An element in intron 1 of the CFTR gene augments intestinal expression in vivo.

The elements controlling the complex developmental and tissue-specific expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene lie outside the basal promoter region and have not been characterized. We previously identified a tissue-specific DNase I hypersensitive site (DHS) in intron 1 (185 + 10 kb) of the CFTR gene. Here we show that removal of the core element abolishes the activity of this DHS in transient transfection assays of reporter/enhancer gene constructs. We then compared expression from a 310 kb yeast artificial chromosome (YAC) that contains the entire CFTR gene with expression from the same YAC from which the DHS element had been deleted. Stable transfection of a human colon carcinoma cell line showed that transcription from the deleted YAC was reduced by approximately 60%. In transgenic mice, deletion of the intron 1 DHS had no effect on expression in the lung, but reduced expression in the intestine by approximately 60%. Thus, the regulatory element associated with the intron 1 DHS is tissue-specific and is required for normal CFTR expression levels in the intestinal epithelium in vivo.

A randomised controlled trial of the effects of screening for ulcer-type dyspepsia.

One hundred and ninety-nine male London office workers with dyspeptic symptoms elicited by a self-administered questionnaire were randomly allocated to intervention and control groups to assess the potential benefits of screening. The members of the intervention group were interviewed and examined, and those men who were considered to have a possible or probable peptic ulcer received a barium meal examination (53%). At the clinical interview the intervention group were advised against both smoking and drinking alcohol. Eighteen months later both groups were recalled for interview and examination and their sickness absence in the intervening period was assessed. The intervention group did not alter their cigarette consumption but did reduce their alcohol intake by an average of 10%. The control group increased their alcohol intake by 20%. Both groups tended to improve symptomatically, and there were no differences in symptoms between the groups at the end of the study. Sickness absence was not affected by the intervention. It is concluded that screening for ulcer-type dyspepsia is not justifiable in male London office workers.