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Type 1 Diabetes : Molecular, Cellular and Clinical Immunology - George S. Eisenbarth

Type 1 Diabetes

Molecular, Cellular and Clinical Immunology

By: George S. Eisenbarth (Editor)

Hardcover

Published: 12th November 2004
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In the field of immunology, type 1 diabetes has become one of the major areas of investigation with studies that span from characterization of key molecules to trials for the prevention of the disease.
Type 1 Diabetes: Molecular, Cellular and Clinical Immunology communicates both the background and the most recent understanding of this disorder, which will almost certainly be central to elucidating the etiology of autoimmunity, and in particular of organ specific autoimmunity. The book covers immunogenetics, immunopathogenesis, epidemiology, disease prediction and clinical application of current knowledge.
Both scientists seeking to understand and prevent type 1 diabetes/autoimmunity as well as physicians caring for families with type 1 diabetes will be interested in this book.

Primer: Immunology/Autoimmunityp. 1
Normal Immune Responsep. 1
Genetics of Autoimmunityp. 5
Triggering of Autoimmunityp. 6
Target Antigensp. 7
Effector Mechanismsp. 9
Therapy of Autoimmunityp. 9
Cell Therapy of Diabetesp. 16
Islet Cell Transplantation - The Beginning of a New Era in Diabetes Treatmentp. 16
The Cell Type in Demand: The Highly Specialized [beta]-Cellp. 17
The Beta-Cell: A Specialized Team-Player Packing a Punch but with a Poor Constitutionp. 19
Overview of Possible [beta]-Cell Sourcesp. 21
[beta]-Cells from [beta]-Cells: Controlling Replicationp. 22
Xenotransplantationp. 22
Embryonic Stem Cells - A Holy Grail or the Epitome of Man's Reduction of Life Through Science?p. 23
Differentiation of Embryonic Stem Cells into Insulin Producing Cellsp. 23
The Active Selection Approachp. 23
The Culture Refinement Approachp. 25
Promises and Pitfalls on the Path to a Cure for Diabetes Using ES Cellsp. 25
Therapeutic Cloning - Taking Advantage of Person-Specific Stem Cellsp. 26
Adult Stem Cells a Resource for Tissue Homeostasis and Regeneration - And Perhaps Conversionp. 27
Plasticity of Adult Stem Cellsp. 27
Liverp. 27
Modified GIP Cells: Intestinal Rescue of a Pancreatic Problemp. 28
Endocrine Tumor Cellsp. 29
Regeneration of [beta]-Cells from Pancreatic Tissuep. 30
Reprogamming Cells - Where Do We Get a Grip?p. 33
What Technology Is Acceptable - And What Does the Patient with Diabetes Wish?p. 34
Perspectivesp. 35
Proprotein Processing and Pancreatic Islet Functionp. 39
Overview and Introductionp. 39
Perspectivep. 41
The Islet as a Neuroendocrine Organp. 41
The Regulated Pathway of Polypeptide Secretionp. 42
The Enzymology of Pancreatic Hormone Proteolysisp. 44
Pathways of Prohormone Processing in the Endocrine Pancreasp. 46
Regulation of Prohormone Processing Activity within the Secretory Pathwayp. 50
The Structure of PC1, PC2 and CPE and Their Post-Translational Processingp. 51
Antiproteases and Chaperonesp. 53
Inherited Defects in Prohormone Processing in the Isletp. 53
Proprotein Processing Peturbations of Nongenetic Originp. 56
Processing of Islet Autoantigens and Type 1A Diabetesp. 58
Stimulus-Secretion Coupling in the Pancreatic Beta-Cellp. 66
Introductionp. 66
Physiology of the Islet of Langerhansp. 66
The Biosynthesis of Insulinp. 67
Physiological Regulation of Islet Hormone Secretionp. 68
Islet Pathophysiology in Type 1 Diabetesp. 69
The Stimulus-Secretion Coupling of the Pancreatic [beta]-Cellp. 71
Concluding Remarksp. 82
Animal Models of Type 1 Diabetes: Genetics and Immunological Functionp. 91
The Nonobese Diabetic Mousep. 91
Genetics of Diabetogenesis in the NOD Mousep. 92
Immunology of the NOD Mousep. 96
TCR Tg Mouse Models of Type 1 Diabetesp. 99
Transgenic Expression of NeoSelf-Antigens in Pancreas and Diabetes Incidencep. 101
Human Autoimmunity Genes Expressed as Transgenes in Micep. 103
BioBreeding Diabetes-Prone (BB-DP) Rat Model of Spontaneous Type 1 Diabetesp. 103
Derivation of BB Ratsp. 104
Genetics of BB Ratsp. 104
Immune Dysfunction in the BB-DP Rat and Its Relationship to Lymphopeniap. 104
Activation and Death of T Cells Homozygous for lyp Mutationp. 106
The lyp Paradoxp. 107
Disease Prevention in the BB-DP Ratp. 107
Concluding Remarksp. 107
Long Evans Tokushima Lean (LETL) Rat Modelp. 108
The Role of T Cells in Beta Cell Damage in Nod Mice and Humansp. 117
The NOD Mousep. 117
Adoptive Transfer of Diabetes by T Cellsp. 117
Checkpoints in the Development of Autoimmune Diabetesp. 118
T Cell Subsets in Type 1A Diabetesp. 118
Mechanism and Mediators of Beta Cell Deathp. 119
The Autoantigensp. 120
Results from Investigations of Human Subjectsp. 122
Histological Investigationsp. 122
Demonstration of in Vitro T Cell Reactivity to Islet Cell Antigensp. 122
Problems Associated with the Detection of T Cell Reactivity in Diabetes - Conclusions from the First International T Cell Workshopp. 123
Summaryp. 123
Type 1 Database Mellitus: An Inflammatory Disease of the Isletp. 129
Genetic Aspects of the Inflammatory Model for the Pathogenesis of Type 1 Diabetesp. 131
Expression Profiling Studies of Genes and Proteins Regulated by Inflammatory Mediatorsp. 136
Signal Transduction of Cytokine-Mediated [beta]-Cell Deathp. 140
The MAPK Pathwaysp. 141
Effector Mechanisms of Cytokine Mediated [beta]-Cell Destructionp. 144
Conclusions and Perspectivesp. 146
The Immunobiology of Pancreatic Islet Transplantationp. 154
Pancreatic Islet Allografting: The Allograft Paradoxp. 155
Antigenicity Versus Immunogenicity of MHC Alloantigensp. 157
Pancreatic Islet Xenografting: The Xenograft Paradoxp. 158
Role of T Cell Subsets in Islet Graft Rejection: A Central Role for CD4 T Cellsp. 160
The Role of Donor APCs in Allograft Versus Xenograft Immunityp. 162
Islet Xenografting in Autoimmune Diabetesp. 162
Future Direction: Donor-Specific Tolerance Inductionp. 162
Type 1 Diabetes Mellitus of Man: Genetic Susceptibility and Resistancep. 170
Introductionp. 170
Inherited Susceptibility Locip. 171
The Major Susceptibility Locus IDDM1p. 171
The Insulin Gene-VNTR Locus IDDM2p. 177
Other Susceptibility Locip. 187
Parental Effects on Inherited Genes Expressionp. 187
Other Nonmendelian Regulatory Mechanismsp. 188
"Acquired" Genetic Polymorphismsp. 190
Concluding Remarksp. 190
Autoimmune Polyendocrine Syndromesp. 204
Autoimmune Polyendocrine Syndrome Type II (APS-II, Schmidt's Syndrome)p. 204
Therapyp. 209
Autoimmune Polyendocrine Syndrome Type I (APS-I)p. 210
XPID (X-Linked Polyendocrinopathy Immune Dysfunction) and Diarrheap. 210
Anti-Insulin Receptor Antibodiesp. 210
Thymic Tumorsp. 210
POEMS Syndromep. 211
Insulin Autoimmune Syndrome (Hirata Syndrome)p. 211
Other Disordersp. 211
Conclusionsp. 211
Epidemiology of Type 1 Diabetes Mellitusp. 219
Type 1 Diabetesp. 219
Natural History of Type 1A Diabetesp. 219
Clinical Onset of Type 1 Diabetesp. 221
Incidence of Type 1 Diabetesp. 222
Remission ("Honeymoon Period")p. 229
Established Diabetesp. 229
Mortalityp. 230
Coronary Artery Diseasep. 233
Summaryp. 233
Humoral Autoimmunityp. 247
Islet Cell Autoantibodies (ICAs)p. 248
Sequenced Autoantigensp. 249
Partially Characterized Autoantigensp. 257
Other Autoantigensp. 258
T Cell Reactivityp. 259
Conclusionsp. 260
Prediction of Type 1 Diabetes: The Natural History of the Prediabetic Periodp. 268
Predictive Factors in Relativesp. 268
Prediction in the General Populationp. 271
Prediction/Diagnosis in Adultsp. 272
At What Stage in Life Is Beta Cell Autoimmunity Initiated? What Is the Initial Target Antigen, and in What Sequence Do Different Autoantibodies Appear?p. 272
Are Environmental Factors Important Either in the Initiation of Beta Cell Autoimmunity or in Modulating the Process Once it Has Begun?p. 274
Once Autoimmunity Is Initiated Are Beta Cells Destroyed in a Progressive Linear Fashion or Are There Spontaneous Remissions?p. 276
Conclusionsp. 281
Clinical Trials for the Prevention of Type 1 Diabetesp. 291
Animal Models for Type 1 Diabetes Preventionp. 291
Clinical Trials for the Prevention of Type 1 Diabetesp. 292
Trials in Newly Diagnosed Subjectsp. 293
Other Immunosuppressive Agents (Rapamycin, Mycophenolate Mofetil, Anti-IL-2 Antibodies, Methotrexate)p. 293
Anti-CD3 Therapyp. 294
High Dose Intravenous Insulinp. 294
Immunostimulationp. 294
Identification of Subjects with PreType 1 Diabetesp. 294
Geneticsp. 295
Immunologicalp. 296
Metabolic Testingp. 297
Trials Using Subjects with PreType 1 Diabetesp. 298
Nicotinamidep. 298
Additional Clinical Trials of Antigen Based Therapiesp. 301
Conclusionsp. 301
Type 1 Diabetes: Molecular, Cellular and Clinical Immunologyp. 306
Can Getting Excited Over Nothing Provoke Autoimmunity?p. 311
Pathogenesis of Type 1 Diabetes: A Viewpointp. 317
Was There Type 1 Diabetes in the Olduvai Gorge?p. 322
Indexp. 327
Table of Contents provided by Rittenhouse. All Rights Reserved.

ISBN: 9780306478710
ISBN-10: 0306478714
Series: Advances in Experimental Medicine and Biology
Audience: Professional
Format: Hardcover
Language: English
Number Of Pages: 335
Published: 12th November 2004
Publisher: Springer Science+Business Media
Country of Publication: US
Dimensions (cm): 25.4 x 17.8  x 1.91
Weight (kg): 1.99
Edition Number: 2