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Hypersecretion of zymogen granules in the pathogenesis of cystic fibrosis
  1. Jeanette Blomfield,
  2. J. Dascalu,
  3. E. W. Van Lennep,
  4. J. M. Brown


    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.

    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.

    Hypersecretion of calcium-containing zymogen granules is postulated as the cause of obstruction in cystic fibrosis.

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    • 1 Supported in part by a grant from the Cystic Fibrosis Association of NSW.