Biomedical subjects
Steven M Dunn
Publications and source records attributed to Steven M Dunn.
Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity.
The mammalian alpha/beta T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR-MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential.
Ultrasound and caudal blocks in children.
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The LMA ProSeal may not be the best option for difficult to intubate/ventilate patients.
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The addition of hydromorphone to epidural fentanyl does not affect analgesia in early labour.
PURPOSE: Epidural fentanyl after a lidocaine and epinephrine test dose, provides adequate analgesia and allows for ambulation during early labour. The current study was designed to determine the influence of hydromorphone added to an epidural fentanyl bolus (e.g., whether there is an increase in duration of analgesia). METHODS: Forty-four labouring primigravid women, at less than 5 cm cervical dilation, who requested epidural analgesia were enrolled in this randomized, double-blind study. After a 3 mL test dose of lidocaine with epinephrine, patients received fentanyl 100 microgram (in 10 mL volume). They randomly received the fentanyl with either saline or hydromorphone (300 microgram). After administration of the initial analgesic, pain scores and side effects were recorded for each patient at ten, 20, and 30 min, and every 30 min thereafter, by an observer blinded to the technique used. RESULTS: The patients were taller in the hydromorphone group (P < 0.04). There were no other demographic differences between the two groups. The mean duration prior to re-dose was not significantly different in the group that received hydromorphone (135 +/- 52 min) compared to the control group (145 +/- 46 min). Side effects were similar between the two groups. No patient in either group experienced any detectable motor block. CONCLUSION: In early labouring patients, the addition of hydromorphone (300 microgram) to epidural fentanyl (100 microgram after a lidocaine and epinephrine test dose) neither prolongs the duration of analgesia nor affects the ability to ambulate, and cannot be recommended according to the current study.