Faculty Bibliography

Alkylation of metal-bound cysteinate residues forms an integral step in both the activation of the DNA-damage sensing Ada protein from E. coli and the reaction mechanisms of several zinc-dependent enzymes. The roles of metal ions and the protein structure in regulating the reactivity of bound cysteinate residues is not well-understood. Variants of a consensus zinc finger peptide were used to determine the effects of alkylation of cysteine residues on both metal binding and stability of the peptide structure. The ability of thioethers to act as ligands was probed through the direct synthesis of peptides with methionine or S-methylcysteine replacing the second histidine within the zinc finger framework. This position can be substituted with cysteine with no significant loss of structure or stability. Two-dimensional 1H NMR studies and water exchange experiments of the peptide with S-methylcysteine in this position showed that methylation affected the structure of the peptide-zinc complex in the last turn of the helix, adjacent to the site of methylation, without disrupting the rest of the structure. Titrations with cobalt revealed that the peptides with methionine or S-methylcysteine do not bind metal ions as tightly as do peptides with histidine or cysteine in this position. Similar to peptides lacking a fourth ligand, these thioether containing peptides form two-to-one peptide-to-cobalt complexes at low metal concentrations. Alkylation of the cobalt complex of the peptide with cysteine as the fourth ligand with dimethyl sulfate in aqueous solution yielded a product with absorption spectral features essentially identical with those of the S-methylcysteine derivative. Methylation of either of the other two cysteine residues within this peptide resulted in the loss of detectable metal binding. The carboxyl terminal cysteine was alkylated at a rate approximately 5-fold higher than the other cysteine residues, potentially due to the relative accessibility of this cysteine sulfur compared with the others which are shielded by peptide amide to sulfur hydrogen bonds. Other studies suggest that all of the cysteine residues in this peptide are less prone to alkylation in the cobalt complex than they are in the unfolded, metal-free form under similar solution conditions. These results indicate that thioether residues have a significantly lower affinity for cobalt(II) and zinc(II) than cysteine or histidine. Thus, significant modulation of metal-bound cysteinate reactivity can be achieved through the position of the cysteinate within the three-dimensional structure of a metal-peptide complex

The nasal valve is the most important region responsible for air flow and nasal resistance. In the past five years, numerous advances have been made in nasal valve analysis and surgery. The discovery that the valve consists of two distinct regions, the external and internal valves, has led to tailored surgical techniques to improve each site independently. Improved objective tests using rhinomanometry, acoustic rhinometry, and magnetic resonance imaging have proven that certain surgical techniques will improve nasal valve function. The roles of septoplasty, inferior turbinate surgery, and cartilage grafting have been objectively analyzed and methodically delineated. The nasal valve is now a prominent factor in planning cosmetic and functional rhinoplasty. This review examines the recent developments in nasal valve surgery and fits them into historical perspective with the evolution of our understanding of the nasal valve

A case of clear-cell follicular adenoma arising in ectopic thyroid tissue is reported. The 2.0-cm tumor arose in the submandibular region in a 29-yr-old female. The diagnosis was established on the basis of light microscopic morphology, a positive thyroglobulin immunohistology, and the presence of normal thyroid tissue surrounding the mass. Preoperative computed tomography (CT) scan and postoperative ultrasound studies revealed a normal orthotopic thyroid gland. No additional tumors have since been detected. The patient is free of recurrent or metastatic disease 54 mo following excision of the mass. Only eight previously published reports have described ectopic thyroid tissue in the submandibular region, all but one of which lacked an orthotopic thyroid gland. In this article, we describe the pathological features of our case and review the existing literature on the subject

The petrous apex is the most inaccessible portion of the temporal bone and surgical exposure presents considerable challenge. The transmastoid precochlear approach offers a direct intra temporal route to this region, providing good visual exposure with cochlea preservation. An anatomic study of 20 human temporal bones was performed to delineate the landmarks for this approach. Measurements to the tegmen tympani, carotid artery, and the anterior-superior limit of the cochlea were made from the cochleariform process, a constant landmark in the middle ear. Distances to the tegmen averaged 5.4 mm (range: 3.5-9 mm), to the carotid artery 9.3 mm (8-11 mm), and the cochlea 3.1 mm (2-5 mm). The entry to the apex admitted an average burr size of 3.5 mm (2-7 mm). We anticipate this approach will prove useful in the treatment of benign petrous apex lesions.