A microarray immobilized with 105 aldehyde-containing small molecules was screened against mammalian cell lysates over-expressing cathepsin L to identify two potent inhibitors, which were subsequently converted into cell-permeable probes capable of live-cell imaging of endogenous cysteinyl cathepsin activities by two-photon fluorescence microscopy.

PURPOSE This study assessed changes in functional dysmetria (FD) and in brain activation observable by functional magnetic resonance imaging (fMRI) during a leg flexion-extension motor task following brain stimulation with a single radioelectric asymmetric conveyer (REAC) pulse, according to the precisely defined neuropostural optimization (NPO) protocol. POPULATION AND METHODS Ten healthy vo...

2-Aminoquinolin-4(1H)-one was reacted with various primary/secondary amines and paraformaldehyde under Mannich reaction conditions. In the case of secondary amines, the reaction in N,N-dimethylformamide yielded expected Mannich products accompanied with 3,3'-methylenebis(2-aminoquinolin-4(1H)-one). Except these main products, the pyrimido[4,5-b]quinolin-5-one derivative was also identified as c...

This work describes the syntheses and antitumoral properties of five prenyl compounds from which antiproliferative activities were predicted by using the TOPS-MODE approach, a computational method for drug design. The syntheses of 2-(3-methylbut-2-enyloxy)acetophenone (2), 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone (3), 2-hydroxy-3-(1,1-dimethylallyl)acetophenone (4), and 5-(3-methylbut-2-eny...

T-61 is an agent used for euthanasia of animals and is primarily administered by iv injection. When so used it rapidly induces deep anesthesia and cerebral death. We report our findings in a case of ingestion of T-61 with suicidal intent. The coroner's report stated that the individual survived for 20 to 30 min and that death was due to cardio-respiratory failure. Levels of embutramide in the b...

C-reactive protein (CRP) is an acute phase reactant the concentration of which increases significantly following tissue injury or inflammation. It is present in the albumin fraction of the serum of patients and is antigenic upon injection into rabbits. We report here the development of a local latex reagent coated with rabbit anti-CRP. For this purpose CRP was isolated from pooled sera of patie...

This paper examines how the concept of 'excessive costs' has been interpreted in the implementation of industrial pollution control in the UK. Since 1984, industrial air pollution regulation in the EU has been guided by the framework concept of Best Available Technology Not Entailing Excessive Costs (BATNEEC). With the introduction of the Integrated Pollution Prevention & Control Directive in 1...

In 1964, Albretch Fleckenstein described an inhibitory action ofverapamil and prenylamine on excitation-contraction coupling that was similar to calcium depletion. By the late 1970s, the clinical use of calcium channel blockers (CCBs) was widely accepted for variety of cardiovascular indications, including hypertension, dysrhythmias, and angina. Later indications, including Raynaud phenomenon, ...

Of the four heart valves, three are tricuspid (aortic, pulmonic, and tricuspid) and one is bicuspid (mitral). Failure of normal function of these valves is due to lesions that make them incompetent and allow backward flow (regurgitation) or to lesions that decrease orifice size and cause restriction of flow (stenosis). In addition, combinations of these lesions may occur within the same valve, ...

One of the major mechanisms involved in acetaminophen (APAP)induced hepatotoxicity is hepatocyte nuclear factor 4a (HNF4a)mediated activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). In the present study, we investigated the role of miR-561 and its target gene DAX-1 encoding a corepressor of HNF4a in the process of APAP-induced hepatotoxicity. We used both human ...