The intestinal lesions in cystic fibrosis of the pancreas

Intestinal bile salts in cystic fibrosis: studies in the patient and experimental animal.

“…These two amino-acids are probably absorbed by separate transport systems (Matthews and Laster, 1965) which suggests that phenylalanine malabsorption may reflect a selective and primary defect of mucosal function in CF. These anormalities are not likely to be related to gross mucosal damage as the only described alterations of mucosal morphology in CF are dilated mucosal glands (Thomaidis and Arey, 1963) and thickening of surface mucus (Freye et al, 1964). The possibility of a primary mucosal defect is supported by the finding that faecal bile salt losses in children with active coeliac disease are not significantly different from controls (Weber et al, 1973), as the mucosal lesion in coeliac disease is predominantly a proximal one.…”

Localization of cystic fibrosis transmembrane conductance regulator mRNA in human fetal lung tissue by in situ hybridization.

“…Studies of tissues from fetuses and infants with CF have documented anatomical abnormalities in the pancreas (33), intestine ( 15), and vas deferens (34), but the results of examination of the lungs have been controversial. Morphological studies have described anatomically normal lungs in neonates and infants with CF and, in general, the earliest anatomic abnormalities observed in the lung consist of mucus obstruction of bronchioles followed by inflammatory changes in the bronchiolar epithelium and mucous gland hyperplasia, usually appearing after the neonatal period (35,36).…”

“…Recent studies have shown that CFTR can function as a Cl channel activated by protein kinase A phosphorylation and nucleoside triphosphates (9,10); mutations in CFTR cause cystic fibrosis (CF) (1 1, 12). Some complications of CF, including meconium ileus and pancreatic duct obstruction, occur before birth (13)(14)(15), suggesting the defective gene product is expressed in epithelia of these tissues prenatally. Therefore, the developmental regulation of CFTR gene expression in the human may bear directly on the timing of the disease onset.…”

Bronchial mucous glands in the newborn with cystic fibrosis

“…In summary although involvement of the pancreas [3], small bowel [19] and vas deferens [20] has been noted in CF patients to begin as early as ten to 12 weeks of foetal life, there is no evidence of a primary histopathological abnormality of bronchial mucous glands developing prenatally or in the immediate postnatal period. The bronchial mucous gland changes in the lung in CF appear to be in response to early infection.…”