Botulinum Neurotoxin and Tetanus Toxin

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