Structural Basis for Complement Factor I Control and Its Disease-Associated Sequence Polymorphisms
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The Production of Coagulation Factor VII by Adipocytes Is Enhanced by Tumor Necrosis Factor-Α Or Isoproterenol
International Journal of Obesity (2015) 39, 747–754 © 2015 Macmillan Publishers Limited All rights reserved 0307-0565/15 www.nature.com/ijo ORIGINAL ARTICLE The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol N Takahashi1,2, T Yoshizaki3, N Hiranaka1, O Kumano1,4, T Suzuki1,4, M Akanuma5,TYui5, K Kanazawa6, M Yoshida7, S Naito7, M Fujiya2, Y Kohgo2 and M Ieko1 BACKGROUND: A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. OBJECTIVE: We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. METHODS: C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. RESULTS: The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. -
Clinical Study High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders
Hindawi Publishing Corporation Autism Research and Treatment Volume 2012, Article ID 868576, 6 pages doi:10.1155/2012/868576 Clinical Study High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders Naghi Momeni,1 Lars Brudin,2 Fatemeh Behnia,3 Berit Nordstrom,¨ 4 Ali Yosefi-Oudarji,5 Bengt Sivberg,4 Mohammad T. Joghataei,5 and Bengt L. Persson1 1 School of Natural Sciences, Linnaeus University, 39182 Kalmar, Sweden 2 Department of Clinical Physiology, Kalmar County Hospital, 39185 Kalmar, Sweden 3 Department of Occupational Therapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran 4 Department of Health Sciences, Autism Research, Faculty of Medicine, Lund University, Box 157, 22100 Lund, Sweden 5 Cellular and Molecular Research Centre, Tehran University of Medical Sciences (TUMS), Tehran, Iran Correspondence should be addressed to Bengt Sivberg, [email protected] Received 17 June 2011; Revised 22 August 2011; Accepted 22 August 2011 Academic Editor: Judy Van de Water Copyright © 2012 Naghi Momeni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Autism spectrum disorders (ASDs) are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Im- mune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine pro- tease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. -
Advances in Hematology
ADVANCES IN HEMATOLOGY Current Developments in the Management of Hematologic Disorders Hematology Section Editor: Craig M. Kessler, MD Atypical Hemolytic Uremic Syndrome: The Role of Complement Pathway Gene Mutation Analysis Ilene C. Weitz, MD Associate Professor of Clinical Medicine Jane Anne Nohl Division of Hematology Keck School of Medicine of USC Los Angeles, California H&O What causes atypical hemolytic uremic H&O Which mutations in complement alternative syndrome (aHUS)? pathway genes are linked to aHUS? IW We think that most people with aHUS have problems IW Multiple genetic mutations have been linked to with regulation of complement. As a result of excess com- aHUS, especially those involved in the complement plement, endothelial and organ damage occur. We know alternative pathway. These include mutations in comple- that mutations in the genes of complement regulatory pro- ment factor H, complement factor I, membrane cofactor teins are associated with aHUS. In addition, factors other protein, complement factor B, and C3 nephritic factor. than underlying mutations may play a role in increasing Mutations may cause the protein to be normal but low in activation and the expression of the clinical syndrome. quantity, or normal in quantity but abnormal in function; the degree of the abnormality may depend on whether the H&O How is the complement system activated patient is heterozygous or homozygous. and regulated? In addition, other factors such as thrombomodulin have been described that work through other enzymes. IW The complement system is a part of the innate Thrombomodulin is involved in complement regulation immune system that is necessary for fighting infections by activating thrombin activatable fibrinolytic inhibitor and aberrant immunologic stimuli. -
367.Full.Pdf
Human Complement Factor I Does Not Require Cofactors for Cleavage of Synthetic Substrates This information is current as Stefanos A. Tsiftsoglou and Robert B. Sim of October 2, 2021. J Immunol 2004; 173:367-375; ; doi: 10.4049/jimmunol.173.1.367 http://www.jimmunol.org/content/173/1/367 Downloaded from References This article cites 41 articles, 17 of which you can access for free at: http://www.jimmunol.org/content/173/1/367.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 2, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Human Complement Factor I Does Not Require Cofactors for Cleavage of Synthetic Substrates1 Stefanos A. Tsiftsoglou2 and Robert B. Sim Complement factor I (fI) plays a major role in the regulation of the complement system. It circulates in an active form and has very restricted specificity, cleaving only C3b or C4b in the presence of a cofactor such as factor H (fH), complement receptor type 1, membrane cofactor protein, or C4-binding protein. -
360 BCBSA Reference Number: 2.01.13
Pharmacy Medical Policy Human Anti-hemophilic Factor Table of Contents • Policy: Commercial • Policy History • Endnotes • Policy: Medicare • Information Pertaining to All Policies • Forms • Coding Information • References Policy Number: 360 BCBSA Reference Number: 2.01.13 Related Policies None Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity Note: All requests for indications listed and not listed on the medical policy guidelines may be submitted to BCBSMA Pharmacy Operations by completing the Prior Authorization Form on the last page of this document. This medication is not covered by the pharmacy benefit. It is covered by the Medical Benefit or as a Home Infusion Therapy. We may cover: Factor VII • Coagulation factor indicated for the treatment of bleeding episodes and perioperative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets & Treatment of bleeding episodes and perioperative management in adults with acquired hemophilia. Factor VIII • Human anti-hemophilic factor (AHF) maintenance therapy (prophylaxis) as needed to maintain trough levels at 1% or greater in patients with severe Hemophilia A (AHF activity less than 1% of normal).1 • Human anti-hemophilic factor (AHF) for treatment and/or management of bleeding episodes in surgical patients with mild hemophilia (AHF activity 5%-30%) or moderately severe hemophilia (AHF activity -
Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................ -
1 Elevated Protein Levels and Altered Cellular Expression of Factor VII
Thorax Online First, published on May 4, 2007 as 10.1136/thx.2006.069658 Elevated protein levels and altered cellular expression of factor VII-activating protease Thorax: first published as 10.1136/thx.2006.069658 on 4 May 2007. Downloaded from (FSAP) in the lungs of patients with acute respiratory distress syndrome (ARDS) Malgorzata Wygrecka1*, Philipp Markart2*, Ludger Fink3, Andreas Guenther2, and Klaus T. Preissner1 Departments of 1Biochemistry, 2Internal Medicine, and 3Pathology, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany Corresponding author: Malgorzata Wygrecka, PhD Department of Biochemistry, Faculty of Medicine, University of Giessen Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany Phone: +49-641-99-47501 Fax: +49-641-99-47509 [email protected] http://thorax.bmj.com/ on September 27, 2021 by guest. Protected copyright. Keywords: acute lung injury, acute respiratory distress syndrome, factor VII and single-chain plasminogen activator-activating protease, hemostasis, hyaluronan binding protein 2 Word count: 4040 * both authors contributed equally to the manuscript 1 Copyright Article author (or their employer) 2007. Produced by BMJ Publishing Group Ltd (& BTS) under licence. ABSTRACT Thorax: first published as 10.1136/thx.2006.069658 on 4 May 2007. Downloaded from Background: ARDS is characterized by inflammation of the lung parenchyma and alterations of the alveolar haemostasis with extravascular fibrin deposition. Factor VII-activating protease (FSAP) is a recently described serine protease in plasma and tissues, known to be involved in haemostasis, cell proliferation and migration. Methods: We investigated FSAP protein (western blotting/ELISA/immunohistochemistry) and activity (coagulation/fibrinolysis assays) in plasma, bronchoalveolar lavage (BAL) fluids and lung tissue of mechanically ventilated patients with early ARDS as compared to patients with cardiogenic pulmonary oedema and healthy controls. -
Factor IX Complex (Human - Bebulin, Profilnine) Reference Number: ERX.SPMN.201 Effective Date: 01/17 Coding Implications Last Review Date: Revision Log
Clinical Policy: Factor IX complex (Human - Bebulin, Profilnine) Reference Number: ERX.SPMN.201 Effective Date: 01/17 Coding Implications Last Review Date: Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Policy/Criteria It is the policy of health plans affiliated with Envolve Pharmacy SolutionsTM that factor IX complex (Bebulin®, Profilnine®) is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Hemophilia B (must meet all): 1. Prescribed by or in consultation with a hematologist; 2. Diagnosis of hemophilia B; 3. Agent will used for prevention/control of bleeding episodes. Approval duration: 3 months B. Other diagnoses/indications: Refer to ERX.SPMN.16 - Global Biopharm Policy. II. Continued Approval A. Hemophilia B (must meet all): 1. Currently receiving medication via health plan benefit or member has previously met all initial approval criteria. Approval duration: 3 months B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via health plan benefit and documentation supports positive response to therapy; or 2. Refer to ERX.SPMN.16 - Global Biopharm Policy. Background Description/Mechanism of Action: Factor IX complex replaces deficient clotting factors including factor X. Hemophilia B, or Christmas disease, is an X-linked recessively inherited disorder of blood coagulation characterized by insufficient or abnormal synthesis of the clotting protein factor IX. Factor IX is a vitamin K-dependent coagulation factor which is synthesized in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation pathway. Activated factor IX (IXa), in combination with factor VII: C, activates factor X to Xa, resulting ultimately in the conversion of prothrombin to thrombin and the formation of a fibrin clot. -
(12) United States Patent (10) Patent No.: US 9,370,583 B2 Oestergaard Et Al
US009370583B2 (12) United States Patent (10) Patent No.: US 9,370,583 B2 Oestergaard et al. (45) Date of Patent: Jun. 21, 2016 (54) COAGULATION FACTOR VII POLYPEPTIDES 2015,0105321 A1 4/2015 Oestergaard et al. 2015,0225711 A1 8, 2015 Behrens et al. (71) Applicant: Novo Nordisk HealthCare AG, Zurich 2015,0259665 A1 9/2015 Behrens et al. (CH) FOREIGN PATENT DOCUMENTS (72) Inventors: Henrik Oestergaard, Oelstykke (DK); WO O158935 A2 8, 2001 Prafull S. Gandhi, Ballerup (DK); Ole WO O2/22776 A2 3, 2002 Hvilsted Olsen, Broenshoe (DK); WO O3O31464 A2 4/2003 Carsten Behrens, Koebenhavn N (DK); WO 2005/O14035 A2 2, 2005 WO 2005, O75635 A2 8, 2005 Paul L. DeAngelis, Edmond, OK (US); WO 2006/127896 A2 11/2006 Friedrich Michael Haller, Norman, OK WO 2006,134174 A2 12/2006 (US) WO 2007022512 A2 2, 2007 WO 2007/031559 A2 3, 2007 (73) Assignee: NOVO NORDISK HEALTHCARE WO 2008/O25856 A2 3, 2008 WO 2008/074032 A1 6, 2008 AG, Zurich (CH) WO 20081277O2 A2 10, 2008 WO 2009 126307 A2 10, 2009 (*) Notice: Subject to any disclaimer, the term of this WO 2010/030342 A2 3, 2010 patent is extended or adjusted under 35 WO 2011092242 A1 8, 2011 U.S.C. 154(b) by 0 days. WO 2011 1 01277 A1 8, 2011 WO 2012/OO7324 A2 1, 2012 WO 2012O35050 A2 3, 2012 (21) Appl. No.: 14/936,224 WO 2014/060401 4/2014 WO 201406.0397 A1 4/2014 (22) Filed: Nov. 9, 2015 WO 2014140.103 A2 9, 2014 OTHER PUBLICATIONS (65) Prior Publication Data Agersoe.H. -
General Considerations of Coagulation Proteins
ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 8, No. 2 Copyright © 1978, Institute for Clinical Science General Considerations of Coagulation Proteins DAVID GREEN, M.D., Ph.D.* Atherosclerosis Program, Rehabilitation Institute of Chicago, Section of Hematology, Department of Medicine, and Northwestern University Medical School, Chicago, IL 60611. ABSTRACT The coagulation system is part of the continuum of host response to injury and is thus intimately involved with the kinin, complement and fibrinolytic systems. In fact, as these multiple interrelationships have un folded, it has become difficult to define components as belonging to just one system. With this limitation in mind, an attempt has been made to present the biochemistry and physiology of those factors which appear to have a dominant role in the coagulation system. Coagulation proteins in general are single chain glycoprotein molecules. The reactions which lead to their activation are usually dependent on the presence of an appropriate surface, which often is a phospholipid micelle. Large molecular weight cofactors are bound to the surface, frequently by calcium, and act to induce a favorable conformational change in the reacting molecules. These mole cules are typically serine proteases which remove small peptides from the clotting factors, converting the single chain species to two chain molecules with active site exposed. The sequence of activation is defined by the enzymes and substrates involved and eventuates in fibrin formation. Mul tiple alternative pathways and control mechanisms exist throughout the normal sequence to limit coagulation to the area of injury and to prevent interference with the systemic circulation. Introduction RatnofP4 eloquently indicates in an arti cle aptly entitled: “A Tangled Web. -
Structural and Functional Analysis of Complement Factor H: a Crucial Protein in Several Disorders
UNIVERSITÀ DEGLI STUDI DI MILANO SCUOLA DI DOTTORATO IN MEDICINA MOLECOLARE CICLO XXVII Anno Accademico 2013/2014 TESI DI DOTTORATO DI RICERCA settore scientifico disciplinare: BIO13 STRUCTURAL AND FUNCTIONAL ANALYSIS OF COMPLEMENT FACTOR H: A CRUCIAL PROTEIN IN SEVERAL DISORDERS Dottorando : Silvia BERRA Matricola N° R09657 TUTORE: Prof. Alberto CLIVIO COORDINATORE DEL DOTTORATO: Prof. Mario CLERICI Sommario Il Fattore H del complemento (FH) è un importante regolatore della via alternativa del complemento: protegge infatti le cellule dell’ospite dall’attacco del sistema del complemento e carenze di FH sia qualitative e quantitative dovute a mutazioni nel gene CFH sono spesso associate ad una serie di malattie umane, come la glomerulonefrite membranoproliferativa (MPGN), la sindrome emolitico-uremica atipica (aHUS) e la degenerazione maculare della retina legata all’età (AMD). Mentre esiste una caratterizzazione genetica per tutte queste malattie, i dati funzionali a livello di proteine sono spesso carenti. Inoltre, il FH gioca un ruolo significativo nelle malattie infettive: molti agenti patogeni sono infatti in grado di reclutare il FH sulla loro superficie sfruttandolo per proteggersi dagli attacchi del complemento. Mentre per alcuni agenti patogeni l'interazione con il FH è stata ben descritta, per gli altri gli "interattori" diretti sono ancora sconosciuti. Tuttavia, lo studio del FH è complicato dalla presenza di proteine FH-related (FHRs) che posseggono un elevato grado di somiglianza con il FH e ne rendono quindi difficile la purificazione e la analisi diretta. Il primo obiettivo di questo progetto è stato lo sviluppo di saggi quantitativi e funzionali FH-specifici, utilizzando un anticorpo monoclonale (Mab 5H5) prodotto nel nostro laboratorio, che si è dimostrato essere specifico per FH. -
Isolation of the Tissue Factor Inhibitor Produced by Hepg2 Hepatoma Cells (Extrinsic Coagulation Pathway/Plasma Lipoprotein) GEORGE J
Proc. Nati. Acad. Sci. USA Vol. 84, pp. 1886-1890, April 1987 Biochemistry Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells (extrinsic coagulation pathway/plasma lipoprotein) GEORGE J. BROZE, JR.*, AND JOSEPH P. MILETICH Departments of Medicine and Laboratory Medicine, Washington University School of Medicine, The Jewish Hospital, St. Louis, MO 63110 Communicated by Philip W. Majerus, December 12, 1986 (receivedfor review November 13, 1986) ABSTRACT Progressive inhibition of tissue factor activity have shown that not only factor VII(a) but also catalytically occurs upon its addition to human plasma (serum). This active factor Xa and an additional factor are required for the process requires the presence offactor VII(a), factor X(a), Ca2+, generation of TF inhibition in plasma or serum. This addi- and another component in plasma that we have called the tissue tional factor, which we call the tissue factor inhibitor (TFI), factor inhibitor (TFI). A TFI secreted by HepG2 cells (human is present in barium-absorbed plasma (19) and appears to be hepatoma cell line) was isolated from serum-free conditioned associated with lipoproteins, since TFI functional activity medium in a four-step procedure including CdCl2 precipita- segregates with the lipoprotein fraction that floats when tion, diisopropylphosphoryl-factor X. affinity chromatogra- serum is centrifuged at a density of 1.21 g/cm3 (18). phy, Sephadex G-75 superfine gel filtration, and Mono Q We have shown (18) that HepG2 cells (a human hepatoma ion-exchange chromatography. The purified TFI contained a cell line) secrete an inhibitory moiety with the same charac- predominant band atMr 38,000 on NaDodS04/polyacrylamide teristics as the TFI present in plasma.