{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T17:15:16Z","timestamp":1765646116199,"version":"3.48.0"},"reference-count":51,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1973,7]]},"abstract":"<jats:p>In the submandibular saliva of 10 cystic fibrosis subjects and 10 controls the turbidity and elevated calcium, protein, and amylase concentrations of the cystic fibrosis secretions, and precipitation of calcium and phosphate in a ratio consistent with hydroxyapatite have been confirmed. By electron microscopy the centrifuged deposits of the cystic fibrosis saliva were seen to be composed predominantly of round or oval subcellular corpuscles. By comparison with submandibular gland, these corpuscles have been identified as inclusion bodies (spherules) from within zymogen granules. Hydroxyapatite crystals formed on standing in the cystic fibrosis saliva. Polyacrylamide gel disc electrophoresis of the cystic fibrosis centrifuged deposits showed five bands, one of which, band 4, was more prominent in the deposit than in the supernatant gels.<\/jats:p>\n                  <jats:p>Comparisons have been made between these results and other studies and have shown (1) elevated calcium and protein in cystic fibrosis exocrine secretions; (2) simultaneous secretion of calcium and enzymes from salivary glands, stomach, and pancreas; and (3) increased salivary secretion of calcium and protein in response to parasympathomimetic and sympathomimetic drugs.<\/jats:p>\n                  <jats:p>Hypersecretion of calcium-containing zymogen granules is postulated as the cause of obstruction in cystic fibrosis.<\/jats:p>","DOI":"10.1136\/gut.14.7.558","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"558-565","source":"Crossref","is-referenced-by-count":25,"title":["Hypersecretion of zymogen granules in the pathogenesis of cystic fibrosis"],"prefix":"10.1136","volume":"14","author":[{"given":"Jeanette","family":"Blomfield","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Dascalu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. W.","family":"Van Lennep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1973,7,1]]},"reference":[{"key":"ref_1","series-title":"The role of the autonomic nervous system in cystic fibrosis. In Research on Pathogenesis of Cystic Fibrosis of the Pancreas (Mucoviscidosis); initial hypersecretion leading to blockage by insoluble products, with subsequent autolysis by trapped proteolytic enzymes","first-page":"208","article-title":"by contents are postulated as the cause ofductal obstruction in the submandibular gland. Because of the correlation between pancreatic enzymes and calcium, a similar mechanism may be proposed for the cystic fibrosis","author":"Barbero, G.J.; Chernick, W.S.","year":"1966","unstructured":"Barbero, G. J., and Chernick, W. S. (1966). The role of the autonomic nervous system in cystic fibrosis. In Research on Pathogenesis of Cystic Fibrosis of the Pancreas (Mucoviscidosis), edited by contents are postulated as the cause ofductal obstruction in the submandibular gland. Because of the correlation between pancreatic enzymes and calcium, a similar mechanism may be proposed for the cystic fibrosis pancreas, that is, initial hypersecretion leading to blockage by insoluble products, with subsequent autolysis by trapped proteolytic enzymes, P. A. di Sant'Agnese, pp. 208-222."},{"key":"ref_2","first-page":"21","article-title":"Zymogen granules in the pathogenesis of cystic fibrosis. In Cystic Fibrosis Club Abstracts, Thirteenth Annual Meeting, Kansas City","author":"Blomfield, J.","year":"1972","unstructured":"Blomfield, J. (1972). Zymogen granules in the pathogenesis of cystic fibrosis. In Cystic Fibrosis Club Abstracts, Thirteenth Annual Meeting, Kansas City, Missouri, p. 21."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/adc.48.4.267","article-title":"Flow rate and the inorganic components of submandibular saliva in cystic fibrosis","volume":"48","author":"Blomfield, J.; Warton, K.L.; Brown, J.M.","year":"1973","unstructured":"Blomfield, J., Warton, K. L., and Brown, J. M. (1973). Flow rate and the inorganic components of submandibular saliva in cystic fibrosis. Arch. Dis. Childh., 48, 267-274.","journal-title":"Arch. Dis. Childh"},{"key":"ref_4","first-page":"30","article-title":"Pathogenesis of turbid submaxillary saliva in patients with cystic fibrosis. In Cystic Fibrosis Club Abstracts, and eventual hypofunction. Despite the higher levels of amylase in parotid saliva compared to submandibular saliva and in cystic fibrosis parotid saliva compared to controls (Mandel et al, 1967b), the calcium concentrations of the parotid secretions are relatively low","volume-title":"In cystic fibrosis sweat, the calcium is also probably normal or only slightly elevated (di Sant'Agnese and Talamo","author":"Boat, T.F.","year":"1970","unstructured":"Boat, T. F. (1970). Pathogenesis of turbid submaxillary saliva in patients with cystic fibrosis. In Cystic Fibrosis Club Abstracts, and eventual hypofunction. Despite the higher levels of amylase in parotid saliva compared to submandibular saliva and in cystic fibrosis parotid saliva compared to controls (Mandel et al, 1967b), the calcium concentrations of the parotid secretions are relatively low (Wotman, Mandel, Mercadante, and Denning, 1971). In cystic fibrosis sweat, the calcium is also probably normal or only slightly elevated (di Sant'Agnese and Talamo, 1967). It is postulated, therefore, that in cystic fibrosis parotid saliva and sweat the calcium would not be sufficiently elevated to form insoluble inorganic or protein complexes. In this event a hypersecretion of secretory granules in these glands would lead to an Eleventh Annual Meeting, Atlantic City, New Jersey, p. 30."},{"key":"ref_5","first-page":"821","article-title":"Chronic atropinization and fibrocystic disease of the pancreas","volume":"82","author":"Boyd, E.M.; Jarzylo, S.","year":"1960","unstructured":"Boyd, E. M., and Jarzylo, S. (1960). Chronic atropinization and fibrocystic disease of the pancreas. Canad. med. Ass. J., 82, 821-824.","journal-title":"Canad. med. Ass. 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