Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo

The slope of the action potential duration (APD) restitution curve may be a significant determinant of the propensity to develop ventricular fibrillation, with steeper slopes associated with a more arrhythmogenic substrate. We hypothesized that one mechanism by which beta-blockers reduce sudden cardiac death is by flattening the APD restitution curve. Therefore, we investigated whether infusion of esmolol modulates the APD restitution curve in vivo. In 10 Yorkshire pigs, dynamic APD restitution curves were determined from measurements of APD at 90% repolarization with a monophasic action potential catheter positioned against the right ventricular septum during right ventricular apical pacing in the basal state and during infusion of esmolol. APD restitution curves were fitted to the three-parameter (a, b, c) exponential equation, APD = a.[1 - e((-b.DI))] + c, where DI is the diastolic interval. Esmolol decreased the maximal APD slope, 0.68 +/- 0.14 vs. 0.94 +/- 0.24 (baseline), P = 0.002, and flattened the APD restitution curve at shorter DIs, 75 and 100 ms (P < 0.05). To compare the slopes of the APD restitution curves at similar steady states, slopes were also computed at points of intersection between the restitution curve and the lines representing pacing at a fixed cycle length (CL) of 200, 225, 250, 275, and 300 ms using the relationship CL = APD + DI. Esmolol decreased APD restitution slopes at CLs 200-275 ms (P < 0.05). Esmolol flattens the cardiac APD restitution curve in vivo, particularly at shorter CLs and DIs. This may represent a novel mechanism by which beta-blockers prevent sudden cardiac death.     

The European Renal Genome Project: An Integrated Approach Towards Understanding the Genetics of Kidney Development and Disease

Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics     

Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE

The purpose of this work was to analyze cDNA encoding human monocyte chemoattractant protein-1 (MCP-1), previously isolated from glioma cell line culture fluid. Screening of a cDNA library from total poly(A) RNA of glioma cell line U-105MG yielded a clone that coded for the entire MCP-1. Nucleotide sequence analysis and comparison with the amino acid sequence of purified MCP-1 showed that the cDNA clone comprises a 53-nucleotide 5'-non-coding region, an open reading frame coding for a 99-residue protein of which the last 76 residues correspond exactly to pure MCP-1, and a 389-nucleotide 3'-untranslated region. The hydrophobicity of the first 23 residues is typical of a signal peptide. Southern blot analysis of human and animal genomic DNA showed that there is a single MCP-1 gene, which is conserved in several primates. MCP-1 mRNA was induced in human peripheral blood mononuclear leukocytes (PBMNLs) by PHA, LPS and IL-1, but not by IL-2, TNF, or IFN-gamma. Among proteins with similar sequences, the coding regions of MCP-1 and mouse JE show 68% identity. This suggest that MCP-1 is the human homologue of the mouse competence gene JE.     

Scaling of the equilibrium sedimentation distribution in dense DNA solutions

DNA molecules, several persistence lengths long in sedimentation equilibrium at speeds high enough to maintain fairly close packing, show a dense, sharply-bounded turbid phase and an isotropic phase (as with shorter fragments) and also an intermediate, somewhat turbid region. The concentration distribution in the isotropic phase is in satisfactory agreement with a simple extension of scaled particle theory in which semiflexible chains are equivalent to straight rods of the same length. The net intermolecular interactions, as inferred from the Zimm cluster integral, are purely repulsive. As in our previous study with short fragments, the results are compatible with a hard-core electrostatic radius, decreasing with increasing salt concentration. However, for the longer fragments it is necessary to infer either a slightly greater mass per unit length or a slightly smaller electrostatic radius for closest agreement with scaled particle theory. The properties of the solution at the boundary with the turbid, presumably strongly ordered phase are consistent with those found for shorter fragments and with theoretical scaling expectation for a hard, asymmetric particle.     

Status of research in stock enhancement and sea ranching

Reviews in Fish Biology and Fisheries -     

Metabolic activation of N-methyl-N-nitrosourea in normal and tumor cells]

N-methyl-N-nitrosourea is metabolised by mouse liver microsomes yielding highly reactive product(s) capable of alkylating cellular macromolecules. Based on cofactor requirement (NADPH, oxygen), inhibition (NaN3) and induction by phenobarbital, 3,4-benz(a)pyrene, and MNU, the reaction is cytochrome P-450-dependent. Analysis of the kinetics and dose dependence of alkylation in vivo and in tissue homogenates confirms the fact that MNU must undergo metabolic activation in vivo.