Machine generated contents note: 1 -- A Brief History of PNH -- Wendell Rosse -- The Diagnosis of PNH 8 -- Summary 15 -- References 16 -- 2 -- Genetics of PNH -- Lucio Luzzatto and Khedoudja Nafa -- Biochemical Genetics of PNH in Somatic Cells 21 -- The PIG-A Gene 23 -- The PIG-A Protein 24 -- Detecting Mutations in the PIG-A Gene 27 -- Germ Line PIG-A Mutations 32 -- The Spectrum of Somatic Mutations in the PIG-A -- Gene 33 -- PIG-A Mutations without PNH 40 -- Structure-Function Relationships 41 -- Correlation between Phenotypes and Genotypes 42 -- Comparison of the Spectrum of Mutations in Three X-Linked -- Genes: PIG-A, FVIII, and G6PD 42 -- Conclusion 43 -- References 44 -- 3 -- Hemolysis in PNH -- Charles J. Parker -- Introduction 49 -- The Classical Pathway of Complement 55 -- The Alternative Pathway of Complement 61 -- Phenotypic Mosaicism 64 -- Functional Basis of the Abnormal Sensitivity of the -- Erythrocytes of PNH to Complement-Mediated -- Lysis 68 -- Treatment of Hemolysis 83 -- Summary and Conclusions 86 -- References 89 -- 4 -- Thrombotic Complications in PNH -- Elaine M. Sloand and Neal S. Young -- Introduction 101 -- Incidence of Thrombosis in PNH 102 -- Factors Associated with Venous Thrombosis 103 -- Platelet Abnormalities in PNH 104 -- Role of Red Cell and Platelet Microvesicles 107 -- Urokinase Activator Receptor (uPAR) and Cell-Mediated -- Fibrinolysis 108 -- Treatment of Thrombosis in PNH 109 -- Summary 109 -- References 110 -- 5 -- Bone Marrow Failure in PNH -- Daniel E. Dunn, Johnson M. Liu, and Neal S. Young -- Introduction 113 -- Pathophysiology of Marrow Failure in PNH 115 -- An Immune Model of PNH Pathogenesis 120 -- Clinical Course and Treatment of Marrow Failure in -- PNH 127 -- Summary 130 -- References 131 -- 6 -- Animal Models of PNH -- Taroh Kinoshita, Monica Bessler, and Junji Takeda -- Introduction 139 -- Mouse Piga Gene 141 -- In Vitro Differentiation of PIGA(-) ES Cells 143 -- Chimeric Mice Bearing PIGA(-) Hematopoietic Stem -- Cells 149 -- Hematopoiesis by Cells from Patients with PNH in SCID -- Mice 154 -- Conclusions and Perspectives 155 -- References 155 -- 7 -- The Function of GPI-Anchored Proteins -- Ian Okazaki and Joel Moss -- Introduction 159 -- GPI-Linked Proteins and Cell Signaling 161 -- Role of GPI-Anchored Proteins in Insulin Action 166 -- GPI-Anchored Proteins Function as Receptors 166 -- GPI Anchors and Membrane Structure 168 -- Summary 170 -- References 171 -- 8 -- GPI in Lower Animals -- Louis Schofield -- Introduction 179 -- Structures of Protozoal GPIs 180 -- Evidence for GPI-Mediated Signaling in Mammalian Cell -- Biology 182 -- Signal Transduction in Host Cells by Protozoal -- GPIs 185 -- Parasite GPIs as Functional Toxins and Pathogenicity -- Factors 187 -- Regulation of Macrophage Function by Glycoconjugates of -- Leishmania 188 -- Regulation of Host Cells by Ceramide-Containing GPIs of -- T. cruzi 189 -- Insulin-Mimetic Activities of Protozoal GPIs 189 -- CD1d-Restricted NK T Cells and Immunity to GPI-Anchored -- Proteins 190 -- Conclusions 191 -- References 192 -- 9 -- Synthesis of the GPI Anchor -- Daniel Sevlever, Rui Chen, and M. Edward Medof -- Introduction 199 -- GPI Biosynthetic Pathway 200 -- Mammalian and Yeast GPI-Anchor Defective -- Mutants 203 -- GPI-Anchor Addition to Proteins 207 -- Biological Implications of GPI Anchoring 210 -- Conclusions 213 -- References 214 -- 10 -- Functional and Structural Organization -- of GPI-Anchored Proteins in -- Cellular Membranes -- Satyajit Mayor -- Introduction 221 -- GPI-Anchor Function and the "Raft" Hypothesis 221 -- Lateral Heterogeneity in Cell Membranes 222 -- Detergent-Resistant Membranes and Their Connection with -- Rafts 223 -- Evidence for Rafts in Living Cell Membranes 227 -- Involvement of Rafts in Biosynthetic and Endocytic -- Sorting 230 -- Rafts and Signaling by GPIAPs 232 -- In Conclusion 233 -- References 233 -- 11 -- Structure and Function of -- GPI-Specific Phospholipases -- Martin G. Low -- Introduction: GPI Anchors and Phospholipases 239 -- Biochemical Properties of Plasma GPI-PLD 245 -- Distribution of GPI-PLD in Tissues and Cells 252 -- Physiological Role of GPI-PLD 257 -- References 262.