A major direction in medical research leading to clinical applications targets the regulation of intracellular calcium and the various human diseases associated with an altered homeostasis of this global second messenger. These diseases include, for example: cardiomyopathy, inflammation, brain disorders, diabetes and cancer. In Calcium-Binding Proteins and RAGE: from Structural Basics to Clinical Applications,expert researchers in the field detail many of the methods which are now commonly used to study calcium binding proteins. These methods and techniques, such as calcium-measurements, screening methods, clinical chemistry, and therapy, are generally applicable to many other areas of basic and medical research as well as to diagnostics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical,Calcium-Binding Proteins and RAGE: from Structural Basics to Clinical Applications underlines the diagnostic and clinical importance of this family of proteins in human diseases and as drug targets.

Claus W. Heizmann and Katharina Braun ore than 10,000 articles were published in 1994 on calcium, M 2 emphasizing the widespread interest and progress in Ca +- 2 related research. This book focuses mainly on Ca + -binding pro- 2 teins in the central nervous system, where Ca + ions have been found to activate fundamental processes such as release of neu- rotransmitters, axonal flow, long term potentiation, cell motility, differentiation, secretion, and apoptosis. It has also been found that a number of neurodegenerative disorders have been attributed 2 1 to aberrations of intracellular Ca + homeostasis. 2 2 Intracellular Ca + levels and Ca + signaling within cells must 2 3 2 be tightly controlled. * Ca + overload as a result of seizures or ischemia is supposed to activate biochemical processes, leading to enzymatic breakdown of proteins and lipids, malfunctioning of 2 mitochondria, energy failure and ultimately cell death. There is 3 experimental evidence that electrically induced irreversible depo- larization of hippocampal neurons, which may be an early indica- 2 tion of neuronal damage, could be prevented by injecting Ca + chelators and thereby increasing intracellular buffering capacity. Thus, it is reasonable to assume that neurons containing certain 2 intracellular Ca +-binding proteins, and therefore having a greater 2 capacity to buffer Ca +, could be more resistant to degeneration.

A major direction in medical research leading to clinical applications targets the regulation of intracellular calcium and the various human diseases associated with an altered homeostasis of this global second messenger. These diseases include, for example: cardiomyopathy, inflammation, brain disorders, diabetes and cancer. In Calcium-Binding Proteins and RAGE: from Structural Basics to Clinical Applications,expert researchers in the field detail many of the methods which are now commonly used to study calcium binding proteins. These methods and techniques, such as calcium-measurements, screening methods, clinical chemistry, and therapy, are generally applicable to many other areas of basic and medical research as well as to diagnostics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical,Calcium-Binding Proteins and RAGE: from Structural Basics to Clinical Applications underlines the diagnostic and clinical importance of this family of proteins in human diseases and as drug targets.

The First European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells was held at the Faculty of Medicine of the "Universit6 Libre de Bruxelles" in Brussels, Belgium, April 20-22, 1989. Delegates from seventeen countries attended. This Symposium was initiated through an EEC Stimulation Program. The formal program included forty verbal presentations by invited speakers and sixty miniposter presentations, and was formulated by the Organizing and Scientific Committee: E. Carmeliet (Leuven), J. P. Collin (Poitiers), S. Forsen (Lund), C. W. Heizmann (Ziirich), D. E. M. Lawson (Cambridge), P. Miroir (Brussels), J. L. Pasteels (Brussels) and R. Pochet (Brussels). This volume contains the papers prepared by the invited speakers. The contributions are grouped according to their general subject matter: Genes of Calcium-Binding Protein Family, Structure/Function Relationships, The Cytoskeleton and Calcium-Binding Proteins, Calcium-Binding Proteins in TransforlIled Cells, Calcium/Lipid-Binding Proteins, Calcium-Binding Proteins Substrates and Immunohistochemistry of Calbindin and Calretinin. The highlights of the symposium are numerous. Among the items to be noted are the growing number of abundant proteins which interact with calcium and sometimes with other second messenger sys- tems; specifically pH associated with the tyrosine kinase calpactin, calcYclin, p9Ka induced by growth fac- tors, MRP-8 and MRP-14 (also called cystic fibrosis antigen, L1 or calgranulins) forming half the soluble protein of granulocytes. New structure/function relationships on calbindin D9K and calmodulin have emerged from nuclear magnetic resonance and site-directed mutagenesis studies.

A wide variety of hormones, neurotransmitters and growth factors exert their cellular effects by reacting first with membrane receptors resulting in an increase of intracellular calcium and the cellular response. The calcium signal in the cell is mediated by the high-affinity calcium binding proteins (characterized by the EF-hand structural element), and by the calcium and phospholipid dependent proteins. Many of these have been discovered most recently. Their purification, distribution, protein and gene structures as well as their physiological roles are discussed. The book is of interest to biochemists and molecular biologists as well as to clinicians and the pharmaceutical industry who can apply the results in this field.

The enormous and varied role of calcium in living systems is now widely appreciated by both cell biologists and clinicians. The identification and characterisation of new calcium binding proteins and regulatory pathways is matched by the recognition of the involvement of calcium binding proteins in a growing number of disease states. This book is intended to introduce clinicians to fundamental biological research, whilst at the same time attracting researchers to the clinical world. The publication of the book coincides with the elucidation of the complete Human Genomic Sequence. As a result of this, scientists now have access to an unprecedented array of data, from which new calcium binding proteins and hence new regulatory pathways will undoubtedly be discovered. It is a further aim of this book to provide a key' to open the door to the new postgenomic era. The book is in three parts. The first section introduces the reader to the role of calcium in cell biology, providing an appreciation of how this small, simple, non-metabolisable agent can move rapidly and silently through the different cellular compartments, thereby influencing and controlling the fate of the cell. This section also illustrates and dissects the often-complex interplay between calcium and numerous agents in muscle and endocrine cells, neurons, hepatocytes, and platelets. In the second section the reader will discover the role of calcium and its partners in common diseases such as migraine and drug dependence. New classes of diseases such as annexinopathies, channelopathies, calcium-sensing disorders, and citrullinemia are discussed, and the authors give many new insights into the molecular mechanisms of the diseases, thereby explaining how and why they occur. Such information is clearly of primary importance for the pharmaceutical industry. New ideas and concepts of neurodegenerative diseases are introduced, which should stimulate new approaches. Clinicians will also have access, in a comprehensive and authoritative yet highly readable chapter, to data from recent large-scale clinical studies on the numerous and widely prescribed calcium antagonists. The final section gives information on new methods and devices for calcium imaging, and illustrates how calcium movement and change can be monitored and ingeniously utilised as a fast, cheap, and accurate drug screening instrument.

The enormous and varied role of calcium in living systems is now widely appreciated by both cell biologists and clinicians. The identification and characterisation of new calcium binding proteins and regulatory pathways is matched by the recognition of the involvement of calcium binding proteins in a growing number of disease states. This book is intended to introduce clinicians to fundamental biological research, whilst at the same time attracting researchers to the clinical world. The publication of the book coincides with the elucidation of the complete Human Genomic Sequence. As a result of this, scientists now have access to an unprecedented array of data, from which new calcium binding proteins and hence new regulatory pathways will undoubtedly be discovered. It is a further aim of this book to provide a key' to open the door to the new postgenomic era. The book is in three parts. The first section introduces the reader to the role of calcium in cell biology, providing an appreciation of how this small, simple, non-metabolisable agent can move rapidly and silently through the different cellular compartments, thereby influencing and controlling the fate of the cell. This section also illustrates and dissects the often-complex interplay between calcium and numerous agents in muscle and endocrine cells, neurons, hepatocytes, and platelets. In the second section the reader will discover the role of calcium and its partners in common diseases such as migraine and drug dependence. New classes of diseases such as annexinopathies, channelopathies, calcium-sensing disorders, and citrullinemia are discussed, and the authors give many new insights into the molecular mechanisms of the diseases, thereby explaining how and why they occur. Such information is clearly of primary importance for the pharmaceutical industry. New ideas and concepts of neurodegenerative diseases are introduced, which should stimulate new approaches. Clinicians will also have access, in a comprehensive and authoritative yet highly readable chapter, to data from recent large-scale clinical studies on the numerous and widely prescribed calcium antagonists. The final section gives information on new methods and devices for calcium imaging, and illustrates how calcium movement and change can be monitored and ingeniously utilised as a fast, cheap, and accurate drug screening instrument.

This detailed volume explores protocols for studying the many facets of Ca2+-imaging, Ca2+-signaling, and Ca2+-binding along with background information on the principles and application of these techniques. The content of the book delves into 48 chapters including subjects such as data analysis and modern technologies to study calcium-binding and signaling in cells, the superfamily of calcium-binding proteins characterized by the EF-hand structural motif, as well as their use as diagnostic and prognostic biomarkers in Laboratory Medicine and novel therapeutic drug targets. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and comprehensive, Calcium-Binding Proteins of the EF-Hand Superfamily: From Basics to Medical Applications presents state-of-the-art, lab-based methods and easy-to-follow protocols for daily use, making it interesting for basic and medical researchers, cell- and molecular biologists, clinicians, clinical chemists, and the diagnostic industry.