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Molecular and Cellular Enzymology

Molecular and Cellular Enzymology addresses not only experienced enzymologists but also students, teachers and academic and industrial researchers who are confronted with enzymological problems during their fundamental or applied research. In this field there is an urgent need for training in order to meet the requirements of both research and industrial endeavours. This book consists of several levels. Practical aspects and elementary explanations are given for the benefit of non-specialists’ and students’ understanding. In order to facilitate the task of students, two typographies have been adopted. The main text corresponds to basic knowledge, whereas text in a smaller font provides more specialised information. Specialists will also find topics more deeply expounded with the principal bibliographic references cited. The bibliography, however, is not exhaustive; the choice includes general books and review articles as well as some specialised articles. In this book, for the first time, the different molecular and cellular aspects of enzymology are presented together. Until now, there has been no book available in which these different aspects are treated in the same volume. In addition, besides the theoretical developments, this book provides a wealth of practical information for experimentalists.

Molecular and Cellular Mechanisms in Disease: 1: Bioenergetics · Cell Specificity · Inborn Errors of Metabolism · Malnutrition · Calcium and Phosphorus Iron and Bile Pigments · Coagulopathies · Hormones Body Fluids and Electrolytes

In spite of ingenious experiments, imaginative theories, and unshakable faith in supreme forces, there is no way to know how life began. What is certain is that in the course of the development of the universe existing sources of energy fused to generate atoms, and atoms mingled to become small molecules. At some point by chance or design-according to one's belief, but no one's evidence-small molecules such as hydrogen, oxygen, carbon dioxide, water, and ammonia reacted to yield larger molecules with the property most essential to life: self-replication. Such molecules had to achieve a proper balance between the stability needed for their survival in the environment and the mutability for the generation of many forms of life. How amino acids were created or how DNA, RNA, and proteins developed remains a mystery. But we know that a simple core of nucleic acid embedded in a protein coat made the simplest unit of life (except for viroids). Whether viruses are a primitive or degenerated form of life is not known. Once proteins appeared, their great structural plasticity allowed them to react with other elements such as sulfur, iron, copper, and zinc. After an incalculable number of years, some of the proteins became capable of catalyzing the synthesis of new nucleic acids, new proteins, and other compounds such as polysaccharides and lipids.

Molecular and Cellular Mechanisms of Antibody Activity

This book focuses on the function of antibodies in vivo. Recent years have seen an exponential growth in knowledge about the molecular and cellular mechanisms of antibody activity. These new results dramatically changed our view of how antibodies function in vivo. The importance of this class of molecules is demonstrated by the heightened susceptibility to infections of humans and mice with an altered capacity to generate pathogen specific antibody responses. Thus, the majority of our currently available vaccines, such as vaccines against influenza, measles and hepatitis focus on the generation of long lasting antibody responses. Recent evidence from a variety of in vivo model systems and from human patient cohorts has highlighted the exclusive role of cellular Fc-receptors for certain immunoglobulin isotypes and subclasses. With the recent discovery of a human Fc-receptor for IgM all different human immunoglobulin isotypes now have a cellular receptor, providing a feedback mechanism and link between antibodies and the cellular components of the immune system. Moreover it has become clear the complement and Fc-receptor system are tightly connected and regulate each other to ensure a well balanced immune response. Among the immunoglobulin isotypes IgG plays a very important protective role against microbial infections and also as a therapeutic agent to kill tumor cells or autoantibody producing B cells in autoimmune disease. Transfer of our knowledge about the crucial function of Fc-receptors has led to the production of a second generation of therapeutic antibodies with enhanced binding to this class of receptors. Binding of antibodies to Fc-receptors leads to the recruitment of the potent pro-inflammatory effector functions of cells from the innate immune system. Hence, Fc-receptors link the innate and adaptive immune system, emphasizing the importance of both arms of the immune system and their crosstalk during anti-microbial immune responses. Besides this pro-inflammatory activity immunoglobulin G (IgG) molecules are long known to also have an anti-inflammatory function. This is demonstrated by the use of high dose intravenous immunoglobulins as a therapeutic agent in many human autoimmune diseases. During the past five years several new insights into the molecular and cellular pathways of this anti-inflammatory activity were gained radically changing our view of IgG function in vivo. Several lines of evidence suggest that the sugar moiety attached to the IgG molecule is responsible for these opposing activities and may be seen as a molecular switch enabling the immune system to change IgG function from a pro- to an anti-inflammatory activity. There is convincing evidence in mice and humans that aberrant IgG glycosylation could be an important new pathway for understanding the impaired antibody activity during autoimmune disease. Besides this tremendous increase in basic knowledge about factors influencing immunoglobulin activity the book will also provide insights into how these new insights might help to generate novel therapeutic approaches to enhance IgG activity for tumor therapy on the one hand, and how to block the self-destructive activity of IgG autoantibodies during autoimmune disease on the other hand.

Molecular and Cellular Mechanisms of Cardiovascular Regulation

This volume contains selected papers presented at the Sendai International Sympo­ sium on Molecular and Cellular Mechanisms of Cardiovascular Regulation held from May 10-12, 1995, to honor the contributions ofProfessorNorio Taira, Chairman of the Department of Pharmacology (1972-1995), Tohoku University School of Medicine, Sendai, Japan. The Department of Pharmacology at Sendai has a long tradition of significant contribution to the development of drug therapy for cardiovascular diseases. The late Professor Koroku Hashimoto, the predecessor of Professor Norio Taira, first suggested the mode of action of calcium antagonists and their potential usefulness in therapy of ischemic heart disease and hypertension at an early stage of their development. The need for greater understanding of the pathophysiology of cardiovascular dis­ eases is more critical now than ever before because modern advances in basic and clinical sciences have prolonged the average life expectancy. Using a wide range of molecular and electrophysiological techniques, major advances are occurring frequently in the field of cardiovascular physiology and pharmacology. Such multifaceted approaches are preferred because human cardiovascular diseases are complex, requiring multiple interventions and an in-depth understanding of molecular mechanisms underlying the disease. The first section of this book focuses on molecular mechanisms of ion channel regulation. Eight of ten chapters in this section are devoted to the recent advances in molecular characterization and regulation of various types of potassium channels in cardiac, vascular, and neuronal tissues. A discussion of the structure and function of sodium and calcium channels is also included.

Molecular and Cellular Mechanisms of Neuronal Plasticity: Basic and Clinical Implications (Advances in Experimental Medicine and Biology #446)

Numerous studies have proven the biological basis of memory formation and have begun to identify the biochemical traces and cellular circuits that are formed by experience, and which participate int the storage of information in the brain, its retention for long durations, and its retrieval upon demand. Cells in the nervous system have the capability of undergoing extremely long-lasting alterations in response to hormonal, pharmacological, and environmental stimulations. The mechanisms underlying this neuronal plasticity are activated by experiential inputs and operate in the process of learning and the formation of memories in the brain. This volume presents research areas which have not been highlighted in the past. In addition to studies on the involement of functional proteins in neuronal adaptation, this volume presents recent developments on the critical roles of bioactive lipids and nucleotides in these processes. In addition to the widely studied role of second messengers, a review of studies on extracellular phosphorylation systems operating on the surface of brain neurons is presented.The first section of the volume presents studies of basic mechanisms operating in a wide range of adaptive processes. The second section presents recent advances in investigations that have demonstrated the clinical implications of this research. These include: state of the art use of transgenic models in studies of molecular and cellular mechanisms implicated in familial Alzheimer's disease and Amyotrophic Lateral Sclerosis; studies of specific proteins implicated in Alzheimer's disease, including an adapter that binds to the beta-amyloid precurser protein (beta-APP) and the microtubular protein Tau and its membrane-bound counterpart. The advantages of using cell culture models for elucidating the causes of neuronal degeneration and for identifying mechanisms of neuroprotection are also presented among the chapters in the section on clinical implications.

Molecular and Cellular Mechanobiology (Physiology in Health and Disease)

This book will cover the cutting-edge developments in molecular and cellular mechanobiology to date. Readers will have a clear understanding of mechanobiology at the molecular and cellular levels, encompassing the mechanosensors, transducers, and transcription. An integrative approach across different scales from molecular sensing to mechanotransduction and gene modulation for physiological regulation of cellular functions will be explored, as well as applications to pathophysiological states in disease. A comprehensive understanding of the roles of physicochemical microenvironment and intracellular responses in determining cellular function in health and disease will also be discussed.

Molecular and Cellular Pediatric Endocrinology (Contemporary Endocrinology #10)

Stuart Handwerger, MD and a distinguished panel of clinicians and experts review the most significant recent developments in molecular and cellular biology, powerful advances that have produced new diagnostic methods and improved treatments for many pediatric endocrine diseases. Topics range from the growth hormone/prolactin/placental lactogen gene family and their regulation of growth, to steroid hormones, sexual development, and mineral corticoid action. Additional chapters examine the pathophysiology of insulin-dependent diabetes mellitus, the molecular genetics of thyroid cancer, the molecular basis of hypophosphatemic rickets, and inherited diabetes insipidus. Molecular and Cellular Pediatric Endocrinology offers today's clinicians and researchers not only the latest findings on endocrine diseases in their pediatric manifestations, but also highly practical insights into today's cutting-edge diagnostics, treatment strategies, and powerful new therapeutics.

Molecular and Cellular Signaling (Biological and Medical Physics, Biomedical Engineering)

Makes connections between diseases, drugs and signaling in those chapters not specifically devoted to pathogens. Reviews background in first 5 chapters then offers chapters on cancers and apoptosis and on bacteria and viruses. Signaling in the immune, endocrine (hormonal) and nervous systems covered along with cancer, apoptosis and gene regulation. Each chapter ends with a problem section to facilitate discussion.

Molecular and Cellular Toxicology: An Introduction

Toxicology is the study of the adverse effects of chemical, physical, or biological agents on people, animals, and the environment. Toxicologists are trained to investigate, interpret, and communicate the nature of those effects. Over the last ten years the subject of toxicology has changed dramatically, moving from a discipline which was once firmly wedded to traditional methods to one which is keen to embrace the innovative techniques emerging from the developing fields of cell culture and molecular biology. There is an acute need for this to be reflected in a paradigm shift which takes advantage of the opportunities offered by modern developments in the life sciences, including new in vitro and in silico approaches, alternative whole organism (non-mammalian) models and the exploitation of ‘omics methods, high throughput screening (HTS) techniques and molecular imaging technologies. This concise, accessible introduction to the field includes the very latest concepts and methodologies. It provides MSc, PhD and final year undergraduate students in pharmacy, biomedical and life sciences, as well as individuals starting out in the cosmetics, consumer products, pharmaceutical and testing industries, with everything they need to know to get to grips with the fast moving field of toxicology and the current approaches used in the risk assessment of drugs and chemicals.

Molecular and Cellular Toxicology: An Introduction

Toxicology is the study of the adverse effects of chemical, physical, or biological agents on people, animals, and the environment. Toxicologists are trained to investigate, interpret, and communicate the nature of those effects. Over the last ten years the subject of toxicology has changed dramatically, moving from a discipline which was once firmly wedded to traditional methods to one which is keen to embrace the innovative techniques emerging from the developing fields of cell culture and molecular biology. There is an acute need for this to be reflected in a paradigm shift which takes advantage of the opportunities offered by modern developments in the life sciences, including new in vitro and in silico approaches, alternative whole organism (non-mammalian) models and the exploitation of ‘omics methods, high throughput screening (HTS) techniques and molecular imaging technologies. This concise, accessible introduction to the field includes the very latest concepts and methodologies. It provides MSc, PhD and final year undergraduate students in pharmacy, biomedical and life sciences, as well as individuals starting out in the cosmetics, consumer products, pharmaceutical and testing industries, with everything they need to know to get to grips with the fast moving field of toxicology and the current approaches used in the risk assessment of drugs and chemicals.

Molecular and Clinical Advances in Anticancer Drug Resistance: Advances In Molecular And Clinical Research (Cancer Treatment and Research #57)

The importance of drug resistance in cancer chemotherapy cannot be over­ stated. The 500,000 patients who die every year from cancer in the United States have, in most cases, been treated with chemotherapy. Many of these patients responded initially to chemotherapy, but death resulted from the development of drug-resistant tumors. In the first volume in the series. Drug Resistance in Chemotherapy the results of comprehensive laboratory studies aimed at understanding the mechanisms for resistance to individual agents and to the development of broad cross-resistance were described. In the past 2 years there has been substantial progress in understanding the molecular biology associated with these mechanisms of drug resistance. For the first time we are starting to understand which mechanisms are playing an im­ portant role in human tumors, and even more importantly, clinical trials have recently been initiated in an effort to reverse specific forms of drug resistance. The purpose of this volume is to describe the new advances, both at the molecular level and in the clinic regarding mechanisms of drug resistance and potential ways this resistance can be circumvented. This volume is focused upon mechanisms of resistance associated with two major classes of anticancer drugs: alkylating agents (including cisplatin) and the natural products (e. g. , adriamycin and vinblastine). The first section of the book describes new insights into the genetic mechanisms associated with drug resistance.

The Molecular and Clinical Pathology of Neurodegenerative Disease

The Molecular and Clinical Pathology of Neurodegenerative Disease brings together in one volume our current understanding of the molecular basis of neurodegeneration in humans, targeted at neuroscientists and graduate students in neuroscience, and the biomedical and biological sciences. Bringing together up-to-date molecular biology data with clinical evidence, this book sheds a light on common molecular mechanisms that underlie many different neurodegenerative diseases and addresses the molecular pathologies in each. The combined research and clinical background of the authors provides a unique perspective in relating clinical experiences with the molecular understanding needed to examine these diseases and is a must-read for anyone who wants to learn more about neurodegeneration. - Provides an up-to-date summary of neurodegeneration at a molecular, cellular, and tissue level for the most common human disorders - Describes the clinical background and underlying molecular processes for Alzheimer's disease, Parkinson's, Prion, Motor Neuron, Huntington's, and Multiple Sclerosis - Highlights the state-of-the-art treatment options for each disorder - Details examples of relevant cutting edge experimental systems, including genome editing and human pluripotent stem cell-derived neuronal models

Molecular and Functional Insights Into the Pulmonary Vasculature (Advances in Anatomy, Embryology and Cell Biology #228)

This book provides a comprehensive review of the structure, function and pathophysiology of the pulmonary vasculature. Emerging evidence reveals the multifaceted roles played by the pulmonary vasculature. To reflect those roles, the individual chapters address topics ranging from pulmonary blood vessel development to vascular endothelial apoptosis, and delve deeply into our current understanding of various aspects of the pulmonary vasculature.

Molecular and Functional Models in Neuropsychiatry (Current Topics in Behavioral Neurosciences #7)

The development of more effective treatments for neuropsychiatric disorders requires scientific progress on a broad front. Animal models have a vital role to play in advancing the field. When deployed in conjunction with detailed study of these diseases in man they bring the power to make controlled experimental interventions which allow the functional consequences of genetic variations and polymorphisms to be understood in terms of their cellular, systems and behavioural effects. Further, they provide a means by which complex cognitive and behavioural phenomena may be dissected and understood. Finally, they provide a bridge to understanding the effects of drugs on the functioning of the central nervous system, thereby improving our understanding of the actions of those drugs in man.

Molecular and Genetic Basis of Renal Disease E-Book: A Companion to Brenner and Rector's The Kidney

This companion to Brenner and Rector's The Kidney offers a state-of-the-art summary of the most recent advances in renal genetics. Molecular and Genetic Basis for Renal Disease provides the nephrologist with a comprehensive look at modern investigative tools in nephrology research today, and reviews the molecular pathophysiology of the nephron as well as the most common genetic and acquired renal diseases. A comprehensive clinical review of Medelian renal disease is also be included.Detailed review of the molecular anatomy and pathophysiology of the nephron that provides relevant basic science to consider when diagnosing and managing patients with these disorders.

Molecular and Multimodality Imaging in Cardiovascular Disease

This book provides the most up-to-date coverage of the combined use of imaging modalities in order to acquire important functional and morphological information on cardiovascular disease and enhance disease detection. The recent developments in PET/MRI, cardiac CT, PET/CT and SPECT/CT and their impact on clinical practice are explained and special attention is also devoted to imaging parameters and protocols for use in practice and research. The utility of multimodality imaging techniques for diagnosis and evaluation is discussed in the context of various clinical scenarios, including ischemic cardiomyopathy, myocarditis, myocardial fibrosis, cardiac sarcoidosis and atherosclerotic plaque disease. Written by renowned researchers and clinicians, the book is an ideal concise reference on today’s most advanced imaging techniques. It will appeal to all clinicians, trainees and technicians who are involved in the diagnosis and risk assessment of cardiovascular disease.

Molecular and Physiological Mechanisms of Muscle Contraction

Thoroughly researched using experimentation and re-examination of all previously published evidence, Molecular and Physiological Mechanisms of Muscle Contraction is a carefully crafted treatise and revision of previous conceptions of muscle contraction. It presents detailed descriptions of new, previously unpublished data and hybrids recent finding

Molecular and Structural Archaeology: Cosmetic and Therapeutic Chemicals (NATO Science Series II: Mathematics, Physics and Chemistry #117)

This book delineates the contours of molecular and structural archaeology as an emergent interdisciplinary field based on structural analysis at the molecular level and examines novel methodologies to reconstruct the synthesis and long-term transformation of materials used in antiquity. The focus of this volume is on cosmetic and therapeutic materials.

Molecular and Therapeutic actions of Thymoquinone: Actions of Thymoquinone

Throughout history black seeds, Nigella sativa seeds, have been highly revered for its medicinal properties. Thymoquinone (TQ), an active principle component of the volatile oil of black cumin seeds, is an emerging natural compound with a wide range of medical applications, and has several beneficial pharmacological actions i.e anti-oxidant, anti-diabetic, anti-inflammatory, anti-microbial, anti-tumor, anti-mutagenic, anti-epileptic, hepatoprotective, neuroprotective, and nephroprotective. As such, it is important to move TQ from the bench to bedside. This book illustrates the therapeutic importance of TQ, offering a detailed account of some of its molecular and therapeutic properties, and discussing in depth its anti-diabetic, anti-cancer, anti-oxidant, anti-inflammatory, anti-microbial, anti-epileptic and hepatoprotective actions. Lastly, the book examines the future prospects of TQ research and its use as a pharmaceutical.

Molecular and Translational Vascular Medicine (Molecular and Translational Medicine)

Molecular and Translational Vascular Medicine will serve as a state-of-the-art resource for physicians and translational medical researchers alike who are interested in the rapidly evolving field of vascular medicine. The text provides new insight into the basic mechanisms of classic vascular pathophysiologic processes like angiogenesis, atherosclerosis, thrombosis, and vasculitis. Furthermore, it covers new areas of investigation including the role of the ubiquitin proteasome system in vascular disease, endothelial progenitor cells for disease treatment, and the genetic basis of thoracic aortic aneurysms. Lastly, this volume includes sections on the newly emerging field of therapeutic angiogenesis, and the developing technology of nanoparticle-based imaging and therapeutic treatment of the diseased vasculature. All chapters are written by established experts in their fields, including pathologists, cardiovascular surgeons, and internists as well as translational biomedical researchers in a wide range of disciplines. While comprehensive, the material is presented in a manner that simplifies the complex pathophysiologic mechanisms that underlie common vascular diseases. Molecular and Translational Vascular Medicine will be of great value to a broad audience including internists, cardiovascular and vascular surgeons, pathologists, residents and fellows, as well as translational biomedical researchers.

Molecular Applications in Cytology

This book is intended for practicing pathologists and cytopathologists, as well as for pathology trainees and cytotechnicians. It starts with a detailed description of the extremely important pre-analytical phase for molecular testing followed by a presentation of the key tests and their application in different organs, e.g. the lung or thyroid. Step-by-step instructions for the different assays, reporting and clinical integration of the test results are discussed. The authors help the reader to benefit from their experiences by providing a valuable tool for the implementation of these techniques in daily practice.Though the use of molecular techniques is well established in surgical biopsies, to date they are not widely used in connection with cytological material. However, in some fields like lung cancer or aspirates from the pancreas and biliary tract the only available material for diagnosis is the cytological preparation a fact that has created a need for the standardization of molecular techniques on cytology.

Molecular Approaches to Ecology and Evolution

Four years ago we edited a volume of 36 papers entitled Molecular Approaches to Ecology and Evolution (Schierwater et ai. , 1994), in which we attempted to put to­ gether a diverse array of papers that demonstrated the impact that the technologi­ cal revolution ofmolecular biology has had on the field ofevolutionary biologyand ecology. The present volume borrows from that theme but attempts to focus more sharply on the impact that molecular biology has had on our understanding of dif­ ferent hierarchical levels important in evolutionary and ecological studies. Because DNA sequence variation is at the heart ofeverypaper in the present volume, we feel it necessary to examine how DNA has affected study at various levels of biological organization. The majority of the chapters in the present volume follow themes es­ tablished in the earlier volume; all chapters by authors in the previous volume are either fully updated or entirely new and expand into areas that we felt were impor­ tant for a more complete understanding of the impact of DNA technology on ecol­ ogy and evolution. The collection of papers in this volume cover a diverse array of ecological and evolutionary questions and demonstrates the breadth of coverage molecular tech­ nology has imparted on modern evolutionary biology. There are also a broad range of hierarchical questions approached by the 17 papers in this volume.

Molecular Approaches to Heart Failure Therapy

G. HASENFUSS, E. MARBAN Heart failure embodies the central irony of modern medicine. As we have become increasingly adept at treating the major proximate causes of death in Western society, we have effectively converted acute illness into chronic malady. The last twenty years have witnessed a revolution in the treatment of acute coronary syndromes, myocardial infarction in particular. Patients who reach the hospital now have every expectation of leaving alive, but not necessarily well. Our ability to blunt the edge of ischemic insults has en­ gendered new problems: a new cohort of patients whose hearts function well enough to enable short-term survival, but at the cost of decreased ex­ ercise tolerance, dyspnea and increased long-term mortality. The irony is compounded by our increasingly sophisticated pharmacopeia for the treat­ ment of heart failure, which, by slowing the progression of ventricular dys­ function, has created a chronic illness. The fact of its chronicity makes heart failure no less deadly. In symptomatic patients, mortality exceeds 5-10% per year even with the best contemporary therapy. Not all heart failure is ischemic, of course, but the final common phenotype is eerily concordant regardless of the proximate cause. No wonder, then, that heart failure is the leading cause of hospitalization in America and in Western Europe and that the prevalence of the disease continues to rise. Drugs have indeed revolutionized heart failure therapy, ACE inhibitors and beta-adrenergic blockers having the most outstanding records to date.

Molecular Aspects of Anti-cancer Drug Action (Topics in Molecular and Structural Biology)

Molecular Aspects of Botulinum Neurotoxin (Current Topics in Neurotoxicity #4)

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation with a focus on clinical application. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.