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Chemistry and Biology of Hyaluronan -

Chemistry and Biology of Hyaluronan (eBook)

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2004 | 1. Auflage
624 Seiten
Elsevier Science (Verlag)
978-0-08-047222-5 (ISBN)
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255,07 inkl. MwSt
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It was probably the French chemist Portes, who first reported in 1880 that the mucin in the vitreous body, which he named hyalomucine, behaved differently from other mucoids in cornea and cartilage. Fifty four years later Karl Meyer isolated a new polysaccharide from the vitreous, which he named hyaluronic acid. Today its official name is hyaluronan, and modern-day research on this polysaccharide continues to grow.



Expertly written by leading scientists in the field, this book provides readers with a broad, yet detailed review of the chemistry of hyaluronan, and the role it plays in human biology and pathology. Twenty-seven chapters present a sequence leading from the chemistry and biochemistry of hyaluronan, followed by its role in various pathological conditions, to modified hylauronans as potential therapeutic agents and finally to the functional, structural and biological properties of hyaluronidases. Chemistry and Biology of Hyaluronan covers the many interesting facets of this fascinating molecule, and all chapters are intended to reach the wider research community.

* Comprehensive look at the chemistry and biology of hyaluronans
* sential to Chemists, Biochemists and Medical researchers
* broad yet detailed review of this rapidly growing research area


It was probably the French chemist Portes, who first reported in 1880 that the mucin in the vitreous body, which he named hyalomucine, behaved differently from other mucoids in cornea and cartilage. Fifty four years later Karl Meyer isolated a new polysaccharide from the vitreous, which he named hyaluronic acid. Today its official name is hyaluronan, and modern-day research on this polysaccharide continues to grow. Expertly written by leading scientists in the field, this book provides readers with a broad, yet detailed review of the chemistry of hyaluronan, and the role it plays in human biology and pathology. Twenty-seven chapters present a sequence leading from the chemistry and biochemistry of hyaluronan, followed by its role in various pathological conditions, to modified hylauronans as potential therapeutic agents and finally to the functional, structural and biological properties of hyaluronidases. Chemistry and Biology of Hyaluronan covers the many interesting facets of this fascinating molecule, and all chapters are intended to reach the wider research community. - Comprehensive look at the chemistry and biology of hyaluronans- Essential to Chemists, Biochemists and Medical researchers- Broad yet detailed review of this rapidly growing research area

Front Cover 1
Chemistry and Biology of Hyaluronan 4
Copyright Page 5
Contents 14
Preface 8
Contributors 10
Chapter 1. Solution Properties of Hyaluronan 20
I. Introduction 20
II. Historical Perspective 20
III. Fundamentals of Hyaluronan Properties 23
IV. Conformation of Hyaluronan in Solution 24
V. Concentration Dependence of Hyaluronan Self-Diffusion 26
VI. Effects of Electrolytes on Hyaluronan Solution Properties 30
VII. The Effects of Alkali pH on Hyaluronan Self-Diffusion and Tracer Diffusion in Hyaluronan Solutions 30
VIII. Temperature Dependence of Hyaluronan Self-Diffusion 33
IX. Effects of Urea on Hyaluronan Properties 33
X. Effects of Hyaluronan Oligosaccharides on Polymeric Hyaluronan Properties 35
XI. Conclusions 35
Chapter 2. Methods for Analysis of Hyaluronan and Its Fragments 40
I. Introduction 40
II. Biological Role of Hyaluronan and Its Fragments 42
III. Preparation and Isolation of Hyaluronan Oligomers 43
IV. Analysis and Characterization of Hyaluronan Oligomers 48
V. Summary and Conclusion 54
Chapter 3. Methods for Determination of Hyaluronan Molecular Weight 60
I. Introduction 60
II. Viscometry 61
III. Electrophoresis 68
IV. Light Scattering and Size Exclusion Chromatography 74
Chapter 4. Biodegradation of Hyaluronan 90
I. Introduction 90
II. Turnover in the Organism and Cellular Uptake 90
III. Summary and Conclusion 98
Chapter 5. The Hyaluronan Receptor: CD44 102
I. Introduction 102
II. Structure of CD44 Primary Transcripts 104
III. Regulation of CD44 Expression 108
IV. Protein Structure of CD44 109
V. Cellular Functions of CD44 116
VI. Concluding Remarks 129
Chapter 6. The Role of the Hyaluronan Receptor RHAMM in Wound Repair and Tumorigenesis 144
I. Introduction 144
II. Hyaluronan in Wound Repair and Cancer 145
III. RHAMM is an Atypical Hyaladherin 148
IV. Classification of RHAMM Protein Forms by Binding Properties and Structure 150
V. RHAMM Expression Influences Wound Repair and Tumor Progression 155
VI. Conclusions 161
Chapter 7. Signal Transduction Associated with Hyaluronan 172
I. Introduction 172
II. CD44 Receptor 173
III. RHAMM Receptor 183
IV. Toll-like Receptor 4 187
V. Layilin 189
VI. PH-20 Hyaluronidase and HA Receptor 190
VII. The LYVE-1 and HARE Receptors for HA Endocytosis and Degradation 191
VIII. Summary and Conclusions 193
Chapter 8. Structural and Functional Diversity of Hyaluronan-Binding Proteins 208
I. Introduction 208
II. The Link Module Superfamily 210
III. Insights into the Molecular Basis of HA Binding 215
IV. Summary 219
Chapter 9. Biological Function of SHAP–Hyaluronan Covalent Complex 224
I. Introduction 224
II. Formation of the SHAP–Hyaluronan Complex 226
III. Physiological Significance of the SHAP–Hyaluronan Complex 228
IV. SHAP–Hyaluronan Complex in Disease 230
V. Future Prospects 235
Chapter 10. Hyaluronan and Associated Proteins in the Visual System 242
I. Introduction 242
II. Physiological Role of Hyaluronan and Its Binding Proteins in Ocular Tissues 242
III. Ocular Diseases Involving Hyaluronan and Its Binding Proteins 251
IV. Summary and Conclusion 254
Chapter 11. Hyaluronan in the Pulmonary Alveolus and Interstitium 266
I. Introduction 266
II. Lung Hyaluronan (HA) 268
III. Hyaluronan Oligosaccharides 271
IV. Hyaluronan in the Alveolus 274
V. Hyaluronan in the Pulmonary Interstitium 277
VI. Conclusion 280
Chapter 12. Hyaluronan in Ventilator-Induced Lung Injury 290
I. Introduction 290
II. Hyaluronan 290
III. Ventilator-Induced Lung Injury 294
IV. Conclusion 298
Chapter 13. The Role of Hyaluronan in Cancer 304
I. Introduction 304
II. Clinical Indications of Hyaluronan in Cancer 305
III. Hyaluronan in Cancer Biology: Expression of Hyaluronan Receptors 307
IV. Hyaluronan in Cancer Biology: Role of Hyaluronan in Adhesion, Migration, and Invasion of Cancer 308
V. Interaction of Hyaluronan with the Extracellular Matrix 311
VI. Hyaluronan and Angiogenesis 312
VII. Hyaluronan-Mediated Signalling Mechanisms in Cancer 313
VIII. Manipulation of HA Function as Potential Therapeutic Strategies 315
Chapter 14. Hyaluronan in Atherosclerosis and Restenosis 326
I. Introduction 326
II. Hyaluronan in Atherosclerosis 327
III. Hyaluronan in Restenosis 329
IV. Hyaluronan in Other Vascular Diseases 333
V. Conclusions 334
Chapter 15. Hyaluronan in the Airways 342
I. Introduction 342
II. Airway Hyaluronan: General Aspects 343
III. Airways Host Defence and Hyaluronan 344
IV. Tissue Kallikrein and Hyaluronan: Interaction and Enzyme Inhibition 345
V. Hyaluronan Serves as an Anchor for Secreted Proteins, Preventing Their Removal by Mucociliary Clearance 346
VI. Receptor for Hyaluronan-Mediated Motility is Expressed at the Apical Border of Epithelial Cells 347
VII. Ciliary Beating and Hyaluronan 347
VIII. Hyaluronan Size and Airway Pathophysiology 348
IX. Concluding Remarks and Outlook 350
Chapter 16. Hyaluronan Biology in Vocal Fold Morphology and Biomechanics 358
I. Introduction 358
II. Hyaluronan Localization in the Vocal Fold 359
III. Hyaluronan Localization in Vocal Fold Pathologies 361
IV. Biomechanical Properties of Hyaluronan 361
V. Therapeutic Uses of Hyaluronan in the Vocal Folds 364
VI. In Vivo Alteration of Hyaluronan Production 366
VII. Future Directions 367
Chapter 17. Hyaluronan in Aging 370
I. Introduction 370
II. Hyaluronan Structures in Solution: Relevance to Tissue Biologic Functions and Aging 372
III. Summary and Conclusion 378
Chapter 18. Hyaluronan and Scarring 386
I. Introduction 386
II. Wound Healing 387
III. Hyaluronan and Wound Healing-Hypotheses 389
IV. Perfect Skin 390
V. Properties of Hyaluronan 391
VI. Role of Hyaluronan in Scarring 393
VII. Medical Applications 395
VIII. Hyaluronan Derivatives 396
IX. Hyaluronan, Wound Healing and Scarring: A New Perspective 401
Chapter 19. Hyaluronan in the Epidermis and Other Epithelial Tissues 414
I. Introduction 414
II. Epidermal Hyaluronan 414
III. Hyaluronan in Epidermal Appendices and Other Derivatives of Ectodermal Epithelium 418
IV. Gastrointestinal and Respiratory Epithelium 419
V. Genital and Urinary Tracts and Mesothelial Cells as Hyaluronan Producers 422
VI. Epithelial Barrier Function and Hyaluronan 424
VII. Hyaluronan in Wound Healing 424
VIII. The Role of Hyaluronan in Transformation and Spreading of Malignant Epithelial Cells 425
IX. Summary and Conclusions 426
Chapter 20. Viscoelastic Properties of Hyaluronan and Its Therapeutic Use 434
I. Elastoviscosity of Hyaluronan Solutions 434
II. Therapeutic Applications 439
III. Viscosurgery 440
IV. Viscoaugmentation 443
V. Viscoseparation 446
VI. Viscosupplementation 448
VII. Viscoprotection 458
VIII. Drug Delivery with Hyaluronan 461
IX. Hyaluronan in Matrix and Tissue Engineering 462
Chapter 21. Medical Applications of Hyaluronan 476
I. Introduction 476
II. Applications of Physicochemical Properties of Hyaluronan 477
III. Application of Cell Biological Functions of Hyaluronan 479
IV. Applications of Both Physicochemical Properties and Cell Biological Functions of Hyaluronan 480
V. Conclusions 487
Chapter 22. Therapeutic Biomaterials from Chemically Modified Hyaluronan 494
I. Introduction 494
II. Chemical Modifications 495
III. Hyaluronan-Based Biomaterials 502
IV. Conclusions 513
Chapter 23. Medicinal Uses of Modified Hyaluronate 524
I. Introduction 524
II. Surgical Adhesion Reduction 526
III. Tissue Augmentation 532
IV. Conjugation of Therapeutic Agents of Hyaluronate 533
V. Summary and Conclusion 537
Chapter 24. Hyaluronan in the Treatment of Ocular Surface Disorders 548
I. Introduction 548
II. Hyaluronan and Ocular Surface 553
III. Hyaluronan as a Tear Substitute 556
IV. Hyaluronan Administration on the Ocular Surface 557
V. Other Uses of Hyaluronan in Ocular Surface Disorders 563
VI. Summary and Conclusions 564
Chapter 25. The Hyaluronan Synthases 572
I. Introduction 572
II. Molecular Size and Biology of Hyaluronan 573
III. Hyaluronan Synthesis by Hyaluronan Synthases 574
IV. Topological Organization of the Hyaluronan Synthase Proteins 576
V. Molecular Size of Functional Hyaluronan Synthases 577
VI. Purification of Hyaluronan Synthases 577
VII. The Class I Hyaluronan Synthases Polymerize Hyaluronan by Addition to the Reducing End 579
VIII. Are Hyaluronan Synthases Processive? 581
IX. Size Distributions of Hyaluronan Products Made by Hyaluronan Synthases 582
X. Summary and Conclusions 583
Chapter 26. Molecular Genetic Dissection of Hyaluronan Function in the Mouse 588
I. Introduction 588
II. Hyaluronan Synthases 590
III. Hyaluronan Synthases Gene Expression 590
IV. Hyaluronan Synthase 2 Null Allele 592
V. Hyaluronan Synthase 3 Null Allele 595
VI. Hyaluronan Synthase 2 Conditional Gene Knockout 596
VII. Summary and Conclusion 598
Chapter 27. Functional, Structural and Biological Properties of Hyaluronidases 604
I. Introduction 604
II. Mammalian-Type Hyaluronidase 604
III. Bacterial Hyaluronidase 610
IV. Summary and Conclusion 612
Index 618

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