Protides of the Biological Fluids

Preface

Acknowledgements

The Twelfth Arne Tiselius Memorial Lecture

Association Between HLA and Diseases: Biological and Clinical Relevance

Section A. Metal Binding Proteins

A.1. Metal Binding Mechanism

Metal Binding to Serum Proteins

Interactions of Pregnancy Associated Plasma Protein-A (PAPP-A) and α2 Macroglobulin (α2M) on Metal Chelate Affinity Chromatography

Interaction of the Histidine-Rich Glycoprotein of Serum with Metals and Plasmin

Binding of Calcium to Intrinsic Factor (IF) and to the Alpha Subunit of its Receptor

Specificity of Metal Binding to Serum Thymic Factor (FTS)

Hydrogen Peroxide Involvement in the Mechanism of Action of Cytochromec Oxidase

Zinc and Iron Absorption in Endotoxin Pretreated Rats

A Sensitive Micromethod for the Study of Iron Uptake by Mitogen-Stimulated Human Blood Mononuclear Leukocytes

Iron-Deficiency Anaemia Modifies Brain Function Via Dopamine Receptor Subsensitivity

A.2. Iron Binding Proteins

A.2.1. Transferrin

The Molecular Basis of Ferrokinetics: The Explanation of the Fletcher-Huehns Phenomenon

The Discovery of Transferrin in Invertebrates

Crossed Immunoaffinity Electrophoresis of Human Transferrin in Normal and Cirrhotic Sera

Heterogeneity of Human Transferrins

No Functional Difference of the Two Iron-Binding Sites of Human Transferrin in Vitro and in Vivo

Transferrin Protein and Iron Uptake by Cultured Mammalian Cells

Interaction Between Transferrin and Tumor Cell Receptor

Redox Reactions in Hepatocyte Iron Uptake

Transferrin as a Donor of Iron to Rat Liver Mitochondria - Effect of Pyrophosphate

The Kinetics o f Duodenal Mucosa Iron Uptake in the Developing Guinea Pig

Transferrin Protein and Iron Uptake by Liver Parenchymal Cells

Intestinal Transferrin

Uptake of 59Fe-125I- Transferrin by K-562 Cells

Isoelectric Focusing of Inherited Transferrin Variants with Immobilized pH Gradients

An ELISA Technique for Measurement of Transferrin Glyco-Variants in Body Fluids Using Lectins Bound to a Solid Phase

Does Iron-Transferrin Saturation Influence the Immunoturbidimetric Determination of Human Serum Transferrin?

A.2.2. Lactotransferrin

The Present State of the Human Lactotransferrin Sequence

Lactoferrin Stimulates the Production of "Leukocyte Migration Inhibitory Factor" (LIF) by Mononuclear Leukocytes

Lactoferrin Uptake by the Reticuloendothelial System of the Mouse Liver

Comparison of the Interaction of Lactoferrin with Hepatocytes, Lymphocytes and Monocytes

Comparative Study of the Iron Binding Sites of Transferrins: Demonstration of the Non-Identity of the Two Sites of Human Lactotransferrin

Lactoferrin Binding to Peripheral Human Leukocytes

Lactoferrin and Transferrin Levels in the Seminal Plasma of Infertile Men

A.2.3. Ovotransferrin

Binding Site Studies of Ovotransferrin by UV and NMR Spectroscopies

A.2.4. Ferritin

Intracellular Iron Metabolism Revisited

The Metabolism of Plasma Ferritin

Amino Acid Sequence Studies on Human Apoferritins

Ferritin Structure and Function

Ferritin and Metal Toxicity

Analysis of Various Isoferritins with Monoclonal Antibodies

Possible Changes in the Isoferritin Profile During Infancy and Childhood

Increased Urinary Excretion of Ferritin in Subjects with Moderate Proteinuria

The Isoferritin Composition of Rat Liver During Bleeding Induced Catabolism of Liver Ferritin

Influence of Heat-Treatment on Rabbit Liver-Ferritin

Iron Mobilization From Cultured Rat Macrophages Loaded with 59Fe Labelled Erythroblasts

Serum Ferritin Level in Hemodialysis Patients

A.2.5. Hemopexin and Others

Structural Studies of Human Hemopexin

Cleavage of Rabbit Hemopexin by Plasmin and Isolation of Two Glycopeptides

Purification of Human Haemopexin by Affinity Chromatography Using Immobilized Cibacron Blue F3GA and Concanavalin A

Purification of the Porcine Duodenal Haem Receptor Using a New Affinity Chromatographic Medium

Uptake and Release of Labelled Ferrioxamine and Desferrioxamine Derivatives by Cultured Hepatocytes and Macrophages

Fluorimetric and Kinetic Characteristics of Erythrocyte Bovine Carbonic Anhydrases

A.3. Copper Binding Proteins

The Domain Structure of the Human Ceruloplasmin Molecule

Copper Loaded Fetal Guinea-Pig — A Model of Wilson's Disease?

Section B. Tumour Markers

B.1. Overviews

Successful Uses of Tumour Markers in Man

Oncodevelopmental Gene Expression: Relevance to Current Views on Cancer

National Cancer Institute Serum Immunodiagnostic Bank at Mayo Clinic — 10 Years Experience

Prevalance of Transformation-Enhancing Activity in the Plasma of Cancer Patients

Methods for Selection of Optimal Combinations in Multiple Tumor Assay

B.2. Tumour Localization in Vivo

Computer Analysis of Antibody Scans

Indium Chelates for the Radioimmunodetection of Tumours

Radioimmunodetection of Endocrine Tumours

Human Breast Carcinoma Localization with a Radiolabelled Monoclonal Antibody

Radioimmunodetection of Cancer Using Radiolabeled Antibodies to α-Fetoprotein

Radioimmunolocalization of Non Seminomatous Testicular Tumours Secreting Alpha-Fetoprotein

Model for the Radioimmunodetection of Tumours

Micrometastases in Breast Cancer

B.3. Immunohistochemistry

Immunohistological Determination of CEA on Breast Tumors: Comparison of Monoclonal and Polyclonal Antibodies

Immunohistological Localization of Carcinoembryonic Antigen (CEA) and Nonspecific Crossreacting Antigen (NCA) in Benign Breast Lesions

Immunohistochemical Demonstration of Carcinoembryonic Antigen (CEA) in Lung Cancer, Its Localization in Relation to Tumor Type and Differentiation

Immunohistochemical Localization of SSEA-1 in Nonseminomatous Testicular Cancer and Retroperitoneal Mature Teratoma After PVB Chemotherapy

Immunohistochemistry of TPA: Notes on the Methodology

Glucose Oxidase Immunostaining for Tumor Marker Antigens

Guanidinobenzoatase as a Marker for Tumour Cells

Adenosine Deaminase Complexing Protein (ADCP): A Transformation Sensitive Marker and Possible Tool in Immunodiagnosis of Solid Tumors

Lectin- and Immunohistochemical Analysis of Renal Adenocarcinomas

Localization Patterns of CEA and Beta-HCG in Uniformly Classified Lung Tumors

B.4. Screening

Usefulness of Different Cancer Markers in Daily Oncological Practice

Capacity of Monoclonal — and Polyclonal Anti-CEA — Antibodies for Discrimination Between Normal Individuals, Patients with Benign Disease and Patients with Cancer

Serum Amyloid A Protein and C-Reactive Protein — A Comparison of Serum Levels in Cancer and Non-Malignant Disease

B.5. Monitoring

B.5.1. Marker Oriented

B.5.1.1 Prealbumin

Prealbumin as a Marker for Carcinoid Tumours

Isolation of Human Embryonic Prealbumin from Amniotic Fluid

B.5.1.2 Alfa-Foetoprotein

Molecular Species of Human α-Fetoprotein and γ-Glutamyltransferase More Specific to Hepatocellular Carcinoma; Demonstration by Differential Affinities to Lectins

Immunohistochemical Study on Alpha-Fetoprotein in Rats During Fetal and Post-Natal Life

Monitoring Very Low Levels of AFP in the Early Detection of Tumor Recurrency

B.5.1.3. Oncomodulin

The Potential of the Calcium-Binding Protein, Oncomodulin, as a Tumour Marker

The Binding of Divalent Cations to Oncomodulin

B.5.1.4 S-100

The S-100 Antigen in Non-Neural Tumours

S-100 Protein Decreases the Fluidity of the Lipid Bilayer of Purified Synaptic Plasma Membranes

B.5.1.5. Blood Group Τ

Blood Group Τ and TN Antigens are Epithelial Cell-Adhesive, Universal, Clonal, Autoimmunogenic Carcinoma Markers

Carcinoma Detection by Quantitation and Interrelation of Serum Anti-T IgM and Total IgM

B.5.1.6. TPA

Overview of TPA: Specificity, Immunochemistry and Biological Basis

Heterologous and Homologous Anti-TPA Antibodies

Distribution of Tissue Polypeptide Antigen (TPA) in Normal and Neoplastic Human Tissues

Serum Levels of TPA in Patients with Gynaecological Cancer

Monitoring of Breast Cancer with the Aid of Tissue Polypeptide Antigen

Tissue Polypeptide Antigen (TPA) in Patients with Breast Cancer and Gynecological Cancer

Tissue Tumor Polypeptide Antigen and Gastrointestinal Cancer

Molecular Weight Heterogeneity of Tissue Polypeptide Antigen (TPA) in Cancer Sera

Monoclonal Antibodies Against Tissue Polypeptide Antigen (TPA)

Tumor Growth, Circulating Human CEA, β-2-Microglobulin and Tissue-Polypeptide-Antigen in Xenografted Nude Mice

Significance of hTG, CEA and TPA as Tumor Markers in Thyroid Cancer

Sensitivity and Specificity of TPA, CEA, and the Index of Both Markers in Various Malignancies

Evaluation of AFP, ß-HCG, TAG, TPA, CEA, and SP1 in Patients with Malignoma of the Testis

Clinical Use of TPA in Cancer of the Urinary Bladder Using CEA for Comparison

Clinical Significance of Combined TPA and CEA Determinations During

Chemotherapy and/or Radiotherapy in Patients with Breast Cancer or Lung Cancer

Sensitivity and Specificity of Tennessee Antigen in Comparison to CEA, TPA, and Their Optimal Combinations

Comparison of Single and Combined CEA and TPA Determination for Tumor Detection in Various Cancer Patients

Initial Experience with TPA, CA-125 and CRP as Tumor Markers in Ovarian Malignancy

Serial Monitoring of CEA, TPA and Tennessee Antigen During Treatment of Tumor Patients by Adjuvant Immunotherapy with OK 432

CEA and TPA in Plasma, Cerebrospinal Fluid and Tumor Homogenate of Patients with Primary Intracranial Tumors

B.5.1.7. Various Markers

Antisera Against Circulating Human Tumor Associated Antigens (TAA)

Usefulness of the Acidic Isoferritin Assay for Diagnosis of Malignancies

Patterns of Expression of Some New Antigens of Human Bronchial Carcinomas

B.5.2. Organ Oriented

B.5.2.1. Mammary Tumor

Clinical Importance of CEA and Ferritin in Lung and Breast Cancer

CEA in Breast Carcinoma. Morphological Results in Correlation with Plasma Values

Use of Serum Phosphohexose Isomerase (PHI) and CEA Determinations in Clinical Management of Breast Cancer

Correlation Between CEA Serum Levels and Estrogen Receptors (ER) in Breast Cancer

The 126 KD Phosphoprotein of Human Breast Carcinoma Cell Surface

Pretreatment Serum CEA Level is an Independent Prognostic Factor in Breast and Lung Cancer Patients

Placental Protein 10 (PP10) in Breast Cancer and Genital Carcinoma

Comparison of CEA and SP-1 Tissue Positivity in Human Mammary Carcinomas

Immunoperoxidase Localisation of Ca Antigen in Mammary Tumours

Biochemical and Immunohistochemical Characterization of a Peanut Agglutinin (PNA) Binding Glycoprotein in Normal and Malignant Breast Tissues

Utilization of the GCDFP-15 Protein as a Marker of Breast Carcinomas with Apocrine Features: Clinical and Pathological Findings

Usefulness of the Determination of Phosphohexose Isomerase (PHI) and Carcinoembryonic Antigen (CEA) in the Early Detection of Metastases of Breast Cancer

Serum Tumor Markers in Patients with Primary Breast Cancer and During the Follow-up

B.5.2.2. Gastrointestinal Tumors

Common and Specific Antigens on Two Tumor Cell Lines

Immunological Assay of Serum Ribonuclease as a Marker for Pancreatic Cancer

Tumor Cell Heterogeneity in Primary and Metastatic Colorectal Carcinoma

A General Tumor Marker in Rats which is Recognized by the Hepatic Asialoglycoprotein Receptor

Lung and Gastrointestinal Tumor Cells Secrete Peptide Hormones

Altered Glycoprotein Secretion in Gastrointestinal Malignancy. Its Value in Assessing High Risk Cancer Patients

Do Bile Acid Receptors Exist in Human Colorectal Cancer?

Isolation of Lectin Binding Glycoproteins from Normal and Malignant Gastric Mucosa

B.5.2.3. Reproductive Organs

Immunobiologic Markers in Benign and Malignant Tumours of the Prostate

Possibilities and Limitations of the Immunological Detection of Prostatic Acid Phosphatase

Immunochemical Estimation of PAP

Alkaline Phosphatase (AP) and Gamma-Glutamyl Transpeptidase (GGT) and Isoenzyme Pattern of AP in Patients with Stage III Nonseminomatous Testicular Tumors

Serumferritin in Patients with Nonseminomatous Testicular Tumors

Value of Tumor Marker Determinations in Patients with Ovarian and Uterine Cancer

A Serum Androgen-Binding Protein Distinct from Sex Hormone-Binding Globulin (SHBG) in Patients with Hydatidiform Mole

Tumour Markers in Gynaecological Tumours

Β.5.2.4. Hematological Disorders

B.5.2.4.1. Lymphocytes

Beta-2-Microglobulin in Haematological Malignancy

Modulation of Lymphoproliferative Responses by Cytosol Fraction of Rat Fibrosarcoma

Phosphohexose Isomerase (PHI) Activity in Lymphocyte Cultures from Cancer Patients

AMP-Deaminase and Cytosolic 5'-Nucleotidase Involvement in Lymphocyte Maturation

Detection of DR Antigens on Human Malignant Lymphocytes

B.5.2.4.2. B-Cells and Hairy Cell Leukemia

Increased Sensitivity of Detection of Homogeneous Immunoglobulins in Murine B-Cell Proliferative Disorders with Special Emphasis on the IgA Isotype

Beta2-Microglobulin in Hairy Cell Leukemia. Study in 49 Patients. Effects of Splenectomy

Idiotype Rescue from Hairy Cell Leukemia by Somatic Cell Hybridization

B.5.2.4.3. T-Cells

Neopterin, An Indicator of T-Cell Activation, in Monitoring Neoplasias

The Effect of Low Doses of Prednisolone on T-Cell Subsets in Rheumatoid Arthritis

B.5.2.4.4. Chronic Lymphoid Leukemia

Release of Platelet-Activating Factor (PAF) from Human Leukaemic Cell Lines

Plasma Cyclic Nucleotide Levels in Experimental Leukaemia and Colorectal Cancer

Plasma Fibronectin in Haematological Disorders

Serum Beta-2 Microglobulin in the Follow-up of Chronic Lymphocytic Leukemia

Surface Fucosyl Glycopeptides of High Molecular Weight in Human Lymphocytic Leukemic Cells

B.5.2.4.5. Myeloid Leukemia

Characterization and Monitoring of the Malignant Cells in the Blastic and Chronic Phase of Chronic Myeloid Leukemia

B.5.2.4.6. Myeloma

Separation of Light Chains in Myelomatosis by Fast Protein Liquid Chromatography™

Multiple Myeloma Assessment by Isoelectric Focusing in Patients with Apparently Increased Beta-Globulin on Cellulose Acetate Electrophoresis

B.5.2.5. Various Organs

Expression of a High Molecular Weight Protein of Kidney Tubular Brush Border Membrane in Renal Carcinomas

Modification of Tumor Cell Proliferation and Peptide Hormone Secretion

Transformation-Enhancing Activity Present in the Plasma of Cancer Patients Binds to Gelatin

Antibodies Against B- and Z-DNA in Patients with SLE

B.6. Prognosis

Elevated Levels of Anti-Malignin Antibody are Quantitatively Related to Longer Survival in Cancer Patients

Tumor Burden and its Relationship to Antigen, Size and Composition of Immune Complexes

Utilization of Alpha-1 -Antitrypsin in Staging of Malignant Diseases

B.7. Treatment

Attempts of Treatment of Hepatoma with Antibody to Alpha-Fetoprotein

Section C. Monoclonal Antibodies

C.1. Drug Targeting

Use of Monoclonal Antibody-Intact Ricin Conjugates in Experimental Allogeneic Bone Marrow Transplantation

Application of Monoclonal Antibody 791T/36 for Radioimmunodetection of Human Tumours and for Targeting Cytotoxic Drugs

Suppression of Growth of a Human Colorectal Tumour in Nude Mice by Vindesine-Monoclonal Anti-CEA Conjugates

Monoclonal Anti-Cea Antibodies for Targeting Chlorambucil to Human Colon Carcinoma Cells in Vitro

Drug Targeting with Monoclonal Antibody for Human Hepatomas

Localisation of a Monoclonal Antibody Labelled with Astatine-211 to a Human Heterograft Tumour in Nude Mice

Preparation and Experimentation of an Antidigitalin Monoclonal Antibody: Interest in Human Treatment

C.2. Immunohistochemistry

Immunohistological Distribution of the Antigenic Determinants Recognized by Monoclonal Antibodies Reacting with Carcinoembryonic Antigen

Antigenic Heterogeneity of Human Mammary Carcinoma Cells Defined by Monoclonal Antibodies

Differential Reactivity of Human Macrophage Subsets to MPS — Specific Monoclonal Antibodies KI-M1-4

Immunoenzymatic Identification of Malignant Cells in Serous Effusions Using Monoclonal Antibodies

Use of Monoclonal Antibodies for the Histological Localization of Melanoma Associated Antigens on Fresh Tumor Material

An Immunohistological Study of Skin Tumours

Use of Monoclonal Antibodies to Keratin in Human Tumor Diagnosis

Identification of AA-Type Amyloid in Tissue Sections Using Monoclonal Antibodies

Can We Predict the Biological Behaviour of Carcinoma of the Breast Using Monoclonal Antibodies and Auto-Antibodies?

Monoclonal Antibodies Against Renal Adenocarcinoma: Evaluation of Epitopes in Common with Placental and Fetal Tissue

Production and Role of Monoclonal Antibodies in Transitional Cell Carcinoma of the Bladder

Immunohistological Diagnosis of Brain Tumours Using Monoclonal Antibodies

C.3. Lymphocytes

Phenotypes of Human Native Natural Killer (NK) Cells and MLC-Activated NK-Like Cells

Characterisation of a Subset of OKT8+, OKT10+, OKT3-, HNK-1- Cells with NK Activity in Cord Blood Lymphocytes

Production and Characterization of Murine Monoclonal Antibodies Against Human Β Cell Surface Determinants

Characterization of a New HGPRT (-) Human Β Lymphoid Cell Line

Analysis with Monoclonal Antibodies of Lymphocyte Membrane Functions in Ageing

Detection of B-Lymphocytes in Peripheral Blood and Other Tissues by Immunohistochemical Methods Using Monoclonal, Ia-Like Antigen Specific, Antibodies

Dynamics in Lymphocyte Subsets with Monoclonal Antibodies in Kidney Transplantation

T-Cell Subpopulations in Peripheral Blood and Synovial Fluid in Rheumatic Diseases

Monoclonal Antibodies Raised Against Diaminopeptidase IV (DAP IV) Occurring in Human Τ Lymphocytes and Myofibroblasts

The Use of Monoclonal Antibodies to Detect Lymphocyte T-Cell Subpopulations within the Human Transplanted Heart

A Haemopoietic Precursor Cell Antigen Shared by Both Τ and Β Cells

C.4. CEA

Diagnostic Value of the Monoclonal Antibodies to Antigenic Determinants on CEA Molecule

Determination of Antigenic Determinants on CEA Molecules of Different Tumor Origin by Monoclonal Antibodies

Characterization of Four Monoclonal Antibodies Directed Against Carcino Embryonic Antigen

Affinity Purification of CEA Using an Immobilised Monoclonal Anti-CEA Antibody

Classification of Anti-CEA Monoclonal Antibodies

Determination of Epitope Specificities of Monoclonal Antibodies Against CEA: Use the Avidin-Biotin System

Differences Among Individual CEA Preparations and Carcinomas of Different Origin as Detected by Monoclonal Anti-CEA Antibodies

Anatomo-Pathological Analysis of Human Tumors with 3 Anti CEA (Carcino-Embryonic Antigen) Monoclonal Antibodies

Detection of Carcinoembryonic Antigen in Cancer Serum by Two-Dimensional Gel Electrophoresis

Prognostic Significance of CEA in Gastrointestinal Cancer

In Vivo Correlation of Circulating CEA and Tumor Volume in Patients with Solitary Metastases

Comparison of Serum and Tissue CEA Levels in Lung Cancer

Preliminary Results of Phosphohexose Isomerase (PHI) and Carcinoembryonic Antigen (CEA) in Primary Lung Cancer

Acute Changes of Serum CEA in Patients Undergoing Surgery for a Colorectal Cancer

Tissue Ferritin and CEA Concentrations in Breast Cancers. Comparison with Serum Levels and Immunohistochemistry Results

Evaluation of Beta Glucuronidase, Carcinoembryonic Antigen, Ferritin and Polyamines as Tumor Markers of Central Nervous System

Ultrastructural Localization of Carcinoembryonic Antigen in a Continuous Human Tumour Line (LS 174 Τ) In Relation to Morphometric Investigations

C.5. Various Antigens

In Vivo Distribution of Anti-Human Melanoma Monoclonal Antibodies

Monoclonal Antibodies Against NCA (Non Specific Cross-Reacting Antigen)

Characterization of Monoclonal Antibodies to Bovine Insulin

Monoclonal Antibodies Directed Against Human Low Density Lipoprotein (LDL) and Their Characterization by the Immunodot Technique

Monoclonal Antibody SRB5B1 Recognizes a Ganglioside Antigen Shared by Human Melanoma and Colon Carcinoma Cell Lines

Monoclonal Antibodies Reveal Saccharide Structures as Differentiation and Tumour Associated Antigens of Haematopoeitic and Epithelial Cells of Man and Mouse

Pericellular Glycoproteins Organization in Tumorigenic and Non Tumorigenic Human Cell Hybrids

Immunochemical Analysis of Normal and Neoplastic Human Mammary Antigens Using Monoclonal Antibody LICR-LON-M18 and Peanut Agglutinin

Interchange of Allospecific MHC Class I Peptide Chains with Xenospecific ß2Microglobulin and its Implications for Genetic Restriction

Sweat Glands and Salivary Glands as Model System for the Characterization of Monoclonal Antibodies Against Differentiation Antigens of the Human Mammary Gland

Monoclonal Antibodies Against Human Milkfat Globule Membranes Useful in Carcinoma Research

Monoclonal Antibodies To Human Mammary Carcinoma Cells

Reactions of Monoclonal Antibodies Against Human Milk Fat Globule Membranes with Embryonal Tissue

C.6. Clinical Assays

Monoclonal Antibodies and a Streptavidin-Biotin System Used in an Enzyme Immunoassay for Carcinoembryonic Antigen

Triple Antibody Precipitation for Radioimmunoassays Employing Monoclonal Antibodies, Exemplified by an Assay for hCG

Selection and Characterization of Monoclonal Antibodies Directed Against Human Chorionic Gonadotropin

A Critical Evaluation of a Two-Site Immunoradiometric Assay of Human Prolactin, Using Monoclonal Antibodies

Monoclonal Antibodies Against Human Chorionic Somatomammotropin (hCS or hPL): Production, Immunological Characterization and Immunohistochemical Use in Pathology

Monoclonal Antibodies as Tools for Kidney Damage Diagnosis

Polyclonal or Monoclonal Antibodies in an AFP Assay

Monoclonal Antibodies Against Human Blood Group Antigens

Monoclonal Antibodies Against Some Blood Group Antigens

Use of Monoclonal Antibodies for Precipitin Reactions

Differences Between the Placental and the Testicular Placental-Like Alkaline Phosphatase as Detected by Monoclonal Antibodies

Use of Monoclonal IgG Subclass Antibodies for Characterization of Antibodies from Sera of HBs Vaccinated Individuals

Different Fine Specificities of Human Monoclonal Anti-Gd Cold Agglutinins

A New Screening Technique for IgM Monomers

The Use of Enzyme-Linked Second Antibodies in Immunodiffusion Techniques on Cellulose Acetate Membranes

Monoclonal Antibodies Against Blood Group Antigens

A Lectin Cell Binding Assay

Author Index

Subject Index