Immunological Significance of Mycobacterium Leprae Cell Walls

Total Page:16

File Type:pdf, Size:1020Kb

Immunological Significance of Mycobacterium Leprae Cell Walls Proc. Nadl. Acad. Sci. USA Vol. 85, pp. 1917-1921, March 1988 Immunology Immunological significance of Mycobacterium leprae cell walls (cell-mediated immunity/delayed-type hypersensitivty/peptidoglycan-protein complex/leprosy/precursor frequency analysis) JOHANNE MELANCON-KAPLAN*, SHIRLEY Wu HUNTERt, MICHAEL MCNEILt, CAROL STEWARTt, ROBERT L. MODLINf, THOMAS H. REAt, JACINTO CONVIT§, PADMINI SALGAME*, VIJAY MEHRA*, BARRY R. BLOOM*, AND PATRICK J. BRENNANt¶ *Department of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461; tDepartment of Microbiology, Colorado State University, Fort Collins, CO 80523; tSection of Dermatology, University of Southern California School of Medicine, Los Angeles, CA 90033; and 1lnstitute de Biomedicine, Caracas 101, Venezuela Contributed by Barry R. Bloom, November 2, 1987 ABSTRACT Cell walls of Mycobacterium leprae, pre- positive healthy contacts of lepromatous patients or from pared by differential solvent extraction, were shown to contain blood or lesions of patients with tuberculoid leprosy, only a arabinogalactan, mycolates, and peptidoglycan. In addition, small proportion of clones tested are responsive to the amino acid analysis revealed the unexpected presence of large known serologically defined recombinant antigens (ref. 5; amounts of protein that retained potent immunological reac- J.M.-K., R.L.M., and B.R.B., unpublished data). tivity. Purified cell walls stimulated proliferation of T cells For many years, significant immune responses to purified from tuberculoid, but not from lepromatous leprosy, patients cell walls of various mycobacteria have been sporadically and elicited delayed-type hypersensitivity skin reactions in reported. For example, cell walls from Mycobacterium guinea pigs and patients sensitized to M. leprae. Analysis ofthe tuberculosis can evoke delayed-type hypersensitivity (DTH) precursor frequency of antigen-reactive human peripheral T responses (6), and, of course, adjuvant activity is associated cells revealed that as many cells (41/6000) proliferate to with the muramyl-dipeptide of the basic peptidoglycan (7). antigen contained in cell walls as to intact M. keprae. Sequen- The present work explores the possibility that M. leprae cell tial removal of mycolates and arabinogalactan resulted in a wall contains antigens important for cell-mediated immunity large peptidoglycan-protein complex that retained all the to this organism. immunological activity. This immunological reactivity and the inherent protein were destroyed by proteolysis. Thus, cell wall protein is a major contributor to cell-mediated immune reac- METHODS AND MATERIALS tivity to this pathogenic mycobacterium. Preparation of Cell Walls of M. eprae. Lyophilized M. leprae (1.42 g) prepared from infected armadillo livers (8) Leprosy is a chronic infectious disease that afflicts 10-13 was exhaustively extracted with CHC13/CH30H (2:1) to million people, primarily living in developing countries (1). remove all lipids, disrupted in a French press followed by Although the incidence of leprosy is declining in many parts sonication and further extraction with refluxing 70% ethanol of the world, largely due to greater control efforts, the cost in water to remove lipoarabinomannan, lipomannan, other of multidrug therapy to combat emergent drug resistance of soluble carbohydrates, and soluble proteins (9). The residue Mycobacterium leprae is high, and the development of an was washed extensively with water to yield 671 mg of cell effective vaccine is widely agreed to offer the best hope for wall insoluble fraction (CWIF). disease eradication (2, 3). Because M. leprae is one of few Cell wall core (CWC) was prepared by stirring CWIF (10 major pathogens of man that has not been successfully mg) in 1-2 ml of 2% NaDodSO4 for 2 hr at 50'C; this cultivated in vitro, the principal available source of antigens extraction was repeated four times. The final insoluble for study and vaccines remains infected tissues of the residue was further extracted 10 times with phosphate- nine-banded armadillo Dasypus novemcinctus, which is in- buffered saline (PBS), followed sequentially by water and evitably limited and costly. Consequently, immunological acetone to yield 6.5 mg of CWC. and molecular biological approaches that permit identifica- Mycolic acids were removed from CWC (10 mg) by tion and production of protective antigens are needed. Thus stirring in 5 ml of 0.5% KOH in C2H5OH at 370C for 48 hr. far, using murine monoclonal antibodies, genes for six major The reaction mixture was centrifuged, and the pellet was antigens of M. leprae have been isolated from Agtll libraries washed three times with 5 ml each of water, ethanol, and (4). ether to yield 6.3 mg of demycolated CWC. To destroy the From a variety of studies, cell-mediated immunity, which covalently bound arabinogalactan, 10 mg of demycolated is regulated by specifically sensitized T lymphocytes, is CWC was stirred into 3 ml of 0.05 M NaIO4 buffered with clearly required for protection and resistance to leprosy (1). 0.03 M sodium acetate, pH 4.0, and kept under dark condi- The disease encompasses an immunological spectrum. At tions at 250C for 42 hr. The insoluble residue after centrifu- one pole, lepromatous leprosy, patients selectively lack gation at 20,000 x g for 20 min was washed extensively with cell-mediated immunity to antigens of M. leprae and fail to water and reduced with NaBH4 (1.25 mg in 250 Al) at 250C restrict the growth of the pathogen; at the tuberculoid end of for 1 hr. The insoluble residue was again thoroughly washed the spectrum, the patients exhibit cell-mediated immunity to with water, and the residual polyols were removed by gentle antigens of M. leprae and develop one or a few sharply hydrolysis (500 1.l of HCl, pH 1.0, at 150C for 18 hr), defined local lesions that contain only few acid-fast bacilli. followed by repeated washing. Exactly 5 mg (dry weight) of However, when we and other workers derived M. leprae- specific CD4 + (helper T cell) clones from strongly lepromin- Abbreviations: CWIF, cell wall insoluble fraction; CWC, cell wall core; PPC, peptidoglycan-protein complex; DTH, delayed-type The publication costs of this article were defrayed in part by page charge hypersensitivity; GC, gas chromatography; PBS, phosphate- payment. This article must therefore be hereby marked "advertisement" buffered saline. in accordance with 18 U.S.C. §1734 solely to indicate this fact. ITo whom reprint requests should be addressed. 1917 Downloaded by guest on September 26, 2021 1918 Immunology: Melancon-Kaplan et al. Proc. Natl. Acad Sci. USA 85 (1988) this peptidoglycan-protein complex (PPC) free of mycolates Table 1. Chemical composition of the cell wall fractions of and arabinogalactan was recovered. M. leprae Proteolytic digestion of CWIF or CWC was accomplished Cell wall fraction,* weight % by adding protease (either one-half the substrate weight of proteinase K or Pronase from Streptomyces griseus; type Whole Demycolyl Cell wall XXI, Sigma) to the sample in 2 ml of PBS containing 0.5% Component M. leprae CWIF CWC CWC PPC Triton X-100. The mixture was sonicated and incubated at Arabinogalactan 15.9 12.9 22.5 33.1 0.6 37°C for 4 hr and centrifuged at 20,000 x g for 20 min; then Other the pellet was further digested under identical conditions. carbohydrates 20.9 2.0 0 0 0 The pellet was again recovered by centrifugation, washed Mycolates 12.8 35.0 37.0 0 0 repeatedly with water, and Iyophilized to yield 6.7 mg of Peptidoglycan 6.3 6.1 6.9 10.7 18.4 protease-digested CWIF. Protein 50.8 42.8 25.9 38.1 60.6 Analytical Procedures. The neutral sugar content and, *Arabinogalactan was estimated by hydrolysis of cell wall fractions from this content, the arabinogalactan content of cell wall with 2 M CF3COOH and GC of the alditol acetates with inositol fractions were measured by hydrolysis of 100-ug samples added as an internal standard. Arabinose represented 77.3% of the containing 9 of inositol added as internal standard with 2 neutral sugars and galactose represented 18.6% with a trace of pg mannose (0.4%). Mycolates were estimated by weighing the sapon- M CF3COOH, conversion to the corresponding alditol ace- ifiable lipids obtained after treatment of cell wall fractions with tates, and resolution by gas chromatography (GC) on a 0.5% KOH in C2HOH. Peptidoglycan and protein amino acids Durabond-1 fused silica capillary column (30 m x 0.25 mm, were estimated as described in the legend for Fig. 2; peptidoglycan 0.25-,um film thickness; J&W Scientific, Rancho Cordova, content was then calculated using the total weights ofglucosamine, CA) (10). To analyze amino acid and aminoglycoside con- muramic acid, diaminopimelic acid, and the weight of one mol tent, 100-pug samples of cell wall were hydrolyzed with 4 M equivalent of alanine, glycine, and glutamic acid as compared with or 6 M HCl at 115°C for 16 hr and converted to the diaminopimelic acid. corresponding N (O for serine and threonine)-heptafluoro- heptafluorobutyryl isobutylglycoside isobutyl esters for glu- butyryl isobutyl esters, for amino acids, and N- or O- cosamine and muramic acid (11). The derivatives were then A chromatographed on the described Durabond-1 capillary 40-0 column. a-Aminoadipic acid was included in each assay as an internal standard to allow measurement. The amino acid E and aminoglycoside assignments were confirmed by gas 30 chromatography and mass spectrometry using electron- impact ionization. CD20 Lymphocyte Transformation and Precursor Frequency Analysis. The precursor frequency of human peripheral L 0 blood T lymphocytes reactive to various antigen prepara- tions from M. leprae was determined by a modified limiting L00 dilution procedure (12). Briefly, T lymphocytes were iso- lated from the blood of lepromin-positive tuberculoid lep- LL BL BT/11 NORMAL rosy patients or contacts, and replicate cultures were estab- I~ n 27 12 25 12 AMINO ACIDS AND AMINO SUGARS OF A OF M.
Recommended publications
  • Introduction to Bacteriology and Bacterial Structure/Function
    INTRODUCTION TO BACTERIOLOGY AND BACTERIAL STRUCTURE/FUNCTION LEARNING OBJECTIVES To describe historical landmarks of medical microbiology To describe Koch’s Postulates To describe the characteristic structures and chemical nature of cellular constituents that distinguish eukaryotic and prokaryotic cells To describe chemical, structural, and functional components of the bacterial cytoplasmic and outer membranes, cell wall and surface appendages To name the general structures, and polymers that make up bacterial cell walls To explain the differences between gram negative and gram positive cells To describe the chemical composition, function and serological classification as H antigen of bacterial flagella and how they differ from flagella of eucaryotic cells To describe the chemical composition and function of pili To explain the unique chemical composition of bacterial spores To list medically relevant bacteria that form spores To explain the function of spores in terms of chemical and heat resistance To describe characteristics of different types of membrane transport To describe the exact cellular location and serological classification as O antigen of Lipopolysaccharide (LPS) To explain how the structure of LPS confers antigenic specificity and toxicity To describe the exact cellular location of Lipid A To explain the term endotoxin in terms of its chemical composition and location in bacterial cells INTRODUCTION TO BACTERIOLOGY 1. Two main threads in the history of bacteriology: 1) the natural history of bacteria and 2) the contagious nature of infectious diseases, were united in the latter half of the 19th century. During that period many of the bacteria that cause human disease were identified and characterized. 2. Individual bacteria were first observed microscopically by Antony van Leeuwenhoek at the end of the 17th century.
    [Show full text]
  • The Complete Genome Sequence of Mycobacterium Bovis
    The complete genome sequence of Mycobacterium bovis Thierry Garnier*, Karin Eiglmeier*, Jean-Christophe Camus*†, Nadine Medina*, Huma Mansoor‡, Melinda Pryor*†, Stephanie Duthoy*, Sophie Grondin*, Celine Lacroix*, Christel Monsempe*, Sylvie Simon*, Barbara Harris§, Rebecca Atkin§, Jon Doggett§, Rebecca Mayes§, Lisa Keating‡, Paul R. Wheeler‡, Julian Parkhill§, Bart G. Barrell§, Stewart T. Cole*, Stephen V. Gordon‡¶, and R. Glyn Hewinson‡ *Unite´deGe´ne´ tique Mole´culaire Bacte´rienne and †PT4 Annotation, Ge´nopole, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France; ‡Tuberculosis Research Group, Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom; and §The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved March 19, 2003 (received for review January 24, 2003) Mycobacterium bovis is the causative agent of tuberculosis in a The disease is caused by M. bovis, a Gram-positive bacillus range of animal species and man, with worldwide annual losses to with zoonotic potential that is highly genetically related to agriculture of $3 billion. The human burden of tuberculosis caused Mycobacterium tuberculosis, the causative agent of human tu- by the bovine tubercle bacillus is still largely unknown. M. bovis berculosis (5, 6). Although the human and bovine tubercle bacilli was also the progenitor for the M. bovis bacillus Calmette–Gue´rin can be differentiated by host range, virulence and physiological vaccine strain, the most widely used human vaccine. Here we features the genetic basis for these differences is unknown. M. describe the 4,345,492-bp genome sequence of M.
    [Show full text]
  • Medical Bacteriology
    LECTURE NOTES Degree and Diploma Programs For Environmental Health Students Medical Bacteriology Abilo Tadesse, Meseret Alem University of Gondar In collaboration with the Ethiopia Public Health Training Initiative, The Carter Center, the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education September 2006 Funded under USAID Cooperative Agreement No. 663-A-00-00-0358-00. Produced in collaboration with the Ethiopia Public Health Training Initiative, The Carter Center, the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education. Important Guidelines for Printing and Photocopying Limited permission is granted free of charge to print or photocopy all pages of this publication for educational, not-for-profit use by health care workers, students or faculty. All copies must retain all author credits and copyright notices included in the original document. Under no circumstances is it permissible to sell or distribute on a commercial basis, or to claim authorship of, copies of material reproduced from this publication. ©2006 by Abilo Tadesse, Meseret Alem All rights reserved. Except as expressly provided above, no part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written permission of the author or authors. This material is intended for educational use only by practicing health care workers or students and faculty in a health care field. PREFACE Text book on Medical Bacteriology for Medical Laboratory Technology students are not available as need, so this lecture note will alleviate the acute shortage of text books and reference materials on medical bacteriology.
    [Show full text]
  • The Approved List of Biological Agents Advisory Committee on Dangerous Pathogens Health and Safety Executive
    The Approved List of biological agents Advisory Committee on Dangerous Pathogens Health and Safety Executive © Crown copyright 2021 First published 2000 Second edition 2004 Third edition 2013 Fourth edition 2021 You may reuse this information (excluding logos) free of charge in any format or medium, under the terms of the Open Government Licence. To view the licence visit www.nationalarchives.gov.uk/doc/ open-government-licence/, write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email [email protected]. Some images and illustrations may not be owned by the Crown so cannot be reproduced without permission of the copyright owner. Enquiries should be sent to [email protected]. The Control of Substances Hazardous to Health Regulations 2002 refer to an ‘approved classification of a biological agent’, which means the classification of that agent approved by the Health and Safety Executive (HSE). This list is approved by HSE for that purpose. This edition of the Approved List has effect from 12 July 2021. On that date the previous edition of the list approved by the Health and Safety Executive on the 1 July 2013 will cease to have effect. This list will be reviewed periodically, the next review is due in February 2022. The Advisory Committee on Dangerous Pathogens (ACDP) prepares the Approved List included in this publication. ACDP advises HSE, and Ministers for the Department of Health and Social Care and the Department for the Environment, Food & Rural Affairs and their counterparts under devolution in Scotland, Wales & Northern Ireland, as required, on all aspects of hazards and risks to workers and others from exposure to pathogens.
    [Show full text]
  • Studies of Endothelial and Leukocyte Cell Adhesion Molecules in Renal Transplantation
    ì1-3-r\"1\, Studies of Endothelial and Leukocyte Cell Adhesion Molecules in Renal Transplantation A Thesis submitted to the University of Adelaide as the requirement for the degree of Doctor of PhilosoPhy by Warwick L Grooby BSc (Hons) Department of Medicine, University of Adelaide and Transplantation Immunology Laboratory The Queen Elizabeth Hospital November \996 I TABLE OF CONTENTS Table of Contents I Summary vlll Declaration x Acknowledgments xi Dedication xii Publications and Presentations xtll Abbreviations xv CHAPTER 1 Introduction 1..L Introduction 2 L.2 Cell Adhesion Molecules 3 1,.2.1, Integrin Family J 8 1.2.1,.1. PL integrin subfamilY 'J,.2.1..2 9 P2 integrin subfamilY 11 1,.2.1.3 P7 integrin subfamilY 1,.2.2 Immunoglobulin (Ig) SuperfamilY 12 1,.2.2.1 ICAM-L (Intercellular adhesion molecule-l) 14 t.2.2.2 ICAM-2 (Letercellular adhesion molecule-2) 15 1..2.2.3 ICAM-3 (Intercellular adhesion molecule-3) 15 t.2.2.4 VCAM-L (Vascular cell adhesion molecule-1) 16 1,.2.2.5 PECAM-L (Platelet-endothelial cell adhesion molecule-1') 18 L.2.2.6 MAdCAM-L (Mucosal addressin cell adhesion molecule-L) 19 1,.2.3 Selectin Family 19 1,.2.3.1 E-selectin 20 1,.2.3.2 P-selectin 22 7.2.3.3 L-selectin 23 1.2.4 Vascular Mucins (addressins) 24 L.2.4.L GIyCAM-1 (Glycosylation-dependent cell adhesion molecule-1) 24 1,.2.4.2 CD34 25 1,.2.5 Cadherins 25 1..2.6 CD4O 26 1.2.7 CDM 27 l1 L.3 Vascular Endothelium 28 L.3.1 MorpholoW of Endothelial Cells 29 1.3.1.1 High Endothelial Venules 30 1.3.2 Study of Endothelial Cells in aitro 31 L.3.2J, Large Vessel Endothelial Cells 31 1.3.2.2 Microvascular Endothelial Cells 32 1,.3.2.3 Transformed Endothelial Cells 33 1.3.3 Heterogeneity of Vascular Endothelium 33 1.3.3.1 Weibel-Palade bodies (WPBs) 33 1,.3.3.2 von Willebrand factor (vWF) 34 1.3.3.3 Biosynthetic Heterogeneity 34 L.3.3.4 Antigenic HeterogeneitY 35 1..3.4 Endothelial Cell Functions 36 1..3.4.1.
    [Show full text]
  • 5 Allergic Diseases (And Differential Diagnoses)
    Chapter 5 5 Allergic Diseases (and Differential Diagnoses) 5.1 Diseases with Possible IgE Involve- tions (combination of type I and type IVb reac- ment (“Immediate-Type Allergies”) tions). Atopic eczema will be discussed in a separate section (see Sect. 5.5.3). There are many allergic diseases manifesting in The maximal manifestation of IgE-mediated different organs and on the basis of different immediate-type allergic reaction is anaphylax- pathomechanisms (see Sect. 1.3). The most is. In the development of clinical symptoms, common allergies develop via IgE antibodies different organs may be involved and symp- and manifest within minutes to hours after al- toms of well-known allergic diseases of skin lergen contact (“immediate-type reactions”). and mucous membranes [also called “shock Not infrequently, there are biphasic (dual) re- fragments” (Karl Hansen)] may occur accord- action patterns when after a strong immediate ing to the severity (see Sect. 5.1.4). reactioninthecourseof6–12harenewedhy- persensitivity reaction (late-phase reaction, LPR) occurs which is triggered by IgE, but am- 5.1.1 Allergic Rhinitis plified by recruitment of additional cells and 5.1.1.1 Introduction mediators.TheseLPRshavetobedistin- guished from classic delayed-type hypersensi- Apart from being an aesthetic organ, the nose tivity (DTH) reactions (type IV reactions) (see has several very interesting functions (Ta- Sect. 5.5). ble 5.1). It is true that people can live without What may be confusing for the inexperi- breathing through the nose, but disturbance of enced physician is familiar to the allergist: The this function can lead to disease. Here we are same symptoms of immediate-type reactions interested mostly in defense functions against are observed without immune phenomena particles and irritants (physical or chemical) (skin tests or IgE antibodies) being detectable.
    [Show full text]
  • Mycobacterium Leprae a Nd Elevation Of
    Lepr. Rev. (1978) 49, 203-213 Absence of jj-Glucuron idase in Mycobacterium leprae and Elevation of the Enzyme in I nfected Tissues K. PRABHAKARAN, E. B. HARRIS AND W. F. KIRCHHEIMER U. S. Public Health Service Hospital. Carville. LA 70 721. USA ,8-Glucuronidase actlVlty was determined in mouse footpads infected with My cobacterium leprae. in the leprosy organisms separated from the liver and spleen of experimentally infected armadillos, and in the armadillo tissues. Enzyme assays in th� mouse footpads were initiated 1 week after inoculation with M. /eprae and continued at monthly intervals for 12 months. In the mouse footpads and in the armadillo tissues, M. leprae infection resulted in remarkable elevations of ,8- glucuronidase leveis. The leprosy bacilli seemed to be devoid of the enzyme. In its properties like pH optimum, reaction velocity and effect of inhibitors, the activity detected in M. leprae resembled the host tis sue enzyme rather than bacterial ,8- glucuronidase; and the activity was found to be superficially adsorbed on the bacilli. lt is well established that phagocytes are rich in lysosomal enzymes. Evidently, the increased ,8-g1ucuronidase of the infected tissues is not derived from the invading organisms, but from the differenttypes of phagocytic cells infiltratingthe tissues. Introduction j3-Glucuronidase is an important hydrolytic enzyme ubiquitously distributed in animal tissues and in tissue fluids. Phagocytic cells are especially rich in j3-g1ucuronidase. In the mammalian liver, the enzyme is largely associated with Iysosomes, and approximately one-third of the activity is distributed in the endoplasmic reticulum. The hydrolase is closely correlated with cellular pro­ liferation and tissue repair; high leveis of the enzyme are found in the reproductive and endocrine organs and in tumours.
    [Show full text]
  • LEARNING from LEPROSY Be Enjoyed by 50%Of the Urbanpopulation, but Only 15% Monoclonal Anti-Interferon (IFN)-Y Antibodies
    0022- 1767/86/137 1 -0OOiSO2.00/0 THEJOURNAL OF 1MMUNOLoGY Vol. 137. No. 1. July 1, I986 Copyright 0 1986 by The American Association of Immunol~lsts Prlnted In U.S.A. American Associationof Immunologists PRESIDENTIALADDRESS LEARNINGFROM LEPROSY:A PERSPECTIVE ONIMMUNOLOGY AND THE THIRDWORLD BARRY R. BLOOM From the Departmentsof Microbiology and Immunology. andCell Biology, Albert Einstein Collegeof Medicine. Bronx,NY 10461 "If we take the widest and wisest view of a Cause. there is no such thingas a Lost Cause, because there is no such thingas a Gained Cause. We fight for Lost Causes because we know that our defeat and dismay may be the preface to our successors' victory, although that victory itself will be temporary; we fi ht rather to keep somethning alive than in the expectation t fl at anything will triumph. "T.S. Eliot "A Map of the World Without Utopia on It Is not Worth Glancing At." "Oscar Wilde Let mebegin with a case history. notof an individual. tussis,tetanus, tuberculosis, polio, and measles, and but ratherof a country. any of the fortypoorest nations consequently 0.5%of them became lame from polio, 1% on earth. Let me ask you to try to imagine our qualityof died from neonatal tetanus. 2% succumbedto whooping life, if life expectancy at birth in this countrywere 42 yr. cough. and 3%died from measles. We would be living in if infant mortality at birth were 140 per thousand.if 40% a country whose average gross national product per cap- of our children suffered from malnutrition. and if only ita would be $310/yr: in which 37% of males, but only 10%of children were immunized against diphtheria, per-14% of females, would be literate.
    [Show full text]
  • C07k - 2021.08
    CPC - C07K - 2021.08 C07K PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D 519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G 69/00; macromolecular products derived from proteins C08H 1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N 15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N 33/00) Relationships with other classification places An amino acid per se is classified in C07D while peptides (starting from dipeptides) are classified in C07K. Subclass C07K is a function oriented entry for the compounds themselves and does not cover the application or use of the compounds under the subclass definition. For classifying such information other entries exist, for example: preservation of bodies of humans or animals or plants or parts thereof; Biocides, e.g. as disinfectants, as pesticides, as herbicides; pest repellants or attractants; plant growth regulators are classified in A01N. Preparations for medical, dental, or toilet purposes are classified in A61K. Amino acids or derivatives thereof are classified in C07C or C07D.
    [Show full text]
  • Mycobacterium Avium Subsp
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Veterinary and Biomedical Sciences, Papers in Veterinary and Biomedical Science Department of July 2001 Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine N. Beth Harris University of Nebraska - Lincoln Raul G. Barletta University of Nebraska - Lincoln, [email protected] Follow this and additional works at: https://digitalcommons.unl.edu/vetscipapers Part of the Veterinary Medicine Commons Harris, N. Beth and Barletta, Raul G., "Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine" (2001). Papers in Veterinary and Biomedical Science. 5. https://digitalcommons.unl.edu/vetscipapers/5 This Article is brought to you for free and open access by the Veterinary and Biomedical Sciences, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Papers in Veterinary and Biomedical Science by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. CLINICAL MICROBIOLOGY REVIEWS, July 2001, p. 489–512 Vol. 14, No. 3 0893-8512/01/$04.00ϩ0 DOI: 10.1128/CMR.14.3.489–512.2001 Copyright © 2001, American Society for Microbiology. All Rights Reserved. Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine N. BETH HARRIS AND RAU´ L G. BARLETTA* Department of Veterinary and Biomedical Sciences, University of Nebraska—Lincoln, Lincoln, Nebraska 68583-0905 INTRODUCTION .......................................................................................................................................................489
    [Show full text]
  • 1 20 August, 1 959, 97, Pp. 1 25-1 34) the Interpretation of the Nature And
    120 LEPROSY REVIEW THE PRO B LEM OF THE NATURE AN D OF THE SJGNI FICANCE OF THE MITSUDA REACT ION TO LEPROMIN R. CHAUSSINAN D (Institut Pasteur, Paris; this paper is reprinted in English translation approved by the author, by kind permission of the Editor, Ann. de I'lnstitut Pasteur. The article appeared August, 1959, 97, pp. 1 25- 1 34) The interpretation of the nature and the significance of the reaction to lepromin becomes more and more difficult. Lepromin is a filtered and autoclaved suspension of I g. of lepromatous nodules, finelygr ound, in 30 ml. of physiological saline, 0.5% carbolised. This antigen contains Hansen's bacilli heatkilled and some tissue debris. The Mitsuda reaction is fo und by injecting 0. 1 ml. of lepromin intradermally. The result is positive when an erythematous infiltration, which reaches its height at the end of 3 to 4 weeks, fo rms at the point of the injection. Small infiltrations of less than 3 mm. in diameter are considered as doubtful. In strongly positive cases, the nodular infiltration can ulcerate. Towards the 30th day the histological aspect of the reaction is tuberculoid in type. Twenty years ago it was considered that sensitivity to lepromin was always a sign of a relative state of immunity against leprosy. This opinion was based on the fo llowing premises : Patients with tuberculoid leprosy, with fe w bacilli, usually react strongly to the Mitsuda reaction, while leprosy patients of the malignant lepromatous kind, whose body is rapidly invaded by Hansen's bacilli, are insensitive to lepromin.
    [Show full text]
  • Metabolism in Mycobacterium Leprae, M. Tuberculosis and Other
    BnaA Mtthcal BidUnm (1988) Vol 44, No 3, pp 547-561 Metabolism in Mycobacterium leprae M. tuberculosis and Downloaded from https://academic.oup.com/bmb/article/44/3/547/283569 by guest on 28 September 2021 other pathogenic mycobacteria P R Wheeler C Ratledge Department of Biochemistry, Untvernty of Hull, Hull Pathogenic mycobacteria have complex lipoidal cell walls. Most of them secrete further lipids which appear as a layer around intracellular organisms. This lipoidal exterior may protect mycobacteria inside macrophages from attempts that those host cells make to kill them Such protection could be especially important in M leprae which unusually lacks catalase, an important 'self-defence' enzyme. Intracellular mycobacteria must obtain key nutrients from the host. The role of mycobactm and exochelm in acquiring iron, the carbon and nitrogen sources—including metabolic intermediates—used, and control of biosynthetic pathways are discussed. M. tuberculosis is capable of synthesismg all its macromolecules but M. leprae depends on the host for purines (precursors of nucleic acids), and maybe other intermediates Pathogenic mycobacteria grow slowly, and the possibilities that permeability of the envelope to nutrients, catabolic or anabolic (particularly DNA, RNA synthesis) reactions are limiting to growth are considered. Some characteristic activities may represent targets for antimycobactenal agents. Although it is a considerable over-simplification, it could be asserted that most mycobacteria are no more than Escherichia coli wrapped up in a fur coat. Metabolic processes in mycobacteria, for 548 TUBERCULOSIS AND LEPROSY the most part, are therefore the same, in broad outline as have been elucidated in the more amenable bacteria. Thus it is the few activities which are characteristically mycobacterial and the differ- ences between pathogenic mycobacteria and more amenable mi- crobes, that we discuss in this article.
    [Show full text]