Botulinum Neurotoxin and Tetanus Toxin

1st Edition - April 28, 1989
Editor: Lance Simpson
Language: English
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 1 4 1 6 0 - 4

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… Read more

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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.

Contributors

Preface

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

References

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

References

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

References

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

References

II. Pharmacology and Toxicology

5. Cell Surface Receptors for Protein Toxins

I. Introduction

II. Receptor Biochemistry

III. Microbial Toxin Receptors

References

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

References

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

References

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

References

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

References

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

References

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

I. Historical Perspective

II. Studies on Isolated Preparations

III. Unifying Hypotheses

References

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

References

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

References

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

References

IV. Clinical Issues

15. Animal Models of Botulism and Tetanus

I. Introduction

II. Botulism

III. Tetanus

IV. Conclusions

References

16. Botulism

I. Introduction

II. Epidemiology

III. Clinical Illness

IV. Evaluation of the Patient with Suspected Botulism

V. Treatment

VI. Summary and Conclusions

References

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

References

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

Index