PubMed Health⌕ Search

Biomedical subjects

T E Jenkins

Publications and source records attributed to T E Jenkins.

6 recordsLinked to original sources

Liquid alumina: detailed atomic coordination determined from neutron diffraction data using empirical potential structure refinement.

The neutron scattering structure factor S(N)(Q) for a 40 mg drop of molten alumina (Al2O3) held at 2500 K, using a laser-heated aerodynamic levitation furnace, is measured for the first time. A 1700 atom model of liquid alumina is generated from these data using the technique of empirical potential structural refinement. About 62% of the aluminum sites are 4-fold coordinated, matching the mostly triply coordinated oxygen sites, but some 24% of the aluminum sites are 5-fold coordinated. The octahedral aluminum sites found in crystalline alpha-Al2O3 occur only at the 2% level in liquid alumina.

Journal Article↗

Design of potent selective zinc-mediated serine protease inhibitors.

Many serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion.

Animals↗

Shape and size changes induced by taurine depletion in neonatal cardiomyocytes.

Taurine is a very important organic osmolyte in most adult cells. Because of this property it has been proposed that large changes in the intracellular content of taurine can osmotically stress the cell, causing changes in its size and shape. This hypothesis was examined by measuring cell dimensions of taurine deficient cardiomyocytes using confocal microscopy. Incubation of isolated neonatal rat myocytes with medium containing 5 mM beta-alanine led to a 55% decrease in intracellular taurine content. Associated with the loss of taurine was a reduction in cell size. Two factors contributed to the change in cell size. First, there was a shift in cell shape, favoring the smaller of the two cellular configurations commonly found in the myocyte cell culture. Second, the size of the polyhedral configuration was reduced after beta-alanine treatment. These same two events also contributed to size reduction in cardiomyocytes incubated with medium containing 30 mM mannitol. Nonetheless, some qualitative differences exist between cells osmotically stressed by increasing the osmolality of the incubation medium and decreasing intracellular osmolality. The results support a role for taurine in the regulation of osmotic balance in the neonatal cardiomyocyte.

Animals↗

The antagonism of nondepolarizing neuromuscular blockade.

The antagonism of the nondepolarizing neuromuscular blockade is accomplished many times in a given day. Fortunately, the incidents of complications are low. If they do occur and are not recognized and treated properly, however, the results can be serious. In this article, the author reviews the curariform group of drugs, anticholinesterases, and anticholinergics, evaluating the antagonism of the nondepolarizing neuromuscular blockade.

Cholinesterase Inhibitors↗