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Geometry and physics of pseudodifferential operators on manifolds

A review is made of the basic tools used in mathematics to define acalculus for pseudodifferential operators on Riemannian manifolds endowed with aconnection: existence theorem for the function that generalizes the phase; analogueof Taylor’s theorem; torsion and curvature terms in the symbolic calculus; the twokinds of derivative acting on smooth sections of the cotangent bundle of the Riemannianm

Errors in medication history at hospital admission : Prevalence and predicting factors

Background: An accurate medication list at hospital admission is essential for the evaluation and further treatment of patients. The objective of this study was to describe the frequency, type and predictors of errors in medication history, and to evaluate the extent to which standard care corrects these errors.Methods: A descriptive study was carried out in two medical wards in a Swedish hospital

Solaris storage ring lattice optimisationwith strong insertion devices

The Solaris synchrotron radiation facility under construction in Krakow will be areplica of the 1.5 GeV storage ring of MAX IV. This compact 3rd generation light source hasbeen designed to have an emittance of 6 nmrad and operate with 500 mA stored current forVUV and and softX-ray production.The lattice consists of 12 doublebend achromats (DBA)where each DBA cell is integrated into one solid iron

Malignancies in Swedish persons with haemophilia : a longitudinal registry study

The aim of the study was to investigate, over time, the incidence of and mortality due to malignant diseases among persons with haemophilia, compared to matched controls. Persons with haemophilia A or B were enrolled via registries at each haemophilia centre, as well as from the National Patient Registry, and were compared to five sex and age-matched controls per patient. Data from the national Ca

Increased catechol-O-methyltransferase activity and protein expression in OX-42-positive cells in the substantia nigra after lipopolysaccharide microinfusion

Activated microglial cells are found in the substantia nigra and the striatum of Parkinson's disease patients. These cells have been shown to express catechol-O-methyltransferase activity which may increase during pathological conditions. Lipopolysaccharides are potent activators of microglial cells. After paranigral lipopolysaccharide infusion to rats we observed intense microglial activation aro

Reduced membrane-bound catechol-O-methyltransferase in the liver of spontaneously hypertensive rats

We have previously reported that methylation of catecholamines by catechol-O-methyltransferase (COMT) was attenuated in spontaneously hypertensive rats (SHR) with acute hypotension as compared with that of Wistar-Kyoto (WKY) rats. Here we examined the soluble (S-) and membrane-bound (MB-) COMT activities and COMT protein in the liver, kidney, and erythrocytes in both strains. Both the activities a

The enhanced contractility of the phospholamban-deficient mouse heart persists with aging

Phospholamban ablation in the mouse is associated with significant increases in cardiac contractility. To determine whether this hyperdynamic function persists through the aging process, a longitudinal examination of age-matched phospholamban-deficient and wild-type mice was employed. Kaplan-Meier survival curves indicated no significant differences between phospholamban-deficient and wild-type mi

Binding of Levosimendan, a Calcium Sensitizer, to Cardiac Troponin C

Levosimendan is an inodilatory drug that mediates its cardiac effect by the calcium sensitization of contractile proteins. The target protein of levosimendan is cardiac troponin C (cTnC). In the current work, we have studied the interaction of levosimendan with Ca2+-saturated cTnC by heteronuclear NMR and small angle x-ray scattering. A specific interaction between levosimendan and the Ca2+-loaded

Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan : Structure-response and binding analysis with analogs of levosimendan

Levosimendan, an inodilatory drag discovered using troponin C as a target protein, has a cardiac effect deriving from the calcium sensitization of contractile proteins. The aim of this study was to give further evidence that levosimendan binds to cardiac troponin C and that the binding involves amino acid residues on helix ε of the N-terminal domain of this calcium-binding protein. Nine organic mo

Phenotype mining in CNV carriers from a population cohort

Phenotype mining is a novel approach for elucidating the genetic basis of complex phenotypic variation. It involves a search of rich phenotype databases for measures correlated with genetic variation, as identified in genome-wide genotyping or sequencing studies. An initial implementation of phenotype mining in a prospective unselected population cohort, the Northern Finland 1966 Birth Cohort (NFB

Conformations of the regulatory domain of cardiac troponin C examined by residual dipolar couplings

Conformations of the regulatory domain of cardiac troponin C (cNTnC) were studied by means of residual dipolar couplings measured from samples dissolved in dilute liquid crystals. Changes in the main chain HN residual dipolar couplings revealed a conformational change in cNTnC due to the complexation with the second binding region (amino acids 148-163) of cardiac troponin I (cTnI). Formation of th

Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport

Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca2+ transport apparent affinity for Ca2+ in cardiac muscle. This inhibitory effect of phospholamban can be relieved through its phosphorylation or ablation. To better characterize the regulatory mechanism of phospholamban, we examined the initial rates of Ca2+-uptake and Ca2+-ATPase activity under identical conditions, using sarcoplasmic

Solution structure and main chain dynamics of the regulatory domain (Residues 1-91) of human cardiac troponin C

Thee three-dimensional structure of calcium-loaded regulatory, i.e. N- terminal, domain (1-91) of human cardiac troponin C (cNTnC) was determined by NMR in water/trifluoroethanol (91:9 v/v) solution. The single-calcium-loaded cardiac regulatory domain is in a 'closed' conformation with comparatively little exposed hydrophobic surface. Difference distance matrices computed from the families of Ca2+

Expression and intracellular localization of catechol O-methyltransferase in transfected mammalian cells

The intracellular localization of soluble and membrane-bound isoforms of rat and human catechol O-methyltransferase (COMT) was studied by expressing the recombinant COMT proteins either separately or together in mammalian cell lines (HeLa and COS-7 cells) and in rat primary neurons. The distribution of soluble and membrane-bound COMT enzyme was visualized by immunocytochemistry. For comparison, th

Genetic polymorphism of catechol-O-methyltransferase (COMT) : Correlation of genotype with individual variation of S-COMT activity and comparison of the allele frequencies in the normal population and Parkinsonian patients in Finland

The catechol-O-methyltransferase (COMT) gene occurs as two polymorphic alleles, which code for a high activity thermostable and low activity thermolabile form of the enzyme. We devised a fast solid-phase minisequencing assay for genotyping the COMT gene at nucleotide position 544 encoding amino acid residue 158. The method was applied to correlate the genotype of the COMT gene with the biological

Compensatory mechanisms associated with the hyperdynamic function of phospholamban-deficient mouse hearts

Phospholamban ablation is associated with significant increases in the sarcoplasmic reticulum Ca2+-ATPase activity and the basal cardiac contractile parameters. To determine whether the observed phenotype is due to loss of phospholamban alone or to accompanying compensatory mechanisms, hearts from phospholamban-deficient and age-matched wild-type mice were characterized in parallel. There were no

Purification methods of mammalian catechol-O-methyltransferase

The protein purification strategies used for obtaining homogeneous rat and human soluble catechol-O-methyltransferase (S-COMT) polypeptides are reviewed. Expression and purification of recombinant rat and human S-COMT in Escherichia coli and for human S-COMT in baculovirus-infected insect cells made it possible to elucidate the S-COMT polypeptides in more detail. The application of these purificat