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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.
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 . . . .
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."
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."
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.
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 recent symposium and the appearance of this new book on Drugs
Affecting Lipid Metabolism take place at a very unusual time for
the development of this area. After the publication and wide
acceptance of the results of the cholestyramine study by the Lipid
Clinics in the USA, showing for the first time a direct association
between drug induced reduction of plasma levels of total and LDL
cholesterol and coronary heart disease in a high risk population,
an unparalleled interest in drugs and other procedures able to
control plasma cholesterol levels has been activated. Two other
significant events occurred during 1986 and 1987: the availability
of compact instruments for the immediate determination of total
cholesterol in plasma or total blood and the developments of new
agents such as the inhibitors of HMG-CoA (hydroxymethyl glutaryl
CoA) reductase and ACAT inhibitors, with potentially great effect
on plasma lipid levels after oral administration. These new
advances, together with the combined efforts of cell biologists and
lipoprotein chemists, have set the pace for an exciting period of
research and clinical applications of diets and drugs af fecting
lipids. This volume, which includes the work of many of the leading
world laboratories, represents an authoritative and up-to-date ap
praisal of the status of the art and a stimulus to future research
at laboratory and clinical level in an area of opportunity for
clinical and preventive medicine."
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."
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."
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.
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.
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.
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 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. . .
. . . . . . . . . . . . . . . . ."
General Aspects: Nutritionally Related Disorders/Diseases in
Africans: Highlights of Half A Century of Research, with Special
Reference to Unexpected Phenomena; A.R.P. Walker. The Evolving
Epidemiology of Fiber & Heart Disease; C. Humble. Complex
Carbohydrates: Overview on Complex Carbohydrates; J. De Vries.
Dietary Guidelines and Complex Carbohydrates; B. Schneeman. Soluble
Fiber: Soluble Fiber and Hypertension; J.M. Keenan. Soluble Fiber
and Energy Regulation: Current Knowledge and Future Directions; S.
Roberts. Short Chain Fatty Acids: Butyrate and the Colonocyte:
Production, Absorption, Metabolism and Nutrient Utilization; M.J.
McBurney. Nutrients Contributing to the Fiber Effect: Resistant
Starch-An Update on Its Physiological Effects; N.G. Asp. Health
Benefits of Non-Digestible Oligosaccharides; M. Roberfroid. Fiber
and Disease: Fiber and Cancer Protection: Mechanisms; D. Klurfeld.
Dietary Fiber & Bile Acid Metabolism-An Update; J.A. Story.
Workshop Reports: Dietary Guidelines/RDA/Daily Value; B. Schneeman.
Soluble Dietary Fiber; J. Marlett. 19 Additional Articles. Index.
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