Proton NMR measurements of bacteriophage T4 lysozyme aided by 15N isotopic labeling: structural and dynamic studies of larger proteins.

A strategy for resolution and assignment of single proton resonances in proteins of molecular mass up to at least 40 kDa is presented. This approach is based on 15N (or 13C) labeling of selected residues in a protein. The resonances from protons directly bonded to labeled atoms are detected in a two-dimensional 1H-15N (or 13C) spectrum.

Therapeutic concentrations of theophylline and enprofylline potentiate catecholamine effects and inhibit leukocyte activation.

Methylxanthines are primary agents used in treatment of hypersensitivity disease. Because polymorphonuclear leukocyte (PMN) activation is associated with generation of potent inflammatory mediators, xanthine effects on the PMN respiratory burst were studied. Enprofylline, a xanthine with important therapeutic potential, does not antagonize adenosine and was contrasted with theophylline.

Doxorubicin and doxorubicinol-induced alterations in human polymorphonuclear leukocyte oxygen metabolite generation.

The effects of doxorubicin and its primary metabolite doxorubicinol on the polymorphonuclear leukocyte (PMNL) respiratory burst were studied using lucigenin and luminol for detection of oxygen metabolite generation. Although both anthracyclines inhibited PMNL activation at concentrations achieved with therapeutic administration of doxorubicin, doxorubicinol was much more potent than doxorubicin. Preincubation of PMNL with either drug caused a persistent inhibition of cell function after drug washout that was not prevented by inclusion of either free radical scavengers or iron chelators in the incubation medium.

Beta-adrenoceptor-mediated modulation of calcium ionophore activated polymorphonuclear leucocytes.

Beta-adrenoceptor-mediated modulation of calcium-mediated stimulus-response coupling was studied using calcium ionophore (A23187) activation of polymorphonuclear leucocytes (PMNL). Oxygen metabolite generation was measured with luminol- and lucigenin-dependent chemiluminescence in both whole blood and isolated PMNL. Isoprenaline reduced PMNL response by 53% in a dose-dependent fashion.