Faculty Bibliography

OBJECTIVE: To demonstrate that the midfacial degloving (MFD) approach can provide the proper exposure to successfully reduce naso-orbital-ethmoid (NOE) and midfacial fractures while eliminating the need for external skin incisions. DESIGN: A retrospective review of patients with NOE and concomitant midfacial fractures that were repaired via the MFD approach for exposure. SETTING: Tertiary care academic medical center. METHODS: The MFD approach was used to access NOE and concomitant midfacial fractures for repair in 9 patients with facial trauma. Physical examination and imaging studies were used for preoperative evaluation. Functional and cosmetic results were assessed during follow-up with serial physical examinations and postreduction films. RESULTS: No significant technical problems were encountered in the treatment of NOE and concomitant fractures, which included 5 Le Fort I, 1 Le Fort II, 1 Le Fort III, 6 orbital rim (1 superior, 4 inferior, and 1 lateral), and 4 zygomatic complex fractures. Physical examination and imaging studies showed adequate reduction in all patients, and all patients were satisfied with their short- and long-term functional and cosmetic results. CONCLUSION: The MFD approach can provide the necessary exposure to properly reduce NOE and midfacial fractures without the need for external skin incisions

BACKGROUND:Orodental rehabilitation of hemipalatomaxillectomy defects can be accomplished by using a prosthetic obturator or a vascularized bone-containing free flap. Whereas prosthetic obturation offers several advantages, including the opportunity for immediate dental restoration without the need for further surgery, vascularized bone grafts provide permanent closure of the oronasal communication and bone sufficient for the placement of osseointegrated implants. OBJECTIVE:To compare the functional and quality-of-life (QOL) outcomes in patients rehabilitated with a prosthetic obturator with defect-matched patients who underwent reconstruction with a vascularized bone-containing free flap. METHODS:Four hemipalatomaxillectomy patients rehabilitated with a tissue-borne prosthetic obturator were compared with 4 defect-matched hemipalatomaxillectomy patients who underwent reconstruction with a vascularized bone-containing free flap. All of the patients were objectively assessed for speech, mastication, and QOL. Functional status was assessed by mastication testing, voice analysis, and nasorhinometry. Swallowing-related QOL was assessed using a patient-reported, validated swallowing QOL questionnaire, and donor site morbidity was assessed using upper extremity and lower extremity questionnaires. RESULTS:Patients who underwent reconstruction with a vascularized bone-containing free flap achieved higher mastication and speech assessment scores with less oronasal reflux than defect-matched patients rehabilitated with a prosthetic obturator. Swallowing QOL and donor site assessments demonstrated that compared with their prosthetic counterparts, reconstruction patients enjoyed a better QOL without incurring significant donor site morbidity. CONCLUSIONS:Although palatomaxillary reconstruction with vascularized bone-containing free flaps requires a second operative site, this method of orodental rehabilitation of the hemipalatomaxillectomy defect can achieve superior functional and QOL outcomes relative to defect-matched patients rehabilitated with a prosthetic obturator.

ACF7 is a member of the spectraplakin family of cytoskeletal crosslinking proteins possessing actin and microtubule binding domains. Here, we show that ACF7 is an essential integrator of MT-actin dynamics. In endodermal cells, ACF7 binds along microtubules but concentrates at their distal ends and at cell borders when polarized. In ACF7's absence, microtubules still bind EB1 and CLIP170, but they no longer grow along polarized actin bundles, nor do they pause and tether to actin-rich cortical sites. The consequences are less stable, long microtubules with skewed cytoplasmic trajectories and altered dynamic instability. In response to wounding, ACF7 null cultures activate polarizing signals, but fail to maintain them and coordinate migration. Rescue of these defects requires ACF7's actin and microtubule binding domains. Thus, spectraplakins are important for controlling microtubule dynamics and reinforcing links between microtubules and polarized F-actin, so that cellular polarization and coordinated cell movements can be sustained.

alphabeta1 integrins have been implicated in the survival, spreading, and migration of cells and tissues. To explore the underlying biology, we identified conditions where primary beta1 null keratinocytes adhere, proliferate, and display robust alphavbeta6 integrin-induced, peripheral focal contacts associated with elaborate stress fibers. Mechanistically, this appears to be due to reduced FAK and Src and elevated RhoA and Rock activities. Visualization on a genetic background of GFPactin shows that beta1 null keratinocytes spread, but do so aberrantly, and when induced to migrate from skin explants in vitro, the cells are not able to rapidly reorient their actin cytoskeleton toward the polarized movement. As judged by RFPzyxin/GFPactin videomicroscopy, the alphavbeta6-actin network does not undergo efficient turnover. Without the ability to remodel their integrin-actin network efficiently, alphabeta1-deficient keratinocytes cannot respond dynamically to their environment and polarize movements.

Expression of beta 3 integrins is increased in invasive melanoma. In this study we show that K1735 cell proliferation is enhanced by the expression of either beta 3 or a constitutively active Src. We investigated possible modulators of FN matrix assembly and found that matrix metalloproteinase 2 (MMP2) was activated by alpha v beta 3. alpha v beta 3 integrin was localized to focal contacts whereas alpha v beta 5 was peripherally distributed. MMP2 was also activated by expression of CASrc. MMP2 activation inversely correlated with FN matrix assembly, in that it dramatically reduced the organization of a FN matrix. K1735 cell migration on VN and invasion through a reconstituted basement membrane were decreased in the presence of anti-MMP2 antibodies. These results demonstrate that the expression of the alpha v beta 3 complex modulates melanoma cell behavior including activation of Src, organization of the cytoskeleton, assembly of the extracellular matrix, cell motility, and activation of MMP2.

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.