472 research outputs found
Treatment of Inborn Errors of Urea Synthesis — Activation of Alternative Pathways of Waste Nitrogen Synthesis and Excretion
Abstract
Children with inborn errors of urea synthesis accumulate ammonium and other nitrogenous precursors of urea, leading to episodic coma and a high mortality rate. We used alternative pathways for the excretion of waste nitrogen as substitutes for the defective ureagenic pathways in 26 infants. These pathways involve synthesis and excretion of hippurate after sodium benzoate administration, and of citrulline and argininosuccinate after arginine supplementation.
The children were treated for seven to 62 months; 22 survived. The mean plasma level of ammonium (±S.E.) was 36±2 μmol per liter, and that of benzoate was 1.5±1.0 mg per deciliter. Alternative pathways accounted for between 28 and 59 per cent of the total effective excretion of waste nitrogen. Nineteen infants had normal height, weight, and head circumference, and 13 had normal intellectual development.
Activation of alternative pathways of waste nitrogen excretion can prolong survival and improve clinical outcome in children with inborn errors of urea synthesis. (N Engl J Med. 1982; 306:1387–92.
Multibeam Maser Survey of methanol and excited OH in the Magellanic clouds: new detections and maser abundance estimates
‘The definitive version is available at www.blackwell-synergy.com.’ Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.12888.xPeer reviewe
The neuroimmunology of chronic pain: from rodents to humans
Chronic pain, encompassing conditions, such as low back pain, arthritis, persistent post-surgical pain, fibromyalgia, and neuropathic pain disorders, is highly prevalent but remains poorly treated. The vast majority of therapeutics are directed solely at neurons, despite the fact that signaling between immune cells, glia, and neurons is now recognized as indispensable for the initiation and maintenance of chronic pain. This review highlights recent advances in understanding fundamental neuroimmune signaling mechanisms and novel therapeutic targets in rodent models of chronic pain. We further discuss new technological developments to study, diagnose, and quantify neuroimmune contributions to chronic pain in patient populations.Peter M. Grace, Vivianne L. Tawfik, Camilla I. Svensson, Michael D. Burton, Marco L. Loggia and Mark R. Hutchinso
Integration of genetics into a systems model of electrocardiographic traits using humanCVD BeadChip
<p>Background—Electrocardiographic traits are important, substantially heritable determinants of risk of arrhythmias and sudden cardiac death.</p>
<p>Methods and Results—In this study, 3 population-based cohorts (n=10 526) genotyped with the Illumina HumanCVD Beadchip and 4 quantitative electrocardiographic traits (PR interval, QRS axis, QRS duration, and QTc interval) were evaluated for single-nucleotide polymorphism associations. Six gene regions contained single nucleotide polymorphisms associated with these traits at P<10−6, including SCN5A (PR interval and QRS duration), CAV1-CAV2 locus (PR interval), CDKN1A (QRS duration), NOS1AP, KCNH2, and KCNQ1 (QTc interval). Expression quantitative trait loci analyses of top associated single-nucleotide polymorphisms were undertaken in human heart and aortic tissues. NOS1AP, SCN5A, IGFBP3, CYP2C9, and CAV1 showed evidence of differential allelic expression. We modeled the effects of ion channel activity on electrocardiographic parameters, estimating the change in gene expression that would account for our observed associations, thus relating epidemiological observations and expression quantitative trait loci data to a systems model of the ECG.</p>
<p>Conclusions—These association results replicate and refine the mapping of previous genome-wide association study findings for electrocardiographic traits, while the expression analysis and modeling approaches offer supporting evidence for a functional role of some of these loci in cardiac excitation/conduction.</p>
Butyltin compounds in a sediment core from the old Tilbury basin, London, UK
Sections from a sediment core taken from the River Thames were analysed for butyltin species using gas chromatography with species-specific isotope dilution mass spectrometry. Results demonstrated that in most samples tributyltin concentrations of 20–60 ng/g accounted for <10% of the total butyltin species present, which is in agreement with data from other sediment samples which were historically contaminated with tributyltin. Vertical distribution of the organotin residues with depth throughout the core, with data on organochlorine compounds and heavy metals allowed for the construction of a consistent hypothesis on historical deposition of contaminated sediments. From this it was possible to infer that the concentrations of tributyltin in sediments deposited during the early 1960s were in the order of 400–600 lg/g by using degradation rate constants derived by other workers. Such values fall well within the range quoted for harbour sediments in the literature
Fast coarsening in unstable epitaxy with desorption
Homoepitaxial growth is unstable towards the formation of pyramidal mounds
when interlayer transport is reduced due to activation barriers to hopping at
step edges. Simulations of a lattice model and a continuum equation show that a
small amount of desorption dramatically speeds up the coarsening of the mound
array, leading to coarsening exponents between 1/3 and 1/2. The underlying
mechanism is the faster growth of larger mounds due to their lower evaporation
rate.Comment: 4 pages, 4 PostScript figure
Haplotyping the human leukocyte antigen system from single chromosomes
We describe a method for determining the parental HLA haplotypes of a single individual without recourse to conventional segregation genetics. Blood samples were cultured to identify and sort chromosome 6 by bivariate flow cytometry. Single chromosome 6 amplification products were confirmed with a single nucleotide polymorphism (SNP) array and verified by deep sequencing to enable assignment of both alleles at the HLA loci, defining the two haplotypes. This study exemplifies a rapid and efficient method of haplotyping that can be applied to any chromosome pair, or indeed all chromosome pairs, using a single sorting operation. The method represents a cost-effective approach to complete phasing of SNPs, which will facilitate a deeper understanding of the links between SNPs, gene regulation and protein function
Analytical solution of generalized Burton--Cabrera--Frank equations for growth and post--growth equilibration on vicinal surfaces
We investigate growth on vicinal surfaces by molecular beam epitaxy making
use of a generalized Burton--Cabrera--Frank model. Our primary aim is to
propose and implement a novel analytical program based on a perturbative
solution of the non--linear equations describing the coupled adatom and dimer
kinetics. These equations are considered as originating from a fully
microscopic description that allows the step boundary conditions to be directly
formulated in terms of the sticking coefficients at each step. As an example,
we study the importance of diffusion barriers for adatoms hopping down
descending steps (Schwoebel effect) during growth and post-growth equilibration
of the surface.Comment: 16 pages, REVTeX 3.0, IC-DDV-94-00
Topological entropy and secondary folding
A convenient measure of a map or flow's chaotic action is the topological
entropy. In many cases, the entropy has a homological origin: it is forced by
the topology of the space. For example, in simple toral maps, the topological
entropy is exactly equal to the growth induced by the map on the fundamental
group of the torus. However, in many situations the numerically-computed
topological entropy is greater than the bound implied by this action. We
associate this gap between the bound and the true entropy with 'secondary
folding': material lines undergo folding which is not homologically forced. We
examine this phenomenon both for physical rod-stirring devices and toral linked
twist maps, and show rigorously that for the latter secondary folds occur.Comment: 13 pages, 8 figures. pdfLaTeX with RevTeX4 macro
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