DOCSLIB.ORG

The Emerging Utility of the Cutaneous Microbiome in the Treatment of Acne and Atopic Dermatitis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Emerging Utility of the Cutaneous Microbiome in the Treatment of Acne and Atopic Dermatitis Journal Pre-proof The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis Taylor E. Woo, MSc, Christopher D. Sibley, MD, PhD, FRCPC PII: S0190-9622(19)32686-6 DOI: https://doi.org/10.1016/j.jaad.2019.08.078 Reference: YMJD 13802 To appear in: Journal of the American Academy of Dermatology Received Date: 14 May 2019 Revised Date: 21 August 2019 Accepted Date: 28 August 2019 Please cite this article as: Woo TE, Sibley CD, The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis, Journal of the American Academy of Dermatology (2019), doi: https://doi.org/10.1016/j.jaad.2019.08.078. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier on behalf of the American Academy of Dermatology, Inc. 1 Title: The emerging utility of the cutaneous microbiome in the treatment of acne 2 and atopic dermatitis 3 4 Authors: Taylor E. Woo MSc 1 and Christopher D. Sibley MD, PhD, FRCPC 2 5 6 1. Cumming School of Medicine, University of Calgary, AB, CAN 7 2. South Ottawa Medical Centre, Ottawa, ON, CAN 8 9 Corresponding Author: 10 Mr. Taylor Woo 11 University of Calgary 12 E: [email protected] 13 Funding Sources: None 14 15 Conflict of Interest: None disclosed 16 17 Word Count: 18 Abstract (168), Capsule Summary (37), Text (2254), Figures (1), Tables (2), 19 References (52) 20 Keywords: microbiome, biotherapy, acne vulgaris, atopic dermatitis 21 22 23 24 25 Abstract 26 The cutaneous microbiome has potential for therapeutic intervention in 27 inflammatory-driven skin disease. Research into atopic dermatitis and acne vulgaris has 28 highlighted the importance of the skin microbiota in disease pathogenesis, 29 prognostication and targets for therapeutic intervention. Current management of these 30 conditions aims to control the inflammatory response thought to be associated with 31 specific pathogens using both topical and systemic antimicrobials. However, commensal 32 microbiota found naturally on the skin have been shown to play an important role in the 33 resolution of disease flares. While often efficacious, the mainstay treatments are not 34 without side effects and raise concerns regarding the development of antimicrobial 35 resistance. Augmentation of microbial communities with targeted biotherapy could 36 revolutionize the way inflammatory conditions of the skin are treated. Herein, we review 37 evidence for the role of the cutaneous microbiome in atopic dermatitis and acne vulgaris 38 and suggest that these conditions highlight the potential for microbiome-directed 39 therapeutics. 40 41 42 43 44 45 46 47 48 Capsule Summary 49 • Cutaneous microorganisms are implicated in the pathophysiology of both acne 50 and atopic dermatitis. 51 • Interventions targeting the cutaneous microbiome are a promising area of 52 therapeutics in acne vulgaris and atopic dermatitis. 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 Introduction 72 Rapid advances in nucleic acid sequencing technologies have enabled the 73 detection of a large number of eukaryotes, bacteria, viruses and other microorganisms, 74 which collectively compose the human microbiome. Skin is the largest human organ 75 (~1.8 m 2) and serves as a physical and immunological barrier to the environment. This 76 interface, with plentiful folds, invaginations and specialized niches, is a harsh 77 environment for microbes with its cool temperature, an acidic pH and a milieu of host 78 defense molecules (proteases, lysozyme and antimicrobial peptides) 1,2 . Despite these 79 conditions, human mucosal surfaces and skin harbor more commensal microbes than the 80 number of eukaryotic cells in the body 3. To maintain human health an interplay between 81 the host’s innate immune system and the microbial communities must transpire 2,4 . A 82 wide breadth of microbial species is organized into complex microbial communities on 83 the skin. The density of these communities is an estimated one million bacteria per 84 centimeter squared 5 and their demographics vary depending on the body site involved 6. 85 Areas such as hair follicles, sebaceous and glandular structures represent unique 86 environmental niches for the colonization of microorganisms. Nineteen phyla represent 87 the core skin microbiome 6 including Actinobacteria (51.8%), Firmicutes (24.4%), 88 Proteobacteria (16.5%) and Bacteroidetes (6.3). At the genus level, Corynebacterium , 89 Propionibacterium and Staphylococcus are most commonly identified. 90 Both commensal and pathogenic microorganisms have been suggested to play an 91 important role in the pathogenesis of inflammatory skin conditions 7. Recent evidence 92 suggests that commensal microbial metabolites contribute to local homeostasis by 93 influencing host cell gene expression 8. Disruption of the balance between the microbiome 94 and the host can lead to a pro-inflammatory environment and the development of clinical 95 disease 9. The transition to a pro-inflammatory state in the skin is often associated with 96 changes in the microbial richness (total number of bacterial species) and evenness (the 97 relative proportion of microorganisms in a community) 10 . Disruption of the normal 98 microbiome homeostasis manifests in atopic dermatitis and acne vulgaris as decreased 99 richness, a decrease in the total bacterial load, or altered evenness 11,12 . As such, targeted 100 interventions focused on restoring the microbial community to a stable anti-inflammatory 101 state are of great interest and represent a shift in the way we manage and treat 102 inflammatory skin disease (Figure 1). 103 Atopic dermatitis is a disease of microbial dysbiosis 104 Atopic dermatitis is a chronic condition contributing to significant morbidity in 105 approximately 7% of the general population 13 . It’s pathogenesis is multifactorial, with 106 important genetic and environmental factors. Atopic dermatitis is highly heritable 14 and 107 most often secondary to loss-of-function mutations in the filaggrin gene 15 . A notable 108 modifiable environmental risk factor, which has been implicated in the exacerbation of 109 disease is the composition and dynamics of commensal skin microbiota that can be 110 associated with more severe clinical presentations 11 . Specifically, an inverse relationship 111 between baseline Shannon diversity (a measurement which takes into account both 112 species richness and evenness of a sample) and the severity of atopic dermatitis has been 113 well documented. For instance, individuals who have lower measures of diversity have 114 more severe disease as compared to healthy controls, which coincides with an 115 overgrowth of Staphylococcus aureus 11 . This corresponds with a decrease in the relative 116 abundance of Streptococcus , Corynebacterium and Propionibacterium . Moreover, 117 resolution of acute flare correlates with the reestablishment of a commensal community 118 with a rich and even structure. 119 S. aureus has a diverse range of virulence factors that contribute to the 120 pathogenesis of atopic dermatitis 16–18 . Virulence factors include superantigen production, 121 which promotes inflammatory pathways through the activation of interleukin-mediated T 122 cell responses 19,20 . While the role of S. aureus in invoking inflammatory responses is 123 clear, understanding how S. aureus interacts with the resident commensal microbiota is of 124 great clinical interest. Milder forms of atopic dermatitis are seen in patients when S. 125 aureus is not the predominant organism 21 . In these cases, patients are colonized 126 predominantly by S. epidermidis , suggesting a broader antagonistic relationship between 127 coagulase-negative Staphylococcus and S. aureus 22 . In addition, Cutibacterium acnes also 128 appears to have an antagonistic relationship with S. aureus 23 . Likely, these observations 129 are due to the ability of commensal microbiota to inhibit the growth of S. aureus through 130 the fermentation of compounds occurring naturally on the skin. Many of the members of 131 the cutaneous microbiome can metabolize glycerol into antimicrobial compounds, which 132 inhibit S. aureus growth 22–24 . This degree of interaction extends beyond the context of 133 atopic dermatitis, suggesting that commensal organisms may attenuate the virulence of S. 134 aureus in polymicrobial diabetic foot infections 25 . 135 136 137 138 139 140 Acne vulgaris is a clinical morphology of pro-inflammatory microbial communities 141 The pathogenesis of acne highlights the interplay between skin microbiota and 142 inflammatory disease. The pathophysiology of acne involves abnormal follicular 143 hyperkeratinization, excessive sebum production, colonization by C. acnes (recently 144 reclassified from Propionibacterium acnes 26 ) and subsequent activation of an 145 inflammatory cascade 27 . Formation of comedones or inflammatory papules, pustules and 146 nodules are a significant source of morbidity and are associated with depressive 147 symptoms, including lower self-attitude,
Load more

Recommended publications
  • 1St Year : Immunity
    Presented by-Suman Bampal Lecturer pharmacy Govt polytechnic, pithuwala Dehradun Introduction Immunology is the science which deals with immunity or resistance to body infection . The lack of ability to resist infection is called susceptibility Preparations use to produce immunity are called immunological preparations Factors affecting immunity 1. Phagocytosis : ingestion of microorganisms by certain cells (Phagocytes ) of the body whereby they are rendered harmless . It is caused by - W.B.C (leucocytes), Cells of R.E.S 2. Antibody production : these are highly specific in nature and attack microorganism or toxins . Antibodies are proteins mainly globulins produced in lymph nodes by the cells of R.E.S Nature of antibodies depends upon the manner in which microorganism produce their harmful effect Bacteria producing exotoxins - antitoxins Bacteria producing endotoxins – these antibodies are named according to their mode of action Antigen-Antibody Reaction Antigen antibody nature of reaction Exotoxin Antitoxin Neutrilization Bacterial cells Agglutinin Agglutination Endotoxin precipitin precipitation of toxin Bacterial cells Bacteriolysin * Lysis of cells . Opsonins Makes pathogens more susceptible to phagocytosis Bacteria + Specific Bacteriolysin – no lysis Bacteria + Complement – no lysis Bacteria + Specific Bacteriolysin + Complement – lysis of the bacteria. immunity 1.Natural immunity 2. Acquired immunity (God gifted) (acquired due to antibodies production) a .Species active passive b . Race (slowly produced but long lasting) (quickly prod. c. individual but short lived) d. Age Naturally acquired Naturally acquired (after infection) ( from mother through placenta) Artificially acquired Artificially acquired (due to admin. of vaccines or antigens) (by admin. of serum) 1.Natural Immunity Species – e.g. Tuberclosis is very fetal to guineapig but not fetal to man.
    [Show full text]
  • Production of Antibodies for Use in a Biosensor- Based Assay for Listeria Monocytogenes
    Production of antibodies for use in a biosensor- based assay for Listeria monocytogenes A thesis submitted for the degree of Ph.D. By Paul Leonard B.Sc. (Hons), August 2003. Based on research carried out at School of Biotechnology, Dublin City University, D ublin 9, Ireland, Under the supervision of Professor Richard O’Kennedy. This thesis is dedicated to my parents for all their encouragement and support over the last number of years. “I am not discouraged, because every wrong attempt discarded is another step forward” -Thomas Edison. Declaration I hereby certify that this material, which 1 now submit for assessment on the programme of study leading to the award of Doctor of Philosophy, is entirely my own work, and has not been taken from the work of others, save and to the extent that such work is cited and acknowledged within the text. Signed Date: Acknowledgements Sincere thanks to Prof. Richard O'Kennedy for his constant support and guidance over the past few years, in particular for sharing his wealth of experience and knowledge throughout my studies. Thanks to all the lab group, past and present and all my friends at DC’U for their companionship and some unforgettable (and more often than not better forgotten) nights out! Special thanks goes to Steve, a great scientist and friend, for his support, knowledge and overall enthusiasm over the last few years. To Monty, Macker, Ryaner and the rest of the “Finian's lads” for their continual ‘good humoured harassment’ and alcohol-based support! Cheers! I would like to thank all my family for their unequivocal support from start to finish, I owe you so much! Finally, 1 would like to reserve a very special thanks to Nerea, my source of inspiration, for her patience, companionship and constant love and support.
    [Show full text]
  • UNIT 3 IMMUNITY Structure
    Microbiology-II UNIT 3 IMMUNITY Structure 3.0 Objectives 3.1 Introduction 3.2 Definitions 3.3 What is Immunity? 3.4 The Three Lines of Defense in the Body 3.5 Inflammation 3.6 Types of Immunity 3.6.1 Innate Immunity 3.6.2 Factors Influencing Innate Immunity in an Individual 3.6.3 Acquired Immunity 3.6.4 Active Acquired Immunity 3.6.5 Passive Acquired Immunity 3.6.6 Differences between Active and Passive Immunity 3.7 The Immune System 3.8 Antigens and Antibodies 3.9 Allergy/Hypersensitivity/Anaphylaxis 3.10 Practical Application of Immunology 3.10.1 Immunizing Agents 3.10.2 Vaccines and Vaccinations 3.10.3 Immunoglobulins 3.10.4 The Immune Responses 3.11 Let Us Sum Up 3.12 Key Words 3.13 Answers to Check Your Progress 3.0 OBJECTIVES After going through this unit, you should be able to: l define Immunity; l differentiate between the older and modern concept of immunity; l determine the three lines of defense in the body; l enumerate the different types of immunity; l differentiate between active and passive immunity; l explain the innate and adaptive immune system; l distinguish between antigens and antibodies; l state the phenomenon of allergy; l describe the various antigen-antibody reactions; l discuss the various immunizing agents; and l define primary and secondary response. 3.1 INTRODUCTION The word ‘Immunity’ comes from a Latin term ‘immunis’ meaning free or exempt. It has been recognised from very early times that those who suffer from infectious diseases such 38 as diphtheria, whooping cough, mumps, measles, small pox etc.
    [Show full text]
  • MULTI-FUNCTIONAL EFFECTOR RESPONSES ELICITED from Igm MEMORY STEM CELLS
    MULTI-FUNCTIONAL EFFECTOR RESPONSES ELICITED FROM IgM MEMORY STEM CELLS Item Type Dissertation Authors Kenderes, Kevin Rights Attribution-NonCommercial-NoDerivatives 4.0 International Download date 29/09/2021 18:50:57 Item License http://creativecommons.org/licenses/by-nc-nd/4.0/ Link to Item http://hdl.handle.net/20.500.12648/2017 MULTI-FUNCTIONAL EFFECTOR RESPONSES ELICITED FROM IgM MEMORY STEM CELLS by Kevin Kenderes A Dissertation in Microbiology and Immunology Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Graduate Studies of State University of New York, Upstate Medical University. Approved ___________________________ (Sponsor’s signature) Date_______________________ Table of Contents List of Figures iv List of Tables vi Abbreviations vii Acknowledgements x Abstract xi Chapter I: Introduction 1 History of Humoral Immunity 2 Development of Naive B cells 4 The Primary B cell Response 7 T cell dependent B cell responses 7 T cell independent B cell responses 10 Secondary B cell Responses 12 Ehrlichia muris 15 Immune Responses to E. muris 17 T-bet-Expressing B Cells 19 Summary 21 Chapter II: Materials and Methods 22 Chapter III: CD11c+ T-bet+ IgM memory Cells Exhibit Stem Cell-like 27 Properties Abstract 28 Introduction 29 Results 33 ii Discussion 76 Chapter IV: Summary 84 Model 85 Future directions 90 Summary 95 Appendix I: Tetanus Toxin binds to bystander B cells following immunization 97 Abstract 98 Introduction 99 Materials and Methods 102 Results 105 Discussion 124 Future Directions 128 References 130 iii List of Figures Figure 3.1. Labeling Aicda-expressing CD11c+ T-bet+ IgM memory cells in vivo 34 Figure 3.S1.
    [Show full text]
  • Amarnath VS Pisipati Doctor of Philosophy
    SINGLE, ULTRA-HIGH DOSE AMINOGLYCOSIDE THERAPY IN A RAT MODEL OF E. COLI INDUCED SEPTIC SHOCK By Amarnath V. S. Pisipati A Thesis Submitted to the Faculty of Graduate Studies of The University of Manitoba In Partial Fulfillment of the Requirements of the Degree of Doctor of Philosophy Department of Medical Microbiology University of Manitoba, Winnipeg, Manitoba, Canada Copyright © 2015 by Amarnath V. S. Pisipati II ABSTRACT Bacterial infections are a major cause of morbidity and mortality in both the community and nosocomial settings, particularly among the elderly and chronically ill. Sepsis is the body’s response to antigens and toxins released by the invasive pathogenic organisms that cause infection. When infection is not effectively controlled, sepsis may develop and progress to severe sepsis and septic shock. Early diagnosis and treatment is pivotal for survival in severe sepsis and particularly, septic shock. Our research focuses on developing a novel treatment strategy for septic shock by using single, ultra-high doses of aminoglycosides. In this project, the effect of a single, ultra-high dose of gentamicin in clearing bacteria from the blood and reducing the bacterial burden in vital organs was evaluated in a rat model of E. coli (Bort strain) induced peritonitis with severe sepsis/septic shock. Serum cytokine levels and serum lactate levels were serially measured. Further, the potential adverse effects of ultra-high dosing of aminoglycoside antibiotics in a short-term (9 h) invasive study and long- term (180 days) non-invasive study were assessed. Neuromuscular paralyses due to ultra-high doses of aminoglycosides were assessed. In addition, renal injury markers such as serum creatinine and urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) were assayed.
    [Show full text]
  • Improving Vaccine Utilization on the Ranch/Farm
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Range Beef Cow Symposium Animal Science Department December 1993 Improving Vaccine Utilization On The Ranch/Farm David L. Morris Colorado State University, Fort Collins, CO Follow this and additional works at: https://digitalcommons.unl.edu/rangebeefcowsymp Part of the Animal Sciences Commons Morris, David L., "Improving Vaccine Utilization On The Ranch/Farm" (1993). Range Beef Cow Symposium. 217. https://digitalcommons.unl.edu/rangebeefcowsymp/217 This Article is brought to you for free and open access by the Animal Science Department at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Range Beef Cow Symposium by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Proceedings, The Range Beef Cow Symposium XIII December 6, 7, & 8, 1993 Improving Vaccine Utilization On The Ranch/Farm David L. Morris, DVM, PhD Department of Clinical Sciences* College of Veterinary Medicine & Biomedical Sciences Colorado State University Fort Collins, CO 80523 Improving vaccine utilization on the ranch or farm begins with a better understanding of common terms used in discussing products or methods used to enhance the animal's ability to prevent or control disease. The following terms and definitions are presented for that reason. Antigen - any substance capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, i.e., with specific antibody or specifically sensitized T lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria, viruses and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant combines with an antibody or a specific receptor on a lymphocyte.
    [Show full text]
  • Immunologic Significance of Vitamins Chester Hamlin Werkman Iowa State College
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1923 Immunologic significance of vitamins Chester Hamlin Werkman Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Allergy and Immunology Commons, Bacteriology Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons, and the Microbial Physiology Commons Recommended Citation Werkman, Chester Hamlin, "Immunologic significance of vitamins" (1923). Retrospective Theses and Dissertations. 14697. https://lib.dr.iastate.edu/rtd/14697 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quafify illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event tfiat tfie author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, dravMngs, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections v\/itii small overlaps.
    [Show full text]
  • (Hons) DEPARTMENT OP ORAL MEDIC
    A STUDY OF IMMUNE MECHANISMS IN THE MOUTH IN RELATION TO ORAL DISEASE PRANCES JANE McEEAN, B.Sc. (Hons) DEPARTMENT OP ORAL MEDICINE AND PATHOLOUY UNIVERSITY OP GLASGOW DENTAL SCHOOL THESIS PRESENTED TO THE UNIVERSITY OP G-LASGOW PACULTY OP MEDICINE POR THE DEGREE OP DOCTOR OP PHILOSOPHY MAY, 1973 ProQuest N um ber: 11017950 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 11017950 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 SUMMARY of A STUDY OF IMMUNE MECHANISMS IN THE MOUTH IN RELATION TO ORAL DISEASE by PRANCES JANE McKEAN, B.Sc. (Hons) DEPARTMENT" OP ORAL MEDICINE AND PATHOLOGY UNIVERSITY OP GLASGOW DENTAL SCHOOL THESIS PRESENTED TO THE UNIVERSITY OP GLASGOW FACULTY OP MEDICINE POR THE DEGREE OP DOCTOR OF PHILOSOPHY MAY, 1973 1. A STUDY OP IMMUNE MECHANISMS IN THE MOUTH ______ IN RELATION TO ORAL DISEASE.________ SUMMARY The evidence to date, from clinical, epidemiological and laboratory investigations, underlines the causal role of bacterial plaque in two of the most prevalent oral diseases i.e.
    [Show full text]
  • International Nonproprietary Names for Pharmaceutical Substances (INN)
    WHO Drug Information, Vol. 31, No. 1, 2017 Recommended INN: List 77 International Nonproprietary Names for Pharmaceutical Substances (INN) RECOMMENDED International Nonproprietary Names: List 77 Notice is hereby given that, in accordance with paragraph 7 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances [Off. Rec. Wld Health Org., 1955, 60, 3 (Resolution EB15.R7); 1969, 173, 10 (Resolution EB43.R9); Resolution EB115.R4 (EB115/2005/REC/1)], the following names are selected as Recommended International Nonproprietary Names. The inclusion of a name in the lists of Recommended International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–113) and Recommended (1–74) International Nonproprietary Names can be found in Cumulative List No. 16, 2015 (available in CD-ROM only). Dénominations communes internationales des Substances pharmaceutiques (DCI) Dénominations communes internationales RECOMMANDÉES: Liste 77 Il est notifié que, conformément aux dispositions du paragraphe 7 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques [Actes off. Org. mond. Santé, 1955, 60, 3 (résolution EB15.R7); 1969, 173, 10 (résolution EB43.R9); résolution EB115.R4 (EB115/2005/REC/1)] les dénominations ci-dessous sont choisies par l’Organisation mondiale de la Santé en tant que dénominations communes internationales recommandées. L’inclusion d’une dénomination dans les listes de DCI recommandées n’implique aucune recommandation en vue de l’utilisation de la substance correspondante en médecine ou en pharmacie. On trouvera d’autres listes de Dénominations communes internationales proposées (1–113) et recommandées (1–74) dans la Liste récapitulative No.
    [Show full text]
  • On Complement-Fixation in Malignant Disease2
    ON COMPLEMENT-FIXATION IN MALIGNANT DISEASE2 BY CHARLES E. SIMON AND WALTER S. THOMAS. (From the laboratory of Dr. Charles E. Simon, Baltimore, Md.) Through the researches of Wassermann and his collaborators it has been established that syphilitic sera may contain substances which in the presence of other substances derived from syphilitic organs are capable of fixing complement, so that upon the subse- quent addition of red corpuscles and homologous hemolytic ambo- ceptor hemolysis is impeded. This phenomenon was originally in- terpreted as meaning that as a consequence of the syphilitic infec- tion specific antibodies are formed which enter into combination with the corresponding antigen--present in syphilitic organs--and that the resultant product is capab!e of binding complement. Sub- sequent study has shown that this conception does not satisfactorily account for the facts observed since similar fixation of complement on the part of syphilitic serum may occur in the presence of non- syphilitic tissue extracts. While a different interpretation of the phenomenon must accordingly be sought, the fact remains that sub- stances are formed in the body of syphilitic individuals which will react with certain tissue constituents and bind complement and that the reaction may in a certain measure be regarded as specific. Wassermann states in a recent communication that approximately a thousand cases have been examined, up to the end of the previous year, from which the diagnostic value of the reaction (ergo, its specificity) is uniformly apparent. Our own work had already been planned at a time when the antigen-antibody interpretation of the syphilitic reaction had not yet been set aside, and when it seemed that the same principle might well be utilized in a search for antibodies in malignant dis- ease.
    [Show full text]
  • Genesis and Development of a Scientific Fact Edited by Thaddeus J
    Genesis and Development of a Scientific Fact Edited by Thaddeus J. Trenn Genesis and and Robert K. Merton ii 'I Translated by Fred Bradley ·1 Development of a •I and Thaddeus J. Trenn :! Scientific Fact Foreword by Thomas S. Kuhn Ludwik Fleck The University of Chicago Press Chicago and London Originally published as Entstehung und Entwicklung einer wissenschaftlichen Tatsache: Einfiihrung in die Lehre vom Denkstil und Denkkollektiv, © 1935 by Benno Schwabe & Co., Basel, Switzerland. Contents The University of Chicago Press, Chicago 60637 The University of Chicago Press, Ltd., London © 1979 by The University of Chicago All rights reserved. Published 1979 Paperback edition 1981 Printed in the United States of America Foreword Vil 19 18 17 16 15 14 13 12 11 10 12 13 14 15 16 Preface xiii ISBN-13: 978-0-226-25325-1 ISBN-10: 0-226-25325-2 Genesis and Development of a Scientific Fact Library of Congress Cataloging-in-Publication Data Overview of Contents xxiii Fleck, Ludwik. Prologue xxvii Genesis and development of a scientific fact. One How the Modern Concept of Syphilis Originated Translation of Entstehung und Entwicklung einer wissenschaftlichen Tatsache. Two Epistemological Conclusions from the Bibliography: p. Established History of a Concept 20 Includes index. Three The Wassermann Reaction and 1. Science-Social aspects. 2. Science-Philosophy. Its Discovery 53 3. Syphilis-Diagnosis-Wassermann reaction. 4. Knowledge, Sociology of. I. Title. Four Epistemological Considerations Concerning Ql 75.5.F5913 507' .2 79-12521 the History of the
    [Show full text]
  • Development of Myeloid Cell-Based Immune Profiling on Microarrays
    Ph.D. thesis Development of myeloid cell-based immune profiling on microarrays Zoltán Szittner Supervisor: József Prechl, MD, PhD Doctoral School of Biology Immunology Program Head: Professor Anna Erdei, DSc Department of Immunology, Institute of Biology Eötvös Loránd University, Budapest, Hungary 2016 TABLE OF CONTENTS List of abbreviations 3 1. INTRODUCTION 5 1.1 Immunoglobulins and their receptors 7 1.2 Complement system and complement receptors 14 1.3 Myeloid cells, monocytes and U937 16 1.4 Autoantibodies in autoimmune diseases – rheumatoid arthritis and systemic lupus erythematosus 18 1.5 Protein microarrays 21 1.5.1 Cellular microarrays 23 1.5.2 Cellular SPR 24 2 AIMS OF THE STUDY 25 3 MATERIALS AND METHODS 26 4 RESULTS 35 4.1 Application of fluorescently labeled U937 cells in antigen and antibody microarrays 35 4.1.1 U937 cells are classical inflammatory monocytes based on cell surface receptor expression 36 4.1.2 U937 cells show unequal binding to hIgG subclasses compared to anti-hIgG antibody 37 4.1.3 U937 cells bind to human IgG subclasses in a dose dependent manner 39 4.1.4 Cell density as a factor determining U937 cell binding to hIgG1-4 40 4.1.5 U937 binding is mediated by IgG Fcγ part, while complement plays a modulatory role in binding to Staphylococcus aureus 41 4.1.6 Deglycosylation of IgG impairs cell binding to immune complexes 42 4.1.7 U937 cells can detect IgG containing ICs in protein microarrays 44 4.1.8 Microfluidic chambers supporting cellular microarray measurements 47 4.2 Application of U937 cell line to detect
    [Show full text]