Researchers involved in the cytogenetics and molecular genetics of human tumors will welcome this comprehensive overview of the type of aberrations that chromosome 12 presents in human solid tumors. The authors study the implications for a cytogenetic subtyping of the tumors involved and strategies for identifying the molecular changes which underlie the karyotypic alterations.
The aberrations of chromosome 12 which the book deals with are very frequent chromosomal alterations in human tumors occuring in frequent benign mesenchymal tumors, such as uterine leiomyomas and lipomas, and in tumors of epithelial origin, such as pleomorphic adenomas of the salivary glands.

Extracellular purines and pyrimidines (ATP, ADP, UTP and adenosine) are released into the extracellular milieu in response to a variety of stress conditions and act as important regulators of vascular homeostasis. This new book is uniquely focused on the signaling actions of extracellular purines in endothelial cells and the crucial role of extracellular purines in regulation of angiogenesis, vascular tone, cell permeability, wound healing, inflammation and cell-to-cell communication. This book examines the responses of endothelial cells, originating from various tissues (such as cornea, pancreas and uterus), to extracellular nucleotides and adenosine under physiological and pathological conditions, i.e. pregnancy, hypoxia, hypertension, inflammation and diabetes. In the book's 12 chapters, the role of purinergic signaling in endothelium-dependent tissue perfusion, regulation of endothelial barrier function, and angiogenesis are discussed. The mechanisms of ATP release and its role in intercellular communication are also presented. In addition, the book provides the most up to date mechanisms of extracellular nucleotide metabolism by purine-converting ecto-enzymes and their contribution to purinergic signaling in endothelial cells originating from various vascular beds. This book is a valuable resource for biomedical research scientists, clinical scientists, graduate students and health science professionals interested in the mechanisms of extracellular purine function in endothelial cells under physiologic and pathologic conditions.

This book shall assist the microscopist in a practical way, with the help of three mainstays, a. clinical information, b. the resources a standard histopathology laboratory may offer and c. the light microscope, to approach and solve the diagnostic problems he/she may face in the field of dermatopathology. In fact, this is the way in which the senior author of this book has been successfully working over thirty years in his capacity as director of a private dermatopathology laboratory.

The term "lymphoma" was originally used by Billroth in 1871 [55], and by Virehow [763] some years before that, for the designation of swelling of lymph nodes that was not due to "eareinoma, sareoma, ehondroma, myxoma, ete. " In his paper, Billroth reeounted sueeessful treatment with arsenie (" Fowler's solution") of multiple "lymphomas" that had developed in a 40-year-old woman during a 10-month period. From this report it is not entirely clear if the multiple" lymphomas" deseribed were infeetious or if they were eonsis- te nt with what we now mean by "malignant lymphoma. " Today, the term "malignant lymphoma" is generally used eolleetively for malignant lymphoproliferative neoplasms that tend to arise in lymph nodes and also eneompasses Hodgkin's disease and non-Hodgkin's lymphomas. The adjeetive "malignant" seems somewhat superfluous sinee, in addition to Bill- roth's original eonnotation, the sense of malignaney is nowadays read into the word "lymphoma. " To be sure, true, i. e. , malignant, lymphomas have to be differentiated from "pseudolymphomas," or to put it more exaetly, "pseudomalignant lymphomas. " In this book, "lymphoma" and "malignant lymphoma" are used interehan- geably for malignant neoplastie lymphoproliferative disorders, and "pseudo- lymphoma" is used for benign lymphomatous proeesses. Our editorial eonsultant, Dr. M. Leider, disagrees with all of this. In his Dictionary of Dermatological Words, Terms, and Phrases [421] and other works, he maintains that there is no etymologieal basis for words bearing the eontrived suffix" -oma" or the true Greek suffix" -ma" to denote malignaney.

This book has its origins in the intensive short courses on scanning elec tron microscopy and x-ray microanalysis which have been taught annually at Lehigh University since 1972. In order to provide a textbook containing the materials presented in the original course, the lecturers collaborated to write the book Practical Scanning Electron Microscopy (PSEM), which was published by Plenum Press in 1975. The course con tinued to evolve and expand in the ensuing years, until the volume of material to be covered necessitated the development of separate intro ductory and advanced courses. In 1981 the lecturers undertook the project of rewriting the original textbook, producing the volume Scan ning Electron Microscopy and X-Ray Microanalysis (SEMXM). This vol ume contained substantial expansions of the treatment of such basic material as electron optics, image formation, energy-dispersive x-ray spectrometry, and qualitative and quantitative analysis. At the same time, a number of chapters, which had been included in the PSEM vol ume, including those on magnetic contrast and electron channeling con trast, had to be dropped for reasons of space. Moreover, these topics had naturally evolved into the basis of the advanced course. In addition, the evolution of the SEM and microanalysis fields had resulted in the devel opment of new topics, such as digital image processing, which by their nature became topics in the advanced course.

Mast cells are versatile, tissue-homing secretory cells, which were first described by Paul Ehrlich in 1878. Mast cells have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. Their functional role, however, has been discovered to be increasingly complex and multifarious. Mast cells have been implicated in various cell-mediated immune reactions, being found in tissues from multiple disease sites, and as a component of the host reaction to bacteria, parasite, and even virus infections. They have also been shown to participate to angiogenic and tissue repair processes after injury. The importance of a possible functional link between chronic inflammation and cancer has long been recognized. As most tumours contain inflammatory cell infiltrates, which often include plentiful mast cells, the question as to the possible contribution of mast cells to tumour development has progressively been emerged. In this book, the general biology of these cells, their development, anatomical distribution and phenotype as well as their secretory products will first be discussed. The biology of tumour cells, their structural and molecular characteristics, the specificity of the tumour microenvironment and the development of a vascular network in the tumour context will be analyzed. The involvement of mast cells in tumour biology and tumour fate will then be considered, with particular emphasis on the capacity of these cells to stimulate tumour growth by promoting angiogenesis and lymphangiogenesis. The last chapter suggest that mast cells may serve as a novel therapeutic target for cancer treatment.

From the preface: "Pathologists are responsible for the interpretation of tissue samples removed for the purpose of establishing a diagnosis. This textbook has been conceived and arranged in a manner that facilitates the task of arriving at a diagnosis through the evaluation of tissues removed from patients afflicted with neurological complaints. The portion of the diagnostic work-up that is purely "clinical", such as the history of the disease and the results of the physical examination are entirely beyond the scope of this textbook...Extensive descriptions of disease processes, which are available in most of the references cited, have been omitted in favor of relatively detailed descriptions and abundant illustrations of the histologic abnormalities that, as a group, constitute a diagnostic entity."

Osteoimmunology pertains to the study of the relationship between the bones, particularly the bone marrow, and the immune system. This monograph pursues the best available evidence, by means of research synthesis, for the characterization of the physiological relevance and pathological implications of the inter-connectedness between the skeletal and the immune system. Research will be discussed that highlights the associated role of the circulatory, nervous and endocrine systems, as well as proteomic and genomic pathways and signatures. Emphasis is given that domain of medicine that relates to the oral cavity, its diseases and their systemic sequelae. This monograph arises from observations that have suggested that the skeletal system and the immune system are intimately intertwined. Chronic inflammatory reactions subsequent to an excessive immune reaction can damage the bones, as in rheumatoid arthritis (RA), osteoporosis, patients seropositive for the human immunodeficiency virus (HIV)-1 and with signs and symptoms of the acquired immune deficiency syndrome (AIDS), and bone cancer. Bones - in particular the bone marrow - are one of the primary locations in which cells of the immune system mature. In brief, this monograph begins to answer a range of questions, such as, what is osteoimmunology all about?, does the immune system and its components affect bone development?, how do stress hormones impact upon the pathophysiology of bone-immune interactions?, can the scientific process of research synthesis, obtain the best available evidence for treatment of diseases involving the bone-immune entity (i.e., osteo immunopathologies) means of evidence-based clinical decision-making directed at the treatment of osteoimmune pathologies?

In recent years a dramatic increase in knowledge of the biology of the lymphomas has been accompanied by the emergence of new treatments offering improvements in efficacy and reduction in toxicity. In this volume an internationally recognized group of experts review relevant aspects of the biology, diagnosis and management, with particular emphasis on the emerging data available for this disease.

The World Health Organization has identified chronic alcohol consumption as one of the top ten risk factors for worldwide burden of disease. The International Agency for Research on Cancer has identified alcohol as carcinogenic to humans, including cancers of the upper aerodigestive tract, colon, liver and breast. Alcohol's actions may be direct e.g. effects on retinoic acid and one-carbon metabolism, or indirect, through metabolites such as acetaldehyde and reactive oxygen species or through various signaling pathways that influence cell cycle and apoptosis that may contribute to carcinogenesis. This report reviews the state of the art in alcohol-related cancer research in ten chapters.

The next revolution in molecular medicine is the application of molecular profiling to individualized patient therapy. Molecular profiling technology has advanced dramatically, particularly in the field of cancer tissue biomarkers. It is now possible to gather complex genomic and proteomic information from a routine clinical needle biopsy or surgical specimen. In "Molecular Profiling: Methods and Protocols," expert researchers in the field focus on the entire process from discovery to commercialization, with practical guides that are not limited to experimental methods. Written in the highly successful "Methods in Molecular Biology" series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, as well as essays and guidelines for grants, patents, and commercialization of products related to molecular profiling.

Authoritative and practical, "Molecular Profiling: Methods and Protocols" seeks to aid scientists in understanding the latest advancements in genomics, proteomics, imagining, and bioinformatics.

This book is designed to provide the busy ophthal inftammation, lacrimal gland tumors and inftamma mologist with a practieal guide to the management tion, lacrimal sac tumors and inftammation, and of lid and ocular adnexal disease. The book encom lid tumors and inftammations. passes more than tumors simply because other in This book provides the ophthalmologist with a ftammatory conditions may mimic tumors in their step-by-step approach to patients with lid and orbital presentation and vice versa. It is not meant to be tumors and inftammations. an encyclopedie, definitive work on a single subject, organized around individual disease entities; instead Acknowledgments it approaches the patient much as clinician does. It concentrates on the patient and considers various disease processes logieally. Work -up, differential We wish to thank all the referring doctors who diagnosis, and initial treatment are discussed. have allowed us to treat their patients with orbital When any patient presents with an orbital or an and ocular adnexal disease and without whom a ocular adnexal mass, the question that needs to be book of this type would have been impossible. We answered is whether the process is due to inftamma also would like to give special thanks to our teachers, Dr. Lorenz E. Zimmerman and Dr. Byron Smith."

Amyloid-forming proteins are implicated in over 30 human diseases. The proteins involved in each disease have unrelated sequences and dissimilar native structures, but they all undergo conformational alterations to form fibrillar polymers. The fibrillar assemblies accumulate progressively into disease-specific lesions in vivo. Substantial evidence suggests these lesions are the end state of aberrant protein folding whereas the actual disease-causing culprits likely are soluble, non-fibrillar assemblies preceding the aggregates. The non-fibrillar protein assemblies range from small, low-order oligomers to spherical, annular, and protofibrillar species. Oligomeric species are believed to mediate various pathogenic mechanisms that lead to cellular dysfunction, cytotoxicity, and cell loss, eventuating in disease-specific degeneration and systemic morbidity. The particular pathologies thus are determined by the afflicted cell types, organs, systems, and the proteins involved. Evidence suggests that the oligomeric species may share structural features and possibly common mechanisms of action. In many cases, the structure function interrelationships amongst the various protein assemblies described in vitro are still elusive. Deciphering these intricate structure function correlations will help understanding a complex array of pathogenic mechanisms, some of which may be common across different diseases albeit affecting different cell types and systems."

Opportunistic, intracellular bacterial infections are in the forefront of research today because of the challenges they present to the immunocompromised patient. In this volume, the pathogenesis and immune reaction of these intracellular infections is featured, as are the most typical problems related to antimicrobial chemotherapy, and current approaches to their solution. Notable chapters set the pace for research on the pathogenic and immune reactions to such infections as * Mycobacterium tuberculosis * Legionella pneumophila * Chlamydia trachomatis and * Brucella.

Gain critical insight into the structure-function relationships and the pathological basis of human disease with Netter's Illustrated Human Pathology. With a visually vibrant approach, this atlas provides clear and succinct representations of common human diseases by relating anatomical changes to the functional and clinical manifestations of disease and their underlying causes and mechanisms. Updated throughout, it offers a superb complement to more comprehensive textbooks and presentations of pathology, including course syllabi. It can also be used as an adjunct for study of gross and microscopic pathology specimens in laboratory exercises, and makes a great review resource for students, medical residents, physicians and other healthcare professionals. Grasp and retain key pathologic concepts and conditions. Beginning with a concise summary of the various pathological processes and diseases, each chapter consists of illustrations of pathological processes and diseases accompanied by concise text aimed at clarifying and expanding the information presented in the illustrations. Gain a superb visual understanding through more than 380 classic Netter and new Netter-style images, gross and microscopic photographs and tables. Reference information effortlessly with numerous tables throughout including 452 figures and 255 slides. Take your learning farther with Student Consult access.

Unique features of the present work include: Only authorized English translation of the original Spanish text, adhering as much as possible to the letter, with correction of the obvious errors already predicted by Cajal in his Preface. Added facts appearing in the French version, with correction of old as well as new errors, the latter probably due to inaccuracies in translating into French some nuances of the Spanish language. Uniform of nomenclature according to contemporary scientific English. Annotations on Cajal s changing concepts over time, the elucidation of certain structures that do not have present day equivalents, and explanations of the many symbols appearing in illustrations but not mentioned in the corresponding original legends. Most illustrations are reproductions of Cajal s original art work, still extant at the Cajal Museum in Madrid, with cross references to figure numbers of the Spanish and French versions. Citations are given by author and year in the text, with an alphabetical list at the end of the volume, completed and corrected for accuracy against original publications. Taxonomy glossary of species appearing in the text, with present scientific names, and their colloquial English counterparts."

The discovery of the human T cell leukemia virus type I in the late 1970s heralded a new era in retrovirology. For the first time, it was demonstrated that a retrovirus could play a role in the development of a human disease, in this case adult T cell leukemia (ATL). Several years later, the acquired immunodeficiency syndrome (AIDS) epidemic began, and it was dem- strated that a retrovirus, originally designated the human T cell lymp- tropic virus type 3, was the causal agent of this syndrome. This virus, later named the human immunodeficiency virus type 1 (HIV-1), has since been extensively studied in terms of its pathogenesis as well as its ability to elicit immune responses. In that time, a tremendous amount of information has been obtained about the virus. Although recent drug regimens have been useful in significantly lowering viral loads and perhaps maintaining an asymptomatic state among individuals infected with HIV-1, an established "cure" for AIDS eludes us. In addition, the effective drug therapies are very expensive, and are not available to infected people in the third world, where greater than 90% of new infections occur. Furthermore, the development of viral resistance against the drug therapies is an additional concern. Despite extensive study, no effective vaccine has been developed. One of the problems in developing an effective vaccine against HIV-1 is the ability of the virus, particularly in the immunogenic envelop glycoprotein, to undergo amino acid hypervariability.

The term "electrophoresis" was first used by Michaelis in 1909, to - scribe the migration of colloids in an electric field. The first practical elect- phoresis method was described by Tiselius in 1937. He used a U-tube filled with buffer layered on top of sample; migration could be monitored using Schlieren optics. In zone electrophoresis, the U-tube was replaced by paper, a support material employed simply to prevent or minimize diffusion of ions, so that ions applied in a narrow strip to the paper will separate and remain as relatively discrete zones. Paper was superceded by a variety of other media, - cluding cellulose acetate, hydrolyzed starch (starch gel), agarose, and polyacry- mide. The latter, in addition to being a support medium, has size-sieving properties. From the basic zone electrophoresis, other means of separation have been dev- oped. These include, isoelectric focusing, isotachophoresis, density gradient el- trophoresis, and various forms of immunoelectrophoresis. In some ways Capillary Electrophoresis (CE) has gone full circle back to the original method of Tiselius. In its simplest form, separations occur in a buffer solution within a glass (fused silica) tube and detection occurs as sample moves past an optical window. CE has rapidly developed into a technique that rivals HPLC in its versatility. All the classical electrophoretic separations-zone, IEF, and isotachophoresis-have their counterparts in CE. Excitingly so, and - thoritatively treated in Clinical Applications of Capillary Electrophoresis.

The TGF-13 superfamily is a large and expanding multigene family which in verte- brates includes the TGF-13 proteins themselves, the bone morphogenetic proteins (BMPs), the growth and differentiation factors (GDF), the activins/inhibins (INH), Mullerian inhibitory substance (MIS), glial derived neurotropic factor (GDNF) and more recently macrophage inhibitory cytokine 1 (MIC-1). They are characterised by conserved structural elements and a broad commonality of function. Major structural elements All members of the TGF-13 superfamily contain as their major structural hallmark a conserved spacing and distribution of seven cysteine residues. This structure is known as the cysteine knot and tethers together regions of the peptide as well as binding the two chains of the dimer to each other. High resolution structures are now available on proteins from three families within this group including glial derived neurotropic factor (GDNF), BMP-7 and several of the TGF-13s. Despite low similarity between some of these proteins (eg, TGF-13s and GDNF are only 13% identical) they share a strikingly similar three dimensional conformation (Fig. 1). These structural elements imbue the protein with some of its familial characteristics. These include its physico-chemical stability due to tight tethering of portions of the peptide chain via criss-crossing disulphide bonds. Much of its surfaces are coated with hydrophobic patches leading to a propensity to bind non-specifically to other proteins as well as to its self. This also causes a marked propensity for aggregation when the recombinant protein is present at high concentration.

course, also aware that many who use this volume One in every three slides examined by a general diagnostic pathologist in the United Kingdom, and will be well familiar with the classical, or 'textbook', in most other countries, comes from a gynaecological appearances of most of the more common conditions patient. Few pathologists can hope, therefore, to and have therefore often chosen an example which, escape a constant exposure to gynaecological path whilst being typical, is not necessarily classical. ology, and it is the aim of this atlas to lessen the We have deliberately chosen not to include any difficulties of this diagnostic burden by acting as an illustrations of gross specimens. This is partly because illustrated guide to the histological diagnosis of of ou r view that such illustrations are of I ittle real value female genital tract abnormalities. to any but the least experienced of pathologists, and Gynaecological pathology does, however, pose a partly because their inclusion would have narrowed number of specific problems: the range and scope of still further our selection of histological figures.

Pocketbook for Cancer Supportive Care Febrile Neutropenia is a comprehensive review on febrile neutropenia, its prevention, risks, management, costs, and special populations affected by the condition. The book was originally commissioned due to advances in the field, and to supplement the series: Pocketbooks in Supportive Cancer Care. Busy healthcare professionals who have a basic understanding of febrile neutropenia but want to learn more a will benefit from this concise guide that will help them quickly understand the complexities of this condition.

Genetic testing has become commonplace, and clinicians are frequently able to use knowledge of an individual's specific genetic differences to guide their course of action. Molecular Genetics and Personalized Medicine highlights developments that have been made in the field of molecular genetics and how they have been applied clinically. It will serve as a useful reference for physicians hoping to better understand the role of molecular medicine in clinical practice. In addition, it should also prove to be an invaluable resource for the basic scientist that wants to better understand how advances in the laboratory are being moved from the bench to the bedside. All chapters are written by experts in their fields and include the most up to date medical information. The authors simplify complex genetic concepts and focus on practical patient related issues. The book will be of great value to pathologists, hematologists/oncologists, clinical geneticists, high-risk obstetricians, general practitioners, and physicians in all other medical specialties who utilize genetic testing to direct therapy.

Twenty years have passed since I became a professor in the First Department of Pathology, Hiroshima University School of Medicine. It is my great pleas ure that Molecular Pathology o[ Gastroenterological Cancer-Application to Clinical Practice has been published by Springer-Verlag Tokyo to commemo rate the 20th anniversary of my professorship. Seeing the academic achievements of our department during these 20 years, I am confident that we could establish a department of oncology to research the pathogenesis of human cancer through systemic application of a variety of molecular techniques. We have demonstrated that the develop me nt and progression of esophageal, gastric, and colon cancer require mul tiple alterations affecting DNA mismatch repair genes, oncogenes, and tumorsuppressor genes, and that common and uncommon genetic changes exist for esophageal, gastric, and colorectal carcinomas. In addition to these genetic changes, the majority of gastrointestinal cancers express telomerase activity, with overexpression of telomerase RNA, indicating a powerful addi tional tool for early detection of gastrointestinal cancer. By transferring these basic observations to the clinic, we now are able to make accurate cancer diagnoses, thus determing the grade of malignancy and patient prognosis. We also can identify patients at high risk for developing cancer and create new therapeutic approaches. In fact, we have routinely implemented a new molecular diagnosis strategy at the Hiroshima City Medi cal Association Clinical Laboratory since August 1993.

This book is designed primarily for anatomic pathologists to facilitate their task of accurately diagnosing embryos and fetuses. A detailed examination of the products of spontaneous and induced abortions is necessary for accurate genetic counseling and for establishing the risk for specific abnormalities or another spontaneous pregnancy loss in the future. The growing interest in the defects of early development reflects the profound change in general life-style. In the past, spontaneous abortions were considered a common, usually sporadic event in a patient's reproductive history. Only reassurance and encour agement were given to the patient and scant attention was paid to the detailed pathology of the abortus. Nowadays, however, as a result of reliable methods of contraception and of the availability of reliable prenatal diagnosis for chromosome abnormalities more frequent in advanced maternal age, significant numbers of parents plan to have pregnan cies later in their reproductive life. Consequently, in a case of spontaneous abortion, the question of "cause" and of "future risk" of recurrence of abortion or an abnormal infant is particularly important. In the era of more elaborate and accurate prenatal diagnostic tests, the pathologist examining products of conception has a primary responsibility to detect, in both spontaneous and induced abortions, any developmental abnormality that would indicate an increased risk of multifactorial, chromosomal, and single gene disorders in a subsequent child.