Biomedical subjects

Byron Ellis

Publications and source records attributed to Byron Ellis.

4 recordsLinked to original sources

PubMed2006

Anterior and posterior cartilage graft dimensions in successful laryngotracheal reconstruction.

OBJECTIVE: To describe the dimensions of cartilage grafts used for successful laryngotracheal reconstruction, with the goal of establishing appropriate sizes for "off-the-shelf" tissue-engineered cartilage grafts. DESIGN: A retrospective review of prospectively maintained operative illustrations of a single surgeon's experience. SETTING: Two tertiary children's hospitals. PATIENTS: A consecutive sample of 54 patients (tracheotomized or intubated) with a diagnosis of subglottic stenosis. INTERVENTIONS: Each patient underwent anterior (n = 30), posterior (n = 3), or anterior and posterior (n = 22) laryngotracheal reconstruction. Rib cartilage was used in 51 patients and thyroid cartilage was used in 3 patients. MAIN OUTCOME MEASURE: Successful or failed extubation. RESULTS: Of the 54 patients, 48 (89%) were successfully decannulated. The mean +/- SEM length of the anterior graft was 20.7 +/- 10.3 mm, and the mean width of the anterior graft was 7.7 +/- 2.5 mm. The mean length of the posterior graft was 13.9 +/- 2.9 mm, and the mean width of the posterior graft was 4.2 +/- 0.9 mm. CONCLUSIONS: With the prospect of tissue-engineered cartilage implants becoming available for laryngotracheal reconstruction, the most appropriate templates for designing these implants should be based on the geometric dimensions of grafts carved from native tissues in cases that have been successfully decannulated. Based on our analysis, the use of 2-mm increments for the posterior grafts suggests a set of molds that are 2, 4, and 6 mm wide and 22 mm long. Using 2 x 2-mm increments for the anterior grafts indicates that 36 mold sizes will be sufficient for 90% of predicted cases.

Cartilage↗

PubMed2004

A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.

GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibitor OSI-774 (Tarceva) described previously. Surprisingly, we found that GW572016 has a very slow off-rate from the purified intracellular domains of EGFR and ErbB-2 compared with OSI-774 and another EGFR selective inhibitor, ZD-1839 (Iressa). Treatment of tumor cells with these inhibitors results in down-regulation of receptor tyrosine phosphorylation. We evaluated the duration of the drug effect after washing away free compound and found that the rate of recovery of receptor phosphorylation in the tumor cells reflected the inhibitor off-rate from the purified intracellular domain. The slow off-rate of GW572016 correlates with a prolonged down-regulation of receptor tyrosine phosphorylation in tumor cells. The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures.

Amino Acid Sequence↗

PubMed2004

Bioconductor: open software development for computational biology and bioinformatics.

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.

Computational Biology↗

PubMed2003

Production and characterization of monoclonal antibodies against the vasoconstrictive peptide human urotensin-II.

We report the production and characterization of four monoclonal antibodies (MAbs) against human urotensin-II (hU-II). The antibodies were raised against human hU-II, which contains the C-terminus cyclic ring (CFWKYC) that is conserved across species. Multiple selection assays were applied to ensure antibody potency and reactivity against the ring structure. The MAbs reacted via ELISA with hU-II bound to plastic, immunoprecipitated [(125)I-Y(9)] hU-II, bound to biotinylated hU-II in BIAcore analysis and, by Western analysis, recognized the full-length human preprourotensin-II expressed in transfected HEK293 cells. All four MAbs cross-reacted with porcine A, porcine B, rat, mouse, and goby U-II in ELISA. By competitive RIA, hU-II(5-11) (identical to the C-terminus of goby U-II) reacted equivalently to hU-II and goby U-II. The IC(50)s were 0.8 nM for one MAb and 1.6 nM for the others. All four MAbs reacted 15-fold less potently with hU-II(5-10) and 50-fold less potently with hU-II(5-10) amide. Thus, the ring structure and terminal Val/Ile comprise the binding site for this group of MAbs. This panel of antibodies could be useful tools to help delineate the biology and pharmacology of U-II. They may also be of diagnostic value in monitoring hU-II in body fluids.

Animals↗