The rollercoaster ride to anti-cancer antibodies.
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Animals↗
Biomedical subjects
Paul Carter
Publications and source records attributed to Paul Carter.
Tech.Sight. Phage display. Affinity selection from biological libraries.
Phage display is a simple yet powerful technology that is used to rapidly characterize protein-protein interactions from amongst billions of candidates. This widely practiced technique is used to map antibody epitopes, create vaccines and to engineer peptides, antibodies and other proteins as both diagnostic tools and as human therapeutics. We overview the history of phage display and several recent applications.
Animals↗
Sequence plasticity in the antigen-binding site of a therapeutic anti-HER2 antibody.
We have examined the plasticity of the antigen-combining site of a high-affinity antibody. In phage-displayed Fab libraries, selected CDR positions and one FR position of the humanized anti-Her2 antibody hu4D5 were substituted with all 20 amino acids. Antigen-binding selections were used to enrich for high-affinity variants, and a large number of sequences were obtained prior to convergence of the selected pool to a small set of clones. As expected, sequence variability of the antigen-binding site is overall diminished compared to known IgG sequences; however, certain positions retain much higher variability than others. The sequence variability map of the hu4D5 binding site is compared with a map derived from previous alanine-scanning of the antibody. Affinities of soluble Fab fragments for antigen confirm that multiple variants were selected with high affinity for antigen, including one variant with a single point mutation that was about threefold improved in affinity compared to the parental hu4D5. Interestingly, this mutation is one of the most radical in terms of changing side-chain chemistry (Trp for Asp) and occurs at the most plastic site as calculated by the Wu-Kabat variability coefficient. Thus variability mapping yields information about the antibody-antigen interaction that is useful and complementary to that obtained by alanine scanning mutagenesis.
Alanine↗
Comparative study of intra-articular lidocaine and intravenous meperidine/diazepam for shoulder dislocations.
The purpose of this study was to compare the analgesic effectiveness of intra-articular lidocaine versus intravenous meperidine and diazepam during the reduction of anterior shoulder dislocations. Patients were randomized to one of the two methods before the reduction of shoulder dislocations. Patients marked a visual analog pain scale at baseline, after anesthesia just before reduction, and at the time of discharge. Interference with the procedure caused by pain or lack of muscle relaxation, perception of adequacy of analgesia by the patient, adverse effects, and time to discharge from the Emergency Department (ED) were measured. Differences of outcomes, relative risks (RR), and 95% confidence intervals (CIs) were derived. Fifty-four patients with anterior shoulder dislocations presenting from May 21, 1998 through January 21, 1999 were included in this study; 29 were randomly assigned to receive intra-articular lidocaine (IAL) and 25 to receive intravenous meperidine/diazepam (IVMD). IAL was less effective than IVMD in relieving pre-reduction pain (p = 0.045) but equally effective in overall pain relief (p = 0.98). IAL was more effective than IVMD in shortening recovery time (p = 0.025). There was an indication favoring IVMD in terms of physician-perceived muscle relaxation and patient's perception of analgesia adequacy. In conclusion, although the IVMD method appears to have some clinically and statistically significant advantages, IAL possesses some favorable features that render it to be an analgesia alternative in shoulder dislocation reduction.
Adult↗
Effects of hyperbaric exposure on the integrity of the internal components of commercially available cochlear implant systems.
HYPOTHESIS: This study investigated whether pressure changes common to scuba diving and to hyperbaric oxygen therapy would not cause crush damage or leakage from critical seals in commercially available cochlear implants. BACKGROUND: The implanted packages of cochlear implants are susceptible to electrical failure caused by leakage from critical seals and to crush injury when exposed to changing barometric pressures encountered in recreational diving and in hyperbaric oxygen therapy. METHODS: Six Clarion 1.2, eight MED-EL Combi-40+, six Nucleus CI22M, and six Nucleus CI24M cochlear implants underwent three exposures at 165 feet of seawater (FSW) (6 ata abs), 99 FSW (4 ata abs), and 60 FSW (2.8 ata abs), simulating rates in accordance with U.S. Navy dive tables for nondecompression dives. Dives to 45 FSW (2.4 ata abs) simulated wound therapy. Before each dive began, after each dive, and after completion of the dive protocol, each device underwent telemetry and electrical integrity checks. All implants were returned to their respective factories for final electrical and quality control testing. RESULTS: All 26 devices completed the dive protocol. One Nucleus CI24M implant had a fault recorded at electrode lead 18 on predive and final product testing, which was absent during interval dive measurements. All 26 devices passed final electrical and quality control testing. In addition, the six Clarion units passed repeat helium leak testing. CONCLUSION: The implanted components of the Clarion 1.2, MED-EL Combi-40+, and Nucleus CI22M and CI24M were safely subjected to repeated pressure changes up to 6 atm abs, equivalent to 165 feet of seawater, without electrical failure from leakage at critical seals or crush damage.
Cochlear Implants↗