Faculty Bibliography

Hypomorphic RAG mutants with severely reduced V(D)J recombination activity cause Omenn Syndrome (OS), an immunodeficiency with features of immune dysregulation and a restricted TCR repertoire. Precisely how RAG mutants produce autoimmune and allergic symptoms has been unclear. Current models posit that the severe recombination defect restricts the number of lymphocyte clones, a few of which are selected upon Ag exposure. We show that murine RAG1 R972Q, corresponding to an OS mutation, renders the recombinase hypersensitive to selected coding sequences at the hairpin formation step. Other RAG1 OS mutants tested do not manifest this sequence sensitivity. These new data support a novel mechanism for OS: by selectively impairing recombination at certain coding flanks, a RAG mutant can cause primary repertoire restriction, as opposed to a more random, limited repertoire that develops secondary to severely diminished recombination activity

BACKGROUND:: Large hemangiomas of the scalp, though uncommon, present unique challenges to the reconstructive surgeon. If not treated early, these lesions can result in large areas of alopecia, distortion of the hairline, or deformation of the ear. Given these potential complications and the relative pliability and redundancy of the infant scalp before 4 months of age, the authors propose early surgical excision. METHODS:: A retrospective review of the senior author's (B.M.Z.) patient records was performed; over a period of 4 years, six infants were identified who underwent resection of a large scalp hemangioma. The surgical planning and execution of each case and follow-up are detailed. RESULTS:: All six hemangiomas were excised completely. In five cases, the excisions were performed in one stage at or before 4 months of age. In a sixth case, a tissue expander was placed before excision and closure in an 18-month-old infant. In three cases, significant ear malposition was corrected by removal of the deforming mass. There were no complications. CONCLUSIONS:: The authors have demonstrated that by taking advantage of the greater elasticity of the infant scalp, large hemangiomas of the scalp can be aggressively and successfully treated with surgical intervention, often in one operation. Beyond the usual indications, early surgical excision of scalp hemangiomas may be advantageous and warranted to prevent the development of large alopecic areas or the permanent distortion of the hairline and aural anatomy

The bony biochemical environment is an active and dynamic system that permits and promotes cellular functions that lead to matrix production and ossification. Each component is capable of conveying important regulatory cues to nearby cells, thus effecting gene expression and changes at the cytostructural level. Here, we review the various signaling molecules that contribute to the active and dynamic nature of the biochemical system. These components include hormones, cytokines, and growth factors. We describe their role in regulating bone metabolism. Certain growth factors (i.e., TGF-beta, IGF-1, and VEGF) are described in greater detail because of their potential importance in developing successful tissue-engineering strategies

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process

Oral squamous cell carcinoma (SCC) has an unpredictable capacity to metastasize to the neck, an event that dramatically worsens prognosis. Metastasis occurs even in earlier stages when no neck lymph node involvement is clinically detectable (N0). Management of the N0 neck, namely when and how to electively treat, has been debated extensively. This article presents the controversies surrounding management of the N0 neck, and the benefits and pitfalls of different approaches used in evaluation and treatment. As current methods of assessing the risk for occult metastasis are insufficiently accurate and prone to underestimation of actual risk, and because selective neck dissection (SND) is an effective treatment and has minimal long-term detriment to quality of life, the authors believe that all patients who have oral SCC, excluding lip SCC, should be prescribed elective treatment of the neck lymphatics. However, this opinion remains controversial. Because of the morbidity of radiation therapy and because treatment of the primary tumor is surgical, elective neck dissection is the preferred treatment. In deciding the extent of the neck dissection, several retrospective studies and one randomized clinical trial have shown SND of levels I through III to be highly efficacious

For years, the notion of chin ptosis was somehow integrated with the concept of witch's chin. That was a mistake on many levels because chin droop has four major causes, all different and with some overlap. With this article, the surgeon can quickly diagnose which type and which therapeutic modality would work best. In some cases the problem is a simple fix, in others the droop can only be stabilized, and in the final two, definite corrective procedures are available. Of note, in certain situations two types of chin ptosis may overlap because both the patient and the surgeon may each contribute to the problems. For example, in dynamic ptosis, a droop that occurs with smile in the unoperated patient can be exacerbated and further produced by certain surgical methods also. This paper classifies the variations of the problems and explains the anatomy with the final emphasis on long-term surgical correction, well described herein. This article is the ninth on this subject and a review of them all would be helpful (greatly) for understanding the enigmas of the lower face