W. TH. DAEMS This volume contains the papers presented at a Boerhaave Course for Post graduate Education on The cell-biological aspects of disease: the plasma membrane and lysosomes. One of the purposes of this introduction is to explain the reasons for this choice of subject. The first question which might be asked - why a postgraduate course on the cell biological aspects of disease was considered neccessary - is not difficult to answer: the impact of the basic sciences on medicine is im measurably strong, and among these sciences cell biology has contributed immensely to the advances made in medicine during recent decades. It has provided clues leading to general insights into etiology and pathogenesis as well as to the development of diagnostic tools and a basis for therapeutic methods. These insights derived mainly from the still-increasing body of knowledge about the architecture of cells. Initially, this knowledge arose from the notion that cells are either simply bags full of enzymes or complex sponge like structures in which all organelles are permanently interconnected (Fig. 1). Later, this notion was replaced by a highly schematized picture of the cell as an essentially two-compartment structure (Fig. 2) in which cell organelles are discrete units separated from each other by membranes, enabling each organelle to maintain an internal microenvironment with optimal conditions for its specific metabolic pro cesses."

Cancer has become the most critical health problem in the United States. It is expected that 25% of the people will develop this dread disease, and many of these will die from the malady. The causes of cancer are varied, but the best estimate available is that 70--90% arise from environmental factors. These statistics have triggered widespread governmental action along two lines: (l) An effort to identify those chemicals and conditions that give rise to malignant processes has been mounted by the Carcino genesis Testing Program, the National Cancer Program, and subse quently, the National Toxicology Program. (2) Regulatory laws have been enacted that are administered by agencies such as TSCA, FIFRA, EPA, FDA, OSHA, and so on, whose mission is to minimize public ex posure to carcinogens. Since direct verification that specific chemicals induce cancer in hu of unanticipated expo mans is necessarily limited to known incidences sure and is therefore rare, most chemicals are identified as carcinogens only by laboratory experiments. At present, the only accepted procedure is long-term animal bioassay, and not only are these studies expensive and time-consuming, but current worldwide resources permit the evalua tion of only 300-400 chemicals per year, a miniscule amount compared to what is available in the commercial world: 30,000 existing chemicals, with approximately 700 new such materials being introduced every year."

The processes of distention and recoil have an essential role in the functions of arteries and lungs. In both organ systems, these processes involve to a great extent the connective tissues, in particular the manner in which the extracellular materials are arranged to afford such movements. This book concerns the microenvironment of the connective tissues in the walls of arteries and the stroma of lungs. Proteoglycans, collagen, and elastic fibers and their interrelationships are discussed by eight scientists who are established researchers in this area. Their reports include important findings on how this microenvironment is altered in diseases such as atherosclerosis, emphysema, and pulmonary fibrosis. The concepts developed result from studies at the biochemical, macromolecular, ultrastructural, and light microscopic levels. Taken col lectively, the reports focus attention upon the role of the connective tissues in arterial and lung distensibility and how alterations in the connective tissues result in the loss of this function. Medical researchers and physicians interested in arterial or lung functions or diseases will find the scientific approaches and findings of the authors innovative and provocative. Students of stereologic morphometry will be particularly interested in the quantitative studies of cells and fibers in arterial walls; histologists and pathologists will find the chapter on histochemical staining interesting from both a scientific and historic viewpoint.

A critical phase in coronary heart disease, unstable angina, is thoroughly discussed in contributions by well-known experts. Since myocardial infarction still belongs to the main causes of death, this topic is highly relevant for the present research and possible future treatment of coronary heart disease. The major recent advances made in the pathophysiology, diagnosis and therapy of unstable angina are reported in depth.

Vor die Therapie setzten die Gotter die Diagnose. Otto NiigeJi Renal biopsy has decisively enriched renal diagnostics. Kidney diseases may be monitored during their entire course, and new techniques - such as immunofluorescence and electron microscopy - may be systematically applied, resulting in novel insights into the morphogenesis, pathogenesis, and etiology of kidney lesions. These insights, in turn, have served as new starting points, in the spirit of the quotation above, for the institution of causal therapy by the clinician. This work presents our findings based on 20 years of experience in evaluating renal biopsies. As of the end of 1974, our computer-supported, systematic clinical, morphologic, and follow-up evaluation of case material consisted of over 2000 biopsies, including 679 examined by electron microscopy and 400 by immunofluorescence microscopy. The subsequent 500 biopsies (400 studied by electron microscopy and 300 by immunofluorescence) were con sidered qualitatively only. In order to enhance qualitative findings with quantitative data, it was necessary to devise new methods for quantifying electron-microscopic findings. Additionally, we attempted to correlate cyto logic and immunofluorescent observations to integrate the isolated findings of electron microscopy into a vital cytologic pattern of reactions. We also attempted to evaluate the almost overwhelming flood of publications, especially those appearing within the last 10 years. The idea for this book was conceived a decade ago. At that time, however, our own experience in renal biopsy diagnostics seemed insufficient to sup port such a major undertaking."

The first International Symposium on Brain Edema was organized by Dr. Klatzo and Dr. Seitelberger and held in Vienna in 1965. The second Symposium was held in Mainz in 1972 and organized by Dr. H. J. Reulen and Dr. K. Schiirmann, the third in Montreal in 1976 by Dr. H. M. Pap- pius, the fourth in Berlin in 1979 by Dr. J. Cervos-Navarro, and the fifth in Groningen in 1982 by Dr. K. G. Go. This volume contains the papers presented at the 6th International Sym- posium on Brain Edema, held in Tokyo, Japan, November 7-10, 1984. The invited lectures by Dr. I. Klatzo, Dr. A. Hirano, Dr. S. I. Rapoport, Dr. B. K. Siesj6, Dr. H. M. Pappi us, Dr. K. A. Hossmann, and Dr. D. M. Long are included as special chapters. On behalf of the organizing committee, I wish to express my deep ap- preciation to all the participants for their contribution toward making this meeting so fruitful and significant. Moreover, the great success of this Sym- posium depended on the high quality of the invited lectures and presen- tations by experts in various fields, as well as on the free and enthusiastic discussion. I was deeply impressed with the papers presented by all the authors, who endeavored to elucidate their subjects. The editors have made only minor corrections and rearrangements, since prompt publi- cation was considered to be important.

This volume contains all the invited papers, symposium contributions and workshop reports of the 7th International Congress of Human Genetics, held in West Berlin from September 22 to 26, 1986. The organizers of this congress made sure to gain the cooperation of the leading scientists in the field from all over the world. These contributions therefore document the enormous progress made in human genetics research in recent years. The volume covers a wide range of topics, from analysis of the human genome to basic mechanisms, diagnosis and therapy of hereditary diseases, and to distribution of normal and pathological genes and DNA variation in human populations. Ethical issues raised by modern developments are discussed thoroughly. The volume is a must for all scientists and medical doctors working in human genetics research, its teaching and practical applications.

This two-volume treatise, the collected effort of more than 50 authors, represents the first comprehensive survey of the chemistry and biology of the set of molecules known as peptide growth factors. Although there have been many symposia on this topic, and numerous publications of reviews dealing with selected subsets of growth factors, the entire field has never been covered in a single treatise. It is essential to do this at the present time, as the number of journal articles on peptide growth factors now makes it almost impossible for anyone person to stay informed on this subject by reading the primary literature. At the same time it is becoming increasingly apparent that these substances are of universal importance in biology and medicine and that the original classification of these molecules, based on the laboratory setting of their discovery, as "growth factors," "lymphokines," "cytokines," or "colony stimulating factors," was quite artifactual; they are in fact the basis of a com mon language for intercellular communication. As a set they affect essentially every cell in the body, and in this regard they provide the basis to develop a unified science of cell biology, germane to all of biomedical research. This treatise is divided into four main sections. After three introductory chapters, its principal focus is the detailed description of each of the major peptide growth factors in 26 individual chapters."

Previous volumes in this series have discussed the current progression have identified a variety of targets and strategies state of our knowledge concerning the pathophysiology of to allow these goals to be realized. This volume critically cancer growth and progression. The complexity of the in reviews approaches towards cancer management in man at teraction of malignant neoplasms and the host, the the levels of: detection, diagnosis, surgery, radiology, heterogeneity of malignant cell subpopulations, and the chronobiology and endocrine treatment. existence of metastatic tumor cells resistant to drug thera Several chapters review selected methods of cancer diag pies remain as significant clinical challenges to clinical on nosis. In addition, a variety of on-going and novel ap cologists. Indeed, conventional treatment regimens of che proaches for cancer treatment are also presented in this volume. Progress in the early detection of malignant neo motherapy, surgery and radiology are often ineffective for the therapy of a large variety of established metastatic can plasms, coupled with novel approaches for the therapy of cer in patients. When one considers the insidiousness of such neoplasms, may ultimately yield safe and well-tolerated agents for the selective therapy of solid malignancies. New progressive neoplastic growth and the emergence of con tinuously more aggressive and malignant cellular subpop therapeutic approaches, directed towards the biochemical ulations one is overwhelmed with the challenges inherent in and molecular targets identified in the earlier volumes of this series, may ultimately lead to the generation of new mo attempting to control malignant neoplasms."

Human Lymphoma: The Clinical Implications of the REAL Classification is a unique volume. It is based on the recent developments in classification and overall understanding of human lymphoid neoplasms which are relatively common neoplasms and which epidemiological evidence suggests are increasing in frequency. This field has been the cause of confusion in the past as a result of conficting ideas on the classification of lymphoma and related diseases. However a new vision of the field has emerged and the is encapsulated in the pioneering REAL classification and in a forthcoming WHO scheme, both of which are covered in the book. The volume will appeal to hematologists, pathologists and oncologists and will, thanks to a diverse and expert authorship, serve to increase the working knowledge of all three groups.

Spinal Cord Injury or disease can happen to anyone at any time and the effects can be devastating. I found this out personally when I was thrown from the back of a pick up truck at age 15 was left paralyzed from the waist down. It was during my recuperation as a young teenager that I first gained insight into the importance of rehabilitation. My family, doctors, nurses, fellow patients and researchers who were dedicated to helping me over come my personal tragedy helped me pull through. Today, rehabilita tion medicine is taking great strides and empowering the person with the injury to take control of their future, overcome their setbacks and, through collaborative support, reach their personal goals and potential. Since 1987 the Legacy raised by my Man in Motion World Tour (24901 miles wheeled around the world March 1985-May 1987) has pro $13 million dollars to research and rehabilitation in the areas vided over of spinal cord injury. I hope that in some small way this funding has contributed to the development of the vital programmes that supported me and many others. The effects of spinal cord injury are traumatic and life-shattering and require a skilled interdisciplinary approach. I congratulate those who have contributed to this book and challenge each one of you to never give up on your dreams to find the answers to the optimum treatment of spinal cord injury and disease."

1. Concepts on the Causal Genesis of Human Intestinal Tumors The action of chemical substances has a significant role in the genesis of human tumors. It is assumed that most human tumors are induced by exogenous chemical noxae (Schmahl, 1970;Heidelberger, 1975; and others). In the course of intensive efforts to discover the principles of tumor etiology, important insights have resulted in recent years. These are that chemical carcinogens do not only arise as products of our tech nological civilization, but that they also occur in nature as potent solitary carcinogens and cocarcinogens (e. g., as plant products). For review, see Hecker (1972) and Preuss mann (1975). Not only "complete" carcinogens are significant for the genesis of tu mors, but also substances which are first transformed to the actual carcinogenic com pound in the organism (Schmahl, 1975). The causal significance of exogenous noxae in carcinogenesis is indicated by the fact emphasized by Bauer (1963) that malignant tumors occur predilectively at those sites in the body which are in direct or indirect contact with the environment. This applies especially to the intestinal tract."

During the past few years, a considerable number of monographs on bone tumors have been published. They are mainly restricted to bone tumors as clinical-pathological entities, since their diagnosis, more than that of other tumors, requires the interdisciplinary cooperation between orthopedic specialist, radiologist, and pathologist. However, investiga tions concerning the histogenesis of bone tumors are rather limited, although they might be helpful in explaining the unique morphological heterogeneity of tumors of the skeletal system. Furthermore, the histo genetic approach in the study of bone tumors may facilitate the inter pretation of the advanced cytobiological methods available for improv ing classification and diagnosis. Therefore, this volume presents recent pathological advances in the biological characterization of bone tumors. A major chapter deals with the differential diagnosis of Ewing's sarcoma as regards its demarcation from the so-called neuroectodermal tumor of bone. The analysis of the ground substances in bone-forming tumors may be helpful for their classification. Therefore the volume includes a chapter on the biochemical and histochemical analysis of different osteosarcoma types. Recently it has become clear that in addition to different collagen types which are not specific for bone tissue, several bone-specific proteins occur, one of which is osteonectin. Its distribu tion is obviously important for the classification and diagnosis of osteo blastic tumors. Proliferative behavior is of major importance for the diagnosis of malignant tumors.

It is difficult for a teacher to accept the fact that not all of the information in his or her field is a necessary part of the armamentarium of the student. This holds for histologists, and for that matter, pathologists, biochemists, and ophthalmologists. It may especially hold for those who were trained during exciting periods in the history of their discipline. In the past two decades, information in every basic medical science has increased greatly, perhaps exponentially, and the basic science curriculum has been compressed to the point where the medical student can reasonably be expected to acquire only a superficial knowledge of anyone of these sciences. Hence the information provided must be carefully selected, effectively presented in retainable doses, and useful for understanding material to be presented later in the curriculum and for the solution of clinical problems. In the compact courses of today, the presentation of only enough data to support basic working concepts of structure and function is appropriate. Additional factual information consti tutes trivia, which in our opinion interferes with effective development, reten tion, and use of the concepts. This philosophy has been the basis for the preparation of this book. Consistent with this philosophy, the text is brief, and the content has been carefully examined for its appropriateness to the needs of the medical student."

, 1m Kleinsten die wirkliche Wahrheit gibt graBen Gedanken erst Klarheit" KARL THOMAS Each year sees the publication of hundreds of reports of experimental work on the lymphatic tissue, yet morphological studies of the cells involved can be counted on the fingers of one hand. Furthermore, anyone who tries to identify these cells by morphological criteria is accused of sophistry and hair splitting, whereas it is accounted scientifically correct and unbiased to speak of "lymphoid cells," "blast cells" etc. Not so many years ago things were different: there were too many names and too many classifi cations and everyone backed his particular fancy. People thought of cells in terms of rigid classes, nothing then being known about the transformability of mononuclear blood cells. Today we must look for the middle way: cells should be named and defined according to morpho logical criteria but their transformation potential should be borne in mind. Once the cells are analysed and subdivided, it will be simple enough to set up proper classifications afterwards. This book arose out of the conviction that there should be more criteria and more information available on the morphology of human lymphoreticular cells; previously such information had been restricted by the difficulty of the special hematological and cytochemical staining methods."

Fresh research has opened up new vistas in forensic pathology that are allowing for closer national and international cooperation between pathologists and scientists in a range of medical and scientific disciplines. At the same time, autopsy and laboratory techniques are undergoing rapid evolution, with new procedures coming on stream while existing processes yield additional -- and more accurate -- results. This sixth volume of reviews in forensic pathology provides professionals working in the field with cutting-edge material on the latest key advances in the fields of traumatic death, sudden natural death and death time estimation. Now with numerous color illustrations, the book gives forensic experts across the world a fully up-to-date guide to contemporary procedures and theory in forensic science and medicine. The chapters cover an exhaustive range of aspects in the discipline, from the analysis of sudden natural deaths in infancy and childhood to the cardiac proteomics approach in the study of cases involving sudden cardiac death. Other specialist chapters deal with the forensic investigation of deaths in aviation and as a result of accidents involving all- terrain vehicles. The volume covers fresh research in the use of protein markers for the estimation of post-mortem intervals, and features a chapter telling the story of the medico-legal investigation into the deaths resulting from the 9-11 terrorist attacks on the World Trade Center.Comprehensive and current, this fresh volume of reviews is an essential resource for professionals who need to stay ahead of the game in a fast-moving and exciting field of scientific endeavor.

Over the last decade, high performance Capillary electrophoresis (HPCE) has emerged as a powerful and versatile separation technique that promises to rival high performance liquid chromatography when applied to the separation of both charged and neutral species. The high speed and high separation efficiency which can be attained using any of the various modes of HPCE has resulted in the increased use of the technique in a range of analytical environments. The procedures are, however, still in the early stages of development and several barriers remain to their adoption as the technique of choice for a range of analytical problems. One such barrier is the selection and optimization of the conditions required to achieve reproducible separations of analytes and it is in this area that this new book seeks to give assistance. The book is written by an international team of authors, drawn from both academic and industrial users, and the manufacturers of instruments. At its heart are a number of tables, divided into specific application areas. These give details of published separations of a wide range of archetypal analytes, the successful separation conditions and the matrix in which they were presented. These tables are based on separations reported since 1992 and are fully referenced to the original literature. The tables are supported by discussions of the problems that a particular area presents and the strategies and solutions adopted to overcome them. The general areas covered are biochemistry, pharmaceutical science, bioscience, ion analysis, food analysis and environmental science.

The idea for this treatise on the radiological anatomy of superficial and deep spinal cord vasculature evolved from daily routine neuroradiological work. This was also the reason for subdividing the monograph into a postmortem anatomical and a clinical part. The actual importance of a clear conception of radio anatomic fundamentals was made clear by many clinical conferences with neurologists, neurosurgeons and orthopedists, where a lack of knowledge about medullary syndromes of suspected vascular origin became evident. Also among neuroradiologists there is still widespread uncertainty in the interpretation of myelograms and angiographies in such cases. A study of the spinal cord's angioarchitecture is all the more justified and necessary considering the vast number of descriptions of cerebro vascular anatomy and pathology. The clinical challenge posed by patients suffering from partial or complete transverse spinal lesions has grown due to new diagnostic and therapeutic approaches. Myelography using water-soluble contrast media, X-ray computed tomography, magnetic resonance imaging and spinal angiography today allow and require both earlier and topographically and pathogenetically more exact classification of diseases of the spinal cord and its surrounding structures. Due to progress in microneurosurgery and interventional neuroradiology, even intramedullary lesions have become more and more accessible and treatable. Therefore this monograph mainly addresses those concerned with invasive therapeutic techniques and who are familiar with the interpretation of radio anatomic findings. A comprehensive description of medullary vascular syndromes would be beyond the scope of this treatise."

This volume is a compilation of papers presented at the Tenth International Symposium on Brain Edema held on October 20-23, 1996, in San Diego, California. This follows the sequence of meetings that was initiated 31 years ago in the First International Symposium held in Vienna. Subsequent symposiums were held in Mainz, Montreal, Berlin, Groningen, Tokyo, Baltimore, Bern, and Tokyo CY okohama). A considerable number of papers was chosen from over 100 papers that were received. The organizers wish to thank the Advisory Committee for the excellent work done in selection of the papers. We also wish to thank all the persons who contributed to the success of the Tenth International Symposium, especially the staff who worked behind the scenes. These papers were reviewed, edited, approved or disapproved by the Editorial Board. Those manuscripts that were felt not pertinent to this publication were not accepted by the Editorial Board. Therefore, the excellent quality of those that are in the book are a reflection of the authors' dedication and work and that of those of the Editorial Board in their review process. For the reader's convenience, the papers are structured according to the various disease processes which are associated with the primary topic: hypertension, hydrocephalus, infection, ischemia, tumor, etc. We do hope that the reader will enjoy the articles and that they will provide an impetus and insight for future work.

Analogue to the first edition, the principal characteristic of this work is its casting of pathology as the common nosographic link in the diagnosis, prognosis and treatment of brain tumours. A result of the author's many years of experience in the study of brain tumours and their pathological and clinical characteristics, the book presents different aspects of neurooncology from the perspective of pathology and its biological and clinical correlates. This new, second and enlarged volume preserves all the qualities of the first edition while further amplifying clinical applications and updating biological and pathological problems. The references have been completely revised and new chapters have been added on topics such as neuroimaging, invasion and angiogenesis.
Professor Schiffer is President of the Italian Association of Neurooncology and of the Italian Association of Neuropathology.

This volume represents the formal presentations and discussions which took place during a three-day meeting in March 1988 at The University of Texas M. D. Anderson Cancer Center in Houston. It is" dedicated to my friend of more than thirty years, Prof. Dr. Klaus Joachim Ziilch, who died in Berlin on December 2. 1988 while this volume was still in preparation. Klaus Zulch had devoted a significant portion of his professional life to a better understanding of central nervous tumors. Over the past two decades he served as the Director of the Collaborating Center for CNS Tumors, under the auspices of the World Health Organization (WHO), and it was largely through his efforts that the work of the CelJ. ter in developing criteria for a histologic classification of these neoplasms was kept alive. Without his stimulus this Houston meeting would probably not have taken place. In early 1987 he approached me with the idea of convening, at an early date, a meeting in Houston in collaboration with the Department of Neuro-Oncology of the Cancer Center, of which I was then Chairman. The purpose of this proposed meeting was to discuss recent research developments that might have a profound influence on the classification of brain tumors and ultimately necessitate revision of the "Blue Book" of the WHO on Histological Typing 0/ Tumours 0/ the Central Nervous System.

This is a book about renal cysts and cystic kidneys. Its contributors have created a resource of current information in a field that once aroused only curiosity, but that now stands at the leading edge of molecular nephrology. Its authorship includes 'oldtimers', who bring the wisdom of experience, and 'newcomers', whose presence attests to the contributions made by the investigative and technological advances of the past decade. Its text is organized to carry the reader from renal cyst to cystic renal disease. Each of its chapters defines or explores a challenge or an advance. Cells that line renal cysts are diverse in structure, type, and perhaps function. The cysts themselves lie within an interstitium that is not normal and may influence cyst development and growth. Experimental analogs of human disease offer increasing opportunities to basic researchers to examine, in sequence and under controlled circumstances, those events that favor nephron dilation, cyst growth and ultimate renal failure.

The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Part I. Approaches to Assessing the Toxicity of Airborne Toxicants Chapter 1. Standard-Setting as an Integrative Exercise: Alchemy, Juggling, or Science? . . . . . . . . . . . . . . . . . . . . . . . 1 D. v. Bates Chapter 2. Species Differences in Inhalation Toxicology: Variations in Exposure-Dose Relationships and Macrophage Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 J. D. Brain Chapter 3. Cell Populations of the Respiratory System: Interspecies Diversity in Composition, Distribution, and Morphology . . . . . . . . . . . . . . . . . . . . . . . . 25 e. G. Plopper, A. Mir, J. St. George, N. Tyler, A. Mariassy, D. Wilson, S. Nishio, D. Cranz, J. Heidsiek, and D. Hyde Chapter 4. Comparative Metabolic Basis for the Disposition and Toxic Effects of Inhaled Materials . . . . . . . . . . . . . . . . . 41 A. R. Dahl Part II. Methodological Issues in Designing and Conducting Studies with Laboratory Animals Chapter 5. Exposure Facilities and Aerosol Generation and Characterization for Inhalation Experiments. . . . . . . . . .

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series which focuses on an emerging area of cancer research. In 1968, R. H. Williams first reported that elevated prostaglandin levels are present in human medullary carcinoma. Since that time, the concept that arachidonic acid metabolites may be involved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family ofbioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respectively. Cyclooxygenase products consist of diverse products such as prostaglandin E2 (PGE2), prostacyclin (PGI2) and thromboxane A2 (TXA2), whereas lipoxygenase products consist ofhydroperoxy fatty acids and mono-, di-and tri-hydroxy acids including leukotrienes, lipoxins, and epoxides. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis --the release of substrate. This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengt Samuelsson's extensive study ofthe metabolism of prostaglandins indicate that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in the vicinity oftarget tissues leading to the concept that prostaglandins are local rrormones or autocoids. Altered production, qualitative and/or quantitative, of prostaglandins and leukotrienes has been implicated in the development of a number of disease states (e. g.