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BACKGROUND Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering. METHODS AND RESULTS The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in(More)
Heterotrimeric AMP-activated protein kinase (AMPK) is crucial for energy homeostasis of eukaryotic cells and organisms. Here we report on (i) bacterial expression of untagged mammalian AMPK isoform combinations, all containing gamma(1), (ii) an automated four-dimensional purification protocol, and (iii) biophysical characterization of AMPK heterotrimers by(More)
Novel drug release microimplants (0.8 x 1.14 mm; custom-made by Leiras, now Schering OY, Finland) of slow- and fast-release types containing either 0.9 mg beclomethasone or no drug at all were placed unilaterally onto the round-window membrane (RWM) of 45 guinea pigs for a maximum duration of 28 days. The following parameters were tested on days 1, 14 and(More)
BACKGROUND The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN The European Lacidipine(More)
The three-dimensional structure of hevamine, a plant enzyme with chitinase and lysozyme activity, has been refined at 1.8 A resolution to an R-factor of 14.9% and a free R-factor of 19.6%. The final model consists of all 273 amino acid residues and 206 ordered water molecules. Two non-proline cis-peptides were identified, involving Phe32 and Trp255, both of(More)
Venom-derived peptide toxins can modify the gating characteristics of excitatory channels in neurons. How they bind and interfere with the flow of ions without directly blocking the ion permeation pathway remains elusive. Here we report the crystal structure of the trimeric chicken Acid-sensing ion channel 1 in complex with the highly selective gating(More)
In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization(More)
BACKGROUND AND OBJECTIVE The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic(More)
BACKGROUND The European Lacidipine Study of Atherosclerosis (ELSA) was a prospective, randomized, double-blind, multinational interventional trial using B-mode ultrasound measurement of carotid intima-media thickness (IMT) in 2259 hypertensive individuals. ELSA showed that 4-year treatment with the calcium antagonist, lacidipine, significantly slowed down(More)
BACKGROUND Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. METHODS In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion(More)