{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T04:42:34Z","timestamp":1765082554906,"version":"3.46.0"},"reference-count":26,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1978,12]]},"abstract":"<jats:p>In vitro cytotoxicity of four different gluten fractions was tested in organ culture for up to 48 hours using flat intestinal biopsies from children with coeliac disease. The fractions were (1) a peptic-tryptic digest of gliadin containing a moderate amount of alpha-gliadin, (2) a peptic-tryptic digest of gluten (Frazer fraction III) froma strain of wheat with a high content of alpha-gliadin, (3) alpha-gliadin, and (4) alpha-GT-18,000, a tryptic fragment of alpha-gliadin. The latter three fractions were toxic to coeliac patients in vivo. In vitro, however, none of these fractions proved to be cytotoxic. When added to the culture medium they were not capable of inhibiting the regeneration of the surface epithelium as visualised by histology and electron microscopy. The only difference between cultures with and without gluten fractions was that the former produced slightly more mucus when maintained in vitro as observed in the dissecting microscope. Furthermore, for Frazer fraction III the absence of apparent toxicity was confirmed by the behaviour of brush border enzyme activities during culture. Our results are not in accordance with those reported in the literature. We believe that the criteria used at the present time for the assessment of gluten toxicity in vitro should be extended to include the process of enterocyte desquamation.<\/jats:p>","DOI":"10.1136\/gut.19.12.1090","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"1090-1098","source":"Crossref","is-referenced-by-count":24,"title":["Re-evaluation of the techique of organ culture for studying gluten toxicity in coeliac disease."],"prefix":"10.1136","volume":"19","author":[{"given":"H P","family":"Hauri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Kedinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Haffen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Gaze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Hadorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Hekkens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1978,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0003-2697(72)90147-9","article-title":"Human small intestine fl-galactosidase: Specific assay for three different enzymes","volume":"47","author":"Asp, N.G.; Dahlqvist, A.","year":"1972","unstructured":"Asp, N. G., and Dahlqvist, A. (1972). Human small intestine fl-galactosidase: Specific assay for three different enzymes. Analytical Biochemistry, 47, 527-538.","journal-title":"Analytical Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0009-8981(66)90080-5","article-title":"Enzymatic digestion of gliadin: The effect of the resultant peptides in adult celiac disease","volume":"14","year":"1966","unstructured":"Bronstein, H. D., Heaffner, L. J., and Kowlessar, 0. D. (1966). Enzymatic digestion of gliadin: The effect of the resultant peptides in adult celiac disease. Clinica Chimica Acta, 14, 141-155.","journal-title":"Clinica Chimica Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1172\/JCI106108","article-title":"Organ culture of mucosal biopsies of human small intestine","volume":"48","author":"Browning, T.H.; Trier, J.S.","year":"1969","unstructured":"Browning, T. H., and Trier, J. S. (1969). Organ culture of mucosal biopsies of human small intestine. Journal of Clinical Investigation, 48, 1423-1432.","journal-title":"Journal of Clinical Investigation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0009-8981(73)90126-5","article-title":"Investigation of possible intestinal peptidase deficiency in coeliac disease","volume":"43","author":"Cornell, H.J.; Townley, R.R.W.","year":"1973","unstructured":"Cornell, H. J., and Townley, R. R. W. (1973). Investigation of possible intestinal peptidase deficiency in coeliac disease. Clinica Chimica Acta, 43, 113-125.","journal-title":"Clinica Chimica Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0022-1759(97)90025-9","article-title":"Wheat grains: a substrate for the determination of gluten antibodies in serum of gluten-sensitive patients","volume":"14","author":"Eterman, K.P.; Hekkens, W.T.J.M.; Pefia, A.; S., LemsVan Kan; H., P.; Feltkamp, T.E.W.","year":"1977","unstructured":"Eterman, K. P., Hekkens, W. T. J. M., Pefia, A, S., LemsVan Kan, P. H., and Feltkamp, T. E. W. (1977). Wheat grains: a substrate for the determination of gluten antibodies in serum of gluten-sensitive patients. Journal of Immunological Methods, 14, 85-92.","journal-title":"Journal of Immunological Methods"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1172\/JCI107582","article-title":"An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on intestinal epithelial cells of patients with gluten-sensitive enteropathy in organ culture","volume":"53","author":"Falchuk, Z.M.; Gebhard, R.L.; Sessoms, C.; Strober, W.","year":"1974","unstructured":"Falchuk, Z. M., Gebhard, R. L., Sessoms, C., and Strober, W. (1974). An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on intestinal epithelial cells of patients with gluten-sensitive enteropathy in organ culture. Journal of Clinical Investigation, 53, 487-500.","journal-title":"Journal of Clinical Investigation"},{"key":"ref_7","article-title":"in vitro Assessment of Gluten Toxicity by Organ Culture of Human Duodenal Mucosa. Third International Coeliac Symposium","author":"Fluge, G.; Asknes, L.","year":"1977","unstructured":"Fluge, G., and Asknes, L. (1977). in vitro Assessment of Gluten Toxicity by Organ Culture of Human Duodenal Mucosa. Third International Coeliac Symposium. Galway, Ireland. MTP Press: Lancaster."},{"key":"ref_8","first-page":"252","article-title":"Gluteninduced enteropathy. The effect of partially digested gluten","volume":"2","author":"Frazer, A.C.; Fletcher, R.F.; Ross, C.A.C.; Shaw, B.; Sammons, H.G.; Schneider, R.","year":"1959","unstructured":"Frazer, A. C., Fletcher, R. F., Ross, C. A. C., Shaw, B., Sammons, H. G., and Schneider, R. (1959). Gluteninduced enteropathy. The effect of partially digested gluten. Lancet, 2, 252-255.","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/0006-3002(60)91282-8","article-title":"A fine-structure genetic and chemical study of the enzyme alkaline phosphate","volume":"38","author":"Garen, A.; Levinthal, C.","year":"1960","unstructured":"Garen, A., and Levinthal, C. (1960). A fine-structure genetic and chemical study of the enzyme alkaline phosphate of E. coli. I. Purification and characterization of alkaline phosphatase. Biochimica Biophysica Acta, 38, 470-483.","journal-title":"Biochimica Biophysica Acta; Purification and characterization of alkaline phosphatase"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0005-2736(77)90310-8","article-title":"Biosynthesis of brush border glycoproteins by human small intestinal mucosa in organ culture","volume":"467","author":"Hauri, H.P.; Kedinger, M.; Haffen, K.; Freiburghaus, A.; Grenier, J.F.; Hadorn, B.","year":"1977","unstructured":"Hauri, H. P., Kedinger, M., Haffen, K., Freiburghaus, A., Grenier, J. F., and Hadorn, B. (1977). Biosynthesis of brush border glycoproteins by human small intestinal mucosa in organ culture. Biochmica Biophysica Acta, 467, 327-339.","journal-title":"Biochmica Biophysica Acta"},{"key":"ref_11","first-page":"307","article-title":"Organ culture of human duodenum and jejunum","volume":"8","author":"Hauri, H.P.; Kedinger, M.; Haffen, K.; Grenier, J.F.; Hadorn, B.","year":"1975","unstructured":"Hauri, H. P., Kedinger, M., Haffen, K., Grenier, J. F., and Hadorn, B. (1975). Organ culture of human duodenum and jejunum. Biologie et Gastro-enterologie (Paris), 8, 307-319.","journal-title":"Biologie et Gastro-enterologie (Paris)"},{"key":"ref_12","series-title":"Coeliac Disease: Proceedings of an International Conference","first-page":"11","article-title":"Some aspects of gliadin fractionation and testing by a histochemical method","author":"Hekkens, W.T.J.M.; Haex, A.J.C.; Willighagen, R.G.J.","year":"1970","unstructured":"Hekkens, W. T. J. M., Haex, A. J. C. and Willighagen, R. G. J. (1970). Some aspects of gliadin fractionation and testing by a histochemical method. In Coeliac Disease: Proceedings of an International Conference, pp. 11-19. Edited by C. C. Booth and R. H. Dowling. Churchill Livingstone: Edinburgh."},{"key":"ref_13","series-title":"Coeliac Disease: Proceedings of the Second International Coeliac Symposium","first-page":"39","article-title":"a-gliadin structure and degradation","author":"Hekkens, W.T.J.M.; Van den Aaisen, C.J.; Gilliams, J.P.; Lems-Van Kan, P.; Bouma-Frolich, G.","year":"1974","unstructured":"Hekkens, W. T. J. M., Van den Aaisen, C. J., Gilliams, J. P., Lems-Van Kan, P., and Bouma-Frolich, G. (1974) a-gliadin structure and degradation. In Coeliac Disease: Proceedings of the Second International Coeliac Symposium, pp. 39-45. Edited by W. T. J. M. Hekkens., and A. S. Pefia. Stenfert Kroese: Leyden."},{"key":"ref_14","first-page":"339","article-title":"Non-specific cytoxicity of wheat gliadin components towards cultured human cells","volume":"1","author":"Hudson, D.A.; Cornell, H.I.; Purdham, D.R.; Rolles, C.J.","year":"1976","unstructured":"Hudson, D. A., Cornell, H. I., Purdham, D. R., and Rolles, C. J. (1976). Non-specific cytoxicity of wheat gliadin components towards cultured human cells. Lancet 1, 339-341.","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1139\/y59-157","article-title":"A modified spectrophotometric determination of chymotrypsin, trypsin and thrombin","volume":"37","author":"Hummel, B.C.W.","year":"1959","unstructured":"Hummel, B. C. W. (1959). A modified spectrophotometric determination of chymotrypsin, trypsin and thrombin. Canadian Journal of Biochemistry and Physiology, 37, 1393-1399.","journal-title":"Canadian Journal of Biochemistry and Physiology"},{"key":"ref_16","article-title":"The intestinal microvillus","author":"Iancu, T.; Elian, E.","year":"1976","unstructured":"Iancu, T., and Elian, E. (1976). The intestinal microvillus."},{"key":"ref_17","series-title":"vitro culturing of biopsies from children. In Coeliac Disease: Proceedings of the Second International Coeliac Symposium","first-page":"91","author":"Jos, J.; Lenoir, G.; De Ritis, G.; Rey, J.","year":"1974","unstructured":"Jos, J., Lenoir, G., De Ritis, G., and Rey, J. (1974). In vitro culturing of biopsies from children. In Coeliac Disease: Proceedings of the Second International Coeliac Symposium, pp. 91-105. Edited by W. T. J. M. Hekkens, and"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/00365521.1975.12096935","article-title":"In vitro pathogenetic studies of coeliac disease. Effects of protein digests on coeliac intestinal biopsy specimens maintained in culture for 48 hours","volume":"10","author":"Jos, J.; Lenoir, G.; De Ritis, G.; Rey, J.","year":"1975","unstructured":"Jos, J., Lenoir, G., De Ritis, G., and Rey, J. (1975). In vitro pathogenetic studies of coeliac disease. Effects of protein digests on coeliac intestinal biopsy specimens maintained in culture for 48 hours. Scandinavian Journal of Gastroenterology, 10, 121-128.","journal-title":"Scandinavian Journal of Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1056\/NEJM197607152950303","article-title":"Gluten sensitive enteropathy. Inhibition by cortisol ot the effect of gluten protein in vitro","volume":"295","author":"Katz, A.J.; Falchuk, Z.M.; Strober, W.; Shwachman, H.","year":"1976","unstructured":"Katz, A. J., Falchuk, Z. M., Strober, W, and Shwachman, H. (1976). Gluten sensitive enteropathy. Inhibition by cortisol ot the effect of gluten protein in vitro. New England Journal of Medicine, 295, 131-135.","journal-title":"New England Journal of Medicine"},{"key":"ref_20","first-page":"450","article-title":"Organ culture of guinea pig and human intestinal mucosa. Ultrastructural, cytochemical and biochemical study","volume":"11","author":"Kedinger, M.; Haffen, K.; Hauri, H.P.; Schang, J.C.; Hadorn, B.; Grenier, J.F.","year":"1974","unstructured":"Kedinger, M., Haffen, K., Hauri, H. P., Schang, J. C., Hadorn, B., and Grenier, J. F. (1974). Organ culture of guinea pig and human intestinal mucosa. Ultrastructural, cytochemical and biochemical study. (Abstract). Digestion, 11, 450-451.","journal-title":"(Abstract). Digestion"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the folin phenol reagent","volume":"193","year":"1951","unstructured":"Lowry, 0. H., Rosebrough, N J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193, 265-275.","journal-title":"Journal of Biological Chemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/0003-2697(66)90280-6","article-title":"A one-step ultramicro method for the assay of intestinal disaccharidases","volume":"14","author":"Messer, M.; Dahlqvist, A.","year":"1966","unstructured":"Messer, M., and Dahlqvist, A. (1966). A one-step ultramicro method for the assay of intestinal disaccharidases. Analytical Biochemistry, 14, 376-392.","journal-title":"Analytical Biochemistry"},{"key":"ref_23","first-page":"162","article-title":"Organ culture of intestinal mucosa in coeliac disease and in cow's milk intolerance. Effects of protein fractions","volume":"63","author":"Ritis, G.De; Jos, J.","year":"1974","unstructured":"Ritis, G. De, and Jos, J. (1974). Organ culture of intestinal mucosa in coeliac disease and in cow's milk intolerance. Effects of protein fractions. (Abstract). Acta Paediatrica Scandinavica, 63, 162.","journal-title":"(Abstract). Acta Paediatrica Scandinavica"},{"key":"ref_24","first-page":"1362","article-title":"Toxicity of wheat gliadin fractions in coeliac disease","volume":"1","author":"Townley, R.R.W.; Bhathal, P.S.; Cornell, H.J.; Mitchell, J.D.","year":"1973","unstructured":"Townley, R. R. W., Bhathal, P. S., Cornell, H. J., and Mitchell, J. D. (1973). Toxicity of wheat gliadin fractions in coeliac disease. Lancet, 1, 1362-1364.","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1056\/NEJM197607152950308","article-title":"Organ-culture methods in the study of gastrointestinal-mucosal function and development","volume":"295","author":"Trier, J.S.","year":"1976","unstructured":"Trier, J. S. (1976). Organ-culture methods in the study of gastrointestinal-mucosal function and development. New England Journal of Medicine, 295, 150-155.","journal-title":"New England Journal of Medicine"},{"key":"ref_26","first-page":"\"1245","article-title":"Epithelial-cell renewal in cultured duodenal biopsies in celiac sprue","volume":"283","author":"Trier, J.S.; Browning, T.H.","year":"1970","unstructured":"Trier, J. S., and Browning, T. H. (1970). Epithelial-cell renewal in cultured duodenal biopsies in celiac sprue. New England Journal of Medicine, 283, 1245-125C. Visakorpi, J. K. (1974). Definition of coeliac disease in children. In Coeliac Disease: Proceedings of the Second International Coeliac Symposium, pp. 10-16. Edited by W. T. J. M. Hekkens and A. S. Pehna. Stenfert Kroese: Leyden.","journal-title":"New England Journal of Medicine; Definition of coeliac disease in children. In Coeliac Disease: Proceedings of the Second International Coeliac Symposium"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.19.12.1090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T03:17:32Z","timestamp":1765077452000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.19.12.1090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1978,12]]},"references-count":26,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1978,12,1]]},"published-print":{"date-parts":[[1978,12]]}},"alternative-id":["10.1136\/gut.19.12.1090"],"URL":"https:\/\/doi.org\/10.1136\/gut.19.12.1090","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[1978,12]]}}}