Glucocorticoid receptor (GR) recycles between an inactive form complexed with heat shock proteins (hsps) and localized to the cytoplasm and a free liganded form that regulates specific gene transcription in the nucleus. We report here that, contrary to previous assumptions, association of GR into hsp-containing complexes is not sufficient to prevent the shuttling or trafficking of the GR across the nuclear membrane. Following the withdrawal of treatment with cortisol or the hormone antagonist RU486, GRs recycled rapidly into hsp-associated, hormone-responsive complexes. However, cortisolwithdrawn receptors redistributed to the cytoplasm very slowly (t1 ⁄2 ‫؍‬ 8 -9 h) and RU486-withdrawn receptors not at all. Persistent localization of these GRs to the nucleus was not due to a gross defect in export, since in both instances the complexed nuclear GRs transferred efficiently between heterokaryon nuclei. Moreover, the addition of a nuclear retention signal to the N terminus of GR induced the transfer of naive receptor to the nucleus in the absence of steroid. These results suggest that the localization of GR to the cytoplasm is determined by fine control of the rates of transfer of GR across the nuclear membrane and/or by active retention that occurs independently from the association of GR with hsps.

This study demonstrates that innervation of free TRAM flaps used for breast reconstruction not only improves sensibility but also has a positive effect on patient-rated quality of life.

Goals of a successful cleft palate repair include separation of the oral and nasal components without fistula, achieving sufficient velar length, and creating functional transverse orientation of the levator muscle sling. A number of techniques have been described to achieve these goals, but they all have the following technical details in common: elevation of oral mucosal flaps based on the greater palatine arteries, tension free nasal lining mobilization, and functional intervelar muscle dissection. After palate repair, speech evaluation needs to be performed by an objective interdisciplinary team following a standardized protocol. Identification of velopharyngeal insufficiency secondary to an incompetent nasopharyngeal port will necessitate secondary speech surgery. These secondary techniques include pharyngeal flaps, soft palate lengthening, or pharyngeal sphincters, which should be tailored to optimize speech, while minimizing the risk of obstructive sleep apnea.