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This book, now in an extensively revised second edition, describes the crucial role of zinc signaling in biological processes on a molecular and physiological basis. Global leaders in the field review the latest knowledge, including the very significant advances in understanding that have been achieved since publication of the first edition. Detailed information is provided on all the essentials of zinc signaling, covering molecular aspects and the roles of zinc transporters, the zinc sensing receptor, and metallothioneins. Detection techniques for zinc signals, involving genetically encoded and chemical probes, are also described. The critical contributions of the zinc signal in maintaining health and the adverse consequences of any imbalance in the signal are then thoroughly addressed. Here, readers will find up-to-date information on the significance of the zinc signal in a wide range of conditions, including cardiovascular disorders, neurodegenerative diseases, diabetes, autoimmune diseases, inflammatory conditions, skin disease, osteoarthritis, and cancer. The book will be of value for researchers, clinicians, and advanced students.

In 1858, Drs. Henry Gray and Henry Vandyke Carter created a book for their surgical colleagues that established an enduring standard among anatomical texts. After more than 150 years of continuous publication, Gray's Anatomy remains the definitive, comprehensive reference on the subject, offering ready access to the information you need to ensure safe, effective practice. This 41st edition has been meticulously revised and updated throughout, reflecting the very latest understanding of clinical anatomy from field leaders around the world. The book's traditional lavish art programme and clear text have been further honed and enhanced, while major advances in imaging techniques and the new insights they bring are fully captured in new state-of-the-art X-ray, CT, MR, and ultrasonic images. Presents the most detailed and dependable coverage of anatomy available anywhere. Regional organization collects all relevant material on each body area together in one place, making access to core information easier for clinical readers. Anatomical information is matched with key clinical information where relevant. Numerous clinical discussions emphasize considerations that may affect medical care. Each chapter has been edited by experts in their field, ensuring access to the very latest evidence-based information on that topic. More than 1,000 completely new photographs, including an extensive electronic collection of the latest X-ray, CT, MR, and histological images. The downloadable Expert Consult eBook version included with your purchase allows you to search all of the text, figures, references and videos from the book on a variety of devices. Carefully selected electronic enhancements include additional text, tables, illustrations, labelled imaging and videos – as well as 24 specially invited ‘Commentaries'on new and emerging topics related to anatomy.

Pathobiology of Human Disease bridges traditional morphologic and clinical pathology, molecular pathology, and the underlying basic science fields of cell biology, genetics, and molecular biology, which have opened up a new era of research in pathology and underlie the molecular basis of human disease. The work spans more than 48 different biological and medical fields, in five basic sections: Human Organ Systems Molecular Pathology/Basic Mechanisms of Diseases Animal Models/Other Model Systems Experimental Pathology Clinical Pathology Each article provides a comprehensive overview of the selected topic to inform a broad spectrum of readers from research professionals to advanced undergraduate students. Reviews quantitative advances in the imaging and molecular analysis of human tissue, new microarray technologies for analysis of genetic and chromosomal alterations in normal and diseased cells and tissues, and new transgenic models of human disease using conditional, tissue-specific gene targeting Articles link through to relevant virtual microscopy slides, illustrating side-by-side presentation of'Normal'and'Disease'anatomy and histology images Fully-annotated with many supplementary full color images, graphs, tables, and video files linked to data sets and to live references, enabling researchers to delve deeper and visualize solutions

Die Orthologie und Pathologie des Wachstums und der Differenzierung waren schon Gegenstand des 1955 erschienenen Bandes VI!I dieses Handbuches. Seine von Biologen und Pathologen verfaßten Kapitel stützten sieh auf die Ergebnisse der klassischen Morphologie. Die morphologischen Probleme des Wachstums standen dabei ganz im Mittelpunkt. Mit der systematischen Anwendung biochemischer Methoden, der Histo­ autoradiographie zur Markierung der Reduplikationsphase der DNS sowie der RNS- und Protein-Synthese, der Cytophotometrie zur quantitativen Messung der Nueleinsäuren und schließlich der elektronenmikroskopischen Cytologie standen in der Erforschung der Orthologie und Pathologie des Wachstums seit einem.Jahrzehnt Methoden von vorher ungeahnter Aussagekraft zur Vel'fügung. So wird jeder, der sich in den vorliegenden Band vertieft, feststellen, daß der Einsatz dieser Methoden zu einer stürmischen Entfaltung der Erforschung von Wachstum und Differenzierung geführt hat. In der Konfrontierung dieses Bandes mit dem 1955 erschienenen wird er zugleich voller Respekt erkennen, wievieles schon in der klassischen Biologie und Pathologie zu diesem Thema grundgelegt war und bis heute fortwirkt. Im ersten Beitrag des vorliegenden Bandes vermittelt R. SCH1NDLER-Bern einen Überblick über'die Biochemie der Regeneration'. Er berichtet über Struktur und Synthese der DNS, deren Störungen durch chemische Faktoren und strahlende Energie, erörtert die RNS-Synthese sowie die Synthese der Proteine und ihre Störungen. Ausführlich stellt er dann die Regulation und den Ablauf der biochemischen Vorgänge während der Regenerationsprozesse am Beispiel der Oberflächenepithelien, der Zellkulturen und bei der Leberregeneration dar und behandelt schließlich die Frage nach denProliferations-auslösenden bio­ chemischen Faktoren.

Zur Biologie und Pathologie der Zelle wurde im Handbuch der Allgemeinen Pathologie 1955 ein erster Band mit dem Thema'Das Cytoplasma'veroffent­ licht. Die Beitrage dieses Bandes waren im wesentlichen Ende 1953 abgeschlossen. So haben sie noch einmal alles das an Ergebnissen und Fragestellungen in ihrer Darstellung und der herangezogenen Literatur gesammelt, was die klassische Orthologie und Pathologie der Zelle in der Epoche der Lichtmikroskopie erarbeitet hatte. Sie haben damit die GroBe dieser Epoche in einem geschichtlichen Wende­ punkt der Zellforschung eindrucksvoll bezeugt. Die Absicht der Herausgeber dieses Handbuches, dem ersten Teilband iiber die Biologie und Pathologie der Zelle alsbald weitere Bande folgen zu lassen, erwies sich allerdings als unerfiillbar. Die Biochemie stand in der Phase, in der sich die Methoden der Isolierung von Zellorganellen aus Gewebshomogenaten mehr und mehr durchsetzten und verfeinerten, und in der sich Zug um Zug die Frage nach den diesen Organellen zugeordneten Stoffen und Prozessen stellte und loste.

Bradykinin is frequently referred to as an elusive substance; the editor of a comprehensive volume dealing with kinins thus has a difficult task. The com­ plexity of the issues calls for a large number of contributors who approach the topics from the various angles that are dictated by the sometimes divergent views of the individuals. The editor saw no reason to prescribe the mode of presentation, which was left to the authors and accounts for the variety of approaches. Contributors from nine countries were asked to participate in the volume. The chapters were organized to present, first, the history of the discoveries and methods of approach to kinin research. Then follows a discussion of the enzymes that release kinins, their substrates, and other enzymes that inactivate the peptides. If the release of kinin is important, then the inhibition of the releasing enzymes is of obvious interest and is described. Since the measurement of kinin­ ogen levels in blood has been frequently used as an indicator of kinin liberation, in addition to a separate chapter, kininogens are also mentioned where the functions of kinins are discussed. The conclusions drawn from establishing structure-action relationships for many analogs and the actions of kinins are indicated and summarized.

The first oral contraceptive became available in 1960 and since then these sub­ stances, which have been used by millions of women, have probably been the most widely studied group of drugs in medical history (Drill, 1966, 1977). Part of the evaluation oCoral contraceptives has involved their effect on the reproductive organs of women, with particular attention directed to evaluation of a possible carcinogenic effect of these steroids. To the extent that cancer of the reproductive organs is a common finding in women, the endogenous female sex hormones have been implicated in the occur­ rence of the cancer. The administration of estrogen has also been reported to in­ crease the incidence of cancer of the breast, cervix or endometrium in some strains or species of animals. Thus, because of the possible tumorigenic effect of estrogens there has been considerable interest in the relationship of oral contraceptives to cancer of the breast and genital tract.

In the previous study (Part I) a description was given of the ultrastructural changes occurring during indirect Wallerian degeneration in the intramedullary root fibre region of the kitten hypoglossal nerve. One of the striking features of this degeneration process was the appearance at an early stage of micro­ glial cells completely covered by myelin, which apparently participated in phago­ cytosis of degenerating axoplasm and to a small extent of their own myelin covering. Evidence was obtained indicating that the numerous degenerating glial cells seen somewhat later in the degeneration process were derived from these myelin-covered microglial cells. Since glial cells of the type described in the previous study have never been implicated in the process of direct Wallerian degeneration, the possibility exists that they may in fact be characteristic for indirect Wallerian degeneration. However, this possibility cannot be adequately assessed unless our present rather scanty knowledge concerning the early glial reaction during direct Wallerian degeneration is extended. Therefore the present study has been undertaken to examine the ultrastructural changes during direct W allerian degeneration in the kitten, with particular reference to the possible occurrence of myelin-covered microglial cells and degenerating glial cells of the type described in the previous study (see Part I). Since no systematic ultra­ structural study on direct Wallerian degeneration in immature animals seem to exist, observations on changes in the myelinated nerve fibres and the different types of glial cells have been included.

(Ergänzung zu Band 5/2)

The progressive changes which occur during the life history of an individual metazoon are summed up under the term development. The adult multicellular organism differs from its early developmental stages by its size, shape, proportions, and by its parts having gradually acquired different structural and functional properties. Accordingly, several main processes involved in development, whose classification is a matter of convention, may be delimitated. Differentiation is considered one of the most important of them. In the broader sense of the word, the term differentiation is used for describing transformations, through which heterogeneity-at all levels (macroscopic, microscopic, submicroscopic)-arises or increases. The basic component of the wider phenomenon of differentiation is differentiation of cells, so-called cytodifferentiation. What is cytodifferentiation? In the course of ontogeny, the cells, starting with the fertilized ovum, via the blastomeres of the segmenting ovum and the germ layer cells, right to the differentiating and fully differentiated cells of tissues and organs, gradually acquire new properties which make them different both from a morphological and functional point of view. All changes involved in this process come under the term cytodifferentiation. Differentiation of cells (though not of all kinds of cells) continues throughout the entire life of the individual, but reaches its maximum at the embryonic period when it becomes the chief feature of development.

The major cause of death in the Western world is some form of vascular disease; and principal among these forms is atherosclerotic heart disease (ASHD). Although much is known about the etiology and treatment of ASHD, there is, as yet, no specific means of prognosis of an impending coronary episode. There are, however, several indications of susceptibility to coronary disease, generally known as risk factors, the foremost of which is hyperlipidemia. Hyperlipidemia is more commonly designated as hypercholesteremia or triglyceridemia, depending upon which moiety is elevated, but since lipids are transported in the blood as members of a lipoprotein complex, the most descriptive general term would be hyperlipoproteinemia. This volume represents an effort to elucidate the origins and metabolic behavior of lipoproteins and their components, to describe aspects of the morphology, biochemistry and experimental induction of ASHD, and to describe modalities of treatment. The contributions to this book include descriptions of cholesterol synthesis and metabolism, as well as the metabolism of bile acids, the principal products of cholesterol metabolism. There are also chapters on the mechanisms of hyperlipidemia and on lipoprotein metabolism. The induction of experimental atherosclerosis and the aortic structural changes caused by this disease are discussed.

When STIEVE published his work on male reproductive organs in this handbook in 1930, a definitive treatment of the morphology of the accessory sex glands seemed accomplished. Nevertheless, the increasing bulk of scientific literature published in the last years on this topic has demonstrated that new methods, e. g., developments in the fields of electron microscopy, cytochemistry and auto­ radiography, pose new questions. These principally morphological techniques have yielded new insights into the fine structure and functional organization of these glands. The stress, however, lay on biochemical questions concerning the mechanism of hormone action, since the accessory sex glands were considered to be primary target organs of hormone action, i. e., their cells bind specific hormones. Besides the basic interest of endocrinologists, morphologists, and biochemists, several unanswered questions arose from the practitioners, e. g., urologists, andrologists, and other clinicians, especially as regards the prostate gland, one of the organs most affected in elderly men. Thus, the epidemiologic investigations of the last years proved this very organ to be one of the most frequent causes of death in elderly men (HANSEN, 1977). The view of the practi­ tioner established a special field of investigation and effected a shift from morphologic analysis to biochemical or endocrine aspects. Nevertheless, mor­ phology, if tempered by experimental or concomitant biochemical studies, pro­ vides a solid base for tracing the pathologic events occurring in these organs.

To lose is human, to win is fortune, but to try is our destiny. EARL C. SUITOR, JR. The idea of a Symposium on'Arthropod Cell Cultures'started in July of 1969 shortly after the untimely death of our colleague, EARL C. SUITOR, JR., at the age of 38. At first we thought an afternoon or evening session would be sufficient, but we were soon convinced that the scope of the Symposium should be greatly enlarged. Interest in this topic was increasing at an astonishing rate. Since EARL SUITOR had made a distinct imprint in this new field, many scientists who knew him well or just casually wished to honor him in this manner. EARL SUITOR was born and raised in New England and received a B. S. degree in bacteriology from the University of Massachusetts in 1952. As a spirited young man, he enlisted in the U. S. Navy to see the world. Instead, he was assigned for most of his four-year'hitch'to the Naval Medical Research Institute. I met him there in 1954, an enthusiastic and imaginative young fellow with many interests, an avid reader of the classics, an occasional writer of poetry, who blended his interest in scientific literature with that of Science Fiction. In 1956, EARL left the Navy to attend George Washington University, where he earned an M. S. degree in 1958 and a Ph. D. degree in 1963.

connective tissues are essential for the physical functioning of the animals's body. The condition of the various connective tissues is governed by biochemical factors, anabolism and catabolism, that are controlled by specific enzymes. Any change outside the normal range of metabolism, for instance induced by immunological reactions, may induce a pathological disturbance. The result can be acute or chronic inflammation, or loss of normal function, expressed in loosening, dilatation, breaking, wear, stiffness, shrinking, scars, stenosis, and cirrhosis or any other kind of fibrosis. A first step toward improving our understanding of the feedback mecha­ nism that maintains the biological status and texture of a given connective tissue is to combine what is known about synthesis and enzymatic degradation of the components of fibers and ground substance. Common pathological phenomena like chronic inflammation of immune reactions can be either the result of the cause of disturbances in the sensitive balance of connective tissue metabolism. Nowadays con­ nective tissues are less and less regarded as brady trophic tissue but rather as a stimulating and many-sided problem of research. Before we can understand the pathogenesis of the connective tissue diseases that result in the destructive processes mentioned above, basic research will be necessary. This research will be furthered by a constant exchange of information and the results of· observations. To promote this exchange of information between scientists, symposia on connective tissue research are organized at regular intervals.

The First International Symposium on the Metabolic Interconversion of Enzymes was held in Santa Margherita Ligure, Italy, in May, 1970, under the direction of Professor G. Bonsignore. Because of rapid developments in this field, a second Symposium was organized a year and a half later in Rottach-Egern, Germany (October, 1971) by Professors E. He1mreich, H. Holzer and O. Wieland. At that time, so much new information had accumulated that it was decided to repeat such conferences approx­ imately every other year; the United States was chosen as the next site. This publi­ cation reports the Proceedings of the Third International Symposium on the Metabolic Interconversion of Enzymes held at the Battelle Seattle Research Center, Seattle, Washington, June 5 - 8, 1973. The conferences were originally designed to examine the control of metabolic reactions by covalent modification of certain key enzymes. Covalent, as opposed to allosteric or metabolic, regulation had first been recognized some fifteen years be­ fore. Initially thought to represent an added sophistication in regulatory processes possibly reserved to higher organisms, covalent regulation has now been found in both prokaryotes and eukaryotes. Those early studies in covalent modification revealed for the first time the existence of special'converter'enzymes whose purpose in life is to switch other molecules from one state of activity to another.

At the 6th International Conference on Plant Growth Substances, held in Carleton University, Ottawa in 1968, it was decided that the 7th should be held in Czecho­ slovakia, following an invitation by Dr. Kutacek. Historical events intervened and in 1969 another venue was sought. An offer from the Academy of Science in Canberra was accepted by the steering committee. This left rather less time than is desirable to organize an international meeting of this nature and it was with surprise and great relief that the Organizing Committee in Canberra welcomed the arrival of 183 delegates, including a relatively large overseas contingent, to the meeting in December, 1970. The aim of these Conferences is, of course, to provide a forum for discussion of new work and recent trends, both in the lecture sessions and in conversation. Although many of those who initiated these meetings (e.g. Skoog, Went, Blackman, Bennet-Clark) were absent from the Canberra conference - some have retired -it was good to see present so many of the new generation of research workers in this field.

This second Volume in the series on Membrane Transport in Biology contains a group of essays on transport across single biological membranes separating the inside and outside of cells or organelles. We have not attempted to include material on all types of plasma and intracellular membranes, but rather have emphasized structures which have been studied relatively thoroughly. Four chapters describe transport of different types of molecules and ions across the plasma membranes of mammalian red cells. Two essays concern the excitable membranes of nerve and muscle cells while the remaining four chapters treat transport across several types of intracellular membranes. Water makes up more than two-thirds of the mass of most living cells. The transport of water between the inside and outside of cells and organelles is important for the function of these structures. As a result of investigations in many laboratories over the past four decades, our picture of the water permea­ bility of the red cell membranes is rather detailed when compared to the water permeability of other biological membranes. In Chapter 1, R. I. Macey describes this picture and also considers the permeability of red cell membranes to non­ electrolytes, including metabolic substrates such as sugars, amino acids, purines and nucleosides.

Moving from a standard clinical reference Garner and Klintworth's Third Edition of Pathobiology of Ocular Disease is now modeled to be both a scientific research tool and a quick reference option for the practicing ophthalmologist, ophthalmic pathologist, optometrist and vision scientist. With the addition of ten new chapters, this edition focuses

This is the companion volume to Daniel Klionsky's Autophagy: Lower Eukaryotes, which features the basic methods in autophagy covering yeasts and alternative fungi. Klionsky is one of the leading authorities in the field. He is the editor-in-chief of Autophagy. The November 2007 issue of Nature Reviews highlighted his article, “Autophagy: from phenomenology to molecular understanding in less than a decade.” He is currently editing guidelines for the field, with 230 contributing authors that will publish in Autophagy.Particularly in times of stress, like starvation and disease, higher organisms have an internal mechanism in their cells for chewing up and recycling parts of themselves. The process of internal “house-cleaning” in the cell is called autophagy – literally self-eating. Breakthroughs in understanding the molecular basis of autophagy came after the cloning of ATG1 in yeast. These ATG genes in yeast were the stepping stones to the explosion of research into the molecular analysis of autophagy in higher eukaryotes. In the future, this research will help to design clinical approaches that can turn on autophagy and halt tumor growth. Establishes the functional roles of specific cellular proteins in selective and nonselective autophagy in mammalian cells, which aides researchers in determining why autophagy is shut down in neoplastia (growth of abnormal tissue mass) and turned on during bacterial invasion Includes methods to evaluate the role of autophagy in the drug-induced cell death of cancer cells in culture, which helps researchers design clinical approaches that can turn on autophagy and halt tumor growth Covers higher eukaryotes including lifespan in C.elegans to marine organisms and bridging into the clinical aspects, including autophagy in chronic myelogenous leukemia (CML is one of four types of leukemia), lung cancer, prostate cancer, and cardiac cells

The 2002 Nobel Prize in Physiology or Medicine was awarded to Sydney Brenner (UK),H. Robert Horvitz (US)and John E. Sulston (UK)'for their discoveries concerning genetic regulation of organ development and programmed cell death.'Cell death is a fundamental aspect of embryonic development, normal cellular turnover and maintenance of homeostasis (maintaining a stable, constant environment) on the one hand, and aging and disease on the other. This volume addresses the significant advances with the techniques that are being used to analyze cell death.•Provides the necessary, trusted methods to carry out this research on the latest techniques. Once researchers understand the molecular mechanisms of the apoptotic pathways, they can begin to develop new therapies •Presents key methods on studying tumors and how these cancer cells evade cell death•Eliminates searching through many different sources to avoid pitfalls so the same mistakes are not made over and over

This book considers the etiology and pathogenesis of the diseases that afflict the tissues of the eye and its adnexa, as well as the visual pathways within the central nervous system. It provides a background for the development of rational therapeutic approaches.

Moving from a standard clinical reference, this third edition is now modelled to be both a scientific research tool and a quick reference option for the practicing ophthalmologist, ophthalmic pathologist, optometrist and vision scientist. With the addition of ten new chapters this edition focuses its attention on the acuses, and mechanisms of ocular disease and is on the forefront of the latest discovered, research methods and on-going research in ocular disease.

Addressing a major field of interest for oncologists, cell biologists, and other biomedical researchers, Beyond Apoptosis provides an overview of how different biological mechanisms of cell death, senescence and mitotic catastrophe stop the growth of tumor cells treated with anticancer agents.Written by internationally renowned contributors, this t

While simultaneous breakthroughs occurring in molecular biology and nanoscience/technology will ultimately revolutionize all of medicine, it is with our efforts to prevent, diagnose, and treat cancer that many of the most dramatic advances will occur. In support of this potential, the U.S. National Cancer Institute (NCI) established the Alliance fo

Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.• Contains the latest information on the subject of neurodegenerative disorders• Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems

Coedited by internationally recognized leaders in gene therapy research, this guide supplies the most recent advances, studies, and expert opinion on gene therapy for neurological disorders. Spanning conditions such as Parkinsons's and Alzheimer's disease, multiple sclerosis, brain tumors, stroke, epilepsy, and brain and spinal cord trauma, this reference presents the basic science and applications of recombinant gene products, immune and stem cell-mediated therapeutic strategies, and brain tumor gene therapy.

Featuring more than 4100 references, Drug-Induced Liver Disease will be an invaluable reference for gastroenterologists, hepatologists, family physicians, internists, pathologists, pharmacists, pharmacologists, and clinical toxicologists, and graduate and medical school students in these disciplines.

This definitive volume presents the clinical and pathological features of bronchopulmonary dysplasia, a disease that accounts for the majority of long-term hospitalizations, slow growth, and recurrent early childhood respiratory ailments that are common in low-birth-weight newborns. Highlights relevant animal models for studying the process of

Psychoneuroimmunology is the emerging science devoted to studying the two-way relationship between the nervous and immune systems. Psychoneuroimmunology, Stress, and Infection highlights the latest information concerning microbial infections in both man and animals as related to stress and especially stress hormones.The volume focuses on psychoneuroimmunology as it impacts the immune system in general and also the relationship between neurological events which influence susceptibility and/or resistance to infectious agents such as bacteria, fungi and viruses, as well as parasites. Prominent researchers describe the involvement of the hypothalamus-pituitary-adrenal (HPA) axis on immunity as a function of the nervous system. The text discusses hormones such as prolactin and growth hormone and steroid induced susceptibility to infection and neuropeptides, including vasoactive intestinal peptide, and substance P. The effects of catacholamines on immunity and susceptibility to infection are also covered. This reference also details the involvement of immune cells in the synthesis of neuropeptides, including hormones and endorphins, their effect on the brain as well as the effects of interleukins and tumor necrosis factor on the central nervous system. The book concludes with an interesting look at the relationship between aging, psychoneuroimmunology, and infection. Although there is much new knowledge concerning the nature and mechanism of immune responses, including the mediators involved, Psychoneuroimmunology, Stress, and Infection also presents important discussions and reviews that are long overdue and provide a major contribution to the area of biomedical knowledge in general and psychoneuroimmunology in particular.