Jarkovsky J

References (2)

Title : Prediabetes\/early diabetes-associated neuropathy predominantly involves sensory small fibres - Divisova_2012_J.Peripher.Nerv.Syst_17_341
Author(s) : Divisova S , Vlckova E , Hnojcikova M , Skorna M , Nemec M , Dubovy P , Dusek L , Jarkovsky J , Belobradkova J , Bednarik J
Ref : J Peripher Nerv Syst , 17 :341 , 2012
Abstract : The aim of this study was to investigate the characteristics of prediabetes (preDM) and early (<3 years) diabetes mellitus type 2 (eDM2)-associated neuropathy and the value of recently proposed diagnostic criteria for diabetic sensorimotor polyneuropathy (DSPN). A prospective case-control study in a group of 48 consecutive patients with eDM2, 16 preDM patients and 40 age- and sex-matched normoglycaemic controls was performed. Clinical and laboratory diagnostic tests were used to detect neuropathic abnormalities; these were further classified in terms of recent diagnostic criteria. Criteria for confirmed DSPN based on abnormal nerve conduction (NC) studies were met in 7 (14.6%) eDM2 patients compared to no control (p < 0.05), and the proportion significantly increased to 37.5% compared to 2.5% controls (p < 0.001), if intraepidermal nerve fibre density (IENFD) was used as an alternative criterion in addition to NC. The subclinical DSPN criteria based on NC abnormalities were met in 4.2% eDM2 patients, while the proportion of preDM and eDM2 cases with subclinical sensory small-fibre involvement documented by IENFD reached 12.5% and 22.9% compared with 2.5% controls (p = 0.005 for eDM2). The absolute IENFD values from distal leg were significantly lower in both eDM2 (p < 0.0001) and preDM patients (p = 0.005) compared to controls. Neuropathy associated with preDM/eDM2 predominantly involves sensory small fibres.
ESTHER : Divisova_2012_J.Peripher.Nerv.Syst_17_341
PubMedSearch : Divisova_2012_J.Peripher.Nerv.Syst_17_341
PubMedID: 22971096

Title : Substrate specificity of haloalkane dehalogenases - Koudelakova_2011_Biochem.J_435_345
Author(s) : Koudelakova T , Chovancova E , Brezovsky J , Monincova M , Fortova A , Jarkovsky J , Damborsky J
Ref : Biochemical Journal , 435 :345 , 2011
Abstract : An enzyme's substrate specificity is one of its most important characteristics. The quantitative comparison of broad-specificity enzymes requires the selection of a homogenous set of substrates for experimental testing, determination of substrate-specificity data and analysis using multivariate statistics. We describe a systematic analysis of the substrate specificities of nine wild-type and four engineered haloalkane dehalogenases. The enzymes were characterized experimentally using a set of 30 substrates selected using statistical experimental design from a set of nearly 200 halogenated compounds. Analysis of the activity data showed that the most universally useful substrates in the assessment of haloalkane dehalogenase activity are 1-bromobutane, 1-iodopropane, 1-iodobutane, 1,2-dibromoethane and 4-bromobutanenitrile. Functional relationships among the enzymes were explored using principal component analysis. Analysis of the untransformed specific activity data revealed that the overall activity of wild-type haloalkane dehalogenases decreases in the following order: LinB~DbjA>DhlA~DhaA~DbeA~DmbA>DatA~DmbC~DrbA. After transforming the data, we were able to classify haloalkane dehalogenases into four SSGs (substrate-specificity groups). These functional groups are clearly distinct from the evolutionary subfamilies, suggesting that phylogenetic analysis cannot be used to predict the substrate specificity of individual haloalkane dehalogenases. Structural and functional comparisons of wild-type and mutant enzymes revealed that the architecture of the active site and the main access tunnel significantly influences the substrate specificity of these enzymes, but is not its only determinant. The identification of other structural determinants of the substrate specificity remains a challenge for further research on haloalkane dehalogenases.
ESTHER : Koudelakova_2011_Biochem.J_435_345
PubMedSearch : Koudelakova_2011_Biochem.J_435_345
PubMedID: 21294712
Gene_locus related to this paper: agrtu-DHAA , brael-e2rv62 , braja-dhaa , myctu-linb , myctu-Rv1833c , rhoba-DHLA , rhoso-halo1 , sphpi-linb , xanau-halo1