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Introduction: Serpins: From the Way It Was to the Way It Is; J. Travis. Serpins: A Mechanistic Class of Their Own; S.R. Stone, et al. Coagulation: Antithrombin-A Bloody Important Serpin; I. Björk, S.T. Olson. Heparin Cofactor II; D.M. Tollefsen. Neurobiology and Cancer: Regulation of Neurons and Astrocytes by Thrombin and Protease Nexin-l: Relationship to Brain Injury; D.D. Cunningham, F.M. Donovan. Maspin: A Tumor Suppressing Serpin; R. Sager, et al.. Fibrinolysis: The Role of Reactive-Center Loop Mobility in the Serpin Inhibitory Mechanism; D.A. Lawrence. Substrate Specificity of Tissue Type Plasminogen Activator; E.L. Madison. Development and Reproduction: Biology of Progesterone-Induced Uterine Serpins; P.J. Hansen, W.-J. Liu. Serpins from an Insect, Manduca sexta; M.R. Kanost, H. Jiang. Inflammation: Serpins and Programmed Cell Death; G.S. Salvesen. Noninhibitor Serpins: Structure-Function Studies on PEDF: A Noninhibitory Serpin with Neurotropic Activity; S.P. Becerra. Abstracts: Coagulation, Neurobiology and Cancer. Fibrinolysis, Development and Reproduction. Inflammation and Noninhibitor Serpins. 10 Additional Articles. Index.

The present volume contains the edited transcript of a Totts Gap Colloquium held May 19-21, 1980 sponsored by the Muscular Dystrophy Association. The aim of the colloquium was to bring into focus data relating to cell membranes that might contribute to understanding the pathogenic mechanism of Duchenne muscular dystrophy. A major impediment to progress in understanding the patho­ genesis of muscular dystrophy has been the failure, so far, to identify the basic genetic defect. Pending the identification of the genetic lesion in Duchenne dystrophy and, in view of scattered but persistent indications of a basic membrane disturbance, it seemed worthwhile to explore in open dialogue the current state of knowledge of membrane morphology and chemistry with an eye to possible leads for further investigation. The participants, drawn from a variety of interested disciplines, attempted to synthesize and reconcile their findings and to identify crucial areas of ignorance in need of exploration. For the most part they avoided specialized jargon and spoke in a language that could be understood by the rest of the group. Apart from providing a review of widely varying approaches to the study of the composition and behavior of cell membranes, the discussions brought together current think~g on strategies and approaches to the study of the pathogenesis of muscular dystrophy. Already the personal contacts made at the colloquium have led to new inter-institutional collabora­ tive investigations.

This book gathers relatively recent and significant topics in the field of ion channel research. Ion channels form the molecular basis for membrane excitability in cells present in the cardiovascular and nervous systems. In many non-excitable cells, ion channels contribute to diverse physiological functions, including the secretion of signaling compounds like hormones and insulin, cell volume regulation, intracellular signaling, especially Ca2+ signaling, etc. Many human diseases have been attributed to abnormal channel functions and defective membrane expression of channel proteins. On the other hand, ion channels are excellent models for studying protein biophysics, especially the allosteric regulation of protein function by miscellaneous stimuli. Therefore, research on ion channels carries significant meaning for the understanding of basic protein biophysics and diverse physiological functions. Such vital information also assists in developing novel and effective treatments for related human diseases. This book provides graduates and scientists in both basic and clinical levels a comprehensive understanding of cutting-edge advances and a useful and stimulating platform for tackling their own questions about ion channels.

Flavonoids in the Living System: An Introduction; J.A.Manthey, B.S. Buslig. Flavonoids and Arbucular-Mycorrhizal Fungi; H. Vierheilig, et al the Role of Glycosylation in Flavonol-Induced Pollen Germination; L.P. Taylor, et al. Expression of Genes for Enzymes of the Flavonoid Biosynthetic Pathway in the Early Stages of the Rhizobium-Legume Symbiosis; H.I. McKhann, et al. Prospects for the Metabolic Engineering of Bioactive Flavonoids and Related Phenylpropanoid Compounds; R.A. Dixon, et al. Flavonoid Accumulation in Tissue and Cell Culture; Studies in Citrus and other Plant Species; M.A. Berhow. Flavonoids of the Orange Subfamily Aurantioideae; J.A. Manthey, K. Grohmann. Citrus Flavonoids: A Review of Past Biological Activity Against Disease: Discovery of New Flavonoids from Dancy Tangerine Cold Pressed Peel Oil Solids and Leaves; A. Montanari, et al. Differentiation of Soy Sauce Types by HPLC Profile Pattern Recognition: Isolation of Novel Isoflavones; E. Kinoshita, et al. Induction of Oxidative Stress by Redox Active Flavonoids; W.F. Hodnick, et al. Flavonoids in Foods as in Vitro and in Vivo Antioxidants; J.A. Vinson. 7 Additional Chapters. Index.

Cellular Mechanisms Involved in the Modulation of the Immune System by Drugs of Abuse; S.L. Chang, et al. Immunomodulation of Macrophage Functions by Opioids; R. Gomez-Flores, R.J. Weber. Morphine Accelerates the Progression of Sepsis in an Experimental Sepsis Model; S. Roy, et al. Morphine Depresses Macrophage Numbers and Function in Mouse Spleens; T.K. Eisenstein, et al. Morphine Depresses Macrophage Numbers and Function in Mouse Spleens; T.K. Eisenstein, et al. Centrally-Mediated Opioid-Induced Immunosupression: Elucidation of Sympathetic Nervous System Involvement; W.J. Brinkman, et al. The Expression of Interleukin-1beta Converting Enzyme (ICE) in Rat is Decreased Following Chronic Exposure to Morphine; Gao-de Wu, et al. Opioid Receptor Gene Expression in the Porcine Immune System; M.S. Pampusch, et al. The Effects of Interaction Between Morphine and Interleukin-1 on the Immune Response; S.L. Chang, et al. Morphine Alters the Immune Response to Influenza Virus Infection in Lewis Rats; M.E. Coussons-Read, et al. Orphan Opioid Receptor Oligonucleotide Inhibit HIV-1 Expression in Human Brain Cells; C.C. Chao, et al. Opiate Effects on in Vitro Human Retroviral Infection; S.B.Nyland, et al. FIV: A Lentivirus Model for Opiate Effects on Disease; J.-N. Billaud, T.R. Phillips. 21 Additional Articles. Index.

Session I: Left Ventricular Hypertrophy: Structural Aspects and Mechanisms.- 1. Relations of Left Ventricular Geometry and Function to Prognosis in Hypertension.- 2. Left Ventricular Hypertrophy, Arterial Compliance, and Aging.- 3. Left Ventricular Hypertrophy and Arterial Blood Pressure in Experimental Models of Hypertension.- 4. Regulation and Role of Myocardial Collagen Matrix Remodeling in Hypertensive Heart Disease.- 5. Ultrasonic Reflectivity of the Heart: A Measure of Fibrosis?.- 6. Local Angiotensin II and Myocardial Fibrosis.- 7. Left Ventricular Anatomy and Function in Primary Aldosteronism and Renovascular Hypertension.- Session II: Pathophysiological and Molecular Aspects.- 8. Hypertension Differentially Affects the Expression of the Gap Junction Protein Connexin43 in Cardiac Myocytes and Aortic Smooth Muscle Cells.- 9. Modulation of Cardiac Hypertrophy by Estrogens.- 10. Salt Sensitivity and Left Ventricular Hypertrophy.- 11. Volume Overload, Atrial Natriuretic Peptide, and Left Ventricular Hypertrophy.- 12. The Renin-Angiotensin System Gene Polymorphism and Left Ventricular Hypertrophy.- 13. Renin-Angiotensin System Gene Polymorphisms and Left Ventricular Hypertrophy: The Case against an Association.- Session III: Pathophysiological and Therapeutic Aspects.- 14. Left Ventricular Hypertrophy and Arterial Hypertrophy.- 15. Relationship between Cardiac Hypertrophy and Microalbuminuria.- 16. Physiological versus Pathological Hypertrophy: The Athlete and the Hypertensive.- 17. Bradykinin and Cardiac Protection.- 18. Left Ventricular Hypertrophy and Sympathetic Activity.- 19. Hypertension, Left Ventricular Hypertrophy, and Heart Rate Variability.- 20. Comparison of Meta-Analyses of Therapeutic Studies on Regression of Left Ventricular Hypertrophy.- 21. Comparison of Therapeutic Studies on Regression of Left Ventricular Hypertrophy.- 22. Prognostic Significance of Left Ventricular Hypertrophy Regression.- Session IV: Myocardial Ischemia.- 23. Hypertension and Coronary Microvascular Disease.- 24. Myocardial Perfusion in Hypertensive Patients with Normal Coronary Arteries.- 25. Endothelial Dysfunction in Hypertension.- 26. Endothelial Dysfunction in Hypertensives: An Uncertain Association.- 27. Hypertension, Left Ventricular Hypertrophy, and Coronary Flow Reserve.- 28. Hypertensive Heart Disease, Ventricular Dysrhythmias, and Sudden Death.- 29. Hypertension and Heart Failure.- Speakers.

General Aspects: Nutritionally Related Disorders/Diseases in Africans: Highlights of Half A Century of Research, with Special Reference to Unexpected Phenomena; A.R.P. Walker. The Evolving Epidemiology of Fiber & Heart Disease; C. Humble. Complex Carbohydrates: Overview on Complex Carbohydrates; J. De Vries. Dietary Guidelines and Complex Carbohydrates; B. Schneeman. Soluble Fiber: Soluble Fiber and Hypertension; J.M. Keenan. Soluble Fiber and Energy Regulation: Current Knowledge and Future Directions; S. Roberts. Short Chain Fatty Acids: Butyrate and the Colonocyte: Production, Absorption, Metabolism and Nutrient Utilization; M.J. McBurney. Nutrients Contributing to the Fiber Effect: Resistant Starch-An Update on Its Physiological Effects; N.G. Asp. Health Benefits of Non-Digestible Oligosaccharides; M. Roberfroid. Fiber and Disease: Fiber and Cancer Protection: Mechanisms; D. Klurfeld. Dietary Fiber & Bile Acid Metabolism-An Update; J.A. Story. Workshop Reports: Dietary Guidelines/RDA/Daily Value; B. Schneeman. Soluble Dietary Fiber; J. Marlett. 19 Additional Articles. Index.

Human Reproduction-The Missing Parts of the Puzzle; B.P. Setchell. Genes, Chromosomes and Fertility: Human Y Chromosome Deletions in Yq11 and Male Fertility; P.H. Vogt. Frequency of Y-Chromosome Microdeletions; (Yq11.22-23) in Men with Reduced Sperm Quality Requesting Assisted Reproduction; A. Bonhoff, et al. Germ Cell Differentiation and Tumorigenesis: Endocrine Control of Germ Cell Proliferation in the Primate Testis: What Do We Really Know?; G.F. Weinbauer, E. Nieschlag. The Role of the Testicular Accessory Cells: Molecular Pathophysiology of the Pituitary-Gonadal Axis; M. Simoni, et al. Compartmentalization, Vascularization and Angiogenesis: Compartmentalization of the Intertubular Space in the Human Testis; A.F. Holstein, M. Davidoff. Post-Testicular Sperm Maturation: The Role of Apocrine Released Proteins in the Post-Testicular Regulation of Human Sperm Function; G. Aumüller, et al. Control of the Male and Female Tracts: Interactions Between Leukocytes and the Male Reproductive System: The Unanswered Question; A.G. Rossi, R.J. Aitken. Gamete Interaction and Fertilization: The Cell Biology of Fertilization; R.J. Aitken. 45 Additional Articles. Index.

Brain Tryptophan Perturbation in Hepatic Encephalopathy: Implications for Effects by Neuropsychoactive Drugs in Clinical Practice; F. Bengtsson, et al. Hepatic Encephalopathy in Acute Liver Failure: Role of the Glutamate System; A. Michalak, et al. Glutamate and Muscarinic Receptors in the Molecular Mechanisms of Acute Ammonia Toxicity and of Its Prevention; M.D. Miñana, et al. Studies on the Pharmacological Properties of Oxindole (2-Hydroxyindole) and 5-Hydroxyindole: Are They Involved in Hepatic Encephalopathy?; F. Moroni, et al. The Involvement of Ammonia with the Mechanisms That Enhance GABA-ergic Neurotransmission in Hepatic Failure; E.A. Jones, A.S. Basile. Direct Enhancement of GABA-ergic Neurotransmission by Ammonia; J.-H. Ha, et al. The Peripheral Benzodiazepine Receptor and Neurosteroids in Hepatic Encephalopathy; M.D. Norenberg, et al. Ornithine Aminotransferase as a Therapeutic Target in Hyperammonemias; N. Seiler. Sparse-Fur (spf) Mouse as a Model of Hyperammonemia: Alterations in the Neurotransmitter Systems; I.A. Qureshi, K.V.R. Rao. Abnormal Gene Expression Causing Hyperammonemia in Carnitine-Deficient Juvenile Visceral Steatosis (JVS) Mice; T. Saheki, et al. 7 Additional Articles. Index.

Introduction. Mono(ADP-ribosyl)Transferases and Related Enzymes: Emerging Gene Families; F. Koch-Nolte, F. Haag. Mono-ADP-ribosylation in Prokaryotes. Crystal Structure of Diphtheria Toxin Bound to Nicotinamide Adenine Dinucleotide; C.E. Bell, D. Eisenberg. Molecular Approaches to Eukaryotic Mono(ADP-ribosyl)Transferases. Sequence and Structural Links Between Distant ADp-ribosyltransferase Families; F. Bazan, F. Koch-Nolte. Moni(ADP-ribosyl)Transferases in the Immune System. Regulation of Cytotoxic T Cell Functions by a GPI-anchored Ecto-ADP-ribosyltransferase; J. Wang, et al. Mono-ADP-ribosylation in Other Animal Tissues. An ADP-Ribosyltransferase from Bovine Erythrocytes Apparently Specific for Cysteine Residues; S. van Heyningen, B. Saxty. Physiology of GPI-Anchored Proteins. Cell Surface Dynamics of GPI-anchored Proteins; F.R. Maxfield, S. Mayor. Relationship of ADP-Ribosyltransferases to NAD+ Glycohydrolases and ADP-ribosyl Cyclases. ADp-Ribose in Glycation and Glycoxidation Reactions; E.L. Jacobson, et al. Special Lecture Commemorating the Retirement of Professor Heinz-Günter Thiele. Appendix. 28 Additional Lectures. 24 Poster Reports. Index.

Historical Perspectives. Morphology of Chemoreceptors. Re-Examination of the Carotid body Ultrastructure with Paying Attention to the Intercellular Membrane Apposition; H. Kondo, H. Iwasa. Biochemistry of Chemoreceptor Mechanisms. Developmental Aspects of Chemoreceptors. Mechanisms of Carotid Chemoreceptor Resetting After Birth: in vitro Studies; J.L. Carroll, et al. Biophysics of Ionic Channels in Chemoreceptors. Molecular Biology of Chemoreceptors. Evaluation of Gene Expression in the Rat Carotid Body Using the Differential Display Technique; J. Chen, et al. Generation of Chemosensory Activity. transmitters Involved in Chemoreception: Acetylcholine. Release of Acetylcholine from the in vitro Cat Carotid Body; R.S. Fitzgerald, M. Shirahata. Transmitters Involved in Chemoreception: Catecholamines. Dopamine Efflux from the Carotid Body During Hypoxic Stimulation; P. Zapata, et al. Transmiters Involved in Chemoreception: Adenosine and Peptides. Transmitters Involved in Chemoreception: Carbon Monoxide and Nitric Oxide. Chemoreflex Pathways. Coherence of Chemosensor Discharges in Catas' Carotid Nerves. Cooperative Inputs or Redundant Afferences?; J. Alcayaga, et al. Chemoreceptors in Ventilatory Regulation. Chemoreflex Integration and Effectors. 65 Additional Articles. Index.

Molecular Mechanisms of Sarcolemar Excitability: Ion Channels and Pumps in Cardiac Function; H.A. Fozzard, G. Lipkind Molecular Mechanisms of K+ Channel Blockade: 4Aminopyridine Interaction with a Cloned Cardiac Transient K+(Kv1.4) Channel; R.L. Rasmusson Integrative Models and Responses in Cardiac Ischemia; S. Horner, M.J. Lab Intracellular Calcium and Muscle Function-SR and Filaments: Sarcomere Function and Crossbridge Cycling; H.E.D.J. ter Keurs Crossbridge Dynamics in Muscle Contraction; A. Landesberg, et al. Mechanisms of the Frank-Starling Phenomena Studies in Intact Hearts; D. Burkhoff, et al. Molecular Manifestations of Cell Adaptation: Metabolic Oscillations in Heart Cells; B. O'Rourke, et al. Regulation of Adenosine Receptors in Cultured Heart Cells; D. ElAni, et al. Ventricular Remodeling in Heart Failure: The Role of Myocardial Collagen; J.S. Janicki, et al. Analysis and Modeling: From Microstructure to Macroperformance: Mechanisms of Endocardial Endothelium Modulation of Myocardial Performance; P. Mohan, et al. Vascular Gene Therapy; M.Y. Flugelman Closure: Toward Modeling the Human Physionome; J.B. Bassingthwaighte 20 additional articles. Index.

Dendritic Cells: Origin and Differentiation: Thymic Dendritic Cells: Surface Phenotype, Developmental Origin, and Function; K. Shortman, et al. Dendritic Cells: Phenotype: Functional CD40 Antigen on B Cells, Dendritic Cells and Fibroblasts; J. Banchereau, et al. Dendritic Cells: Antigen Processing Presentation, Cell Migration: Establishment and Characterization of Antigenpresenting Cell Lines (XS Series) Derived from Newborn Mouse Epidermis; A. Takashima, et al. Follicular Dendritic Cells: Origin, Phenotype, and Maturation: Multiple Lines of Evidence Favoring a Bone Marrow Derivation of Follicular Dendritic Cells (FDCs); A.K. Szakal, et al. Follicular Dendritic Cells: Function: Germinal Center T Cells: Analysis of Their Proliferative Capacity; F. Bouzahzah, et al. Dendritic Cells: Lymphocyte Interactions: Dendritic Cells as Stimulator Cells of MHC Class Irestricted Immune Responses; A. Elbe, G. Stingl Dendritic Cell and HIV: Mechanisms of Retrovirallyinduced Immunosupression Acting via Dendritic Cells; S.C. Knight Dendritic Cells in Transplantation, Allergy, and Oncology: Early Events in Contact Sensitivity; S.I. Katz, et al. 117 additional articles. Index.

Perspective of Neurochemistry in Neurological Disorders.- Selegiline Induces "Trophic-Like" Rescue of Dying Neurons without Mao Inhibition.- Aliphatic Propargylamines, a New Series of Potent Selective, Irreversible Non-Amphetamine-Like MAO-B Inhibitors.- Medical Treatment of Parkinson's Disease.- Neuropharmacological Effects of (-)-Stepholidine and Its Analogues on Brain Dopaminergic System.- Neurotoxicity of MPTP and Uptake of MPPT into Dopamine and Norepinephrine Neurons in Mice.- Linopirdine.- Differential Changes in Regional Brain Ganglioside and Neutral Glycosphingolipid Contents in Alzheimer's Disease.- Action of Organophosphate Anticholinesterases on the Three Conformational States of Nicotinic Receptor.- Purification and Characterization of a Novel Neurotoxin-Kappa Bungarotoxin.- Development of Antidepressant Drugs.- The Identification of Heterogeneity of 5-HT Receptors with [H]Rs-42358-197.- Advances in Clinical Research on Common Mental Disorders with Computer Controlled Electro-Acupuncture Treatment.- The Importance of Glutamate Receptors in Brain Ischemia.- Biochemical Study of the Postischemic Neuronal Damage.- Effects of Ilexonin A on Circulatory Neuroregulation.- Study on Cerebrovascular Disease of the Elderly in China.- Cellular Physiology of Epileptogenic Phenomena.- The Clinical Pharmacology of Antiepileptic Drugs.- Hemodynamic Actions of Huatuo Reconstruction Pill on Anesthetized Animals.- Treatment of Affective Disorders.- Studies of Diagnosis and Pathogenesis of Wilson's Disease.- Evidence for Presynaptic Damage in Myasthenia Gravis.

Calcium Homeostasis: Calcium Homeostasis in Skeletal Muscle; E. Ríos. Calcium Ion Fluxes across Plasma Membranes; G. Vassort. Presynaptic Nerve Function: Biochemical Aspects of Presynaptic Function; F. Valtorta, et al. Biophysical Aspects of Presynaptic Activity; R. Fesce. Nervous Control of Muscle Function: Low Molecular Weight Neurotransmitters; M.Z. Wrona, G. Dryhurst. The Electrochemical Signal Transmission by the Acetylcholine Receptor: Single Channel Conductance Events and Oligochannels; E. Neumann, T. Schürholz. Nervous Control of Cardia Function: Modulation of Pacemaker Activity; D. Di Francesco. Excitation-Contraction Coupling: Excitation-Contraction Coupling in Skeletal Muscle; E. Ríos, et al. Muscle Contraction: Contractile Protein Isoforms in Sarcomeric Muscle: Distribution, Function and Control of Gene Expression; S. Schiaffino, P. Moretti. Thermodynamics of Irreversible Processes: Thermodynamics of Irreversible Processes Applied to Biological Systems: A General Survey; D. Walz. 7 additional articles. Index.

Session I.- Breast Mucin and Associated Antigens in Diagnosis and Therapy.- Peptide Epitopes in Breast Cancer Mucins.- Does a Novel Form of the Breast Cancer Marker Protein, MUC1, Act as a Receptor Molecule that Modulates Signal Transduction?.- Cancer Metastasis Determined by Carbohydrate-Mediated Cell Adhesion.- Experimental Immunotherapy of Breast Cancer Using Alpha Interferon Conjugated to Monoclonal Antibody Mc5.- Circulating and Tissue Markers in the Longitudinal Management of Breast Cancer Patients.- Session II.- Engineering of Antibodies for Breast Cancer Therapy: Construction of Chimeric and Humanized Versions of the Murine Monoclonal Antibody BrE-3.- Humanization of an Anti-Mucin Antibody for Breast and Ovarian Cancer Therapy.- Towards an Immunotherapy for p185HER2 Overexpressing Tumors.- Session III.- Branching N-Linked Oligosaccharides in Breast Cancer.- Specificity of the IgG Response in Mice and Human Breast Cancer Patients Following Immunization Against Synthetic Sialyl-Tn, an Epitope with Possible Functional Significance in Metastasis.- Vaccination Against Breast Cancer - Studies in an Animal Model.- Anti-Idiotype Antibodies as Potential Therapeutic Agents for Human Breast Cancer.- The Simultaneous Expression of c-erbB-2 Oncoprotein and Laminin Receptor on Primary Breast Tumors has a Predicting Potential Analogous to that of the Lymph Node Status.- Multivariate Prognostic Model for Infiltrating Ductal Carcinoma of the Breast in the Axillary Node-Free Patient.- The Use of Monoclonal Antibody Immunoconjugates in Cancer Therapy.- Radioimmunolocalization of Breast Cancer Using BrE-3 Monoclonal Antibody.- Suppression of Human Anti-Mouse Antibody Response to Murine Monoclonal Antibody L6 by Deoxyspergualin: A Phase I Study.- Overview of Radioimmunotherapy in Advanced Breast Cancer Using 1-131 Chimeric L6.- Contributors.

Mechanistic Approaches to Antimutagenesis and Anticarcinogenesis: Multiple Mechanisms; L.M. De Luca. Inhibition of Mutagenesis and Carcinogenesis by Extracellular Mechanisms: Inhibition of Nitrosation; H. Bartsch, et al. Modulation of Metabolism and Blocking of Reactive Species: Organ-Specific Modification of Carcinogenesis by Antitoxidants in Rats; M. Hirose, et al. Modulation of DNA Repair and Control of Gene Expression: Molecular Control of Human Papillomavirus RNA Expression in Neoplasia; J.A. DiPaolo, C.H. Woodworth. Mechanisms of Inhibition of Tumor Promotion, Progression, Invasion, and Metastasis: Mechanisms of Inhibition of Tumor Progression; B.S. Warren, T.J. Slaga. Prospects in Chemoprevention of Mutation and Cancer: Dietary Inhibitors Against Mutagenesis and Carcinogenesis; H. Hayatsu, et al. 35 additional articles. Index.