Botulinum Neurotoxin and Tetanus Toxin

Botulinum Neurotoxin and Tetanus Toxin

1st Edition - April 28, 1989

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  • Editor: Lance Simpson
  • eBook ISBN: 9780323141604

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Botulinum Neurotoxin and Tetanus Toxin covers the mechanism of action, pathogenesis, and treatment of clostridial neurotoxins. The book is organized into four parts encompassing 18 chapters that discuss the origin, structure, pharmacology, toxicology, immunology, assays, and clinical issues of botulinum and tetanus neurotoxins. The introductory part of the book discusses the discovery and production of neurotoxins in various strains of Clostridium bacteria. This text also describes how specific bacteriophages and plasmids mediate the pathogenicity of some types of Clostridium botulinum and Clostridium tetani. The subsequent part provides an overview of issues related to toxin binding, including toxins that may serve as models for botulinum and tetanus neurotoxins. Discussions on the peripheral and central aspects of poisoning transport in the central nervous system and on the antagonistic drugs for clostridial neurotoxins are provided. The third part of the book addresses the antibodies against botulinum neurotoxin. Bioassay in mice and highly sensitive immunoassays, such as reversed passive hemagglutination, reversed passive latex agglutination, radioimmunoassay, and enzyme-linked immunosorbent assay, are presented. The concluding part covers the animal models for these toxins and discusses the diagnosis and treatment of botulism and tetanus in human. The clinical use of Clostridium botulinum toxin type A in ocular and neuromuscular disease is also examined. This book will be of value to protein chemists, microbiologists, virologists, pharmacologists, immunologists, and clinicians.

Table of Contents

  • Contributors


    I. Origin and Structure

    1. Bacterial Sources of Clostridial Neurotoxins

    I. Introduction

    II. Discovery of Neurotoxigenic Clostridia

    III. Organisms That Produce Botulinum Neurotoxin

    IV. Organisms That Produce Tetanus Neurotoxin

    V. Final Considerations


    2. Bacteriophages and Plasmids in Clostridium botulinum and Clostridium tetani and Their Relationship to Production of Toxins

    I. Introduction

    II. General Characteristics of Bacteriophages and Their Bacterial Host

    III. Bacteriophages of Clostridium botulinum Group III and Their Relationship to Neurotoxin Production

    IV. Relationship of Phages to Production of Neurotoxin by Other Groups of Clostridium botulinum

    V. Plasmids and Their Role in Toxigenicity of Clostridium botulinum

    VI. Relationship of Phages to Production of Neurotoxin by Clostridium tetani

    VII. Plasmids and the Toxigenicity of Clostridium tetani

    VIII. Concluding Statements


    3. The Structure of Botulinum Neurotoxin

    I. Macrostructure of Botulinum Neurotoxin

    II. Chemical Structure of the Neurotoxin

    III. Conformation (Secondary and Tertiary Structure) of the Neurotoxin

    IV. Structural Domains

    V. Endogenous Conversion of the Single to Dichain Neurotoxin

    VI. Probable Cause of Activation


    4. The Structure of Tetanus Toxin

    I. Introduction

    II. Nomenclature

    III. Gross Structure of the Molecule

    IV. Primary Structure

    V. Secondary Structure

    VI. Antigenic Substructure

    VII. Similarities between Tetanus and Botulinum Neurotoxin Molecules

    VIII. Concluding Remarks


    II. Pharmacology and Toxicology

    5. Cell Surface Receptors for Protein Toxins

    I. Introduction

    II. Receptor Biochemistry

    III. Microbial Toxin Receptors


    6. Entry of Bacterial Toxins into Mammalian Cells

    I. Introduction

    II. Receptor-Mediated Endocytosis

    III. Inhibition of Receptor-Mediated Endocytosis

    IV. Entry of Diphtheria and Pseudomonas Toxins into Mammalian Cells

    V. Entry of Botulinum Neurotoxins and Tetanus Toxin into Mammalian Cells


    7. Peripheral Actions of the Botulinum Toxins

    I. Introduction

    II. Summarizing the Model for Neurotoxin Action

    III. Tissue Binding

    IV. Internalization of Neurotoxin

    V. Mechanism of Neurotoxin Action

    VI. Clostridial Binary Toxins


    8. Peripheral Actions of Tetanus Toxin

    I. Introduction and Historical Perspective

    II. Neuromuscular Transmission

    III. Exocytosis of Adrenergic Transmitter

    IV. Comparison of Action of Tetanus Toxin and Botulinum Toxins

    V. Concluding Remarks


    9. Axoplasmic Transport and Transynaptic Movement of Tetanus Toxin

    I. Introduction

    II. Toxin Fixation

    III. Internalization of Bound Tetanus Toxin

    IV. Retrograde Transport of the Toxin

    V. Transynaptic Movement of Tetanus Toxin

    VI. Relationships between Transport and Biological Activity of Tetanus Toxin

    VII. Use of Tetanus Toxin-Derived Fragments as Specific Carriers for Drugs to the CNS

    VIII. Retrograde Transport and Neurotropism


    10. Clostridial Toxins and the Central Nervous System: Studies on In Situ Tissues

    I. Spinal and Supraspinal Neurons of Arrival for Tetanus and Botulinum Toxins

    II. Actions of the Toxins on the Function and Structure of the Neurons of Arrival

    III. Transsynaptic Transport of Tetanus Toxin

    IV. Fixation of Tetanus Toxin and Botulinum Toxin at Presynaptic Terminals

    V. Action of Tetanus and Botulinum Toxin on Spinal Motor Functions

    VI. Action of Tetanus Toxin on the Activity of Autonomie Efferents

    VII. Action of Tetanus Toxin after Microinjection into Groups of Neurons in the Central Nervous System

    VIII. Biochemical Actions of Tetanus Toxin in Situ


    11. Clostridial Neurotoxins and the Central Nervous System: Functional Studies on Isolated Preparations

    I. Historical Perspective

    II. Studies on Isolated Preparations

    III. Unifying Hypotheses


    12. Pharmacologic Antagonism of Clostridial Toxins

    I. Introduction

    II. Possible Sites of Antagonism

    III. Drugs Antagonizing the Paralysis Caused by Botulinum and Tetanus Toxins

    IV. Restoration of Function in Botulinum Toxin Paralysis by Experimental Nerve Regeneration

    V. Conclusions


    III. Immunology and Assays

    13. Antibodies against Botulinum Neurotoxin

    I. Introduction

    II. Immunologic Properties of Botulinum Toxins as Studied with Polyclonal Antibodies

    III. Generation and Properties of Monoclonal Antibodies against Neurotoxin

    IV. Application of Polyclonal and Monoclonal Antibodies to Immunologic Diagnosis

    V. Preparation and Effectiveness of Vaccine for Human Use

    VI. Conclusion


    14. Assays for Botulinum and Tetanus Toxins

    I. Introduction

    II. Bioassay for Botulinum Toxin

    III. Bioassay for Tetanus Toxin

    IV. Immunoassays for Botulinum Toxin

    V. Concluding Remarks


    IV. Clinical Issues

    15. Animal Models of Botulism and Tetanus

    I. Introduction

    II. Botulism

    III. Tetanus

    IV. Conclusions


    16. Botulism

    I. Introduction

    II. Epidemiology

    III. Clinical Illness

    IV. Evaluation of the Patient with Suspected Botulism

    V. Treatment

    VI. Summary and Conclusions


    17. Clinical Aspects of Tetanus

    I. Introduction

    II. Epidemiology of Tetanus

    III. Clinical Manifestations of Tetanus

    IV. Diagnosis

    V. Therapy for Tetanus

    VI. Prevention of Tetanus

    VII. Conclusion


    18. Clostridial Toxins as Therapeutic Agents

    I. Introduction

    II. Mechanism of Toxin Action

    III. Clinical Results

    IV. Complications and Side Effects

    V. Conclusions

    References and Bibliography for Further Reading


Product details

  • No. of pages: 436
  • Language: English
  • Copyright: © Academic Press 1989
  • Published: April 28, 1989
  • Imprint: Academic Press
  • eBook ISBN: 9780323141604

About the Editor

Lance Simpson

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