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• W1982147939 abstract "The search for a basic functional defect in CF appears to be converging on a defect in the regulation of epithelial Cl- permeability and perhaps protein secretion. Fundamental issues that remain unresolved include (1) the identity of the CF gene, (2) the precise role played by the CF gene product in regulating Cl- permeability and protein secretion, and (3) the identities and properties of alternate pathways for regulating Cl- permeability and protein secretion that are not compromised in CF. The first issue should be resolved in the near future as molecular genetic approaches are used to pinpoint the location of the CF locus on chromosome 7. The second issue is more complex and will require the development of generally useful assays of Cl- permeability and protein secretion that can be used to assess the abilities of candidate CF gene products to complement, or correct, the functional defect in CF cells. Characterizing the precise function of the CF gene product may be difficult if the regulatory pathways that control these cellular processes are complex (ie, involve multiple regulatory steps and second messengers) or if the CF gene is a regulatory gene (rather than a structural gene) that represses or induces the synthesis of proteins involved in modulating Cl- permeability and protein synthesis. The third issue relates to the development of therapeutic strategies for treating CF patients that involve elevating epithelial Cl- permeability or modulating protein secretion by pharmacologically activating regulatory pathways that are unaffected in CF. In this regard, it is important to note that the stimulation of the Cl- permeabilities of airway epithelial cells by Ca2+-mediated secretagogues appears not to be compromised in CF. Pharmacological manipulation of this or other regulatory pathways may provide a means to activate the Cl- permeabilities of CF affected cells." @default.
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• W1982147939 date "1989-10-01" @default.
• W1982147939 modified "2023-09-24" @default.
• W1982147939 title "Defective Regulation of Epithelial Cl- Permeability and Protein Secretion in Cystic Fibrosis: The Putative Basic Defect" @default.
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• W1982147939 doi "https://doi.org/10.1016/s0272-6386(89)80216-1" @default.
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