Hepatic cells are involved in the metabolization and elimination of a variety of endogenous and exogenous substances. They mediate the uptake, processing and subsequent secretion of biliary compounds, such as various drugs or hormones, and the passage of metabolites to be released into different blood compartments. To perform vectorial passages hepatocytes show a strong polarity with sites for endocytotic processes or specific carrier molecules, and a specified system of organelles for intracellular transport and sorting, metabolization and secretion of compounds. Several aspects, e.g. regulation, control and mechanisms of hepatic traffic are reported in detail - complemented by methodological approaches to analyse and monitor these processes.

Protein-protein interactions are involved in muscle contraction and signal transduction. This book describes how synthetic peptides may be used, much like antibodies, both as specific inhibitors and as molecular probes to explore the cognitive interfaces between interacting proteins and their functional significance. This offers the prospect of very selective intervention in cellular mechanisms. These timely contributions by several experts will appeal to the researchers in muscle physiology, cardiovascular pharmacology and cell biology who are interested in this new approach.

The synthetic chemistry of carbohydrates has advanced at a scarcely equalled rate in the last 25 years, due to the great interest of biologically active natural products coritaining sugar moieties. It suffices to note that in the review by J. D. Dutcher appearing in "Advances in Carbohydrate Chemistry" vol. 18, 1963, only the structures of less than ten aminodeoxy sugars were reported. This book deals exclusively with a single class of carbohydrates, namely the aminodeoxy sugars of antibiotics, the most popular of which is probably daunosamine, a compound for which more than 20 different synthetic approaches have been reported in the literature since the publication of its structure in 1964. No compound in the 3-amino-2-deoxY-L-hexose series had been prepared by chemical synthesis when we started our synthetic work in this field in 1972 on the wave of the successful therapeutic applications of adriamycin. The compounds with xylo stereochemistry were unknown even in the more easily accessible D-series. The size of this book documents the rapid development of the field. I wish to add that the improvements of chemical methodology reported in. the volume outspan the specific field and are of importance in the design of synthetic approaches to other carbohydrate structures. These also include compounds involved in chemical interactions of great biological interest, but hitherto un explained at the molecular level, such as those related with cell recognition, adhesiveness and differentiation."

During the past decade there have been many changes in the perfumery industry which are not so much due to the discovery and application of new raw materials, but rather to the astronomic increase in the cost of labour required to produce them. This is reflected more particularly in the flower industry, where the cost of collecting the blossoms delivered to the factories has gone up year after year, so much so that most flowers with the possible exception of Mimosa, have reached a cost price which has compelled the perfumer to either reduce his purchases of absolutes and concretes, or alternatively to substitute them from a cheaper source, or even to discontinue their use. This development raises an important and almost insoluble problem for the perfumer, who is faced with the necessity of trying to keep unchanged the bouquet of his fragrances, and moreover, to ensure no loss of strength and diffusiveness. Of course, this problem applies more especially to the adjustment of formulae for established perfumes, because in every new creation the present high cost of raw materials receives imperative con sideration before the formula is approved."

Volume 36 of "Progress in Drug Research" contains 5 articles and the various indexes which facilitate its use and establish the connec tion with the previous volumes. While all articles deal with some of the topical aspects of drug research, the contribution by Robert R. Ruffolo et al. on "Drug receptors and control of the cardiovas cular system: Recent advances" is indeed in its own right a mono graphic presentation of this important domain. The remaining four reviews provide an overview of the work in volved in the search for new and better medicines, with a focus on chemical, pharmacological, toxicological, biological, biochemical and molecular modeling studies. In the 31 years this series has existed, the Editor has enjoyed the help and advice of many colleagues. Readers, the authors of the in dividual articles, and, last but not least, the reviewers have all con tributed greatly to the success of PDR. Although many comments received have been favorable, it is nevertheless necessary to analyze and to reconsider the current position and the direction of such a series. So far, it has been the Editor's aim to help spread informa tion on the vast domain of drug research, and to provide the reader with a tool helping him or her to keep abreast of the latest develop ments and trends."

INHALT: The Concept of the BBB: an Historical Perspective Anatomy of the BBB Pathophysiology of BBB * Brain oedema Breakdown of the BBB BBB Dysfunction after SAH * Clinical Monitoring Neuroradiological Evaluations of BBB Dysfunction after SAH * Computerised Tomography and Magnetic Resonance * SPECT and PET Experimental Data * Literature Review of BBB Dysfunction after Experimental SAH * Qualitative Assessments * Quantitative Assessments * Time Course of BBB Dysfunction after SAH * Additional Pathophysiological Changes after SAH - Cerebral Vasospasm - CSF Eicosanoids - Cerebral Metabolism - Behavioural and Neurological Deficits - Intracranial Pressure - Blood Pressure, Blood Gases, Plasma pH, Plasma Glucose, Body Temperature Strategies for Pharmacological Interventions * Hydroxyl Radical Scavenger AVS * Glutamate Antagonist Felbamate * Calpain Inhibitor II Challenges and Future Directions * Advances in Cerebrovascular Pathophysiology Elucidation * Gene Therapy

Contents/Information: N.P. Johnson, J.-L. Butour, G. Villani, F.L. Wimmer, M. Defais, V. Pierson, Toulouse, France; V. Brabec, Kralovopolska, CSSR: "Metal Antitumor " "Compounds: The Mechanism of Action of Platinum Complexes " "Pertaining to the Design of Anticancer Agents"B.K. Keppler, M. Henn, U.M. Juhl, M.R. Berger, R. Niebl, Heidelberg; F.E. Wagner, Garching, FRG: "New Ruthenium Complexes for the " "Treatment of Cancer"G. Mestroni, E. Alessio, Trieste, M. Calligaris, Pavia, Italy; W.M. Attia, Ismailia, Egypt; F. Quadrifoglio, S. Cauci, Udine, Italy; G. Sava, S. Zorzet, S. Pacor, C. Monti-Bragadin, M. Tamaro, L. Dolzani, Trieste, Italy: "Chemical, Biological and Antitumor Properties of " "Ruthenium (II) Complexes with Dimethylsulfoxide"N. Farrell, Burlington/VT, USA: "Metal Complexes as Radiosensitizers"S.C. Srivastava, L.F. Mausner, M.J. Clarke, Upton/NY, and Chestnut Hill/MA, USA: "Radioruthenium-Labeled Compounds for " "Diagnostic Tumor Imaging"P. Kopf-Maier, Berlin, FRG: "The " "Antitumor Activity of Transition and Main-Group Metal " "Cyclopentadienyl Complexes"E.V. Scott, G. Zon, L.G. Marzilli, Atlanta/GA and Foster City/CA, USA: "NMR Relaxation " "Footprinting: The ACr(NH3)6U3+ Cation as a Probe for Drug " "Binding Sites on Oligonucleotides"J.E. Schurig, H.A. Meinema, K. Timmer, Wallingford/CT, USA; B.H. Long, A.M. Casazza, Zeist, NL: "Antitumor Activity of " "BisABis(Diphenylphosphino)Alkane and AlkeneU Group VIII " "Metal Complexes"M.E. Heim, H. Flechtner, Mannheim; B.K. Keppler, Heidelberg, FRG: "Clinical Studies with Budotitane -" "A New Non-Platinum Metal Complex for Cancer Therapy""

When this book was first conceived as a project the expanding interest in the clinical use of platinum and gold complexes made a survey of the relevant biological properties of metal complexes timely and appropriate. This timeliness has not diminished during the gestation and final publica tion of the manuscript. The introduction contains an explanation of the layout and approach to the book, which I wrote as an overall survey of the wide variety of biological properties of metal complexes. Hopefully, the reader will see the parallels in mechanisms and behavior, even in different organisms. The writing was considerably helped by the enthusiasm and confidence (totally unearned on my part) in the project of Professor Brian James and lowe him my special thanks. I also owe a great debt of gratitude to my colleagues, and especially to Eucler Paniago, of the Universidade Federal de Minas Gerais, for their comprehension and for the initial leave of absence which allowed me to begin the project. To those who read some or all of the manuscript and made suggestions, Bernhard Lippert, Kirsten Skov, and Tom Tritton, as well as the editor's reviewer I am also grateful. As usual, the final responsibility for errors or otherwise rests with the author."

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued un resolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Interest in chemical entities capable of blocking or modifying cell metabolism ultimately goes back to the discovery of the structure of DNA in the 1950s. Understanding of the biochemical processes involved in cell metabolism rapidly led to the idea that compounds could be designed which might interfere with these processes, and thus could be used in the treatment of the diseases caused by viral infection. Since then, several classes of drugs have been discovered which depend for their effect on modification of the proper functioning of nucleic acids and, with the introduction of acyclovir for the treatment of Herpes infections, nucleoside analogues have become the cornerstone of antiviral chemotherapy. The success of the early nucleoside agents, the toxicity and metabolic instability of many nucleoside analogues, and the effects of viral pathogens on public health are driving the design, synthesis and evaluation of new nucleoside analogues, with much attention turning to nucleosides containing non natural' sugar analogues. This book focuses on the development of these agents, and draws together all the available material in an easily consulted form, which at the same time guides the reader into the research literature on the subject. Written primarily for the medicinal chemist, coverage includes both synthetic strategies and outline guidance on the main trends in biological activity. Particular attention is drawn to the comparison of synthetic routes to compounds with their natural analogues. Finally, the important antiviral activities of the compounds are treated, including anti-retrovirus, anti-hepadnavirus and anti-herpes virus properties. Written mainly for medicinal chemists in the pharmaceutical industry and synthetic organic chemists in academe, this book will also be attractive to researchers in institutions focusing on cellular metabolism. Advanced students of organic chemistry will find the clear discussion of the synthetic strategies adopted in the development of these compounds a useful introduction to this exciting and challenging area.

The intestine, particularly the small bowel, represents a large surface (in the adult 2 human approximately 200 m ) through which the body is exposed to its environ ment. A vigorous substrate exchange takes place across this large surface: nutrients and xenobiotics are absorbed from the lumen into the bloodstream or the lymph, and simultaneously, the same types of substrate pass back into the lumen. The luminal surface of the intestine is lined with a "leaky" epithelium, thus the passage of the substrates, in either direction, proceeds via both transcellular and intercellular routes. Simple and carrier-mediated diffusion, active transport, pinocytosis, phagocytosis and persorption are all involved in this passage across the intestinal wall. The term "intestinal permeation" refers to the process of passage of various substances across the gut wall, either from the lumen into the blood or lymph, or in the opposite direction. "Permeability" is the condition of the gut which governs the rate of this complex two-way passage. The pharmacologist's interest in the problem of intestinal permeation is twofold: on the one hand, this process determines the bioavailability of drugs and contributes significantly to the pharmacokinetics and toxicokinetics of xeno biotics; on the other hand, the pharmacodynamic effects of many drugs are manifested in a signigicant alteration of the physiological process of intestinal permeation.

Die Arzneimittelforschung hat sich in den letzten zwanzig J ahren stiirmisch ent- wickelt und bewegt sich nicht mehr nur auf den naheliegenden Disziplinen der Chemie, Pharmakologie, Toxikologie und Medizin, sondern greift auch auf die der Physiologie, Biochemie, physikalischen Chemie und Physik iiber. Dem einzelnen ist es deshalb kaum noch moglich, die Originalliteratur zu verfolgen, soweit sie auBerhalb seiner eigenen Forschungsrichtung liegt, und auch da besteht die groBe Gefahr der aIlzu engen Spezialisierung. Die Erkenntnis dieser Entwicklung und ihrer Folgeerscheinungen hat den Herausgeber vor einigen J ahren dazu bewogen, diese Monographienreihe ins Leben zu rufen, und er empfindet groBe Genugtuung, hiermit bereits den sechsten Band seinen Lesern iibergeben zu konnen. Er ergreift freudig die Gelegenheit, nicht nur den Autoren flir ihre Bereitwilligkeit, mit welcher sie einzelne Forschungsgebiete in Ubersichtsreferaten dargestellt haben, sondern auch befreundeten Forschern und Fachkollegen fiir ihre vielen wertvollen Anre- gungen, Kritiken und Vorschlage zu danken, ist es ihm doch nur dank dieser Unter- stiitzung von seiten der Fachwelt ermoglicht worden, diese Zusammenarbeit auf internationaler Ebene zu organisieren und die Fortschritte der Arzneimittel/orschung zu einem niitzlichen Werk auszugestalten. Er hofft, daB ihm diese wertvolle Unter- stiitzung, ohne die die Fortsetzung eines derartigen Werkes unmoglich ware, auch weiterhin in vollem Umfang erhalten bleibt. In den bis jetzt vorliegenden sechs Banden wurden ganz verschiedene Gebiete der Arzneimittelforschung dargesteIlt, und die Arbeiten flir die Berichterstattung werden nach verschiedenen aktuellen Richtungen hin weiter vorgetrieben.

Despite the long association of organohalogen compounds with human activities, nature is the producer of nearly 5,000 halogen-containing chemicals. Once dismissed as accidents of nature or isolation artifacts, organohalogen compounds represent an important and ever growing class of natural products, in many cases exhibiting exceptional biological activity. Since the last comprehensive review in 1996 (Vol. 68, this series), there have been discovered an additional 2,500 organochlorine, organobromine, and other organohalogen compounds. These natural organohalogens are biosynthesized by bacteria, fungi, lichen, plants, marine organisms of all types, insects, and higher animals including humans. These compounds are also formed abiogenically, as in volcanoes, forest fires, and other geothermal events.In some instances, natural organohalogens are precisely the same chemicals that man synthesizes for industrial use, and some of the quantities of these natural chemicals far exceed the quantities emitted by man.

Wir prtiften die Wirkung von Verapamil (V) auf die Reizleitungszeit innerhalb des akut ischamischen Myokards bei 10 Hunden (5 Kontrollgruppe, 5 behandelt mit V) nach Unterbindung des RIVA. Verapamil wurde in einer Dosis von 0,15 mg/kg in- travenos als Bolus, unmittelbar nach KoronarverschluB bei 5 Hunden verabreicht; anschlieBend wurde eine Dosis von 7,5 J. 1g/kg/Min infundiert. Die Unterbindung des RIV A erfolgte in zwei Stufen: in einer ersten Phase distal vom 2. R. diagonalis und in einer zweiten Stufe 30 Min spater distal vom 1. R. diagonalis. Endokardiale bipolare Elektrokardiogramme wurden mittels mehrerer Nadelelektroden vor sowie 5, 15 und 30 Min nach jeder Unterbindung aufgezeichnet. Die Untersuchung wurde bei konstanter Vorhofstimulation (200/Min) und vorzeitigen Stimuli mit einem Kopplungsintervall von 50070 durchgefiihrt. Die Reizleitungszeit (definiert als der Zeitintervall zwischen der vorzeitigen Schrittmacherstimulation und der ersten hochfrequenten Schwingung im endokardialen EKG) wurde im ischamischen sowie normalen Muskelareal beider Untersuchungsgruppen gemessen. Ergebnis: (1) Vor KoronarverschluB war die Reizleitungszeit innerhalb des normalen Myokardiums bei beiden Untersuchungsgruppen gleich. (2) Nach VerschluB des RIVA verzogerte sich die Reizleitungszeit signifikant innerhalb des ischamischen Areals bei der Kon- trollgruppe. (3) In der mit Verapamil behandelten Gruppe unterschied sich die Reiz- leitungszeit innerhalb des ischamischen Myokards nicht signifikant von Werten vor dem KoronarverschluB. Dies war signifikant unterschiedlich von Werten in der Ver- gleichsgruppe. Folgerung: Nach KoronarverschluB verhindert die intravenose Gabe von Verapa- mil die Verzogerung der Impulsfortleitung im ischamischen Areal.

Volume 28 of 'Progress in Drug Research' contains 8 articles, a subject index for this volume, an alphabetic subject index for volumes 1-28, and an author and subject index for all the volumes which have so far been published. The contributions of volume 28 are particularly con cerned with biogenic amines, with immunology and the pharmacology of the immune system, with antiviral agents, with amino-quinoline an timalarials, with the axoplasmic transport, with drug treatment of asthma and with the role of adipose tissue in the distribution and stor age of drugs. The authors have tried, and I think they have succeded, not only to summarize the current status of particular fields of drug research, but also to provide leads for future research activity. The articles of this volume will be of special value to those actively engaged in drug re search, and to those who wish to keep abrest ofthe latest developments influencing modern therapy. In addition, it is believed that the 28 volu mes of 'Progress in Drug Research' now available represent a useful reference work of encyclopedic character. l The editor would like to take the bccasion of the publication of this volume to express his gratitude both to, the authors and to the readers."

Most often when the subject of antimicrobial resistance is discussed, the organizational emphasis is on individual antimicrobial agents or groups of agents. Thus we tend to see discussion of resistance to f3-lactams, tetracyclines, amino glycosides etc. In this book many of the authors were asked to emphasize the mechanism of resistance in their discussion and from that to show how susceptibility to various agents was affected. In part this was done to help emphasize the enormous contribution that the study of antimicrobial resistance has made to our understanding of fundamental physiologic and genetic processes in bacteria. When one looks back over the study of antimicrobial resistance, it is clear that it has been the birthplace of many fundamental advances in molecular biology and of an appreciation of the role of many key functions in the life of a bacterium. In addition, and hopefully to an increasing extent in the future, such study has also contributed to advances in antimicrobial chemotherapy. Through out the book resistance mechanisms have been placed in perspective as to their significance as causes of resistance to key drugs or groups of drugs. Some are of much greater significance than others in terms of the prevalence or the degree of resistance produced. Whatever their numerical significance, however, each of the mechanisms, without question, throws light on fundamental cellular processes and the way in which they interact with antimicrobial agents."

BARTON und COHEN haben r9S7 in einer Arbeit "Some Biogenetic Aspects of Phenol Oxidation" (3) Dienone der allgemeinen Formel (I) als biogenetische Vorstufen bestimmter Aporphin-Alkaloide postuliert (S. 260). Strukturen dieses Typs wurden erstmals r963 fUr die Alkaloide D-( +)-Pronuciferin und D-( +)-Crotonosin bewiesen [BERNAUER (II); HAYNES, STUART, BARTON und KIRBY (35)]. Der fur solche Verbin- dungen vorgeschlagene Sammelname "Proaporphine" (23, 65) bringt den in zwischen experimentell bewiesenen* biogenetischen Zusammenhang mit der Gruppe der Aporphin-Alkaloide zum Ausdruck, ist aber auch vom praparativ-chemischen Standpunkt sinnvoll, da sich Proaporphine (I) leicht in Aporphine (2) umwandeln lassen (S. 2S0). AuBer den Alkaloiden mit Dienongruppierung sind auch solche be- kannt geworden, in welchen eine oder mehrere Doppelbindungen des Dienonsystems aushydriert sind; sie werden sinnvollerweise den Pro- aporphinen zugerechnet. Dieser Aufsatz berucksichtigt alle natiirlichen Alkaloide und ihre wichtigsten Derivate sowie alle synthetischen Ver- bindungen, die das Skelett (3) besitzen (Tabellen I-3, SS. 270-279). Er macht ausschlieBlich von der in (3) angegebenen Bezifferung Gebrauch, welche der Nomenklatur der IUPAC und der Chemical Abstracts ent- spricht. Verbindung (I, R = H) ist wie folgt zu bezeichnen: 2',3',8',8'a-Tetra- hydro-S',6'-dihydroxy-spiro[2,S-cyclohexadien-r,7'(r'H)-cyclopent[ij]-iso- chinolin ]-4-on. R2 (2) K=H oder Alkyl (I) R=H oder Alkyl Rt=H,OH oder O-Alkyl Proaporphine Aporphine In den Originalarbeiten sind verschiedene, von der in (3) angegebenen ab- weichende Bezifferungsarten verwendet worden. Keine hat sich allgemein durch- gesetzt. Auch die von SLAViK (69) fur das sauerstofffreie Grundgerust der Pro- aporphine vorgeschlagene Bezeichnung Mecambran hat keinen Eingang in die Literatur gefunden.

Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin, where they may be more relevant to human physiology and diseases, as in animal models. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of etiology and mechanism. For example, whilst the argument continued unresolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis-retinoic acid was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on etiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as an important step in the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Cyclic nucleotides are intimately involved in the consequences of either stimulation or blockade of receptors; therefore, an understanding of the biochemistry of cyclic nucleotides ought to be important for pharmacologists. Pharmacology is a science that among other things investigates chemical compounds that affect the physiology of cells, tissues and organs. Frequently pharmacologists account for the effect of low concentrations of a drug upon a tissue by invoking the presence of a receptor upon the surface of the cell. Traditional pharmacologists excelled at identifying and classifying the properties of receptors. A. J. CLARK'S monograph in the earlier series of the Handbook of Experimental Pharmacology (CLARK 1937) summarized the mathematics underlying the traditional pharmacological approach towards receptors. By its nature, however, classic pharmacology provided little useful information about the intracellular events occurring as a consequence of occupying a receptor; for example, ALQUIST (1948) identified the beta-adrenocep tor, but he did not provide any insight into how stimulation of the receptor produces tissue-specific physiological responses. The discovery of cyclic AMP by RALL and SUTHERLAND (see RALL, Vol. I) led to biochemical investigations of many different receptors (including ALQUIST'S beta-adrenoceptor) that share a cyclic nucleotide as a common factor in the biochemical mechanisms that translate the occupancy of receptors into physiological effects. Ten years ago, in the introduction to their monograph on cyclic nucleotides, ROBISON et al. (1971) commented on the rapid growth of interest in cyclic nucleotides over the preceding years."

Starting in 1986, the European School of Oncology has expanded its activities in post graduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meet ings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminat ing the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It was decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a com mon problem in medical literature: that of the material being outdated even before publication. Umberto Veronesi Chairman, Scientific Committee European School of Oncology Position Paper on the Application of Human Tumour Xenografts as a Model for Preclinical Phase" Studies in the Evaluation of New Anticancer Compounds Outcome of a seminar on Human Tumour Xenografts organised by the European School of Oncology, Milan, 26th-27th May, 1986.

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."

Resin glycosides are part of a very extensive family of secondary metabolites known as glycolipids or lipo-oligosaccharides and are constituents of complex resins (glycoresins) (1) unique to the morning glory family, Convolvulaceae (2). These active principles are responsible for the drastic purgative action of all the important Convolvulaceous species used in traditional medicine throughout the world since ancient times. Several commercial purgative crude drugs can be prepared from the roots of different species of Mexican morning glories. Their incorporation as therapeutic agents in Europe is an outstanding example of the assimilation of botanical drugs from the Americas as substitutes for traditional Old World remedies (3). Even though phytochemical investigations on the constituents of these drugs were initiated during the second half of the nineteenth century, the structure of their active ingredients still remains poorly known for some examples of these purgative roots. During the last two decades, the higher resolution c- abilities of modern analytical isolation techniques used in conjunction with pow- ful spectroscopic methods have facilitated the elucidation of the active principles of these relevant herbal products. This chapter describes the ethnobotanical information associated with the p- gative morning glory species and how traditional usages were instrumental in plant selection for chemical studies. The advantages and limitations of available analy- cal techniques for the isolation, puri?cation, and structure characterization of the individual constituents of these complex glycoconjugates are also discussed.

The volumes of this classic series have appeared under the Springer imprint ever since L. Zechmeister founded the series in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . xiii . . . . . . . . . . . . . Part I. Integrative Approach to Assessing Human Health Risk: Two Contemporary Problems Chapter 1. Integrating Diverse Data Sets to Assess the Risks of Airborne Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 R.o. McClellan, R.G. Cuddihy, w.e. Griffith, and J. L. Mauderly Chapter 2. Risk Assessment for Radon Inhalation Based on Animal Exposure Data and Human Epidemiology . . . . . . . 23 . F. Steinhausler Part II. Types of Evidence: General Strengths and Weaknesses Section 1. Epidemiological Chapter 3. Inhalation Hazards: The Interpretation of Epidemiologic Evidence. . . . . . . . . . . . . . . . . . . . 39 . . . . . . . J.e. Bailar Chapter 4. Problems in Interpreting Epidemiological Data 49 P.N. Lee Section 2. Animal Chapter 5. Rodent Carcinogenicity Studies: Their Value and Limitations. . . . . . . . . . . . . . . . . . . . . . . . . . 61 . . . . . . . . . .