{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:13:31Z","timestamp":1791242011319,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,11,23]]},"abstract":"<jats:p>\n                    A deficiency in essential fatty acid metabolism has been reported\n in plasma from patients with cystic fibrosis (CF). However, its\n etiology and role in the expression of disease is unknown. The\n objective of this study was to determine whether alterations in fatty\n acid metabolism are specific to CF-regulated organs and whether they\n play a role in the expression of disease. A membrane lipid imbalance\n was found in ileum, pancreas, and lung from\n                    <jats:italic>cftr<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice characterized by an\n increase in phospholipid-bound arachidonic acid and a decrease in\n phospholipid-bound docosahexaenoic acid (DHA). This lipid imbalance was\n observed in organs pathologically affected by CF including lung,\n pancreas, and ileum and was not secondary to impaired intestinal\n absorption or hepatic biosynthesis of DHA. As proof of concept, oral\n administration of DHA to\n                    <jats:italic>cftr<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice\n corrected this lipid imbalance and reversed the observed pathological\n manifestations. These results strongly suggest that certain phenotypic\n manifestations of CF may result from remediable alterations in\n phospholipid-bound arachidonic acid and DHA levels.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.24.13995","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"13995-14000","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":254,"title":["A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in\n                    <i>cftr<\/i>\n                    <sup>\u2212\/\u2212<\/sup>\n                    mice"],"prefix":"10.1073","volume":"96","author":[{"given":"Steven D.","family":"Freedman","sequence":"first","affiliation":[{"name":"Departments of Medicine and Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; and Division of Laboratory 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