Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator.

BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. In the search for new CF therapies, small molecules have been identified that rescue the defective channel gating of CF mutants (termed CFTR potentiators). Here, we investigate the long-term effects of genistein, the best-studied CFTR potentiator, on the expression and function of CFTR. EXPERIMENTAL APPROACH: We pre-treated baby hamster kidney (BHK) cells expressing wild-type or F508del-CFTR (the most common CF mutant) with concentrations of genistein that potentiate (30 microM) or inhibit (100 microM) CFTR function for 2 or 24 h at 37 degrees C before examining CFTR maturation, expression and single-channel activity. KEY RESULTS: Using the iodide efflux technique, we found that genistein pre-treatment failed to restore function to F508del-CFTR, but altered that of wild-type CFTR. Pre-treatment of cells with genistein for 2 h had little effect on CFTR processing, whereas pre-treatment for 24 h either augmented (30 microM genistein) or impaired (100 microM genistein) CFTR maturation. Using immunocytochemistry, we found that all genistein pre-treatments increased the localization of CFTR protein to the cell surface. However, following the incubation of cells with genistein (100 microM) for 2 h, individual CFTR Cl(-) channels exhibited characteristics of channel block upon channel activation. CONCLUSIONS AND IMPLICATIONS: Genistein pre-treatment alters the maturation, cell surface expression and single-channel function of CFTR in ways distinct from its acute effects. Thus, CFTR potentiators have the potential to influence CFTR by mechanisms distinct from their effects on channel gating.

Using the hospital Intranet to meet competency standards for nurses.

Regulatory agencies increasingly require hospitals to provide evidence of employee compliance with mandated competencies. This article provides information on the innovative use of Intranet-delivered computer-based training as an effective and efficient method of providing and documenting training to meet regulatory requirements. The authors discuss the advantages and disadvantages of Intranet-based instructional modules, instruction on developing Intranet-based modules, and an example of a healthcare system that is effectively using intranet-based modules for competency training.

Shoulder movement after the treatment of early stage breast cancer.

At 18 months after surgery and post-operative radiotherapy, the function of the ipsilateral shoulder joint was assessed both subjectively and objectively in 141 patients with early stage breast cancer. Half of the patients said that function was reduced compared with before (any) treatment. Overall, 48% had measured limitation of at least one shoulder movement. Mastectomy patients had more problems than those who had a wide local excision (79% versus 35%) as did those (node positive patients) who had axillary irradiation (73%) compared with those who did not (35%). Patients with dysfunction of shoulder movement before radiotherapy had a 60% chance of persistent movement problems at 18 months, compared with 24% of those with normal postoperative function. Informal exercise did not appear to have had any impact on the development of movement limitation.

Simplified radiography of the zygomatic arches (the rat's head view).

Using these projections, the radiographer can effectively demonstrate depressed fractures or pathology of the zygomatic arches. Proper use of magnification techniques allows maximum detail without distortion for simplified viewing.