David Kritchevsky – författare

The role of nutrition in neoplasia has been of longstanding concern. The subject was addressed by investigators in the first decade of this century, but was dropped. Vigorous attention was paid to this area of oncology in the 1940s, primarily due to the efforts of Dr. A. Tannenbaum at the Michael Reese Hospital in Chicago and the group at the University of Wisconsin in Madison. However, interest waned again until the 1970s when the question of diet and cancer was addressed and it has since been at the forefront of cancer research. The present volume (7) of Human Nutrition: A Comprehensive Treatise summarizes current knowledge in the area of nutrition and cancer. The first chapter is an overview written by John Higginson, whose contribution to understanding of cancer and nutrition spans several decades. The next essays cover epidemiology and physiology. The ensuing chapters address, in tum, those dietary factors relating to nutrition and cancer, namely, carbohydrates, protein, fat, cholesterol, calories, lipotropics, fiber, fruits and vegetables, vitamins, and alcohol. In a field moving as rapidly as this one is now, we can expect to miss a few late-breaking developments, but generally, the literature has been well covered through some time in 1988. Work relating to the effects of diet on oncogenes is in its very early development and has not been addressed as an entity per se.

This book was inspired by a gatheringofscientists in Los Angeles in 1994 under the auspices of the UCLA Clinical Nutrition Research Unit which is funded by the National Cancer Institute to promote new research into nutrition and cancer prevention. This unit supports research integrating basic and metabolic/clinical investigations which examine observations from epidemiologic studies and their application to the prevention ofcommon forms ofcancer through nutritional intervention. There is a great deal ofinformation from epidemiologic, experimental and metabolic studies implicating elements ofthe diet as important in the development and progression of common forms ofcancer including breast cancer, colon cancer, prostate cancer, and uterine cancer. When these forms ofcancerareexaminedcarefully, it isclearthat they share anumber ofcommon etiologic factors related to dietary fat, lipids, and hormones. A human cancer is usually discovered at a point where it has formed a detectable mass. For many forms of cancer, this may require 10 to 15 years from the time when the cancer is first initiated. Nutritional efforts at prevention may delay the progression ofcancer to a detectable mass resulting in reduced incidence and may retard the clinical progression and metastatic spread ofcancer after its primary treatment.

Twenty years ago the very idea of an international conference on the fiber contained in plant food would have been totally inconceivable. At that time fiber was generally viewed as an inert component of food of no nutritional value and consequently consid­ ered as a contaminant, the removal of which would enhance the purity of a product. It was measured by a now obsolete and almost worthless test introduced in the last century for veterinary rather than human nutrition, and what was measured was referred to as "crude fiber," containing part of the cellulose and lignin but none of the numerous components of fiber now known to play important roles in the maintenance of health. There were a few lone voices prior to the last two decades who had extolled the laxative properties of the undigested portion of food, assuming that these were related to its irritant action on the bowel mucosa. In retrospect this was a total misconception, and "softage" would have been a more appropriate term than "roughage," since its presence insured soft, not irritating, colon content.

Over a decade has elapsed since the last volume in this series was published. At that time we considered that we had comprehensively covered all aspects relating to bile acid chemistry and physiology. However, major strides have been made in our understanding of the physiology and pathophysiology of bile acids, due largely to the great advances which have taken place in analytical technology. As a result, the need to document these advances was felt acutely, and therefore this volume is devoted to methodologies in bile acid analysis and their applications. This volume includes twelve chapters written by prominent scientists in the field of bile acid research. The initial chapter discusses techniques of extraction and isolation of bile acids from biological fluids. It is followed by descriptions of physical methods of analysis and discussions of the way these techniques have been applied in the field of bile acid research. Of practical value is the inclusion of a comprehensive list of spectra obtained for refer­ ences by nuclear magnetic resonance spectroscopy and mass spectrometry . These chapters are followed by reviews of biological methods of immuno­ assay and bioluminescence. Specific applications of these techniques are then addressed in contributions relating to bile acid analysis of tissue, serum, urine, and feces. With this integrated approach we have attempted to provide a volume which represents a comprehensive review of the analytical field of bile acids, while also serving as a useful reference book for those workers involved in bile acid analysis.

This book was inspired by a gatheringofscientists in Los Angeles in 1994 under the auspices of the UCLA Clinical Nutrition Research Unit which is funded by the National Cancer Institute to promote new research into nutrition and cancer prevention. This unit supports research integrating basic and metabolic/clinical investigations which examine observations from epidemiologic studies and their application to the prevention ofcommon forms ofcancer through nutritional intervention. There is a great deal ofinformation from epidemiologic, experimental and metabolic studies implicating elements ofthe diet as important in the development and progression of common forms ofcancer including breast cancer, colon cancer, prostate cancer, and uterine cancer. When these forms ofcancerareexaminedcarefully, it isclearthat they share anumber ofcommon etiologic factors related to dietary fat, lipids, and hormones. A human cancer is usually discovered at a point where it has formed a detectable mass. For many forms of cancer, this may require 10 to 15 years from the time when the cancer is first initiated. Nutritional efforts at prevention may delay the progression ofcancer to a detectable mass resulting in reduced incidence and may retard the clinical progression and metastatic spread ofcancer after its primary treatment.

Only 15 years ago a conference on dietary fiber, let alone an international conference, would have been considered an extremely unlikely, and in fact an unthinkable, event. Yet in recent years a number of such conferences have taken place at the international level and in different parts of the world; the conference of which the present volume is an outgrowth is the second to have been held in Washington, D. C. This extraordinary development of interest in a hitherto largely neglected component of diet has been reflected by a veritable explosion of scientific literature, with published articles increasing 40-fold, from around ten to over 400 per year, within the decade 1968-1978. Not only has the growth of interest in and knowledge of fiber made it perhaps the most rapidly developing aspect of nutritional science in recent history if not in all time, but epidemiologic studies relating fiber intake to disease patterns, subsequently broadened to include other food components, have been largely responsible for the current concept of diseases characteristic of modern Western culture and lifestyle. The potential importance of this realization is forcefully underlined by the considered judgment of Thomas MacKeown, epidemiologist and medical historian of Birmingham University, England.

The Proceedings of the Eight International Symposium on Drugs Affecting Lipid Metabolism (8th D.A.L.M.) is the subject of this volume. Since the first symposium in 1960, each successive meeting has broken new ground in the field of pharmacological control of lipid levels - offering new and stimulating insights and exposing the audience to the state of the art. The field has progressed sufficiently to permit discussion of the cellular biology of athero­ sclerosis. The opening session was devoted to pathology, macrophages, lipoproteins and their receptors and choles­ terol ester metabolism. Because of the recent emergence of new apolipoprotein technology, a workshop devoted sole­ ly to apolipoprotein methodology was introduced followed by a plenary session devoted to their metabolism and structure. Another rapidly developing area of atherosclerosis research is non-invasive assessment of this condition. Accordingly, a session was devoted to new techniques for this research modality. The final plenary sessions were devoted to the roles of drugs and diet in athero~ scl~rosis - cause, treatment and mechanisms of action. The meeting was summarized by Dr. O.J. Pollak, one of the "founding fathers" of this field. There were nine sessions of proffered papers whose abstracts appear in this volume. In addition, special workshops (to be reported elsewhere) were devoted to several drugs including Oiyzanol, Probucol and Etofibrate.

The science of nutrition has advanced beyond expectation since Antoine La­ voisier as early as the 18th century showed that oxygen was necessary to change nutrients in foods to compounds which would become a part of the human body. He was also the first to measure metabolism and to show that oxidation within the body produces heat and energy. In the two hundred years that have elapsed, the essentiality of nitrogen-containing nutrients and of proteins for growth and maintenance of tissue has been established; the ne­ cessity for carbohydrates and certain types of fat for health has been docu­ mented; vitamins necessary to prevent deficiency diseases have been identified and isolated; and the requirement of many mineral elements for health has been demonstrated. Further investigations have defined the role of these nutrients in metabolic processes and quantitated their requirements at various stages of development. Additional studies have involved their use in the possible prevention of,and therapy for, disease conditions.

There is a unique nutritional commonality developing in research relating to coronary heart disease and cancer. The primary aim of this conference was to provide a forum for the leading researchers, clinicians, educators and administrators in these two fields to present a program on heart disease and cancer which included a) the major historical milestones, b) the present areas of greatest interest in research and therapy, c) the latest nutritional, molecular, and biotechnological advances, and d) a perspective on the most promising areas for future research and therapy. Scientists have long contended that research marches on the feet of methodology. Thus there are numerous examples of research fields opening secondary to methodological advances. Some examples are: 1) thin layer and gas-liquid chromatography which, along with high pressure liquid chromatography have broadened the line of advances in lipid research and 2) peR and the resultant impact on molecular biological approaches to several fields of science. The organizers of this conference thought the time was propitious for bringing together knowledge on newer aspects of molecular biological research with current advances in the two major areas of degenerative disease--coronary heart disease and cancer. Our knowledge of these "killer diseases" has expanded greatly in the past few years and the advance has been catalyzed by use of an array of molecular biological techniques. Thanks to these, medical thinking in these areas is changing from considerations of treatment to strategies for prevention.

This volume carries the proceedings of the Vahouny Fiber Symposium, which took place in Washington DC, in March of 1996. George V. Vahouny pioneered this conference, which was conceived as a means of exchanging information on the latest advances in fiber research. The conference was renamed in George Vahouny's honor after his untimely death. In this volume we have included the reminiscences of Prof. A.R.P. Walker, one of the pioneers in the field, and discussion of the epidemiological findings relating dietary fiber to heart disease, cancer, and gastrointestinal disease. As the overall definition of fiber has broadened we have included for discussion other aspects of carbohydrate chem­ istry and metabolism. Complex carbohydrates were the subject of a full session and resis­ tant starch and the role(s) of oligosaccharides were discussed later in the meeting. Another area of fiber metabolism that is beginning to burgeon is that of the short chain fatty acids, and this too was the subject of presentations and discussion. In addition, the more familiar topics in dietary fiber were updated. Workshops devoted to specific areas of fiber research have now become a mainstay of these meetings, and they were repeated successfully. Due to restraints on spending, the attendance at this meeting was somewhat smaller than usual but the discussion was lively and pertinent. We are deeply grateful to our sponsors and contributors for their continuing interest in dietary fiber research, and for their generous support of this symposium.

Dietary fiber is a topic that has burgeoned from an esoteric interest of a few research laboratories to a subject of international interest. This growth has been helped by the intense public interest in the potential benefits of adding fiber to the diet. The general popularity of fiber may have been helped by the perception that, for once, medicine was saying "do" instead of "don't. " There has been a proliferation of excellent scientific books on dietary fiber. Why another? The Spring Symposium on Dietary Fiber in Health and Disease was an outgrowth of our belief that informal discussion among peers-a discussion in which fact is freely interlaced with speculation-was the most effective way to organize our knowledge and direct our thinking. The normal growth progression of a discipline inc1udes its branching into many areas. Soon the expertise, which was once general, is broken into many specialties. Intercommunication becoIlles increasingly difficult. It was our intent to provide a forum that would expose its participants to developments in areas related to their research interest. Free exchange under these conditions could not help but broaden everyone's knowl­ edge and expand his horizons. We feel that this symposium was singularly successful in achieving its goals. It resulted in a free and friendly exchange of knowledge and ideas. It helped to establish seeds for future collaborations based on mutual interest and friendship. The proceedings of this conference will serve as yet another basic resource in the fiber field.

The science of nutrition has advanced beyond expectation since Antoine La­ voisier as early as the 18th century showed that oxygen was necessary to change nutrients in foods to compounds which would become a part of the human body. He was also the first to measure metabolism and to show that oxidation within the body produces heat and energy. In the two hundred years that have elapsed, the essentiality of nitrogen-containing nutrients and of proteins for growth and maintenance of tissue has been established; the ne­ cessity for carbohydrates and certain types of fat for health has been docu­ mented; vitamins necessary to prevent deficiency diseases have been identified and isolated; and the requirement of many mineral elements for health has been demonstrated. Further investigations have defined the role of these nutrients in metabolic processes and quantitated their requirements at various stages of development. Additional studies have involved their use in the possible prevention of, and therapy for, disease conditions.

The science of nutrition has advanced beyond expectation since Antoine La­ voisier as early as the 18th century showed that oxygen was necessary to change nutrients in foods to compounds which would become a part of the human body. He was also the first to measure metabolism and to show that oxidation within the body produces heat and energy. In the two hundred years that have elapsed, the essentiality of nitrogen-containing nutrients and of proteins for growth and maintenance of tissue has been established; the ne­ cessity for carbohydrates and certain types of fat for health has been docu­ mented; vitamins necessary to prevent deficiency diseases have been identified and isolated; and the requirement of many mineral elements for health has been demonstrated. Further investigations have defined the role of these nutrients in metabolic processes and quantitated their requirements at various stages of development. Additional studies have involved their use in the possible prevention of,and therapy for, disease conditions.

After the appearance of the four-book series Human Nutrition: A Compre­ hensive Treatise, it became apparent to the editors that an important area of nutrition had been overlooked, namely, behavioral aspects of nutrition. There are two areas in which nutrition and behavior interact. On the one hand, mal­ nutrition may play a major role in determining behavior; alternatively, often aspects of behavior influence the eating habits of populations and individuals and thus affect their nutritional status. Volume 5 of this series speaks eloquently to both features of this important topic. Various aspects of the influence of behavior modification and nutrition have been explored by a number of qualified investigators. It is hoped that this volume will prove a valuable addition to the subjects covered in the other volumes. Roslyn B. Alfin-Slater David Kritchevsky Los Angeles and Philadelphia ix Contents Introduction: The Challenge of Nutrition and Environment as Determinants of Behavioral Development .................... . Janina R. Galler References ............................................. 5 Part I • Nutritional Deficiencies or Excesses Modifying Behavioral Outcome Chapter 1 Methological Requirements for Conceptually Valid Research Studies on the Behavioral Effects of Malnutrition David E. Barrett 1. Introduction ......................................... 9 2. Statistical-Conclusion Validity. . . . . . . . . . . . . . . . . . . . . 11 . . . . . . . 3. Internal Validity ...................................... 14 4. External Validity ..................................... 16 5. Construct Validity of Putative Causes and Effects . . . . . . . . .. . . . 19 6. Conclusions and Recommendations . . . . . . . . . . . . . . . .. . . . 28 . . . .

This volume comprises the proceedings of the sixth International Symposium on Drugs Affecting Lipid Meta­ bolism. Since the first of these symposia in 1960 these triennial meetings have been devoted to the exploration of new ideas, new data and new concepts related to lipid metabolism and atherosclerosis. The sixth Meeting was particularly stimulating in this regard. The concept of the "protective" action of HDL was thoroughly explored within the framework of its molecular biology with data on its epidemiological as well as its in vitro mechan­ ism(s) of action being discussed. The action of drugs on arterial and HDL metabolism was also discussed as were newer aspects of platelet aggregation, especially as related to prostaglandins. New ground was also broken in discussions of lipid mobilization and mechan­ isms of hypocholesteremia. We are indebted to the many organizations who con­ tributed generously to the support of this meeting. Among the sponsors, the assistance of the Lorenzini Foundation was especially helpful. As in all meetings of this type, the hard work of the local organizing committee was instrumental in its success. We are grateful to Mrs. Caroline Hyatt and Mr. Ralph Hollerorth for their invaluable help in the secretariat. We are also deeply indebted to Miss Jane T. Kolimaga for her expert assistance in the preparation of this volume. David Kritchevsky Rodolfo Paoletti William L. Holmes vii Contents LIPOPROTEINS AND DRUGS Lipoprotein Metabolism - New Insights from Cell Biology. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 D. Steinberg Lipoprotein Metabolism in Man. . . . . . . . . . . . . . . . . . . .

The role of nutrition in neoplasia has been of longstanding concern. The subject was addressed by investigators in the first decade of this century, but was dropped. Vigorous attention was paid to this area of oncology in the 1940s, primarily due to the efforts of Dr. A. Tannenbaum at the Michael Reese Hospital in Chicago and the group at the University of Wisconsin in Madison. However, interest waned again until the 1970s when the question of diet and cancer was addressed and it has since been at the forefront of cancer research. The present volume (7) of Human Nutrition: A Comprehensive Treatise summarizes current knowledge in the area of nutrition and cancer. The first chapter is an overview written by John Higginson, whose contribution to understanding of cancer and nutrition spans several decades. The next essays cover epidemiology and physiology. The ensuing chapters address, in tum, those dietary factors relating to nutrition and cancer, namely, carbohydrates, protein, fat, cholesterol, calories, lipotropics, fiber, fruits and vegetables, vitamins, and alcohol. In a field moving as rapidly as this one is now, we can expect to miss a few late-breaking developments, but generally, the literature has been well covered through some time in 1988. Work relating to the effects of diet on oncogenes is in its very early development and has not been addressed as an entity per se.