Computational modeling of flow and gas exchange in models of the human maxillary sinus.

The present study uses numerical modeling to increase the understanding of sinus gas exchange, which is thought to be a factor in sinus disease. Order-of-magnitude estimates and computational fluid dynamics simulations were used to investigate convective and diffusive transport between the nose and the sinus in a range of simplified geometries. The interaction between mucociliary transport and gas exchange was modeled and found to be negligible. Diffusion was the dominant transport mechanism for small ostia and large concentration differences between the sinus and the nose, whereas convection was important for larger ostia or smaller concentration differences. The presence of one or more accessory ostia can increase the sinus ventilation rate by several orders of magnitude, because it allows a net flow through the sinus. Estimates of nitric oxide (NO) transport through the ostium based on measured sinus and nasal NO concentrations suggest that the sinuses cannot supply all the NO in nasally exhaled air.

Measurement of alpha(1-3) fucosyltransferase activity using scintillation proximity.

The alpha 3 fucosyltransferases are a family of glycosyltransferases involved in the addition of fucose onto glycoproteins and glycolipids. One of the best defined roles for the alpha 3 fucosyltransferases is in the biosynthesis of the carbohydrate antigen sialyl Lewis X, the minimal ligand for the selectin family of adhesion molecules. We describe here the development of a single-step assay for the measurement of alpha 3 fucosyltransferase activity based on the principle of scintillation proximity. The fucosyltransferase catalyses the transfer of [3H]fucose, from GDP-[3H]fucose, onto the sugar chains of a glycoprotein acceptor noncovalently bound to a scintillant-impregnated microsphere (SPA bead). The resultant signal can be used as a measure of enzyme activity. Due to the nature of this assay no steps are required to separate unused substrate from product. Kinetic data from the assay compare favorably with those obtained from assays currently used for the alpha 3 fucosyltransferases. This SPA-based assay appears generic for the alpha 3 fucosyltransferases and readily adaptable for other glycosyltransferases. The particular advantage of the assay is anticipated to be found in the simple, routine testing of a large number of samples.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.