{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:36:33Z","timestamp":1791185793435,"version":"4.1.0"},"reference-count":32,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1996,12]]},"abstract":"<jats:p>BACKGROUND: Coeliac disease (CD) mucosa is flattened despite epithelial hyperproliferation. AIMS: To establish mechanisms of cell loss in CD. PATIENTS: 14 controls, 17 active CD patients, and 16 maintained with gluten free diet. METHODS: Programmed cell death was examined in small intestinal biopsy specimens by staining fragmented DNA using terminal uridine deoxynucleotidyl nick end labelling (TUNEL), in comparison with haematoxylin and eosin stained adjacent sections. Double staining with anti-CD45 antibodies determined the origin of apoptotic cells. Apoptosis was graded from 1-3 (&lt; 5, 5-20, &gt; 20% respectively). Proliferating cells, immunostained by Ki-67 (MIB-1) antibody, were counted. RESULTS: Apoptotic cells were seen rarely by haematoxylin and eosin but more readily by TUNEL. In controls, 1.4 +\/- 0.2% of epithelial cells were apoptotic (mean grade 1.1), mainly located in the upper villus. In active CD, frequent apoptotic cells were distributed throughout the crypt-villus unit (mean grade 2.4), decreasing after treatment to 1.1 (p &lt; 0.001) even when still histologically abnormal. CD45 antibodies rarely stained apoptotic cells in active CD. The number of TUNEL positive cells correlated with proliferating cell number (p &lt; 0.001). CONCLUSION: Enterocyte apoptosis is greatly increased in untreated CD, correlates with proliferation, and falls to normal with a gluten free diet, before histological improvement. Increased apoptosis may be responsible for villous atrophy in CD.<\/jats:p>","DOI":"10.1136\/gut.39.6.811","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"811-817","source":"Crossref","is-referenced-by-count":134,"title":["Increased small intestinal apoptosis in coeliac disease."],"prefix":"10.1136","volume":"39","author":[{"given":"S F","family":"Moss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Attia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J V","family":"Scholes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P R","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"ref_1","first-page":"1643","article-title":"Coeliac disease","volume-title":"Textbook of gaseroeneerology. Vol 2","author":"Kagnoff, M.F.","year":"1995","unstructured":"Kagnoff MF. Coeliac disease. In: Yamada T, ed. Textbook of gaseroeneerology. Vol 2. 2nd ed. Philadelphia: JB Lippicott, 1995: 1643-61.","edition":"2nd ed"},{"key":"ref_2","first-page":"2","article-title":"Goeliac disease and other nutrientrelated injuries to the gastrointestinal tract","volume":"89","author":"Goggins, M.; Kelleher, D.","year":"1994","unstructured":"Goggins M, Kelleher D. Goeliac disease and other nutrientrelated injuries to the gastrointestinal tract. Am J Goastroenterol 1994; 89 (suppl): S2-17.","journal-title":"Am J Goastroenterol"},{"issue":"3","key":"ref_3","first-page":"295","article-title":"Dynamics of the mucosa of the small intestine in idiopathic steatorrhea","volume":"1962","author":"Creamer, B.","unstructured":"Creamer B. Dynamics of the mucosa of the small intestine in idiopathic steatorrhea. Gut 1962; 3: 295-300.","journal-title":"Gut"},{"key":"ref_4","first-page":"735","article-title":"A morphologic and histochemical anlaysis of the human jejunal epithelium","volume-title":"nontropical sprue. Gastroenterology 1961","volume":"40","author":"Padykula, H.A.; Strauss, E.W.; Ladman, A.J.","unstructured":"Padykula HA, Strauss EW, Ladman AJ, et al. A morphologic and histochemical anlaysis of the human jejunal epithelium in nontropical sprue. Gastroenterology 1961; 40: 735-65."},{"issue":"267","key":"ref_5","first-page":"1173","article-title":"Coeliac disease: a study of the jejunal epithelium before and after a glutenfree diet","volume":"1962","author":"Yardley, J.H.; Bayless, T.M.; Norton, J.H.","unstructured":"Yardley JH, Bayless TM, Norton JH, et al. Coeliac disease: a study of the jejunal epithelium before and after a glutenfree diet. NEnglJ Med 1962; 267: 1173-9.","journal-title":"NEnglJ Med"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1056\/NEJM197012032832302","article-title":"Browning TH. Epithelial-cell renewal in cultured duodenal biopsies in coeliac sprue","volume":"283","author":"Trier, J.S.","year":"1970","unstructured":"Trier JS, Browning TH. Epithelial-cell renewal in cultured duodenal biopsies in coeliac sprue. N Engl J7 Med 1970; 283: 1245-50.","journal-title":"N Engl J7 Med"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1136\/gut.14.9.701","article-title":"Cell kinetics in flat (avillous) mucosa of the human small intestine","volume":"14","author":"Wright, N.; Watson, A.; Morley, A.; Appleton, D.; Marks, J.","year":"1973","unstructured":"Wright N, Watson A, Morley A, Appleton D, Marks J. Cell kinetics in flat (avillous) mucosa of the human small intestine. Gut 1973; 14: 701-10.","journal-title":"Gut"},{"key":"ref_8","first-page":"154","article-title":"The use of a stathmokinetic technique with crypt microdissection to estimate the crypt cell production rate in cultured explants of the duodenal mucosa in coeliac disease","volume":"39","author":"Challacombe, D.N.; Wheeler, E.E.","year":"1992","unstructured":"Challacombe DN, Wheeler EE. The use of a stathmokinetic technique with crypt microdissection to estimate the crypt cell production rate in cultured explants of the duodenal mucosa in coeliac disease. Hepatogastroenterology 1992; 39: 154-7.","journal-title":"Hepatogastroenterology"},{"key":"ref_9","first-page":"269","article-title":"Novel insights into human intestinal epithelial cell proliferation in health and disease using confocal microscopy","volume":"26","author":"Savidge, T.C.; Walker-Smith, J.A.; Phillips, A.D.","year":"1995","unstructured":"Savidge TC, Walker-Smith JA, Phillips AD. Novel insights into human intestinal epithelial cell proliferation in health and disease using confocal microscopy. Gut 1995; 26: 269-74.","journal-title":"Gut"},{"key":"ref_10","first-page":"144","article-title":"Gastrointestinal cell loss in man: its measurement and significance","volume":"8","author":"Croft, D.N.; Cotton, P.B.","year":"1973","unstructured":"Croft DN, Cotton PB. Gastrointestinal cell loss in man: its measurement and significance. Digestion 1973; 8: 144-60.","journal-title":"Digestion"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/0016-5085(93)90953-A","article-title":"A novel mechanism for the disposing of effete epithelial cells in the small intestine of guinea pigs","volume":"105","author":"Iwanaga, T.; Han, H.; Adachi, K.; Fujita, T.","year":"1993","unstructured":"Iwanaga T, Han H, Adachi K, Fujita T. A novel mechanism for the disposing of effete epithelial cells in the small intestine of guinea pigs. Gastroenterology 1993; 105: 1089-97.","journal-title":"Gastroenterology"},{"key":"ref_12","first-page":"3569","article-title":"Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis","volume":"107","author":"Hall, P.A.; Coates, P.J.; Ansari, A.; Hopwood, D.","year":"1994","unstructured":"Hall PA, Coates PJ, Ansari A, Hopwood D. Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis. J CeU Sci 1994; 107: 3569-77.","journal-title":"J CeU Sci"},{"key":"ref_13","first-page":"819","article-title":"In situ detection of enterocytic apoptosis in normal colonic mucosa and in familial adenomatous polyposis","volume-title":"Gut","volume":"37","author":"Strater, J.; Koretz, K.; Gunthert, A.R.; M6ller, P.","year":"1995","unstructured":"Strater J, Koretz K, Gunthert AR, M6ller P. In situ detection of enterocytic apoptosis in normal colonic mucosa and in familial adenomatous polyposis. Gut 1995; 37: 819-23."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1126\/science.7878464","article-title":"Apoptosis in the pathogenesis and treatment of disease","volume":"267","author":"Thompson, C.B.","year":"1995","unstructured":"Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456-62.","journal-title":"Science"},{"key":"ref_15","first-page":"3","article-title":"Apoptosis, oncosis and necrosis: an overview of cell death","volume":"146","author":"Majno, G.; Joris, I.","year":"1995","unstructured":"Majno G, Joris I. Apoptosis, oncosis and necrosis: an overview of cell death. AmJ3Pathol 1995; 146: 3-15."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/BF00331373","article-title":"Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA","volume":"278","author":"Kressel, M.; Groscurth, P.","year":"1994","unstructured":"Kressel M, Groscurth P. Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA. Cell Tissue Res 1994; 278: 549-56.","journal-title":"Cell Tissue Res"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","article-title":"Identification of programmed cell death via specific labelling of nuclear DNA fragmentation","volume":"119","author":"Gavrieli, Y.; Sherman, Y.; Ben-Sasson, S.A.","year":"1992","unstructured":"Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death via specific labelling of nuclear DNA fragmentation. J Cell Biol 1992; 119: 493-501.","journal-title":"J Cell Biol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1136\/gut.38.4.498","article-title":"Helicobacter pylori infection induces gastric epithelial apoptosis in vivo","volume":"38","year":"1996","unstructured":"Moss SF, Calam J, Agarwal B, Wang S, Holt PR. Helicobacter pylori infection induces gastric epithelial apoptosis in vivo. Gut 1996; 38: 498-501.","journal-title":"Gut"},{"key":"ref_19","first-page":"6342","article-title":"Apoptosis in mouse bowel by 1,2-dimethylhydrazine, methylazoxymethanol acetate and gamma rays","volume":"49","author":"Ijiri, K.","year":"1989","unstructured":"Ijiri K. Apoptosis in mouse bowel by 1,2-dimethylhydrazine, methylazoxymethanol acetate and gamma rays. Cancer Res 1989; 49: 6342-6.","journal-title":"Cancer Res"},{"key":"ref_20","first-page":"63","article-title":"Intemucleosomal cleavage of DNA as the sole criterion for apoptosis may be artifactual","volume":"124","author":"Enright, H.; Hebbel, R.; Nath, K.","year":"1994","unstructured":"Enright H, Hebbel R, Nath K. Intemucleosomal cleavage of DNA as the sole criterion for apoptosis may be artifactual. Y Lab Clin Med 1994; 124: 63-8.","journal-title":"Y Lab Clin Med"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0304-3940(88)90346-1","article-title":"The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system","volume":"85","author":"Shu, S.; Ju, G.; Fan, L.","year":"1988","unstructured":"Shu S, Ju G, Fan L. The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system. Neurosci Letts 1988; 85: 169-7 1.","journal-title":"Neurosci Letts"},{"key":"ref_22","first-page":"741","article-title":"Differences in epithelial apoptosis and apoptosis-related gene expression between the rat small","volume-title":"and large intestine. Gastroenterology 1995","volume":"108","author":"Moss, S.F.; Arber, N.; Guan, R.; Heydari, A.R.; Krajewski, S.; Reed, J.C.","unstructured":"Moss SF, Arber N, Guan R, Heydari AR, Krajewski S, Reed JC, et al. Differences in epithelial apoptosis and apoptosis-related gene expression between the rat small and large intestine. Gastroenterology 1995; 108: A741."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1440-1746.1990.tb01411.x","article-title":"Quantitative study of apoptosis in normal rat gastroduodenal mucosa","volume":"5","author":"Benedetti, A.; Mancini, R.; Marucci, L.; Paolucci, F.; Jezequel, A.M.; Orlandi, F.","year":"1990","unstructured":"Benedetti A, Mancini R, Marucci L, Paolucci F, Jezequel AM, Orlandi F. Quantitative study of apoptosis in normal rat gastroduodenal mucosa. J Gastroenterol Hepatol 1990; 5: 369-74.","journal-title":"J Gastroenterol Hepatol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0022-5320(77)80071-3","article-title":"Ultrastructure of Cell Loss in Intestinal Mucosa","volume":"60","author":"Potten, C.S.; Allen, T.D.","year":"1977","unstructured":"Potten CS, Allen TD. Ultrastructure of Cell Loss in Intestinal Mucosa. J Ultrastructure Res 1977; 60: 272-7.","journal-title":"J Ultrastructure Res"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1679\/aohc.58.205","article-title":"The fate of epithelial cells at the villus tips of the human small intestine","volume":"58","author":"Shibahara, T.; Sato, N.; Waguri, S.; Iwanaga, T.; Nakahara, A.; Fukutomi, H.; Uchiyama, Y.","year":"1995","unstructured":"Shibahara T, Sato N, Waguri S, Iwanaga T, Nakahara A, Fukutomi H, Uchiyama Y. The fate of epithelial cells at the villus tips of the human small intestine. Arch Histol Cytol 1995; 58: 205-19.","journal-title":"Arch Histol Cytol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/09553009414550101","article-title":"Characterization of radiation-induced apoptosis in the small intestine and its biological implications","volume":"65","author":"Potten, C.S.; Merritt, A.; Hickman, J.; Hall, P.; Farando, A.","year":"1994","unstructured":"Potten CS, Merritt A, Hickman J, Hall P, Farando A. Characterization of radiation-induced apoptosis in the small intestine and its biological implications. IntJ Radiat Biol 1994; 65: 71-8.","journal-title":"IntJ Radiat Biol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1093\/carcin\/13.12.2305","article-title":"A possible explanation for the differential cancer incidence in the intestine, based on distribution of the cytotoxic effects of carcinogens in the murine large bowel","volume":"13","author":"Potten, C.S.; Li, Y.Q.; O'Connor, P.J.; Winton, D.J.","year":"1992","unstructured":"Potten CS, Li YQ, O'Connor PJ, Winton DJ. A possible explanation for the differential cancer incidence in the intestine, based on distribution of the cytotoxic effects of carcinogens in the murine large bowel. Carcinogenesis 1992; 13: 2305-12.","journal-title":"Carcinogenesis"},{"key":"ref_28","first-page":"766","article-title":"Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Thl or ThO profile dominated by interferon gamma","volume-title":"Gut","volume":"37","author":"Nilsen, E.M.; Lundin, K.E.; Krajci, P.; Scott, H.; Sollid, L.M.; Brandtzaeg, P.","year":"1995","unstructured":"Nilsen EM, Lundin KE, Krajci P, Scott H, Sollid LM, Brandtzaeg P. Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Thl or ThO profile dominated by interferon gamma. Gut 1995; 37: 766-76."},{"key":"ref_29","first-page":"52","article-title":"Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge","volume-title":"Gut","volume":"37","author":"Kontakou, M.; Przemioslo, R.T.; Sturgess, R.P.; Limb, G.A.; Ellis, H.J.; Day, P.","year":"1995","unstructured":"Kontakou M, Przemioslo RT, Sturgess RP, Limb GA, Ellis HJ, Day P, et al. Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge. Gut 1995; 37: 52-7."},{"key":"ref_30","first-page":"4147","article-title":"Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen._ Immunol","volume":"155","author":"Abreu-Martin, M.T.; Vidrich, A.; Lynch, D.H.; Targan, SR","year":"1995","unstructured":"Abreu-Martin MT, Vidrich A, Lynch DH, Targan SR. Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen._ Immunol 1995; 155: 4147-54."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1126\/science.7533326","article-title":"The fas death factor","volume":"267","author":"Nagata, S.; Goldstein, P.","year":"1995","unstructured":"Nagata S, Goldstein P. The fas death factor. Science 1995; 267: 1449-56.","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1365-2036.1995.tb00376.x","article-title":"Manipulation of cell death - the development of novel strategies for the treatment of gastrointestinal disease","volume":"9","author":"Watson, A.J.M.","year":"1995","unstructured":"Watson AJM. Manipulation of cell death - the development of novel strategies for the treatment of gastrointestinal disease. 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