Numerous improvements in our understanding of the mechanisms that underlie neuropathic pain states have come from the development of animal models, most of which involve partial peripheral nerve injury. The animal models have shown that nerve injury initiates a cascade of events resulting in altered neurochemistry and molecular biology of the peripheral neurons, the dorsal root ganglion cell, and changes in neurotransmitter and receptor expression in the dorsal horn of the spinal cord. Moreover, nerve injury produces anatomical changes with functional consequences.
This volume summarises the current understanding of the pathophysiological processes in the peripheral and central nervous system that contribute to the neuropathic pain. It provides a timely review of neuropathic pain mechanisms, written by experts in the field.

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

Assembling the latest research by an international group of contributors, this volume covers the epidemiology, pathogenesis, clinical features, and control measures of this elusive microorganism. It will provide a deeper understanding of the pathogen to physicians and surgeons caring for patients infected, or at risk of becoming infected, with Pseudomonas Aeruginosa.

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

Especially the past two decades have seen renewed interest in the vasculitides. In this volume an international expert group presents the current state of knowledge and concentrates on principles of immune modulating therapy. Drawing from their work in rheumatology, nephrology, internal medicine, connective tissue disease and clinical immunology, they present new concepts in classificiation, diagnosis and pathophysiology of the vasculitides. Evidence from experimental and clinical trials is reviewed, as well as the outlook for further research.

Today, advances in the area of immunology and breast cancer are made at an increasing rate, yielding an amount of information that can become unwieldy. The opportunity for scientists in this area of research to gather together to exchange results and working hypotheses represents, in my belief, a very attractive proposition. With this in mind, these workshops have been convened with two year intervals for the last ten years. In each of them, selected topics have been highlighted. The present workshop underscores the large advancements made in the molecular biology of both breast cancer associated antigens and their corresponding antibodies. Understanding the genetic information for the expression of these antigens has been recently advanced leading to preparation of molecularly engineered reagents for use in vaccination, serum assays, and immunizations for novel antibody production. In the anti-breast cancer antibody field the availability of molecular engineering approaches to humanize murine antibodies has induced intense interest in the creation of less immunogenic antibody forms that are now available for clinical testing. Clinical studies using anti-breast murine antibody continue to be carried out and are presented at this meeting establishing a base line for safety and efficaciousness in imaging and immunotherapy that it is hoped will be superseded by the humanized forms. Basic immunology and immunochemistry studies in breast cancer are also included in this workshop that demonstrate the fast pace at which this research is advancing in many laboratories worldwide.

Acute lung injury (ALI) impacts patient care in every ICU in the world. Our collective understanding of this condition has grown immensely over the past decade but morbidity and mortality remain unacceptably high. To enhance the understanding of clinicians and researchers, this book addresses the pathophysiology of acute lung injury from a molecular and cellular standpoint; includes animal models of acute lung injury and points to potential therapeutic advances based on scientific findings. It is a concise compendium of the multiple pathways, mechanisms and molecules involved in the pathophysiology of acute lung injury and is intended to help caregivers understand the process and thus care for patients more effectively.

TheNATO AdvancedStudiesInstituteseries"TargetingofDrugs"wasoriginatedin 1981. It is nowamajorinternationalforum,heldeverytwo yearsin CapeSounion,Greece,in whichthepresentandthefutureofthisimportantareaofresearch in drugdeliveryisdiscussed in greatdepth. PreviousASIsoftheseriesdealtwith drugcarriersofnaturalandsynthetic origin,theirinteractionswith thebiologicalmilieu, waysby whichthefunctionofdrugcarriers iscircumvented and,morerecently,with avarietyofapproaches to carrierdesignor modificationthatcontributeto optimalcarrierfunction. Thepresentbookcontainsthe proceedings ofthe8thNATO ASI, "TargetingofDrugs:Strategies for Oligonucleotideand GeneDelivery in Therapy", held in CapeSounionduring24June-5 July 1995. Asthetitle implies,thebookdealswith avarietyofsystemsin termsoftheirability to transportnucleic acidsto targetareasin vitro andin vivo in waysthateffectivelymodify,supplement, correct, orcurtailthefunctionofgenesin therapy. Weexpressourappreciation to Mrs. ConchaPerringfor herassistance with the organizationoftheASI. TheASI washeldunderthesponsorship ofNATO ScientificAffairs Division andco-sponsored andgenerouslyfinancedby SmithKlineBeechamPharmaceuticals (KingofPrussia). Financialassistance wasalsoprovidedby SandozPharma(Baseland Athens),GeneMedicine (Houston,USA), ChironCorporation(Emeryville,USA), BYK GuldenLombergChemische (Konstanz,Gernlany),HelpSA(Athens,Greece),Avanti Polar Lipids Inc (Birmingham,USA), OxfordMolecular(Oxford,UK), Pfizer(Kent,UK), andAlza Corporation(PaloAlto, USA). GregoryGregoriadis BrendaMcCormack v CONTENTS Gene Therapy for Inherited Genetic Disease: Possibilities and Problems c. *Coutelle Gene Delivery and Therapy: The Case for Cystic Fibrosis 15 E. W. F. W. Alton Immune Responses with Direct Gene Transfer: DNA Vaccines and 21 Implications for Gene Therapy H. L. Davis Oligonucleotides: Molecular Versions for Optimal Use in Vivo 31 E. Saison-Behmoaras, A. Van Aerschot, I. Duroux, C. Hendrix, C. Helene, and P. Herdewijn Retrovirus Vectors in Gene Therapy: Targeting to Specific Cells 45 AJ. Kingsman, Y. Bae, J. c. Griffiths, N. Kim, E. E. Ramsdale, G. Romano, Y. Soneoka, P. M. Cannon, and S. M. Kingsman Adenovirus as Vectors for Gene Therapy 53 M. G. Lee Receptor-Mediated Gene Delivery with Synthetic Virus-like Particles 67 E. Wagner, M. Cotten, and K. Zatloukal Controllable Gene Therapy: Recent Advances in Non-Viral Gene Delivery 79 A.

This volume is based on the program of the Second International Conference on Drugs of Abuse, Immunity and AIDS, held in Clearwater Beach, FL in June 1992. The Conference was supported in part by the University of South Florida College of MediCine with financial assistance from the National Institute on Drug Abuse. The focus of this conference was the effects of drugs of abuse on immunity. It is now widely recognized that psychoactive drugs of abuse, including marijuana, cocaine, and opiates, as well as alcohol, have marked effects in an individual, including effects on their nervous system and behavior. In the past two decades, the scope of studies concerning the effects of some drugs of abuse have also involved investigations of alterations of various physiologic parameters including effects on the immune system. and the influence of such immune alterations on normal physiological responses. In this regard, participants in this Second International Conference provided newer information concerning both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiencies. In this regard, advances have been made in recent years concerning the nature and mechanisms whereby the immune system is regulated and the possible mechanisms by which drugs of abuse influence such immune systems. In particular, the emergence of psychoneuroimmunology as a new discipline the last decade has heightened interest in the immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving both clinical and basic scientists, including microbiologists, immunologists, physiologists, psychiatrists, oncologists, psychologists, etc.

The National Institute of Dental Research sponsored a workshop on "Genetically Engineered Vaccines: Prospects for Oral Disease Prevention," held at the National Institutes of Health (NIH) on November 6-8, 1991. The purpose of the workshop was to convene molecular biologists and immunologists to address the state of the science in vaccine development and to explore the potential of developing vaccines for prevention of oral diseases. The goal was to elicit new research initiatives and recommendations for vaccine development with emphasis on the prevention of oral diseases and diseases affecting the orofacial tissues. The workshop was attended by more than 100 persons who heard 30 presentations, and the speakers provided the papers for this volume. The workshop focused on the following topics: oral diseases and host immune responses, update on vaccines and vaccine development, vaccines and the mucosal immune system, optimizing mucosal and systemic immune responses, delivery systems and immune analysis, target antigen selection and vaccine development, immunological correlates of protection and future direc tions/recommendations. Three key areas were identified: Optimizing the Mucosal Immune Response, Antigen Delivery Systems, and Target Antigens and Immunological Correlates of Protection. The summary and recommendations from these deliberations is included at the end of this volume."

The topicS in this book represent the presentations given at the Fifth Annual Meeting entitled "Cardiac Surgery: Current Issues" held at the Frenchman's Reef Beach Resort. St. Thomas. U.S. Virgin Islands. November 11-14. 1992. This symposium was sponsored by the Division of Cardiothoracic Sur gery. the School of Cardiovascular Perfusion and the Department of Nursing Education and QUality Assurance of Cooper Hospital/University Medical Center. the University of Medicine and Dentistry of New Jersey. Robert Wood Johnson Medical School. Camden. New Jersey. as well as the Academy of Medicine of New Jersey. Chapter authors were charged with the task of writing brief overviews of major issues related to the field of cardiac surgery. The book is specifically tailored to the needs of cardiothoracic surgeons. cardiovascular perfusionists. allied health professionals and nursing personnel involved in all phases of caring for the cardiac surgical patient. Although intended as a reference source with emphasis on up-dated approaches applied in cardiac surgery. it is hoped that the discussion of these topics will compliment other texts and manuscripts. Obviously.';ibook of this length cannot cover the whole multidiSciplinary and complex field of cardiac surgery. However. co-editors are certain that the annual appearance of this text will highlight comprehensive. new and interesting approaches to the field of cardiac surgery."

Corona- and related viruses are important human and animal pathogens that also serve as models for other viral-mediated diseases. Interest in these pathogens has grown tremendously since the First International Symposium was held at the Institute of Virology and Immunobiology of the University of Wiirzburg, Germany. The Sixth International Symposium was held in Quebec City from August 27 to September I, 1994, and provided further understanding of the molecular biology, immunology, and pathogenesis of corona-, toro-, and arterivirus infections. Lectures were given on the molecular biology, pathogenesis, immune responses, and development of vaccines. Studies on the pathogenesis of coronavirus infections have been focused mainly on murine coronavirus, and mouse hepatitis virus. Neurotropic strains ofMHV (e.g., JHM, A59) cause a demyelinating disease that has served as an animal model for human multiple sclerosis. Dr. Samuel Dales, of the University of Western Ontario, London, Canada, gave a state-of-the-art lecture on our current under standing of the pathogenesis of JHM-induced disease.

The success of vaccination in controlling infectious diseases is well documented. However, low profitability, expense and liability have hindered research and development of vaccines. Recently, increasing realization (enhanced by the AIDS pandemic) of the need to overcome such difficulties has led to steps being taken by national authorities, non-profit and commercial organizations to resolve them. This has been facilitated by developments in recombinant DNA techniques, the advent of monoclonal anti bodies and progress in the understanding of the immunological structure of proteins which have laid the foundation of a new generation of vaccines. Such vaccines are defined at the molecular level, can elicit immune responses controlling infectious organisms and are therefore potentially free of the problems encountered in conventional ones. Unfortunately, subunit and synthetic peptide vaccines are often only weakly or non inmunogenic. However, developments in both antigen production and immuno potentiation of weak antigens have opened new avenues with exciting prospects for vaccine design.

In recent years, the area of pharmacotherapy of GI inflammation has witnessed important progress, with new drugs and therapeutic approaches being introduced. The volume reviews the pharmacotherapy of selected gastrointestinal inflammatory conditions chosen on the basis of their clinical importance and/or the areas where important and exciting progress has been made recently. Besides discussing current pharmacotherapy to treat the most important GI inflammation conditions, the book also indicates possible future therapeutic avenues likely to become available in a few years.
The book is of interest to various sectors of the scientific community ranging from clinicians to pharmacologists and from biochemists to microbiologists, who will find it a useful tool for their clinical practice and research activity.

1. 1. Invasive versus Non-Invasive Clinical Measurements in Medicine Clinical measurement has become an essential complement to traditional physical diagnosis. An ideal clinical measurement should be quantitative, have a high level of reliability and accuracy, be safe, acceptable to the patient, easy to perform and non-invasive. The latter demands that the technique should not break the skin or the lining epithelium and should be devoid of effects on the tissues of the body by the dissipation of energy or the introduction of infection [1]. It is therefore logical that for a given measurement, a non-invasive test will be preferred if it provides the same information with the same accuracy and precision. In the following sections, we will discuss the role of various non-invasive or relatively non-invasive methods to assess airway inflammation in asthma and concentrate on the only direct method of induced sputum examination. 1. 2. Why Is Assessment of Airway Inflammation Important in Asthma? Inflammation is a localized protective response elicited by injury or destruc tion of tissues which serves to destroy, dilute or wall off both the injurious agent and the injured tissue [2]. The role of inflammation in asthma was rec ognized long ago. In his textbook The Principles and Practice of Medicine, in 1892, Sir William Osler described "bronchial asthma . . . in many cases is a spe cial form of inflammation of the smaller bronchioles . . .

Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.

From the basic science to potential and approved clinical applications the most recent data in the rapidly growing field of bone morphogenetic proteins (BMPs) are summarized in this topical volume. Distinguished scientists present reviews on a range of scientific topics, including biochemistry, biology, molecular biology and preclinical animal studies on spinal fusion, cartilage repair, craniofacial and dental reconstruction using BMPs, as well as approved clinical applications in human bone non-unions.

This book provides a resource not only for experts in the field, but also for undergraduate students, newcomers and clinicians worldwide, given that the use of BMPs in orthopedic reconstruction has been already approved in Europe, Australia, Canada and the USA.

Immunosuppression in solid organ transplantation is currently experiencing a worldwide revival since new drugs are now available and others are under development. In order to contribute to the design of future strategies, a critical approach of surrogate endpoints is given and long-term side effects are analysed, together with the impact of non-compliance, quality-of-life and economical parameters. In this book, international specialists have set up the scientific rationale and provided new bases for further immunosuppressive strategies.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Fluorescence is a very powerful tool for work at the frontier of cell biology, photobiology and bioinstrumentation. The stated aim of the workshop was to highlight the significance of fluorescence work for the understanding of cell and tissue physiology, physiopathology and pharmacology, particulary in terms of the analytical use of fluorescent probes in oncology. In the organization of the workshop a multidisciplinary approach was selected. The purpose of the Advanced Research Workshop (ARW) was to bring together researchers in the various disciplines of tissue optics, imaging, microspectrofluorometry and state of the art probes, in order to explore the full benefits that can be derived in biomedicine through the convergence of these approaches. When applied to in vivo and in situ studies, fluorescence and related optical methods enable us to explore within tissues, cells and organelles photon effects previously understood only in solution photochemistry. Processes which can be studied at the molecular level by photophysics, photochemistry and physical chemistry can be evaluated in living tissue by fluorescence spectroscopy and imaging at the intracellular level in terms of structure and function. Thus, fluorescence adds a new dimension to cell biology and physiology. This approach is now supported by a full and versatile, rapidly growing armamentarium of new selective probes for organelles, enzymes, cations, cytoskeleton and metabolic control.

Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye disease. Each chapter is written by an expert and truly represents the current state of the art on the particular topic. This book can therefore almost be considered a textbook on this enigmatic disorder. Recent Developments in Graves' Ophthalmopathy is designed for all those interested in this disease, including basic scientists, clinical endocrinologists, ophthalmologists, radiotherapists, and orbital surgeons. The book gives a comprehensive overview of all aspects of Graves' ophthalmopathy. Subjects covered include the pathology of Graves' eye disease and the controversial views on its autoimmune pathogenesis; assessment of the eye changes using reliable measurements; medical management of Graves' eye disease with an overview of the many treatment options available to the clinician, including orbital radiotherapy and other immunosuppressive treatments; management of the thyroid disease; and finally, the techniques for performing various surgical procedures, which are explained and illustrated.

This volume offers an analysis of the scale and nature of the immunological issues facing regenerative medicine, drawing on the expertise of laboratories around the world who have taken up the challenge of applying their expertise in immunology to the vagaries of stem cell biology. In Part I, we explore the extent to which the principles of allograft rejection, learned over several decades from our experiences of whole organ transplantation, apply within the unique context of cell replacement therapy. Part II discusses various innovative ways of addressing the issues of immunogenicity, while, in Part III, we focus exclusively on the induction of immunological tolerance through a variety of novel approaches. It is our hope that this systematic analysis of the current state of the field will galvanise efforts to solve an issue which has so far remained intractable.

The wealth of research results in the area of breast cancer diagnosis and therapy with monoclonal antibodies presented in previous workshops is now complemented with a new rendition of the proceedings of the 4th Workshop on Monoclonal Antibodies and Breast Cancer. held in San Francisco on November 5-6. 1990. Basic science findings reported in previous workshops have now percolated to the clinical level and have become immunoassays and imaging and therapy reagents. as the program shows us. Thus. the latest discoveries in immunology. biochemistry and molecular biology of breast epithelial antigens and their corresponding antibodies have produced newer diagnostic tests and therapeutic approaches that are altering and improving the way we attack breast cancer. The recent spectacular and rapid advancements in the molecular biology of several of the breast epithelial antigens are presented in this volume. The way in which the final assembly of different components of the breast antigens is achieved and their functions are now within our grasp as a result of new understanding of molecular structure of these breast antigens. In addition. newer immunoassays aiming at the earliest detection of the disease are also described that integrate with promising attempts at imaging and radioimmunotherapy to set the stage for new oncological possibilities in breast cancer treatment. All these areas of intense involvement of scientists with diverse specialties are presented in this volume. which proves the need for multidisciplinary approaches to increase our chances for success in this field of medical research.

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

Novel molecular motifs named Immunoreceptor Tyrosine-based Inhibition Motifs (ITIMs) have recently been recognized in the intracytoplasmic domains of a still-increasing number of receptors which control cell activation and proliferation. Research on ITIM-bearing molecules has developed exponentially during the last three years, generating new concepts with important consequences in basic research and with exciting potential clinical applications. The present volume contains 15 reviews written by authors who all made significant contributions to the identification of ITIM-bearing molecules and the study of their biological properties. It constitutes the first synthesis ever published that is specifically devoted to this emerging topic.