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Biomedical subjects

Andrew J Kaufman

Publications and source records attributed to Andrew J Kaufman.

7 recordsLinked to original sources

A CK2-dependent mechanism for degradation of the PML tumor suppressor.

The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in human tumors through unknown posttranslational mechanisms. Casein kinase 2 (CK2) is oncogenic and frequently upregulated in human tumors. Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517. Consequently, PML mutants that are resistant to CK2 phosphorylation display increased tumor-suppressive functions. In a faithful mouse model of lung cancer, we demonstrate that Pml inactivation leads to increased tumorigenesis. Furthermore, CK2 pharmacological inhibition enhances the PML tumor-suppressive property in vivo. Importantly, we found an inverse correlation between CK2 kinase activity and PML protein levels in human lung cancer-derived cell lines and primary specimens. These data identify a key posttranslational mechanism that controls PML protein levels and provide therapeutic means toward PML restoration through CK2 inhibition.

Amino Acid Sequence↗

Bilateral vermilion rotation flap.

BACKGROUND: Principles of aesthetic reconstruction recommend repair within cosmetic units with tissue of similar color, texture, and thickness. Because of the central facial location and primary functional and aesthetic importance of the lips, successful repair is critical in this location. Numerous procedures to reconstruct the lip have been reported; however, many result in a significant decrease in the oral aperture as well as dysesthesias, limitation of mobility, and significant scarring. OBJECTIVE: The purpose of this study was to describe a reconstructive option that repairs with skin of similar characteristics and avoids crossing into adjacent cosmetic subunits or sacrifice of normal skin or muscle. The proposed procedure is able to repair surgical defects up to 40% of the vermilion width in one stage and minimize the risk of nerve damage, scarring, or functional impairment. METHODS: The bilateral vermilion rotation flap permits repair within cosmetic subunits, repairs with skin of identical surface characteristics, and avoids surgery to the adjacent cutaneous or muscular portions of the lip. By keeping the pedicle intact, injury to neurovascular structures is minimized. RESULTS: The procedure provides an excellent repair for selected defects of the vermilion lip by following guidelines for optimum aesthetic and functional repair (i.e., repair within cosmetic subunits using skin of identical characteristics while avoiding trauma to the uninvolved cutaneous lip or orbicularis oris). CONCLUSION: The bilateral vermilion rotation flap is a useful technique for repair of surgical defects on the vermilion lip. It avoids unnecessary sacrifice of cutaneous or muscular lip tissue and provides an excellent cosmetic and functional result.

Basal Cell Carcinoma↗

Periorbital reconstruction with adjacent-tissue skin grafts.

BACKGROUND: Reconstruction in the periorbital area is challenging owing to the complex function of the eye, relative lack of adjacent loose tissue, free anatomic margin, central facial location, and the need to maintain symmetry with the contralateral eye. Reconstructive options risk crossing anatomic margins, deviation of the lid margin (ectropion), persistent lymphedema, and repair with skin of dissimilar color, texture, and thickness. OBJECTIVE: The purpose was to describe a reconstructive option that would avoid crossing cosmetic units or subunits, minimize the risk of ectropion, repair with tissue of similar surface characteristics, and maintain function and symmetry with the contralateral side. METHODS: The adjacent-tissue skin graft provides closure in cosmetic units and subunits, avoids tension on the lid margin, and provides similar skin for repair. The procedure is demonstrated by graphic and photographic examples. RESULTS: The procedure provides for esthetic repair of the periorbital area and minimizes the risk of ectropion, lymphedema, asymmetry, and dysfunction of the lids and lacrimal system. CONCLUSION: Adjacent-tissue skin grafts are a useful alternative for reconstruction of partial-thickness defects on the eyelid and periorbital area.

Basal Cell Carcinoma↗

Adjacent-tissue skin grafts for reconstruction.

BACKGROUND: Large defects not easily repaired with local flaps and defects near anatomic free margins or crossing anatomic units present unique challenges for reconstruction. Cosmetic results of full-thickness skin grafts may appear unsatisfactory owing to differences in color, texture, and thickness between donor and recipient sites. OBJECTIVE: The objective was to describe a skin-graft reconstructive method that better approximates skin characteristics between donor and recipient sites while following other criteria to improve the final aesthetic and functional result. METHODS: Careful evaluation of the tissue surrounding a surgical defect determines tissue laxity available for skin grafting and whether the defect crosses anatomic units or may distort anatomic free margins or landmarks. Through partial closure of the large surgical defect, preferably within cosmetic units, a tricone is created large enough to graft the remaining wound. RESULTS: Creating smaller wounds within cosmetic units or subunits, there is less chance of distortion of nearby anatomic free margins or landmarks. Skin grafting is accomplished with tissue of similar color, texture, and thickness CONCLUSION: Adjacent-tissue skin grafts provide a suitable reconstruction option for surgical defects too large for simpler repair or defects crossing cosmetic units or near free margins. This procedure permits repair with a full-thickness skin graft of more similar skin characteristics to the recipient site.

Aged↗