c-Myc alters the DNA damage-induced G2/M arrest in human mammary epithelial cells.

Effects of c-Myc overexpression on the DNA damage-induced G2/M checkpoint were studied in finite lifespan, normal human mammary epithelial cells (HMECs). Previously, we showed that c-Myc attenuates G1/S arrest and leads to an inappropriate entry of cells with damaged DNA into the S phase, following treatment with ionising radiation (IR). Here we show that, in striking contrast to control cells, c-Myc-overexpressing HMECs demonstrate a significant attenuation of the G2/M arrest, following IR, and enter into inappropriate mitoses. At the molecular level, ectopic overexpression of c-Myc leads to an unusually high level of expression of cyclin B1, and the elevated levels of cyclin B1 were maintained, after gamma-irradiation. Introduction of DNA damage in c-Myc-overexpressing, normal mammary epithelial cells eventually induces apoptosis, indicating a dramatic sensitisation by c-Myc of DNA damage-induced apoptosis. These two remarkable phenotypes, checkpoint attenuation and sensitisation to apoptosis, resulting from a deregulation of the protooncogene c-myc, may produce a unique pattern of alternating cycles, consisting first of amplification of DNA damage, followed by apoptosis-assisted selective pressure. The result of this alternating pattern of damage apoptosis could facilitate the selection of certain genomic alterations required for cellular survival and cellular transformation.

Rhinoplasty: personal evolution and milestones.

Over the past 35 years, aesthetic rhinoplasty has evolved from a generic, reductive operation to a highly individualized, problem-specific operation that often combines augmentation with reduction. The author's experience has been marked by the following conceptual and technical milestones that have contributed to an ongoing exploration and advancement of nasal surgery: (1) vestibular stenosis: diagnosis of a surgical consequence; (2) etiology and treatment of supratip deformity: the dynamic relationship of soft-tissue contour to skeleton; (3) etiology and treatment of the tip with inadequate projection: tip graft design; (4) practical aesthetics of balance: the augmentation-reduction approach to rhinoplasty; (5) support of the middle vault: functional and aesthetic effects; (6) malposition of the lateral crura: recognition and management; and (7) the significance of the middle crura: clinical and aesthetic considerations.

Tip graft: a 20-year retrospective.

This paper chronicles a personal experience with nasal tip grafts over 20 years. In the first period (1968-1975), the original graft was designed for use in secondary rhinoplasty cases to obtain both projection of the tip and increased angulation at the columellar-lobular junction. The use was soon expanded to primary patients with inadequate tip projection. During the middle period (1975-1982), the applications for tip grafting were expanded to include many kinds of tip problems (both primary and secondary), cleft lip noses, and various ethnic noses, especially those with thick skin. The incidence of postoperative displacement and/or visibility of the graft was reduced as multiple grafts of solid, bruised, and crushed cartilage became routine. Ear cartilage was first used and ethmoid was abandoned as a primary graft. The incidence of infection was significantly reduced. The current period (1982-1991) is marked by refinements in technique and materials. Greater versatility with graft composition and materials makes possible a variety of tip configurations, custom-made for individual requirements.

The expert teaching system: a new method for learning rhinoplasty using interactive computer graphics.

We have developed software that employs interactive computer graphics to simulate the surgical experience of rhinoplasty by allowing the surgeon to experiment within a model of nasal behavior. For any of three preoperative noses, the surgeon can choose and see the effects of dorsal resection, modification of nasal spine or caudal septum, alar cartilage resection, osteotomy, alar wedge resection, and a variety of nasal grafts. The available choices and views total nearly 3000 images, or approximately 200 different surgical solutions. The surgeon can get textual analysis at any time or see accelerated healing to the projected nasal appearance at 1 year. We believe that the ability to experiment without risk, to safely learn the biological laws governing nasal behavior, should augment the development of surgical judgement in rhinoplasty.

Spreader graft: a method of reconstructing the roof of the middle nasal vault following rhinoplasty.

Submucosal placement of strips of cartilage along the anterior border of the septum--the spreader graft--has proved to be an effective method for reconstructing the roof of the middle vault. It is recommended in all primary rhinoplasty patients in whom resection of the roof of the upper cartilaginous vault is a necessary part of the surgical plan.

Tarsal fixation in lower blepharoplasty.

Proceeding from the premise that a "youthful" eyelid has a pretarsal bulge while a "senile" eyelid has a pretarsal flatness, the tarsal fixation technique for lower blepharoplasty has been introduced--to reposition part of the orbicularis in front of the tarsus to produce a pretarsal bulge. The technique is presented as a suggested adjunct to the usual types of lower blepharoplasty.

A change in the technique of supratarsal fixation in upper blepharoplasty.

Fixation of the orbicularis muscle to the levator muscle in an upper blepharoplasty can create a higher supratarsal fold in selected caucasians. The technique that I introduced two years ago has been refined to eliminate one of the major problems (postoperative morbidity).

Secondary rhinoplasty.

Secondary rhinoplasty is a highly complex, judgmental type of surgery. It is only through analysis of the successful treatment of various problems in secondary rhinoplasty that meaningful information can be obtained.