This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.

For decades it has been known that structured conformations are important for the proper functioning of most cellular proteins. However, appreciation that protein folding to the functional conformations as well as the structural maintenance of protein molecules are very complex processes has only emerged during the last ten years. The intimate interplay uncovered by this scientific development led us to realize that perturbations of the protein folding process and disturbances of conformational maintenance are major disease mechanisms. This development has given rise to the concept of conformational diseases and the broader signature of protein folding diseases, comprising diseases in which mutations or environmental stresses may result in a partial misfolding that leads then to alternative conformations capable of disturbing cellular processes. This may happen by self-association (aggregation), as in prion and Alzheimer s diseases, or by incorporation of alternatively folded subunits into structural entities, as in collagen diseases. Another possibility is that folding to the native structure is impaired or abolished, resulting in decreased stea- state levels of the correctly folded protein, as is observed in cystic fibrosis and 1-antitrypsin deficiency, as well as in many enzyme deficiencies. In addition, deficiencies of proteins that are engaged in assisting and supervising protein folding (protein quality control) may impair the folding of many other proteins, resulting in pathological phenotypes. Examples of this are the spastic paraplegia attributable to mutations in mitochondrial protease/chaperone complexes."

The Liver in Biology and Disease was conceived as a sequel in the series "Principles of Medical Biology," whose general aim continues to be the integration of human biology and molecular cell biology into modern molecular medicine. It is a volume molded by the Information Revolution which few will deny has forced the teaching faculties in our medical schools to curtail and prune the teaching load and focus on fundamentals and principles. With this intention in mind, a volume of this nature takes into account the close dependence of progress in the medical sciences on bioinformatics (gene and protein analysis) or more precisely, computational biology and of course, the Internet. In general, it follows the pattern of its predecessors.
*Chapters are illustrated with numerous figures and references are current
*Clear, concise and accurate text about a large number of liver diseases
*Describes the liver's histology, biochemistry, and pathology in molecular terms

Mitochondrial cytopathies are mutations in the inherited maternal mitochondrial genome, or the nuclear DNA-mutation. Mitochondrial respiratory chain disorders (RCD) are a group of genetically and clinically heterogeneous diseases, due to the fact that protein components of the respiratory chain are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure and function of mitochondria, including DNA replication, transcription, and translation, all require nuclear encoded genes. Since mitochondria are present in every cell, every tissue, mitochondrial disorder usually affects multiple organs.

Hepatic sinusoidal cells such as sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and pit cells play an important role in hemodynamic and metabolic function and are involved in various liver diseases. The frequent involvement of sinusoidal cells in pathologic conditions is explained by the diverse actions of those cells, an understanding of which is essential to clinicians. Generously illustrated, this volume presents results of recent studies on hepatic sinusoidal cells in liver diseases, with an introduction to the structure and function of the various types of sinusoidal cells. The in-depth focus of the book is on the role of hepatic sinusoidal cells in relation to liver injury and regeneration, hepatic sinusoidal microcirculation, alcoholic liver diseases, hepatic fibrosis, liver tumor, liver transplantation, cholestasis, and congenital lipidosis, thus providing a valuable reference source for practitioners and researchers.

This first edition volume demystifies the complex topic of flow cytometry by providing detailed explanations and nearly 120 figures to help novice flow cytometry users learn and understand the bedrock principles necessary to perform basic flow cytometry experiments correctly. The book divides the topic of flow cytometry into easy to understand sections and covers topics such as the physics behind flow cytometry, flow cytometry lingo, designing flow cytometry experiments and choosing appropriate fluorochromes, compensation, sample preparation and controls and ways to assess cellular function using a variety of flow cytometry assays. Written as a series of chapters whose concepts sequentially build off one another, using the list of materials contained within each section along with the readily reproducible laboratory protocols and tips on troubleshooting that are included, readers should be able to reproduce the data figures presented throughout the book on their way to mastering sound basic flow cytometry techniques. Easy to understand and comprehensive, Flow Cytometry Basics for the Non-Expert will be a valuable resource to novice flow cytometry users as well as experts in other biomedical research fields who need to familiarize themselves with a basic understanding of how to perform flow cytometry and interpret flow cytometry data. This book is written for both scientists and non-scientists in academia, government, biotechnology, and medicine.

This second edition offers 88 chapters divided among three volumes providing the most comprehensive source of know-how in the wide-ranging field of Mitochondrial Medicine. Volume I guides readers through chapters on QSAR models, DQAsomes, synthesis of Triphenylphosphonium Phospholipid Conjugates, testing of novel isomeric mitochondriotropic derivatives, mTRIP, mitochondria-targeted imaging nanoplatforms, live-cell assessment, mitochondrial coenzyme Q10, rat liver Mitochondrial Lipidome, and Mito-SinCe2. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, application details for both the expert and non-expert reader, and tips on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Mitochondrial Medicine, Second Edition, Volume 1: Targeting Mitochondria aims to be a comprehensive source of know-how in the wide-ranging field of Mitochondrial Medicine.

This book discusses the role of oxidative stress in human reproduction with a focus on men's health. The physiological roles of reactive oxygen species (ROS) in male fertility are the focus in this book. This topic is important because oxidative stress is a result of the imbalance between ROS and antioxidants in the body which may lead to sperm damage (DNA or count), deformity, and eventually, male infertility. Therefore, for a better understanding of the molecular mechanisms related to male genotoxicity and its regulation in infertility, this book provides an up-to-date view on the impact of oxidative stress factors in male reproduction . The main aim of this book is to collect a series of research articles and reviews from a diverse group of scientists to share their research work on the role of ROS or oxidative stress in physiological and pathological states in relation to (in)fertility in the male. This book presents various state-of-the-art chapters of the recent progress in the field of cellular toxicology and clinical manifestations of various issues related to men's health and fertility. Topics include cell signaling, DNA damage and infertility, the pathophysiology of disease instigation and distribution, immune toxicity and prevention.

This volume focuses on the investigatory methods applied to autosomal dominant polycystic kidney disease (ADPKD), one of the most common human genetic diseases. ADPKD is caused by mutations in PKD1 and TRPP2, two integral membrane proteins that function as receptor/ion channels in primary cilia of tubular epithelial cells. Thus, ADPKD belongs to ciliopathies, a group of disorders caused by abnormal cilia formation or function. This proposed book will cover the state-of-the-art methods ranging from molecular biology, biochemistry, electrophysiology, to tools in model animal studies. Key Features Explores the role of cilia in polycystic kidney disease Focuses on myriad state-of-the-art methods and techniques Reviews specific mutations integral to this autosomal genetic disease Includes discussions of model systems

This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors.

Cells respond to environmental cues through a complex and dynamic network of signaling pathways that normally maintain a critical balance between cellular proliferation, differentiation, senescence, and death. One current research challenge is to identify those aberrations in signal transd- tion that directly contribute to a loss of this division-limited equilibrium and the progression to malignant transformation. The study of cell-signaling m- ecules in this context is a central component of cancer research. From the knowledge of such targets, investigators have been able to productively advance many insightful hypotheses about how a particular cancer cell may misinterpret, or respond inappropriately to, growth regulatory cues in their environment. Despite these key insights, the rapidly evolving nature of cell signaling research in cancer has necessitated a continuous revision of these theoretical constructs and the updating of methods used in their study. One contemporary example of the evolution of this field is provided by an analysis of the Human Genome Project data, which reveal a previously unsuspected diversity in the multigene families encoding for most signaling pathway int- mediates. In assessing the usefulness of a particular methodological approach, therefore, we will need to keep in mind that there is a premium on those p- tocols that can be easily adapted for the analysis of multiple members within a gene family. Cancer Cell Signaling: Methods and Protocols brings together several such methods in cell signaling research that are scientifically grounded within the cancer biology field.

The function and life span of endothelial cells have a large impact upon the quality and expectancy of an individual's life. During low perfusion, the adaptation of different cells to hypoxia precipitate the aggressive progression of diseases. Although the clinical studies have convincingly shown that endothelial dysfunction occurs whenever the biological functions or bioavailability of nitric oxide are impaired, in all these scenarios, the role of endothelial cell-destructive process cross-talk is yet poorly understood. This book focuses on the contribution of molecular mechanisms to endothelial dysfunction in related metabolic disorders.

Focusing on all the major cytokine families, this reference book provides coverage of cytokine regulatory processes in the lung and other tissues and comprehensive descriptions of cytokine functions specific to the lung.;Discussing the diverse cytokine-binding proteins and the role of cytokines in tissue injury and repair processes and extracellular matrix regulations, the book supplies information on amino acid structure and gene regulatory sequences, examines the receptor biology of individual cytokines, illustrates cytokine interactions with their cognate receptors and surveys the phenotypic effects of individual cytokines on target cells. With over 2700 literature citations and figures, this book is a resource for pulmonologists, physiologists, immunologists, cell and molecular biologists, environmental toxicologists, oncologists, and graduate-level and medical school students in these disciplines.

"...excellent, well-organized, and timely." -Lester Packer and Enrique Cardenas, University of Southern California, Los Angeles, from the Series Preface The liver is a vital organ that is responsible for a wide range of functions, most of which are essential for survival. The multitude of functions the liver performs makes it vulnerable to a wide range of diseases. Mitochondrial dysfunction plays an important role in many liver diseases including drug-induced liver injury, alcoholic liver disease, and nonalcoholic fatty liver disease. Mitochondria in Liver Disease gathers the most current research regarding the role of mitochondria in the liver and various diseases to which it is susceptible. The book is separated into two sections, the first of which highlights the latest developments in mitochondrial research. It includes cutting-edge topics such as the regulation of mitochondrial respiration using hydrogen sulfide and the regulation of mitochondrial fusion-fission via the endoplasmic reticulum. The second section reviews the most current research on the role of mitochondria in a wide range of liver diseases. It also addresses novel topics such as the importance of liver mitochondrial constituents as biomarkers of liver injury in plasma and as regulators of the immune system. Mitochondria in Liver Disease represents the current state of knowledge and research on mitochondrial roles in liver diseases. Written by a group of global experts, it provides an authoritative and comprehensive overview of the latest advances and methods that mark key starting points for future research.

Histopathology of Seed-Borne Infections is the first book to provide comprehensive coverage of seed infection and disease. It includes an up-to-date account on the development and structure of seed, pointing out the structural variations in seeds of the plant families to which most crop plants belong. The text presents techniques and advice for histopathological studies, as well as a discussion on physiogenic seed disorders and the penetration of ovule/seed by fungi. Featuring an extensive bibliography, this book serves as a springboard for further research in seed biology and provides a literature review in a field where it is difficult to access older sources. It will be a valuable resource for seed and plant scientists, plant pathologists, crop scientists, ecologists, and seed chemists, as well as researchers and students involved in seed and plant pathology, seed technology, and agriculture. Features Includes separate chapters on seed-borne microorganisms (fungi, bacteria, viruses, nematodes) and their diseases Covers the penetration of ovule/seed by fungi Discusses physiogenic seed disorders Provides common techniques and tips for histopathological studies

This second edition offers 88 chapters divided among three volumes providing the most comprehensive source of know-how in the wide-ranging field of Mitochondrial Medicine. Volume I guides readers through chapters on QSAR models, DQAsomes, synthesis of Triphenylphosphonium Phospholipid Conjugates, testing of novel isomeric mitochondriotropic derivatives, mTRIP, mitochondria-targeted imaging nanoplatforms, live-cell assessment, mitochondrial coenzyme Q10, rat liver Mitochondrial Lipidome, and Mito-SinCe2. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, application details for both the expert and non-expert reader, and tips on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Mitochondrial Medicine, Second Edition, Volume 1: Targeting Mitochondria aims to be a comprehensive source of know-how in the wide-ranging field of Mitochondrial Medicine.

When cells are damaged, as often occurs during trauma and metabolic stress, a highly evolved cell healing process follows that was designed to enhance cell survival or remove irreparably injured cells. Following injury, cells attempt to seal breaks in their membranes, chaperone removal or refolding of altered proteins, repair damaged DNA, or if necessary commit to programmed cell death.

When cell injury is too extensive to permit reparative responses, acute cellular necrosis or apoptosis can result. Understanding injury at the subcellular organelle and molecular levels is essential for development of new therapeutic strategies and for optimal management of injured victims.

In this volume, various modes of injury that can occur are described, as well as the basic molecular healing responses and pathways of metabolic survival or death. The approach taken here is to look at these processes at the cellular and subcellular levels, rather than at the tissue level, and this volume will be a valuable resource to anyone interested in wound healing, biological stress responses, molecular chaperones, radiobiology, biomechanics, and biomedical engineering, as well as trauma and critical care medicine.

"NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit" "www.blackwellpublishing.com/nyas."

"ACADEMY MEMBERS Please contact the New York Academy of Sciences directly to place your order (""www.nyas.org"). Members of the New York Academy of Science receive full-text access to the Annals online and discounts on print volumes. Please visit http: //www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member.

"...excellent, well-organized, and timely." -Lester Packer and Enrique Cardenas, University of Southern California, Los Angeles, from the Series Preface The liver is a vital organ that is responsible for a wide range of functions, most of which are essential for survival. The multitude of functions the liver performs makes it vulnerable to a wide range of diseases. Mitochondrial dysfunction plays an important role in many liver diseases including drug-induced liver injury, alcoholic liver disease, and nonalcoholic fatty liver disease. Mitochondria in Liver Disease gathers the most current research regarding the role of mitochondria in the liver and various diseases to which it is susceptible. The book is separated into two sections, the first of which highlights the latest developments in mitochondrial research. It includes cutting-edge topics such as the regulation of mitochondrial respiration using hydrogen sulfide and the regulation of mitochondrial fusion-fission via the endoplasmic reticulum. The second section reviews the most current research on the role of mitochondria in a wide range of liver diseases. It also addresses novel topics such as the importance of liver mitochondrial constituents as biomarkers of liver injury in plasma and as regulators of the immune system. Mitochondria in Liver Disease represents the current state of knowledge and research on mitochondrial roles in liver diseases. Written by a group of global experts, it provides an authoritative and comprehensive overview of the latest advances and methods that mark key starting points for future research.

Advances in molecular and genetics based diagnostics are driving an increased interest in cytopathology as cytological specimens are the ideal substrate for this new technology. This book fulfills the need for an easy-to-use and authoritative synopsis of breast cytopathology. The volume fits into the lab coat pocket and is ideal for portability and quick reference. Each volume in the series is heavily illustrated with a full color art program, while the text follows a user-friendly outline format.

The maturation phenomenon, first described by Ito et al. in 1975, refers to postischemic changes that develop hours or days after an ischemic insult. The delayed neuronal death of CA1 pyramidal cells of the hippocampus is a classic example. The report of the phenomenon boosted research in the field, as it became evident that ischemic damage is not a sudden event, but a process potentially susceptible to therapeutic intervention. Since then a growing number of studies have improved our knowledge on mechanisms of cell death and recovery. This volume contains the presentations of the 4th international symposium, held in New Orleans in October/November 1999, grouped in sections covering apoptosis and/or necrosis, neuronal recovery vs. death, and protection against infarction. It outlines the present status of investigations and provides further stimulation for research in this field.

The Maturation Phenomenon, described by Ito et al. in 1975 [3) on the basis of his to logical observations in the hippocampus as well as other portions of the cerebral hemisphere, refers to the hours or days of delay in the development of pathological changes in various parameters of ischemic injury following the restoration of blood flow to the ischemic brain. There is a direct relationship between the intensity of ischemic insult and the speed and rate of maturation of ischemic injury, a lesser intensity being associated with slower and less severe development of the lesions. The delayed neuronal death of CAl pyramidal cells of the hippocampus [8) is a classic example. In the cerebral cortex, with increasing intensity of the ischemic insult, the maturation phenomenon of ischemic injuries intensifies, seamlessly, from less exten sive to more extensive disseminated selective neuronal necrosis (DSNN), and then further to cerebral infarction upon reaching a critical threshold [1,2,4,6,7). We also have found that following ischemic insults just under the threshold level required to induce infarction, only disseminated selective neuronal necrosis (DSNN) progresses, while following ischemic insults at the threshold level, initially only DSNN develops, followed by the evolution of a gradually enlarging infarcted focus [5, 7). The reporting of this phenomenon boosted research in the field, as it became evi dent that ischemic damage is not a sudden event, but a process potentially susceptible to therapeutic intervention.

This volume focuses on the investigatory methods applied to autosomal dominant polycystic kidney disease (ADPKD), one of the most common human genetic diseases. ADPKD is caused by mutations in PKD1 and TRPP2, two integral membrane proteins that function as receptor/ion channels in primary cilia of tubular epithelial cells. Thus, ADPKD belongs to ciliopathies, a group of disorders caused by abnormal cilia formation or function. This proposed book will cover the state-of-the-art methods ranging from molecular biology, biochemistry, electrophysiology, to tools in model animal studies. Key Features Explores the role of cilia in polycystic kidney disease Focuses on myriad state-of-the-art methods and techniques Reviews specific mutations integral to this autosomal genetic disease Includes discussions of model systems

In 1989, the First International Symposium on Cytokines in Hemopoiesis, Oncology, and AIDS was held in Hanover, FRG. Since then there has been an explosion of knowledge in this field. New cytokines have been discovered, on which data are presented in this book, and receptors have already been cloned for many cytokines. In clinical application, some cytokines such as TNF have almost completely left the stage, but this may not be for ever. Enormous progress has been made in the field of hemopoietic growth factors, for which clinical studies from phase I to phase III have been conducted, and some of which have even been registered for routine use. In spite of this rapid development our knowledge of how to clinically exploit the effects of cytokines is very limited and lies far behind the advances made in basic research. Even for the hemopoietic growth factors, questions regarding the effect of adjuvant therapy on survival and or on general outcome in chemother apy have still not been answered. Discussion and exchange between those involved in basic science and clinical research is still urgently needed. We hope to successfully contribute to this process by continuing the series proceedings of the International Symposia on Cytokines in Hemopoiesis, Oncology, and AIDS. Hannover, in July 1992 Mathias Freund Hartmut Link Reinhold E. Schmidt Karl Welte List of Contributors Abbadessa, V. Istituto die Clinica Medica III, Centro Interdipartimenta de Ii Ricerche in Oncologia Clinica, 90100 Palermo, Italy Abecassis, M."

The clinical and experimental effects of cytokines have been realized for a long time. The clinical effects of tumor necrosis factor were noted almost 100 years ago. The basic biological effects of interferons and the hemopoietic growth factors have been known for more than 20 years. Given the basis of modern molecular biotechniques, information concern ing the mediators of cellular interactions is expanding almost exponentially. New principles in the regulation of cell growth, microenvironment, immune response, and malignancy are being discoverd right now. New therapeutic options are becoming available and have, in some areas, already crossed the threshold of clinical application. However, the way forward might be more complicated than we are in a position to recognize today. Some of the first optimistic expectations have not yet been fulfilled. Nevertheless, we are experiencing a revolution in medicine. To contribute to this process and to stimulate scientific communi in this field, we have initiated the international symposia on cytokines cation in hemopoiesis, oncology and aids. Major contributions from the first sym posium are published in this book. We thank all the authors for their contri butions, particularly those from the Hannover Medical School, who have worked hard to realize the congress and prepare these proceedings. We also thank the pharmaceutical companies whose support made this book possible. Finally we thank Professors Deicher, Poliwoda, and Riehm, heads of the Departments of Hematology and Oncology, Immunology, and Pediatric Hematology and Oncology, respectively, who encouraged us and gave us their firm support."

Cytologic diagnosis by examination of exfoliated cells in serous cavity fluids is one of the most challenging areas in clinical cytopathology. Almost 20% of the effusions examined are directly or indirectly related to the presence of malignant disease, with carcinoma of the lung as the most common underlying culprit. This volume published in the Essentials in Cytopathology book series will fulfill the need for an easy-to-use and authoritative synopsis of site specific topics in cytopathology. These guide books fit into the lab coat pocket, ideal for portability and quick reference. Each volume is heavily illustrated with a full color art program, while the text follows a user-friendly outline format.