The acute hepatic porphyrias

The acute hepatic porphyrias are the result of hereditary partial deficiencies of individual enzymes in the pathway of haem biosynthesis. Seven enzymes are known to be involved in the pathway, converting glycine and succinyl CoA first to porphyrin precursors and then to porphyrins and finally to haem. The rate of the process is regulated by the initial enzyme, delta-aminolaevulinic acid (ALA) synthase,which is under negative feedback control, by haem. The partial block in this pathway, in each of the acute porphyrias,results in compensatory increased activity of ALA synthase and,consequently,overproduction of porphyrins and precursors formed prior to the deficient enzyme. Patients with acute porphyria generally enjoy good health,but exposure to certain recognised factors, namely specific drugs, alcohol, hormones and fasting; may precipitate severe clinical attacks characterized by gastro-intestinal symptoms, psychiatric disturbances and neuropathy. All of the systemic manifestations of the attack are thought to be explained by neurological dys function,but the mechanism by which the abnormal haem biosynthesis causes the neuropathy is not known. Following a general description of haem biosynthesis and the porphyrias, this thesis concentrates on the management of acute hepatic porphyria studying, in turn, the detection of subjects with the genetic trait, the factors which may precipitate attacks in these subjects and the treatment of patients in established attack. Much of the work presented is based upon the ability to measure the activities of the individual enzymes of haem biosynthesis in human peripheral blood cells. The mitochondrial enzymes, ALA synthase, coproporphyrinogen oxidase and ferrochelatase, are measured in leucocytes and the cytosolic enzymes, ALA dehydratase, uroporphyrinogen-1-synthase (URO synthase) and uroporphyrinogen decarboxylase, in erythrocytes. The measurement in peripheral blood cells of the activities of both the rate-controlling enzyme, ALA synthase, and the appropriate genetically deficient intermediate enzyme, is shown to be a sensitive and specific means of detecting latent cases of acute porphyria,the majority of whom have normal excretion of porphyrins and precursors. Enzymatic screening of affected families confirms that the genetic trait is inherited in an autosomal dominant sex-independent manner. The family studies also demonstrate that the vast majority of subjects with the trait remain clinically latent, and the reason why the minority of patients experience clinical manifestations is examined. The activity of the partially deficient enzyme is similar in latent and manifest cases, but ALA synthase activity is higher in patients who have experienced an attack and this may reflect higher circulating levels of endogenous inducing agents. Drugs are an important exogenous precipitating factor for acute porphyria, and an important aspect of the prevention of attacks is the identification of potentially porphyrinogenic drugs. The testing of 26 commonly prescribed drugs, by assessing their effect on hepatic ALA synthase activity in rats, is described. The mechanism by which drugs stimulate ALA synthase activity is examiaed with particular reference to the role of induction of the mixed function oxidase enzyme (MFO) system. A close correlation is noted between induction of the MFO system, as reflected in increased hepatic cytochrome P450 content, and increased activity of ALA synthase, though not the converse. Sequential studies following commencement of phenytoin administration to rats show that the rise in ALA synthase activity is transitory and coincides with the rise in hepatic cytochrome P450 content which is maintained. These observations indicate that induction of the MFO system demands increased ALA synthase activity to provide the additional haem for synthesis of the haemoprotein, cytochrome P450. (Abstract shortened by ProQuest.)

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease1. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion2, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy3, which are presumptive precursors of gastric cancer4. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine5 and a powerful inhibitor of gastric acid secretion6,7. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

The International Surface Pressure Databank version 2

The International Surface Pressure Databank (ISPD) is the world's largest collection of global surface and sea-level pressure observations. It was developed by extracting observations from established international archives, through international cooperation with data recovery facilitated by the Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative, and directly by contributing universities, organizations, and countries. The dataset period is currently 1768–2012 and consists of three data components: observations from land stations, marine observing systems, and tropical cyclone best track pressure reports. Version 2 of the ISPD (ISPDv2) was created to be observational input for the Twentieth Century Reanalysis Project (20CR) and contains the quality control and assimilation feedback metadata from the 20CR. Since then, it has been used for various general climate and weather studies, and an updated version 3 (ISPDv3) has been used in the ERA-20C reanalysis in connection with the European Reanalysis of Global Climate Observations project (ERA-CLIM). The focus of this paper is on the ISPDv2 and the inclusion of the 20CR feedback metadata. The Research Data Archive at the National Center for Atmospheric Research provides data collection and access for the ISPDv2, and will provide access to future versions

The Vehicle, 1963, Vol. 5

Vol. 5 Table of Contents Milepostspage 3 Rhyme Conceived At DawnDaun Alan Leggpage 4 NightRoss Kokospage 4 UncrownedOra Blanche T. Kingpage 4 SunfishingL.J.G.page 5 The Man Who Went To New YorkEric Crookspage 7 The DreamPauline B. Smithpage 18 Open WindowsDavid Helmpage 19 SalvationChristine McCollpage 19 The Chess GamePierre Hooverpage 20 CataclysmRaymond Kapraunpage 20 A Microscopic ViewKenneth L. Vadovskypage 21 See How Love ComesLiz Puckettpage 21 A Can Of Beer For AndyKenneth L. Vadovskypage 22 A MonsterDixie Lee Motleypage 28 InconstancyJanice Brookspage 29 DreamerDaun Alan Leggpage 29 The Third WishGlenda Vursellpage 30 The MiracleJanice Brookspage 32 What Lives Where Love Once Dwelt?Vernell Vyvialpage 33 The Most Unforgettable Person I Have Ever KnownJames Flingpage 34 Winter ThoughtsPauline B. Smithpage 35 A Winter NightPeggy Lambertpage 35 The Silver WhaleL.J.G.page 36 RaindropsDixie Lee Motleypage 40 Conflict Of Soul IJean Konzelmanpage 40 JudyChristine McCollpage 41 Sadness No. 3 (Vergessen)Sherry Sue Frypage 41 Lost GoldLarry Pricepage 42 EchoesCharles Cooleypage 48 TruthDaun Alan Leggpage 48 SunsetCarol Bennettpage 48 Cover designTom Windsor Illustration for winning storyJoel E. Hendrickshttps://thekeep.eiu.edu/vehicle/1011/thumbnail.jp

Microglial brain region−dependent diversity and selective regional sensitivities to aging

Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good