\/gut.30.3.311","article-title":"Enhancement by tetragastrin of experimental induction of gastric epithelium in the duodenum","volume":"30","author":"Tatsuta, M.; Iishi, H.; Yamamura, H.; Yamamoto, R.; Taniguchi, H.","year":"1989","unstructured":"Tatsuta M, Iishi H, Yamamura H, Yamamoto R, Taniguchi H. Enhancement by tetragastrin of experimental induction of gastric epithelium in the duodenum. Gut 1989; 30: 311-5.","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/path.1700400203","article-title":"The healing of artificial defects of the duodenal mucosa","volume":"40","author":"Florey, H.; Harding, H.","year":"1935","unstructured":"Florey H, Harding H. The healing of artificial defects of the duodenal mucosa. J Pathol Bacteriol 1935; 40: 211-8.","journal-title":"J Pathol Bacteriol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1136\/jcp.43.12.981","article-title":"Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation","volume":"43","author":"Wyatt, J.I.; Rathbone, B.J.; Sobala, G.M.; Shallcross, T.; Heatley, R.V.; Axon, A.T.","year":"1990","unstructured":"Wyatt JI, Rathbone BJ, Sobala GM, Shallcross T, Heatley RV, Axon AT, et al. Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation. J Clin Pathol 1990; 43: 981-6.","journal-title":"J Clin Pathol"},{"key":"ref_20","first-page":"53","article-title":"The migration pathway of epithelial cells on the human duodenal villi: the origin and fate of 'gastric metaplastic' cells in duodenal mucosa","volume":"1","author":"Liu, K.; Wright, N.","year":"1992","unstructured":"Liu K, Wright N. The migration pathway of epithelial cells on the human duodenal villi: the origin and fate of 'gastric metaplastic' cells in duodenal mucosa. Epithelial Cell Biol 1992; 1: 53-8.","journal-title":"Epithelial Cell Biol"},{"key":"ref_21","first-page":"1239","article-title":"Intravenous epidermal growth factor\/urogastrone increases small intestinal cell proliferation in congenital microvillous atrophy","volume":"ii:","author":"Walker-Smith, J.; Phillips, A.; Walford, N.; Gregory, H.; Fitzgerald, J.; MacCullagh, K.","year":"1985","unstructured":"Walker-Smith J, Phillips A, Walford N, Gregory H, Fitzgerald J, MacCullagh K, et al. Intravenous epidermal growth factor\/urogastrone increases small intestinal cell proliferation in congenital microvillous atrophy. Lancet 1985; ii: 1239-40.","journal-title":"Lancet"},{"key":"ref_22","first-page":"1300","article-title":"Role of epidermal growth factor in healing of chronic gastroduodenal","volume-title":"ulcers in rats. Gastroenterology 1988; 94","author":"Konturek, S.; Dembinski, A.; Warzecha, Z.; Brzozowski, T.; Gregory, H.","unstructured":"Konturek S, Dembinski A, Warzecha Z, Brzozowski T, Gregory H. Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology 1988; 94: 1300-7."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/BF00158289","article-title":"The production and characterization of a new monoclonal antibody to the trefoil peptide human spasmolytic polypeptide","volume":"26","author":"Elia, G.; Chinery, R.; Hanby, A.; Poulsom, R.; Wright, N.","year":"1994","unstructured":"Elia G, Chinery R, Hanby A, Poulsom R, Wright N. The production and characterization of a new monoclonal antibody to the trefoil peptide human spasmolytic polypeptide. Histochem J 1994; 26: 644-7.","journal-title":"Histochem J"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/0016-5085(93)90830-6","article-title":"Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease","volume":"104","author":"Wright, N.A.; Poulsom, R.; Stamp, G.; Van Noorden, S.; Sarraf, C.; Elia, G.","year":"1993","unstructured":"Wright NA, Poulsom R, Stamp G, Van Noorden S, Sarraf C, Elia G, et al. Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. Gastroenterology 1993; 104: 12-20.","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/0016-5085(94)90590-8","article-title":"Spasmolytic polypeptide: a trefoil peptide secreted by rat gastric mucosal cells","volume":"106","author":"Jeffrey, G.; Oates, P.; Wang, T.; Babyatsky, M.; Brand, S.","year":"1994","unstructured":"Jeffrey G, Oates P, Wang T, Babyatsky M, Brand S. Spasmolytic polypeptide: a trefoil peptide secreted by rat gastric mucosal cells. Gastroenterology 1994; 106: 336-45.","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1365-2559.1983.tb02213.x","article-title":"The endoscopically abnormal duodenum in patients with dyspepsia: biopsy findings in 60 cases","volume":"7","author":"Shousha, S.; Spiller, R.C.; Parkins, R.A.","year":"1983","unstructured":"Shousha S, Spiller RC, Parkins RA. The endoscopically abnormal duodenum in patients with dyspepsia: biopsy findings in 60 cases. Histopathology 1983; 7: 23-34.","journal-title":"Histopathology"},{"key":"ref_27","first-page":"193","article-title":"The effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum","volume-title":"Gut","volume":"36","author":"Khulusi, S.; Mendall, M.; Badve, S.; Patel, P.; Finlayson, C.; Northfield, T.C.","year":"1995","unstructured":"Khulusi S, Mendall M, Badve S, Patel P, Finlayson C, Northfield TC. The effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum. Gut 1995; 36: 193-7."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/343082a0","article-title":"Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells","volume":"343","author":"Wright, N.A.; Pike, C.; Elia, G.","year":"1990","unstructured":"Wright NA, Pike C, Elia G. Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature 1990; 343: 82-5.","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0016-5085(83)80007-9","article-title":"Epidermal growth factor inhibits cystamine-induced duodenal ulcers","volume":"85","author":"Kirkegaard, P.; Olsen, P.; Peulsen, S.; Nexo, S.","year":"1983","unstructured":"Kirkegaard P, Olsen P, Peulsen S, Nexo S. Epidermal growth factor inhibits cystamine-induced duodenal ulcers. Gastroenterology 1983; 85: 1277-83.","journal-title":"Gastroenterology"},{"key":"ref_30","first-page":"62","article-title":"Increased pS2 secretion in the serum of Crohn's disease patients","volume":"3","author":"Duclos, B.; Rio, M.-C.; Reimund, J.; Chaumark, P.; Baumann, R.; Chambon, P.","year":"1991","unstructured":"Duclos B, Rio M-C, Reimund J, Chaumark P, Baumann R, Chambon P, et al. Increased pS2 secretion in the serum of Crohn's disease patients. European Journal of Gastroenterology and Hepatology 1991; 3: S62.","journal-title":"European Journal of Gastroenterology and Hepatology"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.37.2.205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T05:43:31Z","timestamp":1765691011000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.37.2.205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,8]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1995,8,1]]},"published-print":{"date-parts":[[1995,8]]}},"alternative-id":["10.1136\/gut.37.2.205"],"URL":"https:\/\/doi.org\/10.1136\/gut.37.2.205","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[1995,8]]}}}