Recently, attention has been called to the role that microvascular organization plays in the functional morphology of all organs and tissues, both in normal and pathological conditions. Since its development by Murakami, the corrosion cast method for scanning electron microscopy has come to be considered one of the most efficient means in clarifying the three-dimensional features of the microcirculation of organs and tissues. Scanning Electron Microscopy of Vascular Casts: Methods and Applications was planned to supply fundamental and new information regarding microcirculation studies to general biologists, anatomists, pathologists and clinicians. The contributions to this volume, contain original findings and excellent electron micrographs obtained by using recently improved corrosion cast methods. The rich variety of papers in this book will be useful to many, and will provide both the basic and clinically oriented readers with good ideas, suggestions, and original and worthwhile information.

The 'Formation of the Heart and its Regulation' reviews in considerable detail the major events in heart development and their control via genes, cell-cell interactions, growth factors and other contributing elements. In addition, there is an extensive and useful overview of the field of heart development taken as a whole. The book will appeal to all students and researchers working on cardiovascular development and to pediatric cardiologists.

We have considered it to be a demanding assignment to provide a complete exposition dealing with the nature of radiation, its effects, and protection against it to workers in health-related activities. "Radiation" (and more precisely "ionizing radiation") is emitted by X-ray machines, nuclear reactors, and nuclear weapons, but also comes from natural sources to which we are all exposed. It would have been easier to deal with this subject area with the terminology and mathematics employed by specialists. However, although most of the potential readers probably have obtained further pertinent knowledge, we assume no more than a high school education in science and mathematics and the challenge was to provide maximum information within this constraint. This book contains five sections: (A) Radiation Physics, (B) Radiological Physics, (C) Radiation Biology, (D) Radiation Effects on Human Populations, and (E) Radiation Protection. Each section is preceded by a synopsis covering its essential features. It provides sufficient information to enable readers to obtain a general under standing of the subject of the section and an adequate background for comprehension of other sections. The more detailed presentation in the bulk of each section is followed by appendixes that generally contain more advanced topics. This scheme necessarily involves some repetition but permits a more flexible approach for readers who are especially interested in the contents of particular sections.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis tant. I hope you find this resource useful. Laurence S. Baskin, M.D.

The overall scope of this new series will be to evolve an understanding of the genetic basis of (1) how early mesoderm commits to cells of a heart lineage that progressively and irreversibly assemble into a segmented, primary heart tube that can be remodeled into a four-chambered organ, and (2) how blood vessels are derived and assembled both in the heart and in the body. Our central aim is to establish a four-dimensional, spatiotemporal foundation for the heart and blood vessels that can be genetically dissected for function and mechanism. Since Robert DeHaan's seminal chapter "Morphogenesis of the Vertebrate Heart" published in Organogenesis (Holt Rinehart & Winston, NY) in 1965, there have been surprisingly few books devoted to the subject of cardiovascular morpho genesis, despite the enormous growth of interest that occurred nationally and inter nationally. Most writings on the subject have been scholarly compilations of the proceedings of major national or international symposia or multi authored volumes, without a specific theme. What is missing are the unifying concepts that can often make sense out of a burgeoning database of facts. The Editorial Board of this new series believes the time has come for a book series dedicated to cardiovascular mor not only as an important archival and didactic reference phogenesis that will serve source for those who have recently come into the field but also as a guide to the evo lution of a field that is clearly coming of age.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

If one were to design the ideal nuisance for cell cultures, the resultant might well be similar to mycoplasmas. These micro organisms are very prevalent in nature, being found in the oral cavity, blood, the mucous membranes of the respiratory and uro genital tract and other tissues of both man and animals. They are relatively difficult to detect microbiologically and chemically. Lacking cell walls, they do not routinely produce turbidity in cell cultures and are resistant to antibiotics that act on cell walls. Mycoplasmas grow to high titers in cell cultures. Concen 7 8 trations of 10-10 colony forming units per ml of supernatant medium are representative. Additionally, more numbers are attached to cell membranes. Further, mycoplasmas have been shown to mimic in vitro effects of viruses and toxic chemicals. In various cell culture systems, mycoplasmas have been known to cause cell death, decrease or increase cell growth, affect virus tite s, induce interferon, cause chromosome damage, induce transformation, cyto pathic effects, alter phenotypic expression, and significantly alter metabolic pathways and products of cells. The presence of such high concentrations of mycoplasmas in cell cultures constitutes a true in vitro infection. Such infected cell cultures, with a 8 9 total of 10 _10 or more actively metabolizing mycoplasmas, have no place in controlled, standardized cell culture procedures. Numerous reports have been published on mycoplasma assay pro cedures, effects of infection, and preventive and elimination measures."

Heme oxygenase is rapidly taking its place as the centerpiece of multiple inter acting metabolic systems. Only 25 years ago heme oxygenase and its metabolic prod ucts appeared to be merely a simple metabolic system-one substrate, heme; one enzyme, heme oxygenase; and one set of products, iron to be recycled, and bilirubin and carbon monoxide to be disposed. From a group of about 25 people in 1974, as judged by attendance at various Gordon conferences, heme oxygenase has, in the year 2000, attracted working scientists-and clinicians I might add-by the hundreds and has produced referenced publications by the thousands. It is well-deserved attention. Heme oxygenase system is now similar to the metabolic networks surrounding glucose in those complex maps of glycolytic and non-glycolytic metabolic pathways, which we had to memorize as students. The relevance of heme oxygenase to regulatory biology was recognized many years ago, but the work conducted over the past five years has created a new wave of emphasis focusing on genetic manipulation to alter heme oxygenase gene expression, the regulatory actions of heme oxygenase products including carbon monoxide, and the significance of changes in the heme oxygenase system. The physiological and pathological relevance of heme oxygenase in the brain, heart, liver, bone marrow, organ transplant, lung and kidney, opens many areas of investigation in various dis ciplines. Advances in the pharmacology of bilirubin and its ability as an antioxidant have provided a new avenue in clinical research.

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 Eighth Annual Research Conference of the American Institute for Cancer Research, held in Washington, D.C., September 3-4, 1998, was on the subject "Colon Cancer Prevention: Dietary Modulation of Cellular and Molecular Mechanisms," with participants representing various disciplines interested in this area. One of the speak ers provided an appropriate quote from 17th century physician Thomas Adams: "Pre vention is better than healing because it saves the labor of being sick," which aptly describes the need for the prevention of cancer. An overview of normal and abnormal colonic development emphasized that although the typical human colon undergoes 1013 cell divisions by age 60, with the asso ciated possibilities for error, relatively few colon tumors develop. Since dietary modu lation leads to extremely small changes in colonic cells over a long period, animal models are useful to time, observe, and delineate the events associated with colon cancer. In the development colon cancer, the inactivation of the adenomatous polyposis coli (Apc) gene is one of the earliest known events. Normally Apc downregulates the cellular protein beta-catenin, but this is lost during cancer development. Beta-catenin may itself be an oncogene; it has a short half-life, but it is stabilized by binding to is more prevalent in the cell nucleus, the gene shuttles caherin. Although the Apc between the nucleus and the cytoplasm."

Over one million readers have turned to "Strength Training Anatomy" for strength training's most effective exercises. Now put those exercises to work for you with "The Strength Training Anatomy Workout."

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In the last two decades, investigations at the cellular level have progressively gained ground in the context of hypertension research. This choice of approach is due to some extent to the build up of know-how that molecular and cellular biology have been producing at a continuous rate. As the contents list of this volume shows, a large mass of work has been directed to gaining some insight into pathogenetic mechanisms. The pathogenesis of primary hypertension has been progressively categorized as a distinct biological problem, not amenable to the theoretical models that proved successful in understanding the nature of secondary forms of hypertension. At the same time, great efforts have been made to simplify this problem by sorting out, if possible, a few crucial mechanisms from the network of contributory factors in the regulation of blood pressure. The idea that what is to be sought is a primary structural and/or functional fault in arterial muscle has met with widespread acceptance. The strength of this argument lies in the fact that peripheral vascular resistance is increased in all forms of hypertension and, in turn, the diameter of resistance vessels is the dominant factor in the computation of total per ipheral resistance. On the basis of this, cardiovascular structural adaptation was proposed as a positive feedback mechanism tending to maintain hypertension, once begun, whatever the initiating factor is.

The fetal period of human growth and development has become an area of intense study in recent years, due in large part to the development of diagnostic ultrasound. More than 2,000 articles have been published in the last five years describing anatomy and pathology in utero, as reflected in sonographic images. Yet, no stan dard reference exists to correlate these images with fetal gross anatomy and at tempts to draw parallels from adult structure have often led to false assumptions. The dictum "the newborn is not a miniature adult" is all the more valid for the fetus. This text aims to provide a comprehensive reference for normal sectional anat omy correlated with in utero ultrasound images. In addition, magnetic resonance images of therapeutically aborted or stillborn fetuses are paired with similar gross sections to serve as a foundation upon which current in vivo studies may build. Lastly, a miscellaneous section illustrates several anatomic points useful in the understanding of fetal anatomy. These points include the changing anatomy of the fetal brain during gestation and the anatomy of the meninges, the fetal heart, and ductus venosus. It is our hope that this atlas will provide a clear picture of fetal anatomy, rectify some of the confusion which exists in antenatal diagnosis, and stimulate further interest in fetal development."

During October 18-31, 1980, the first course of the Inter- national School of Pure and Applied Biostructure, a NATO Advanced Study Institute was held at the "Et tore Majorana Center for Scien- tific Culture" in Erice, Sicily, co-sponsored by national and international agencies. The subject of the course was "Cell Growth", with participants (from 16 different countries) selected worldwide. The study of cell growth has been one of humanity's most challenging problems and it has been approached from many differ- ent points of view, such as biochemistry, genetic engineering, cell biology, zoology, oncology, immunology, biophysics and a few other fields. It has been very difficult to keep such varied points of view all in one room and in one audience, because of the heterogeneity of background and inherent difficulty of communica- tion, with occasional nominalistic rather than factual debates. This Institute aimed to bypass those limitations by approaching in a structured and tutorial fashion the problem of cell growth in three dimensions: (1) in terms of the various disciplines involv- ed, from molecular to cellular biology, from genetic engineering to clinical oncology, from biophysics to immunology; (2) in terms of the system studied, from prokaryotes to eukaryotes and cancer cells; (3) in terms of the various levels of macromolecular orga- nization, from membrane to cytoskeleton and chromatin.

Advances in Cell Biology has been initiated as a continuing, multi-volume series to report on the progress of a wide spectrum of problems of cell structure and cell func tion. In arranging these volumes individual contributors are asked not only to review the major new information, but especially to present the state of a given problem or area by discussing the current central issues, speculations, concepts, hypotheses, and technical problems. We intend, in addition, that these volumes will not be concerned with comprehensive reviews of the recent literature but will consist rather of presenta tions of an interpretative and integrative nature, based on selection of major research advances. It is our aim that these volumes should provide the means whereby cell biologists may keep themselves reasonably well informed about the current progress in research areas in cell biology in which they are not immediately or directly involved themselves. The articles, nevertheless, are expected to bring into focus the experimental objectives of the specialists in a given research area. D.M.P. L. G. E. M. vii Contents v Contributors Preface vii Bacterial Chromosome Replication 3 I. Peter L. Kuempel 57 2. Structure and Replication of Eukaryotic Chromosomes David M. Prescott Ultrastructure and Interaction of the Kinetochore and Centriole 3.

This volume documents the proceedings of a symposium on "Lung in its Environment" held at the Ettore Majorana 'Center for Scientific Culture, in Erice, Sicily, between 16th June and 21st June 1980. This was attended by about 200 participants drawn from Europe as a whole, but the majority were from Southern Europe. The discussion was recorded either in English or Italian and the tapes were reduced to a verbatim typescript by the Ente Nazionale Interpreti Congresso. The verbatim typescript has been edited using a few guiding principles as follows: - 1. Titles and honorifics have been eliminated unless the statement is addressed to a specific person. 2. The style of the speakers in the discussion has been preserved as far as possible and not reduced to a strictly grammatical format. 3. Where references to illustrations (e.g., on the blackboard) are made, the comments have been left unaltered and many are understandable. Removing them detracted from the sense. 4. The air of informality in the proceedings has been preserved so far as possible. 5. The responsibility for the discussion rests solely with the editors, and no contributor has had the opportunity of correcting what he said. 6. No manuscript was received from two participants, but the discussion of their presentations has been included since it contains some points of substance. 7.

Many factors may influence the release of neurotransmitters from airway nerves 1]. This is likely to be important in physiological control of airway functions and may be particularly relevant in airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Neural elements in airways interact in a complex manner and the activation of certain neural pathways may profoundly influence the release of transmitters from other neural pathways. Similarly inflamma tory mediators released from inflammatory cells in the airways may also modulate neurotransmitter release. There are marked differences be tween species in airway innervation and in neuromodulatory effects and, wherever possible, studies in human airways have been emphasised, although information on neuromodulation in human airways is some what limited at present. Release of neurotransmitters from nerve terminals occurs via a Ca2+ dependent secretion evoked by a nerve action potential, but may also be evoked experimentally by a high extracellular K + concentration which directly depolarises the nerve terminal membrane. Modulation refers to the alteration of neurotransmitter release, which may either be increased (facilitation) or reduced (inhibition) by the action of a particular agent, thus changing the magnitude of the neurally-mediated response. Such agents would normally act on receptors on the nerve terminal which are referred to as pre-junctional (or presynaptic) receptors, in contrast to post-junctional (or post-synaptic) receptors located on the target cells which are influenced by that particular transmitter."

Prior to the emergence of the sliding filament model, contraction theories had been in abundance. In the absence of the kinds of structural and biochemical information available today, it has been a simple matter to speculate about the possible ways in which tension generation and shortening might occur. The advent of the sliding filament model had an immediate impact on these theories; within several years they fell by the wayside, and attention was redirected towards mechanisms by which the filaments might be driven to slide by one another. In terms of identifying the driving mechanism, the pivotal observa tion was the electron micrographic indentification of cross-bridges extending from the thick filaments. It was quite naturally assumed that such bridges, which had the ability to split ATP, were the molecular motors, i.e., that they were the sites of mechanochemical transduction. Out of this presumption grew the cross-bridge model. in which filament sliding is presumed to be driven by the cyclic interaction of cross-bridges with complementary actin sites located along the thin filaments."

vi The word ppotein, coined one and a half century ago from the 1TpOTE:toa ("proteios" = of primary importance), underlines the "primary importance" ascribed to proteins from the time they were described as biochemical entities. But the unmatched compl~xity of the process involved in their biosynthesis was (understandably) overlooked. Indeed, protein biosynthesis was supposed to be nothing more than the reverse of protein degradation, and the same enzymes known to split a protein into its constituent amino acids were thought to be able, under adequate conditions, to reconstitute the peptide bond. This oversimplified view persisted for more than 50 years: It was just in 1940 that Borsook and Dubnoff examined the thermodynamical aspects of the process, and concluded that protein synthesis could not be the reverse of protein degradation, such an "uphill task being thermody- namically impossible *** * " The next quarter of a century witnessed the unravelling of the basic mechanisms of protein biosynthesis, a predictable aftermath of the Copernican revolution in biology which followed such dramatic de- velopments as the discovery of the nature of the genetic material, the double helical structure* of DNA, and the determination of the ge- netic code. Our present understanding of the sophisticated mechan- isms of regulation and control is a relatively novel acquisition, and recent studies have shed some light into the structure and organi- zation of the eukaryotic gene.

Since the appearance of photosynthesis on our planet, all living organisms have been facing a new abundant, extremely reactive element, oxygen. This element is used for the synthesis of highly energetic compounds, but can also generate molecules capable of damaging constituents of living structures, including proteins, nucleic acids and lipids. It is therefore no surprise that all biological organisms have evolved multiple and sophisticated ways to reduce the detrimental effects of oxygen. For cells and tissues of highly organized animals, particularly cells of the immune system, superoxidation products play an important role, via oxidative stress, in activation, inflammation and viral and bacterial infections. We must be grateful to Drs. C. Pasquier, C. Auclair, L. Packer and R. Olivier for having brought together many specialists in an international meeting held in Paris in March 1993, at the Ministry of Research. This book comprises an impressive amount of recent knowledge, a real mine for the reader in this fast developing field of research. Furthermore, we should not forget that this basic research may lead in the future to new therapeutic approaches to the most important pathologies of the latter part of this century, including AIDS.

In the ever-expanding field of heart research the needs of established re searchers, students and general readers can vary considerably, making it difficult therefore to cater for all types of audience within a single volume. The aim of this book has been to provide a comprehensive and up-to-date review of the structure of the heart, including its cell biology. The ultrastructure of the working myocardium and all portions of the conduction system, together with their development, is covered in detail. Also included are chapters on the morphometry of cardiac muscle, the innervation of the heart, cardiac hyper trophy and regeneration, and the development of the coronary circulation. A detailed review of cardiac muscle in cell culture is also provided. It is to be hoped that readers, whatever their background, will find the information contained herein useful for their needs. This work was supported by a grant from the National Heart Foundation of Australia. The authors wish to gratefully acknowledge the following people for their invaluable assistance in preparation of the manuscript: Professor Yasuo Uehara, D'r. Takashi. Fujiwara, Dr. Peter Baluk, Dr. Seiji Matsuda and Bill Kaegi for providing unpublished micrographs; Fabian Bowers, Patricia Murphy and Janet Bennett for typing; and Lucy Popadynec, Nella Puglisi, Maggie Mackie, Mary Delafield and Liana Butera for assistance with references and figure preparation. THE AUTHORS Contents A. General Introduction 1 Morphology of Cardiac Muscle 8 B."

The progress in Micromorphology and Biochemistry of the last decades has led to a rather far reaching understanding of the function of the genes. Much is also known about their morphological organization within the cell, particularly their reduplication and segregation in connection with the process of cell division. The intensive light microscopic studies of the earlier cytological era on cell division and chromosomes, which laid the basis for this understanding are very comprehensively covered by WASSERMANN (1929) in his masterly contribution "Wachstum und Vermehrung der lebendigen Masse" in this handbook. There exist also many more recent reviews on chromosomes and on cytogene tics (e. g. SWANSON, 1960; MAZIA, 1961; TURPIN and LEJEUNE, 1965; WmTEHousE, 1969; HAMERTON, 1971; FORD, 1973). However, although some of them cover the more recent findings in man, they have either had to rely on more favorable species for detailed basic information or handled cytogenetic problems from a more practical and clinical point of view. Since moreover, the last few years have brought a flood of new information on chromosomes due to new cytological techniques, a new review on human chromosomes would seem justified within the frame of this handbook. This review will be restricted to human somatic chromosomes, i. e. it wi11leave out meiosis, and will provide information on other species only if this seems necessary for increased clarity."

Uncontrolled proliferation of vascular smooth muscle cells (SMC) in response to vessel injury is a problem with a considerable therapeutic impact. Specifically, restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a clinical problem without any effective drug therapy so far. Thus, there is need for an improved drug therapy but also for an improved understanding of the pathophysiology of growth control in SMC. Cyclooxygenase products, such as prostaglandins and thromboxane, are intimately involved in growth responses. Vasodilatory prostaglandins, such as PGI, PGE or their analogues, have 2 1 been shown to inhibit SMC proliferation. There is also evidence for a markedly increased endogenous prostaglandin production during neointirna formation under the influence of growth factors which includes induction of COX-2. These data suggest that prostaglandins might be considered both targets and tools of growth control. However, there are still many open questions, including the possible interaction of prostaglandins with other growth modulating factors, in particular NO, the intracellular signal transduction pathways and the role of oxidative stress."

A major vehicle for the transition of carrier-mediated drug delivery from a theoretical/experimental status to one with practical uses has been the NATO Advanced Studies Institute series "Targeting of Drugs." Three previous ASls of the series 1-3], also held in Cape Sounion, dealt with carriers of natural and synthetic origin, their preparation and drug incorporation as well as a wide range of applications. This book contains the proceedings of the 4th NATO ASI "Targeting of Drugs: Anatomical and Physiological Considerations" held in Cape Sounion, Greece during 20 June - 1 July 1987. Historically, carrier systems have been chosen on the basis of selective affinity for target sites. For instance, monoclonal antibodies bind selectively to antigens on the surface of cells and the same applies to ligands such as certain glycoproteins which bind to cell receptors. Colloidal carriers on the other hand, are "passively" targeted to the reticuloendothelial system. However, effective drug delivery depends not only on demonstration of affinity of the carrier system for its target but also, and perhaps crucially, on the way(s) by which the carrier-drug entity interacts with the interposed biological milieu. The book deals in depth with a number of biological milieus as travelled space for carriers en route to their destination, difficulties arising from unfavorable milieu-carrier interactions and ways to circumvent such difficulties. It also identifies, when possible, situations where proposed uses would or would not be realistic and provides perspectives for future goals.

The contributions to this volume were presented at a Symposium entitled "Current Topics in Muscle and Nonmuscle Motility" held in Dallas 19-21 November 1980 under the auspices of the A. Webb Roberts Center for Con tinuing Education, Baylor University Medical Center Dallas, and the Univer sity of Texas Health Science Center at Dallas. This very useful opportunity for a group of active investigators in motility to meet and discuss their latest findings was made possible in part by the income from an endowment fund established by a generous gift from Dr. Albert P. D'Errico in the Baylor University Medical Center. Dr. D'Errico was the first formally-trained neurosurgeon to practice in the Dallas area, the first Chief of Neurological Surgery, and a member of the Medical Board of the Baylor University Medi cal Center Dallas (1947 -1964). The income from this fund is used to promote the dissemination of up-to-date information in the Neurosciences, to provide intellectual stimulation, to add to the fund of knowledge, and improve the skills of neurosurgeons, neurologists, internists, and others in specialized fields of medicine. We are all indebted for this generous gift that made this enriching educational experience possible. We are also grateful for support the Symposium received from Electron Microscopy Sciences, Forma Scien tific, J. E. O. L. USA, Inc. , Ladd Research Industries, M. J. O. Diatome Co. , Or ganon Co. , Upjohn Co. , G. D. Searle & Co. , and Smith, Kline and French. Robert M.