RESUMEN
OBJECTIVES: To determine whether there are differences in measures of longitudinal right ventricular (RV) systolic function among Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) compared with healthy control Boxer dogs. To explore relationships between markers of RV systolic function and age, body weight, gender, arrhythmia frequency, and markers of left ventricular (LV) systolic function in Boxer dogs. ANIMALS: The study included 50 client-owned Boxer dogs. METHODS: This is a retrospective echocardiographic study. Tricuspid annular plane systolic excursion (TAPSE) and pulsed wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (S') were measured in healthy control Boxers (n = 18), Boxers with ARVC and normal LV systolic function (n = 19), and Boxers with ARVC and reduced LV systolic function (n = 13). RESULTS: Tricuspid annular plane systolic excursion (p=0.002) and S' (p=0.001) were significantly different between affected and control groups. Significant correlations were found between measures of left heart size and function and both TAPSE and S'. No correlations were found between RV function parameters and age, gender, or body weight in this fairly homogeneous, single-breed population. Receiver operating characteristic curve analysis revealed that both TAPSE and S' had an area under the curve of 0.77 in distinguishing healthy Boxers from those with ARVC. CONCLUSIONS: Tricuspid annular plane systolic excursion and S' are reduced in Boxers with ARVC. In contrast to prior studies evaluating these parameters in dogs of different breeds and body types, no correlation was found between markers of RV function and body weight in this population of Boxer dogs.
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Displasia Ventricular Derecha Arritmogénica/veterinaria , Enfermedades de los Perros/fisiopatología , Ecocardiografía/veterinaria , Función Ventricular Derecha , Factores de Edad , Animales , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Perros , Femenino , Masculino , Factores SexualesRESUMEN
Research on terminology services has resulted in development of applications and definition of standards, but has not yet led to widespread use of (standardized) terminology services in practice. Current terminology services offer functionality both for concept representation and lexical knowledge representation, hampering the possibility of combining the strengths of dedicated (concept and lexical) services. We therefore propose an extensible architecture in which concept-related and lexicon-related components are integrated and made available through a uniform interface. This interface can be extended in order to conform to existing standards, making it possible to use dedicated (third-party) components in a standardized way. As a proof of concept and a reference implementation, a SOAP-based Java implementation of the terminology service is being developed, providing wrappers for Protégé and UMLS Knowledge Source Server. Other systems, such as the Description Logic-based reasoner RACER can be easily integrated by implementation of an appropriate wrapper.
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Programas Informáticos/normas , Vocabulario Controlado , Integración de Sistemas , Terminología como AsuntoRESUMEN
The active site of penicillin acylase of Escherichia coli contains two conserved arginine residues. The function of these arginines, alphaArg145 and betaArg263, was studied by site-directed mutagenesis and kinetic analysis of the mutant enzymes. The mutants alphaArg145-->Leu (alphaArg145Leu), alphaArg145Cys and alphaArg145Lys were normally processed and exported to the periplasm, whereas expression of the mutants betaArg263Leu, betaArg263Asn and betaArg263Lys yielded large amounts of precursor protein in the periplasm, indicating that betaArg263 is crucial for efficient processing of the enzyme. Either modification of both arginine residues by 2,3-butanedione or replacement by site-directed mutagenesis yielded enzymes with a decreased specificity (kcat/K(m)) for 2-nitro-5-[(phenylacetyl)amino]benzoic acid, indicating that both residues are important in catalysis. Compared with the wild type, the alphaArg145 mutants exhibited a 3-6-fold-increased preference for 6-aminopenicillanic acid as the deacylating nucleophile compared with water. Analysis of the steady-state parameters of these mutants for the hydrolysis of penicillin G and phenylacetamide indicated that destabilization of the Michaelis-Menten complex accounts for the improved activity with beta-lactam substrates. Analysis of pH-activity profiles of wild-type enzyme and the betaArg263Lys mutant showed that betaArg263 has to be positively charged for catalysis, but is not involved in substrate binding. The results provide an insight into the catalytic mechanism of penicillin acylase, in which alphaArg145 is involved in binding of beta-lactam substrates and betaArg263 is important both for stabilizing the transition state in the reaction and for correct processing of the precursor protein.