• Expression and localization of human endothelin-converting enzyme-1 isoforms in symptomatic atherosclerotic disease and saphenous vein.

      Jackson, C.D.; Barnes, K.; Homer-Vanniasinkam, Shervanthi; Turner, A.J. (2006)
      Endothelln-converting enzyme (ECE-1) is a critical enzyme in the production of the potent vasoconstrictor peptide endothelin (ET-1). It has previously been shown that the levels of both ET-1 and ECE-1 are raised in atherosclerosis, but the possible relevance of the isoforms of ECE-1 in these changes has not yet been investigated. The aim of this study was to examine the expression of the ECE-1a and ECE-1c isoforms in human atherosclerotic pathologies. Immunohistochemical analysis was carried out on sections from atherosclerotic and non-atherosclerotic vascular tissue using a combination of ECE-1 isoform-specific antibodies, anti-¿-actin antibodies to identify smooth muscle cells (SMC) and anti-CD68 antibodies to identify macrophages. ECE-1 isoform expression was also examined in cultured SMC and in macrophages isolated from human blood. Results indicated differences in isoform expression in atherosclerotic lesions, with distinct patterns of staining for ECE-1 a and ECE-1 c. ECE-1 c immunoreactivity was seen in macrophages, and also correlated with actin staining. ECE-1a was also localized to macrophages and SMC. Results of this study suggest that these local changes influence the expression patterns of the ECE-1 isoforms within individual cell types. Correlation of these isoform expression patterns with the stage of atherosclerosis could provide novel indicators of disease progression.
    • QUASI: A general purpose implementation of the QM/MM approach and its application to problems in catalysis

      Kendrick, John; Sherwood, P.; De Vries, A.H.; Guest, M.F.; Schreckenbach, G.; Catlow, C.R.A.; French, S.A.; Sokol, A.A.; Bromley, S.T.; Thiel, W.; et al. (2003)
      We describe the work of the European project QUASI (Quantum Simulation in Industry, project EP25047) which has sought to develop a flexible QM/MM scheme and to apply it to a range of industrial problems. A number of QM/MMapproaches were implemented within the computational chemistry scripting system, ChemShell, which provides the framework for deploying a variety of independent program packages. This software was applied in several large-scale QM/MM studies which addressed the catalytic decomposition of N2O by Cu-containing zeolites, the methanol synthesis reaction catalysed by Cu clusters supported on ZnO surfaces, and the modelling of enzyme structure and reactivity.