Abstract
Mice were fed a lithogenic diet containing 1% cholesterol and 0.5% cholic acid, and the sequence of morphologic changes in the gallbladder was followed. Histologic changes were studied with light microscopy and cell proliferation with autoradiography. Mucus glycoprotein production was studied with a spectrum of glycoprotein histochemical stains and electron-microscopic morphometry of membrane-bound mucus secretory granules. There was a rapid and early increase in cell proliferation of the epithelial cells and an increase in mucus production, which took place long before any observable cholesterol crystal precipitation. The gallbladder epithelial cells showed early focal pseudostratification and large numbers of degenerative cells. These changes culminated in glandular metaplasia and the formation of Rokitansky-Aschoff sinuses later in the gallstone induction phase. These observations clearly indicated that gallbladder epithelial injury had taken place before gallstone formation. The authors hypothesize that the consequences of these cellular changes play a contributory role in causing gallstone formation.
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- Adler R. D., Metzger A. L., Grundy S. M. Biliary lipid secretion before and after cholecystectomy in American Indians with cholesterol gallstones. Gastroenterology. 1974 Jun;66(6):1212–1217. [PubMed] [Google Scholar]
- Bouchier I. A., Cooperband S. R., el-Kodsi B. M. Mucous substances and viscosity of normal and pathological human bile. Gastroenterology. 1965 Oct;49(4):343–353. [PubMed] [Google Scholar]
- Bouchier I. A., Freston J. W. The aetiology of gallstones. Lancet. 1968 Feb 17;1(7538):340–344. doi: 10.1016/s0140-6736(68)90801-5. [DOI] [PubMed] [Google Scholar]
- Caldwell F. T., Jr, Levitsky K., Rosenberg B. Dietary production and dissolution of cholesterol gallstones in the mouse. Am J Physiol. 1965 Sep;209(3):473–478. doi: 10.1152/ajplegacy.1965.209.3.473. [DOI] [PubMed] [Google Scholar]
- Carey M. C., Small D. M. The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. J Clin Invest. 1978 Apr;61(4):998–1026. doi: 10.1172/JCI109025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Englert E., Jr, Harman C. G., Freston J. W., Straight R. C., Wales E. E., Jr Studies on the pathogenesis of diet-induced dog gallstones. Am J Dig Dis. 1977 Apr;22(4):305–314. doi: 10.1007/BF01072187. [DOI] [PubMed] [Google Scholar]
- FORTNER J. G. Experimental studies of gallstone formation. Surgery. 1954 Nov;36(5):932–940. [PubMed] [Google Scholar]
- Freston J. W., Bouchier I. A., Newman J. Biliary mucous substances in dihydrocholesterol-induced cholelithiasis. Gastroenterology. 1969 Dec;57(6):670–678. [PubMed] [Google Scholar]
- Hayward A. F., Freston J. W., Bouchier I. A. Changes in the ultrastructure of gall bladder epithelium in rabbits with experimental gallstones. Gut. 1968 Oct;9(5):550–556. doi: 10.1136/gut.9.5.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holan K. R., Holzbach R. T., Hermann R. E., Cooperman A. M., Claffey W. J. Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology. 1979 Oct;77(4 Pt 1):611–617. [PubMed] [Google Scholar]
- Lee S. P., Carey M. C., LaMont J. T. Aspirin prevention of cholesterol gallstone formation in prairie dogs. Science. 1981 Mar 27;211(4489):1429–1431. doi: 10.1126/science.7466399. [DOI] [PubMed] [Google Scholar]
- Lee S. P. Hypersecretion of mucus glycoprotein by the gallbladder epithelium in experimental cholelithiasis. J Pathol. 1981 Jul;134(3):199–207. doi: 10.1002/path.1711340304. [DOI] [PubMed] [Google Scholar]
- Lee S. P., LaMont J. T., Carey M. C. Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones. J Clin Invest. 1981 Jun;67(6):1712–1723. doi: 10.1172/JCI110209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee S. P., Lim T. H., Scott A. J. Carbohydrate moieties of glycoproteins in human hepatic and gall-bladder bile, gall-bladder mucosa and gall stones. Clin Sci (Lond) 1979 Jan;56(6):533–538. doi: 10.1042/cs0560533. [DOI] [PubMed] [Google Scholar]
- Lee S. P., Scott A. J. Dihydrocholesterol-induced gallstones in the rabbit: evidence that bile acids cause gallbladder epithelial injury. Br J Exp Pathol. 1979 Jun;60(3):231–238. [PMC free article] [PubMed] [Google Scholar]
- Lee S. P., Scott A. J. Further observations in lincomycin-induced cholelithiasis in guinea-pigs. J Pathol. 1980 Jun;131(2):117–125. doi: 10.1002/path.1711310204. [DOI] [PubMed] [Google Scholar]
- Lee S. P. The mechanism of mucus secretion by the gallbladder epithelium. Br J Exp Pathol. 1980 Apr;61(2):117–119. [PMC free article] [PubMed] [Google Scholar]
- Luciano L. Dein Feinstruktur der Gallenblase und der Gallengänge. I. Das Epithel der Gallenblase der Maus. Z Zellforsch Mikrosk Anat. 1972;135(1):87–102. [PubMed] [Google Scholar]
- Osuga T., Portman O. W., Mitamura K., Alexander M. A morphologic study of gallstone development in the squirrel monkey. Lab Invest. 1974 Apr;30(4):486–493. [PubMed] [Google Scholar]
- Palmer R. H., Ruban Z. Production of bile duct hyperplasia and gallstones by lithocholic acid. J Clin Invest. 1966 Aug;45(8):1255–1267. doi: 10.1172/JCI105432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Putz P., Willems G. Effect of a lithogenic diet on cell proliferation in the murine gallbladder epithelium. Digestion. 1981;22(1):16–23. doi: 10.1159/000198590. [DOI] [PubMed] [Google Scholar]
- Scott A. J. Are there proliferative compartments in the gallbladder? Gastroenterology. 1974 Dec;67(6):1231–1237. [PubMed] [Google Scholar]
- Scott A. J. Epithelial cell proliferation in diverse models of experimental cholelithiasis. Gut. 1978 Jun;19(6):558–562. doi: 10.1136/gut.19.6.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott A. J. Lincomycin-induced cholecystitis and gallstones in guinea pigs. Gastroenterology. 1976 Nov;71(5):814–820. [PubMed] [Google Scholar]
- TEPPERMAN J., CALDWELL F. T., TEPPERMAN H. M. INDUCTION OF GALLSTONES IN MICE BY FEEDING A CHOLESTEROL-CHOLIC ACID CONTAINING DIET. Am J Physiol. 1964 Mar;206:628–634. doi: 10.1152/ajplegacy.1964.206.3.628. [DOI] [PubMed] [Google Scholar]
- Tepperman J., Weiner M. Experimental gallstones: an adventure in biological geology. Yale J Biol Med. 1968 Oct;41(2):107–119. [PMC free article] [PubMed] [Google Scholar]
- Trotman B. W., Bernstein S. E., Bove K. E., Wirt G. D. Studies on the pathogenesis of pigment gallstones in hemolytic anemia: description and characteristics of a mouse model. J Clin Invest. 1980 Jun;65(6):1301–1308. doi: 10.1172/JCI109793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahlin T., Bloom G. D., Carlsö B., Rhodin L. Effects of fasting and refeeding on secretory granules of the mouse gallbladder epithelium. A quantitative electron microscopic study. Gastroenterology. 1976 Mar;70(3):353–358. [PubMed] [Google Scholar]
- Wahlin T. Effects of lithogenic diets on mouse gallbladder epithelium. A histochemical, cytochemical and morphometric study. Virchows Arch B Cell Pathol. 1976 Dec 2;22(4):273–286. doi: 10.1007/BF02889221. [DOI] [PubMed] [Google Scholar]
- Womack N. A. The development of gallstones. Surg Gynecol Obstet. 1971 Dec;133(6):937–945. [PubMed] [Google Scholar]
- van der LINDEN, CHRISTENSEN F., DAM H. Cholecystectomy and gallstone formation in the golden hamster. Acta Chir Scand. 1959 Dec 28;118:113–116. [PubMed] [Google Scholar]






