THE SYNTHESIS, KINETIC CHARACTERIZATION AND APPLICATION OF A NOVEL BIOTINYLATED AFFINITY LABEL FOR CATHEPSIN-B

In this study we report on the synthesis, kinetic characterization and application of a novel biotinylated and active-site-directed inactivator of cathepsin B. Thus the peptidyliazomethane biotinyl-Phe-Ala-diazomethane has been synthesized by a combination of solid-phase and solution methodologies and has been shown to be a very efficient inactivator of bovine and human cathepsin B. The respective apparent second-order rate constants (k0bs./[I]) for the inactivation of the human and bovine enzymes by this reagent, namely approximately 5.4 x 10(4) M-1 and approximately 7.8 x 10(4) M-1, compare very favourably with those values determined for the urethane-protected analogue benzloxycarbonyl-Phe-Ala-chloromethane first described by Green & Shaw [(1981) J.Biol. Chem. 256, 1923-1928], thus demonstrating that the presence of the biotin moiety at the P3 position is compatible with inhibitor effectiveness. The utilization of this reagent for the detection of cathepsin B in electrophoretic gels, using Western blotting and in combination with a streptavidin/alkaline phosphatase detection system, is also demonstrated. Given that the peptidydiazomethanes exhibit a pronounced reactivity towards cysteine proteinases, we feel that the present label may well constitute the archetypal example of a wide range of reagents for the selective labelling of this class of proteinase, even in a complex biological milieu containing additional classes of proteinases.

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study.

We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

Oeuvres d'Omer et de Denis Talon,.... Tome 1 / ; publiées sur les manuscrits autographes, par D.-B. Rives,...

Comprend : [Discours de Pierre Lallemant sur la mort d'Omer Talon,...]

Oeuvres d'Omer et de Denis Talon,.... Tome 6 / ; publiées sur les manuscrits autographes, par D.-B. Rives,...

Comprend : [Discours de Pierre Lallemant sur la mort d'Omer Talon,...]

Oeuvres d'Omer et de Denis Talon,.... Tome 2 / ; publiées sur les manuscrits autographes, par D.-B. Rives,...

Comprend : [Discours de Pierre Lallemant sur la mort d'Omer Talon,...]

Oeuvres d'Omer et de Denis Talon,.... Tome 3 / ; publiées sur les manuscrits autographes, par D.-B. Rives,...

Comprend : [Discours de Pierre Lallemant sur la mort d'Omer Talon,...]

Oeuvres d'Omer et de Denis Talon,.... Tome 5 / ; publiées sur les manuscrits autographes, par D.-B. Rives,...

Comprend : [Discours de Pierre Lallemant sur la mort d'Omer Talon,...]

Oeuvres d'Omer et de Denis Talon,.... Tome 4 / ; publiées sur les manuscrits autographes, par D.-B. Rives,...

Comprend : [Discours de Pierre Lallemant sur la mort d'Omer Talon,...]

Traité de Ponce sur l'art épistolaire (13), précédé d'un calendrier lunaire (1) et des Méditations de saint Bernard (7).

Quincye "Mss bibliothec. du marquis de Quincy venant de Mr Fevret de Fontette...", "Donné par le marquis de Quincy aux manuscrits du roy" (1); cf. B.n.F., Imprimés, D 5373, ex dono "Donné à la bibliotheque du roy 1770, le marquis de Quincye"

"[B. Bernardi libri V de consideratione].

Acquis le 8 mars 1822 de M. Royez, libraire, pour le prix de 15 francs; cf. B.n.F., département des Manuscrits, Archives Modernes 492ter, registre des acquisitions du département des Manuscrits 1821-1830, f. 61"Lettres de s. Bernard au pape Eugène, in 8°, 13e s."; nouv. acq. fr. 5523, f. 227.

Extraits des œuvres de s. Bernard, de s. Augustin, etc.; morceaux ascétiques, etc.

Acquis le 5 janvier 1822, suite à la vente Baroud du 28 novembre 1821 à Paris (n° 56* du catalogue, cf. B.n.F., département des Imprimés, Delta 5899), par l'intermédiaire de M. de Bure, pour le prix de 21 francs; cf. B.n.F., département des Manuscrits, Archives Modernes 492ter, registre des acquisitions du département des Manuscrits 1821-1830, f. 49 et 59 "B. Bernardi epistola, in fol., et alia in eodem vol."; — ancienne cote "Mauger. 100" (contreplat)