Drug resistance in epilepsy: human epilepsy.

The basis of drug resistance in human epilepsy is not understood. Parallels with resistance in cancer suggest that drug resistance proteins may have a role. To examine this possibility, we have studied human brain tissue containing pathologies capable of causing refractory epilepsy. Using immunohistochemistry for P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1), we examined both pathological tissue and control tissue. We demonstrate expression of Pgp and MRP1 in glia from cases of malformation of cortical development studied both before and after the onset of epilepsy, as well as in cases of hippocampal sclerosis and dysembryoplastic neuroepithelial tumours. In one particular type of malformation, we also demonstrate that dysplastic neurons express MRP1. The pattern of immunolabelling suggests overexpression is concentrated particularly around vessels in most of the pathologies. The timing shows that expression may be constitutive in some pathologies. These findings suggest that drug resistance proteins may contribute to drug resistance in refractory epilepsy.

Application of the charge regulation model to transport of ions through hydrophilic membranes: one-dimensional transport model for narrow pores (nanofiltration).

The charge regulation concept is combined with the Navier-Stokes and Nernst-Planck equations to describe the ion retention of nanofiltration membranes consisting of narrow cylindrical pores. The charge regulation approach replaces the assumption of a constant charge or a constant potential at the membrane pore surface, and accounts for the influence of pH, salt concentration, and type of electrolyte on ion retention. In the current model, radial concentration and potential gradients are considered to be negligibly small (valid for narrow enough pores), resulting in a one-dimensional transport description. The model describes typical experimental data for nanofiltration membranes, such as the change of ion retention with pore radius, ion concentration, pH, and pressure both for monovalent and multivalent ions. For a constant solvent velocity, the model in some cases predicts an optimum pore size for retention. Nonequal retentions for anions and cations are predicted at low and high pH values, as well as a minimum solvent velocity for very low salt concentrations. For higher salt concentrations, and at a fixed pressure difference, an increase in solvent velocity with increasing ion concentrations is predicted, in agreement with other one-dimensional transport descriptions found in the literature, but in contrast to some experimental data.

Molecular cloning and characterization of a novel transglutaminase cDNA from a human prostate cDNA library.

The primary sequence of a cDNA encoding a novel transglutaminase from a human prostate cDNA library is reported. The sequence is compared to other known transglutaminases in a multiple alignment. The deduced peptide sequence is 51% identical to a rat prostate transglutaminase.