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Preview Highlights |
| INTRODUCTION |
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Intersociety themes this year are cardiovascular biology; cell injury, inflammation and repair; cellular growth and development; epithelial cell biology; metabolic and disease processes; neurobiology; respiratory biology; and signal transduction and gene regulation.
A sampling of the mulitdisciplinary sessions appears below. The Program and Abstracts issues contain considerably more details and are mailed to preregistrants before the meeting. For up-to-date information, visit http://www. faseb.org.
| The American Physiological Society |
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This symposium will highlight recent studies of the processing and integration of baroreceptor input through neural pathways residing in the medulla oblongata, including a review of neuroanatomical studies of the synaptic connections among cell groups of the medulla oblongata that constitute pathways mediating reflex control of sympathetic nerve activity; the neurochemical mechanisms responsible for activation of the nucleus tractus solitarii (nTS) neurons that receive arterial baroreceptor input; inhibitory neurotransmitter systems, which constitute an important element of the baroreflex arc for regulation of sympathetic outflow; how peptidergic pathways impinging on components of the central baroreflex arc modulate the baroreceptor response; the role of angiotensin II in this context will be reviewed as it relates to the development of hypertension; the parasympathetic nervous system as the other arm of the autonomic nervous system, which plays a crucial role in baroreceptor reflex regulation of the heart, incorporated in a discussion of the neurochemical mechanisms responsible for regulation of parasympathetic motoneuron activity and function will be addressed; and an exploration of the utility of dynamic systems modeling as an approach to understanding information processing of baroreceptor related signals at various sites within the barorelex pathway. Participants hope to generate new investigative approaches to further understanding of the normal and pathological functions of the baroreceptor reflex by discussing these diverse approaches of neuroanatomy, neurophysiology, and dynamic systems modeling.
Control of Mitochondrial Free Fatty Acid Uptake and Oxidation in Working Skeletal Muscle
Chair: G.A. Brooks
In resting skeletal muscle and the unstimulated heart, lipids, mainly blood-borne free fatty acids comprise most of the energy substrate. However, as power output increases, in skeletal muscle use of carbohydrate-derived fuels (glycogen, glucose and lactate) increases, whereas lipid (free fatty acid and intramuscular triglyceride) oxidation decreases. Similarly, under resting conditions, the heart depends mostly on FFA oxidation, but as work of the heart increases, glucose and lactate become important energy substrates. What explains the switch from lipid to carbohydrate-derived energy sources in working muscle? To address this and related questions, contemporary workers in the field evaluate the central role of carnitine palmitoyl transferase 1 (CPT-1) by malonyl-CoA. Specifically, participants will discuss the biochemical pathways and original research on mechanisms regulating the switch toward increased use of carbohydrate-derived fuels when cardiac muscle is stressed; results of research on the effects of exercise and exercise training on malonyl-CoA responses in rodent muscle and a description of the acute and chronic effects of exercise on induction of key regulatory enzymes, such as acetyl-CoA carboxylase (ACC); results of work on regulation of pyruvate dehydrogenase (PDH) and the interrelationships among activities of PDH, phosphorylase, and CPT-1 in working human muscle; results of studies on exercising humans in which malonyl-CoA:CPT-1 hypothesis was evaluated by using isotopic tracers, and the effects of exercise intensity and previous endurance training on substrate flux in men and women.
Emerging Technologies' Role In Physiology Instruction
Chairs: R.G. Carroll and M.J. Davis
Technological innovation proceeds at an accelerating pace and has facilitated many recent research advances. Emerging technologies, however, have found a limited application in undergraduate and professional physiology instruction. This symposium will examine the strengths and limitations of four different technologies that are being introduced into instructional settings: 1) the use of teleconferencing and other forms of distance learning; 2) multimedia developments, i.e., the role of the publishing house in multimedia development and projects and an evaluation of student and faculty performance and reaction to the multimedia resource developed and in use since 1993 at Medical College of Georgia; and 3) the use of World Wide Web resources in the Medical Physiology course at Texas A&M University. There will be demonstrations projects where attendees can test the technologies discussed.
Vascular Biology of Homocysteine
Chairs: S. J. Elliott and K.S. McCully
Homocysteine is a risk factor for atherosclerosis. The molecular and chemical mechanisms by which homocysteine promotes vascular occlusive disease are poorly understood. Participants will explore 1) the reaction of homocysteine with low-density-lipoprotein to form the reactive metabolite, homocysteine thiolactone, and the reaction of homocysteine with nitrosating agents to form S-nitrosohomocysteine and 2) the potentially adverse effects of homocysteine thiolactone and the potentially protective effects of S-nitrosohomocysteine. Homocysteine is converted to cystathionine via cystathionine-ß-synthase, and in patients with cystathionine-ß-synthase deficiency, the development of premature arteriosclerosis is common, prompting a discussion of the vascular phenotype of the cystathionine-ß-synthase knockout mouse. The multidisciplinary slate of speakers will vertically integrate homocysteine chemistry, vascular wall biology, and the functional genomics of homocysteine metabolism.
Intestinal Adaptations to Fasting
Chairs: R.P. Ferraris and H.V. Carey
This session will focus on the response of the intestinal mucosa to fasting, a practice common in weight management and an accepted presurgical procedure. Prolonged fasting or caloric restriction has also attracted enormous interest because of its dramatic effect on lifespan. The symposium will present an overview of how mucosal growth is influenced by local nutrition and various regulatory molecules released during feeding; describe changes in gene expression that occur during fasting and refeeding, including alterations in levels of transcription factors and brushborder proteins in response to hormones and growth factors provided exogenously; outline the influence of fasting on intestinal ion transport and permeability, and how the absence of luminal nutrients alters regulation of ion transport; and describe adaptations in hormonal and nutrient transporter gene expression to acute fasting and to caloric restriction.
Interaction between Vascular Endothelium and Smooth Muscle: Advances in Physiology and Pathophysiology
Chairs: G-W. He and R.A. Cohen
There has been great progress in understanding the function of vascular endothelium and smooth muscle in the last decade. In particular, the interaction between endothelium and smooth muscle has greatly interested not only basic scientists but also clinicians. The important role of endothelium in the physiological and pathophysiological status of blood vessels has been recognized with regard to the following: How does the endothelium modulate the vascular tone through its interaction with vascular smooth muscle? What is the target in the smooth muscle for individual endothelium-derived relaxing factors such as nitric oxide and endothelium-derived hyperpolarizing factor (EDHF)? How to protect the coronary circulation with regard to its endothelium and smooth muscle during ischemia? What is the role of the interaction between endothelium and smooth muscle on the development of atherosclerosis such as post-transplant vascular disease? World-renowned researchers will lecture in these areas, connect the basic science findings to clinical problems, and pique interest in further exploration of the interaction between endothelium and smooth muscle.
New Perspectives of Pulmonary Blood Flow Distribution
Chair: M.P. Hlastala
The primary framework for interpreting pulmonary blood flow data over the past 30 years has been the zone model developed by West, Hughes, and colleagues. Recent experimental findings, with enhanced spatial resolution, take issue with gravity as the dominant factor determining perfusion distribution. Experiments performed on astronauts in the Space Shuttle have revealed a considerable amount of heterogeneity in gas exchange at zero G. On the earth's surface, detailed micro sphere measurements of pulmonary perfusion distribution demonstrate a considerable degree of heterogeneity within isogravimetric planes. Thus, the relative importance of gravity versus pulmonary vascular structure in determining distribution of perfusion is questioned. This symposium will bring together the leaders in this controversy: original developers of the zone model; the developer of the fluorescent micro sphere technique, which has provided data contrasting with the zone model; and obtainers of the first respiratory gas exchange dataa prolonged zero G demonstrating persistent heterogeneity in the absence of gravity. Data obtained on the centrifuge at Brooks Air Force Base that quantifies the relative importance of increased inertial force on pulmonary perfusion heterogeneity will be presented.
Mechanisms of Adaptation to Hypoxia: Organizational, Cellular and Molecular Responses
Chairs: F. Ismail-Beigi and C.M. Beall
Maintaining adequate delivery of oxygen to cells and tissues is critical for the survival of homeotherms. A decrease in the availability of oxygen (hypoxia) results in a variety of cellular derangements, which in turn leads to a host of acute and chronic adaptive responses. In acute hypoxia, major responses include stimulation of glycolytic ATP synthesis, modulation of ion channels, release of neurotransmitters, and channeling of ATP usage toward `essential' cellular functions. Adaptive responses to prolonged hypoxia, on the other hand, are mediated by additional events including regulation of gene expression, phenotypic remodeling of specific tissues and organs, and angiogenesis. Examination of mechanisms underlying these adaptive responses constitute an important and a highly active area of investigation. This symposium will summarize the current understanding of mechanisms mediating the adaptive responses to both acute and chronic hypoxia, examining the hypoxic adaptive responses from the level of the organism to cellular and molecular levels. Thus, speakers will discuss the contrasts between the responses of Tibetan and Andean high-altitude natives to chronic hypoxia and explore the genetic basis for the observed differences; the cellular energetic responses in the acute phase of adaptation to hypoxia utilizing noninvasive NMR techniques; the regulatory role of hypoxia-inducible factor-1 (HIF-1) in the expression of specific genes, including erythropoietin, glycolytic enzymes, and vascular endothelial growth factor (VEGF); the role of vascular endothelial growth factor expression of angiogenesis in response to hypoxia; and the expression and function of stress proteins (especially that of HSP-70) in the adaptive response to hypoxia and ischemia.
Molecular Mechanisms of Protein Traffic and Secretion
Chairs: K.L. Kirk and H.J. Bellen
The intracellular traffic of physiologically relevant proteins such as ion channels and hormone receptors can be regulated in response to specific physiological cues. This symposium will introduce physiologists to the basic paradigms that have led to our current understanding of the protein traffic machinery. These paradigms include genetic approaches to studying membrane traffic, the reconstition of regulated secretion in semi-intact cells and the combined use of cell biological approaches and high resolution electron microscopic methods to study membrane vesicle formation. Invited speakers have used these paradigms to provide novel insights into the molecular basis of protein traffic. Discussion should expose the audience to current views of the protein traffic machinery and illustrate how this information can improve our understanding of basic physiological processes that are regulated by this machinery (e.g., neurotransmitter secretion and ion transport).
Is the Development of Atherosclerotic Lesions Determined by Monocyte-Endothelial Adhesion?
Chairs: K. Ley and A.L. Beaudet
Atherosclerosis is known to have an inflammatory component. Monocytes recruited into early lesions are believed to differentiate into macrophages and foam cells. These cells secrete cytokines and growth factors that may promote smooth muscle proliferation and formation of a fibrous cap. Recently, interventional studies have become possible that bear the potential of elucidating the role of endothelial-leukocyte adhesion molecules in the atherosclerotic process. This interdisciplinary symposium will explore the interrelation between hemodynamic forces, shear stress-induced and -suppressed gene products, lipoproteins, and endothelial cell adhesion molecules in the formation and maturation of atherosclerotic lesions. The techniques used by the presenting investigators include endothelial cell biology, differential display, flow modeling, and transgenic and gene-targeted mice.
Neuronal Assembly Dynamics: Cellular and Network Mechanisms in Cardiorespiratory Control
Chairs: S.M. Barman and B.G. Lindsey
Participants will highlight recent advances in our understanding of how brain function emerges from dynamic interactions among neurons: higher order properties in an invertebrate motor system that depend on cellular and molecular mechanisms for their expression and stability; mammalian brainstem networks involved in cardiorespiratory control; cellular and network properties of the respiratory oscillator and computer models, which suggest cooperative mechanisms that produce the timing and phases of breathing; recent results from models of intracellular signal transduction pathways as a computational network as a link to the neuron's connectional network activity; time and frequency domain analysis of cooperative phenomena in brainstem networks that coordinate sympathetic activity; repeated patterns of synchrony in neuronal assemblies, which may reflect distributed mechanisms involved in the dynamic regulation of breathing by baroreceptors and chemoreceptors.
Strength, Functional Capacity and Trainability of Aging Skeletal Muscle
Chair: R.S. Mazzeo
The well-documented loss of muscle mass and function associated with advancing age carries with it clinical and health consequences. As the elderly population continues to grow at a dramatic rate, it becomes imperative to have a better understanding of the causes, mechanisms and possible interventions for sarcopenia. This symposium will present a comprehensive overview of what is currently known regarding sarcopeniafrom the functional implications to the potential underlying molecular mechanisms. As disuse atrophy of muscle appears to contribute significantly to the pathophysiology of this disorder, the role of exercise (both aerobic and strength training) as a possible intervention or therapeutic modality will also be examined. Specifically, speakers will discuss the remodeling of the motor unit that occurs with advancing age as well as the potential mechanisms for this observation; the molecular mechanisms associated with sarcopenia and the influence of possible interventions; intrinsic age-related changes in muscle that render them more susceptible to contraction-induced injury as well as a decrease in ability to recover from injury; and the functionally and health-related consequences of sarcopenia and the extent to which regular exercise can preserve or prevent muscle loss with age.
Hemodynamic and Renal Tubular Interactions of Endothelin and Nitric Oxide
Chairs: D.M. Pollock and T.D. Warner
The enormous interest in endothelin (ET) and nitric oxide (NO) has led investigators to focus on how these factors directly interact. It has been known for some time that the vasodilator actions of ET were due, in part, to release of NO. More recently, however, it has been reported that some of the vasoconstrictor responses to inhibition of NO production are mediated by ET. It has also been postulated that the tubular actions of ET are mediated by NO. This symposium will specifically address the question of how ET and NO interacts to regulate cardiovascular and renal function. Studies using molecular to whole animal techniques will be discussed to provide a comprehensive analysis of this interaction. The physiological conditions under which NO regulates ET activity and the mechanism for this regulation will be a key component of this symposium. Several speakers will address issues related to how ET and NO may influence function within the renal tubules, as well as the role of ET and NO in endothelial cell migration and angiogenesis. It is expected that speakers will offer their latest insights into this fascinating relationship in an effort to further our understanding of endothelial cell function.
Current Mechanisms of Blood Coagulation
Chairs: S.T. Rapundalo and B.R. Lucchesi
Speakers will discuss recent advances in understanding the pathobiology of thrombosis, particularly as it relates to the function and regulation of specific molecular components of the coagulation cascade: the molecular and biochemical characteristics of protein-protein interactions between tissue factor and factor VIIa; emerging structural evidence that may explain the interplay between these two components and thereby define their roles as primary cellular initiators of coagulation; the key role of Factor X in thrombogenesis will emphasize the specific residues in the molecule that are critical for its function in the prothrombinase complex as the primary activator of thrombin; new advances in understanding structure-function of the thrombin receptor, its cell signaling pathways, and implications for pathophysiology, much of it based on studies that use a genetic mouse knockout model; and various coagulation processes will be integrated at a physiological and pharmacological level by a description of the use of novel antithrombotic agents to regulate clotting in clinically relevant animal models. The session will create a unique forum for an interdisciplinary dialogue regarding current concepts and state-of-the-art knowledge of coagulation protein function.
Role of Sex Steroids in Cardiovascular-Renal Physiology and Pathophysiology
Chairs: J.F. Reckelhoff and L. Share
Gender has long been known as a predisposing factor for increased cardiovascular-renal disease. For example, men are at greater risk for chronic cardiovascular and renal diseases than are pre-menopausal women. As such, sex steroids have been implicated in the mechanisms responsible for the higher incidence in men and protection in women. That the incidence of cardiovascular disease increases in post-menopausal women suggests that estrogen may play a protective role in preventing cardiovascular disease, whereas numerous studies in rats have shown that the progression of hypertension and subsequent renal injury can be ameliorated by gonadectomy in males. The exact mechanisms by which androgens promote and estrogens may protect against cardiovascular-renal disease is not completely understood and has thus recently been given increased scientific investigation. This symposium will address the highlights of the recent advances into the mechanisms by which sex steroids are involved in cardiovascular and renal function and also address the important research questions yet to be answered.
The Role of Tight Junctions in the Regulation of Tissue Permeability
Chairs: L. Reuss and K.R. Spring
The junctions between epithelial or endothelial cells constitute an essential barrier to the movement of solutes. This symposium will address regulation of the solute and water permeability of these junctions by a variety of intracellular and extracellular factors. Recent advances in our understanding of the molecular structure of epithelial tight junctions have been paralleled by evidence for functional regulation of junctional tightness by a wide range of substances. Presentations will include state-of-the-art talks on: the molecular structure and organization of tight junctions; the relationship between the tight junction and the cytoskeleton; regulation of the intestinal epithelial tight junctional barrier in both physiologic and pathophysiologic states; modulation of water permeation through epithelial tight junctions; factors that alter the structure and permeability of the endothelial cell cleft, and junctional tightness in capillaries.
Protein Phosphatases in Cell Signaling Pathways
Chairs: A.V. Somlyo and C.B. Klee
Protein phosphorylation/dephosphorylation is a major cellular signal-transduction mechanism. It has only recently become apparent that protein phosphatases, like protein kinases, are also highly regulated and important participants in many signaling pathways in a wide variety of cells. Speakers will present examples reflecting this diversity: the interplay of the calcium-calmodulin-activated phosphatase, protein phosphatase 2B, with transcription factors and immunophilins in T-cell signaling; the regulation of ion transporters by phosphatases; an example of a unique mode of phosphatase regulation by coupling Ca2+ -dependent dephosphorylation to the redox state of the cell; the ability of protein tyrosine phosphatases to serve as receptors for adhesion molecules; and the role of the small GTPase RhoA in the regulation of smooth muscle myosin light chain phosphatase and, through it, smooth muscle contraction and non-muscle cell motility.
Pleuripotent Effects of Tumor Necrosis Factor
on Insulin-Sensitive Tissues
Chairs: J.M. Stephens and P.A. Kern
In conditions of obesity and insulin resistance, TNF-
is produced from adipocytes and has been shown to play a key role in mediating the pathogenesis of obesity-associated insulin resistance. TNF-
has a number of effects on adipocytes including the regulation of glucose transport, interference with insulin signaling, stimulation of lipolysis, and regulation of gene expression. Since the bulk of glucose disposal in the body is mediated by the muscle, more recent studies have examined the effects of TN-
in muscle. An important consideration is whether TNF-
derived from adipocytes acts in an endocrine manner on muscle or whether local production of TNF
from muscle is necessary. This symposia will focus on the actions of TNF-
in fat and muscle that are associated with obesity. There are conflicting issues in this area, particularly concerning the mechanisms involved in the interference of insulin receptor signaling. The session will examine comprehensively the considerable regulation of insulin-sensitive tissues by TNF-
and the relatedness of these effects. The future direction considered is the role of thiazolidinediones in their ability to overcome TNF-
-induced insulin resistance and the implications of these observations.
Molecular Approaches to Understanding Cellular Responses to Stress
Chair: K.B. Storey
Comparative physiologists and biochemists strive to find out how animals `work', i.e., how they adapt, endure, and prosper under a range of environmental stresses and constraints. The focus of comparative research has gradually shifted `downwards' from whole organism to organ, cell, and metabolic levels in order to unravel the mechanisms of adaptation. The last remaining frontier is that of the gene. Molecular biologists working with mammalian cell lines are making great strides in identifying gene responses to external stresses (e.g., osmotic, temperature, oxygen) applied in vitro, although using systems that are largely stress-intolerant. Comparative physiologists and biochemists have a range of naturally stress-tolerant organisms, but are only beginning to become acquainted with molecular techniques that could be applied to their systems. This symposium will introduce the techniques and approaches of molecular biologists to the field of comparative physiology and biochemistry. Most speakers are molecular biologists who are at the forefront of their fields in stress-induced gene expression and who will illustrate the enormous scope of this approach for identifying the genes and gene products that are upregulated as adaptive responses to stress.
The Na-K-2Cl Cotransporters: Heterogeneity of Structure, Function and Regulation
Chairs: S.M. Wall and B. Forbush III
The Na-K-2Cl cotransporters serve a variety of functions including net acid secretion, volume regulation, and both NaCl secretion and absorption. The physiological role and the regulation of the cotransporters is varied and often tissue-specific. The Na-K-2Cl cotransporters are encoded by two distinct genes, BSC-1 and BSC-2. BSC-1, or the absorptive isoform, is kidney-specific and localized to the apical membrane of the thick ascending limb of Henle's loop. The secretory isoform of the cotransporter, BSC-2, is widely distributed. It is found in non-epithelial cells and on the basolateral membrane of epithelia. Recent cloning of both cotransporters has revealed numerous splice variants and has enabled study of the tissue distribution of the cotransporters and their molecular regulation. This symposium will explore the diversity of the cotransporters in structure, function, and regulation, including discussion on the structure and functional expression of the cotransporters, the role of the cotransporters in fluid secretion and volume regulation, and the contribution of the cotransporters to urinary concentration and acid secretion.
Glutamate Transport, Metabolism and Physiological Responses
Chair: T.C. Welbourne
Speakers will discuss the role of glutamate and glutamate transporters in regulating cellular processes both in the CNS kidneys and intestine. In the mammalian CNS, glutamate sequestration and regulation of glutamate transporters are seen from the perspective of the fine tuning excitatory neurotransmission and maintaining extracellular glutamate below neurotoxic levels. In epithelial cells, the role of glutamate and glutamate transporter turnover is viewed from the perspective of regulating multiple cellular processes involving metabolic, osmolar, and acid-base homeostasis. Functional expression of the transporters, ionic and substrate fluxes, as well as gene expression, will be matched, when possible, with the physiological stimuli promoting their activity in order to define these systems (gia/neurons; nephron segments; intestine) in a biologically meaningful manner. Multiple levels of investigation include molecular (cloning, gene expression, protein structure) and physiological (functional expression, ionic and metabolic fluxes, signaling pathways and organ responses). The aim is to provide coherence that is attractive to investigators across multiple disciplines and to invite further exploration.
APS Public Affairs Symposium: Institutional Animal Care and Use Committee Issues Roundtable
Chairs: C.T. Hawk and S.W. Mifflin
This session is intended to serve as a forum where scientists who serve on Institutional Animal Care and Use Committees (IACUCs) can compare how their institutions' committees respond to various issues in protocol review. Among the issues likely to come up for discussion are death as an end-point, justification of animal numbers, verification that research is not duplicative, footpad injections, and other areas that the USDA regulations and the Guide for the Care and Use of Laboratory Animals leave to the discretion of each IACUC. Symposium organizers also invite audience discussion of what scientists find frustrating and rewarding about IACUC service, as well as what scientists would like to see changed in the current animal care regulatory framework.
Alternative Pre-messenger RNA Splicing: Biology and Pathology
Chairs: E.J. Benz and P.A. Sharp
The appearance of intrans in the genomes of organisms created the necessity for a molecular mechanism that provided for the elimination of transcripts of the intrans from messenger on precursors, and the precise ligation of, in the correct register, the exons that ultimately form mature messenger RNA. This process, called pre-messenger RNA splicing, has been extensively studied with respect to both its fundamental biochemical mechanisms and the elements responsible for modulating it in different tissues. In particular, the identical pre-messenger RNA transcripts are spliced differently in different tissues, yielding an array of messenger RNA products that, in turn, can cope for an array of proteins of like, but non-identical, function. This symposium will focus on the role of intrans and posttranscriptional pre-messenger RNA splicing in normal cell physiology, the anatomy and physiology of splicing apparatus that supports pre-messenger RNA splicing, emerging information about the factors that govern the use of alternative mRNA splicing pathways in different tissues, and examples, drawn from the impact of normal and abnormal alternative mRNA splicing in health and disease.
Understanding Biological Systems Through Mathematical Modeling
Chairs: J.C. Collins and R.C. Boston
This cross-disciplinary symposium has been organized to honor the memory of Loren Zech, senior scientist in the Mathematical Biology Laboratory of the National Cancer Institute. An endocrinologist and engineer, his interests, knowledge, and influence spanned a wide spectrum and crossed several FASEB societies. The talks in this symposium center on his interests and contributions, including the development and dissemination of SAAM and CONSAM, the compartmental analysis software distributed from his laboratory at the NCI, and his uncanny and unique understanding of the human body from an engineering systems point of view. Two presentations describe novel uses of the Internet to promulgate models developed by Loren Zech and others and to develop from shared databases a new generation of models linking genomic and molecular information to health care practice.
Transport Phenomena in Cellular and Molecular Processes
Chair: S.L. Diamond
This session will report recent advances in the study of transport phenomena as it regulates biological processes from the molecular to cellular level. With the increase of computational power and the advance of computational techniques that include molecular and Brownian dynamics, statistical mechanics, large-scale simulation, and rapid imaging, this session is timely. Speakers have been selected to provide insight and discussion on topics of microscale diffusion and convective transport. Topics will cover: ion mobility through gap junctions; intracellular calcium diffusional dynamics; the role of reaction and transport on endocytotic systems inside the cell; diffusive and convective/reactive events in human blood, and mechanochemical coupling in biological systems whereby chemical energy drives mechanical events and transport. This session will be attractive to a range of biophysicists, biologists, bioengineers, and clinicians interested in fundamental processes of transport phenomenon at the microscale.
Engineering Gene Therapeutics
Chair: M.L. Yarmush and J.R. Morgan
Gene therapy, which holds great promise for the treatment of a variety of inherited and acquired diseases, during the past decade, has spawned the development of numerous, diverse gene transfer technologies for the introduction of therapeutic genes into cells in vitro as well as tissues in vivo. They range from the complex viral-mediated approaches to the more simple chemical and mechanical methods. Although each gene transfer technology fundamentally seeks to attain the same goalintroduction and expression of a therapeutic gene into a target cell or tissuethe success of the clinical application of these technologies will ultimately depend on the advantages and limitations of each technology and its suitability to its medical application. At this juncture in the progress of gene therapy, the limiting factor is not the availability of therapeutic genes; rather, the limitations lie within the dynamics of the gene transfer processes. The objective of this session is to highlight the studies in life sciences and bioengineering that are addressing these issues, which include the production of high titer stocks, the efficiency of gene delivery in vitro, the trafficking and targeting of genes and gene delivery vehicle in vivo, the persistence and level of gene expression after gene delivery, and the inflammatory consequences and immunogenicity of in vivo gene delivery vehicles. Leading experts from academia and the biotechnology industry will discuss recent advances by life scientists as well as the new and emerging efforts of the bioengineering community to address these issues.
Molecular and Cellular Changes During Aging
Chairs: P. Shyi-Gang Wang and Y-H. Wei
The topics in gene expression, signal transduction, and mitochondria role will be included to discuss the relationship between aging and cellular or molecular changes: the temporal relationship between down regulation of thymidine kinase and changed levels of cell cycle regulators, p16, p21 and E2F-1, during senescence of human diploid fibroblasts; the inhibition of transforming growth factor beta 1 on prolactin synthesis and mRNA expression, but not on prolactin secretion, is age-dependent; the correlation between cAMP production and steroidogenesis in rat testicular interstitial and adrenocortical cells with different ages; the hypothesis of the oxidative stress theory of aging by using pertinent data to elaborate on the involvement of free radicals in the oxidative modification of protein, DNA, and lipids involved in cellular structure and function during aging, and the vicious cycle that operates in various cells at different rate and leads to differential accumulation of oxidative damage and to mutation of mitochondria DNA, which may explain the difference in functional decline and structural deterioration of different tissues in human aging.
Refresher Course
Teaching Renal Physiology
Chairs: V.L. Brooks and A.J. Vander
This workshop, which will review concepts and teaching strategies related to renal physiology, will consist of poster presentations, demonstrations (e.g., computer simulations); exhibits (e.g., books, lecture outlines; problem-based learning cases), and didactic lectures. The didactic portion will begin with three 30-minute lectures, each with 10-minute discussion periods, and will review selected important topics of renal physiology. These topics include renal transport mechanisms; regulation of potassium excretion; and renal aspects of acid-base balance. The emphasis will be to enhance the understanding of renal physiology and to provide an update on new information. A short lecture will focus on miscellaneous areas of renal physiology that are difficult to teach. A panel discussion will draw not only from the previous lectures, but also from other questions submitted in writing by the audience.
| American Society for Pharmacology and Experimental Therapeutics |
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There is significant interest in pharmacotherapeutic management of tissue healing mechanisms regardless of the nature, origin, or causation of tissue injury. Because this field overlaps both basic and clinical sciences, the symposium is organized around the desired clinical end point of tissue healing and restoration of tissue structure and function. This symposium will bring experts in representative areas of this field who will illuminate cutting-edge developments.
Proteinase-activated receptors: molecular biology, pharmacology, and physiology
Chairs: D.D. Ku and M.D. Hollenberg
The recent cloning of the thrombin receptor and its unique proteinase-activating receptor (PAR) mechanism of action has opened this new field of research. Presentations will focus on the molecular biology of the different subtypes, the physiological consequences of receptor activation, structure-activity relationships of various receptor agonists and antagonists, and the role of such receptors as possible clinical targets in coronary artery disease. Preliminary findings on the pathophysiological effects in PAR knockout mice will be presented.
New insights into the actions of G-protein-coupled receptors
Chair: N.M. Nathanson
Experts in the field will discuss the latest research by using knockout mice to study the possible role of MC-5 receptors in a hypothalamic-pituitary exocrine axis, the pleiotropic consequences of muscarinic acetylcholine receptor gene disruption, a genetic dissection of the endothelin pathway, and a genetic analysis of chemoattractant receptors.
Nitric oxide, redox targets and apoptosis
Chair: J.S. Stamler
Topics will focus on the regulation by nitric oxide of the caspase family of enzymes and in the hepatocyte, in particular. The role of nitric oxide in apoptosis in lymphocytes and neuronal cells will be discussed
Tyrosine kinase receptor (TKR)-mediated vascular regulation: implications in hypertension
Chair: R.D. Feldman
Vascular tone is regulated by a number of paracrine, endocrine, and neural hormones. Acute alterations in tone are appreciated to reflect the interaction of hormones interacting through G-protein-coupled pathways and guanylyl cyclase. Tyrosine kinase receptor activation, although linked to mechanisms of vascular hypertrophy-hyperplasia, has not been appreciated to be important in acute regulation of vascular tone. This will highlight the emerging concepts relating to the role of TKR activation in regulation of vascular tone and how alterations in this pathway may be linked to vascular disease.
Cyclooxygenase-2: from discovery to a new therapeutic target for multiple diseases
Chairs: P.V. Halushka and P. Needleman
This symposium will highlight the discovery and pharmacology of cyclo-oxygenase -2 and its physiological and pathophysiological role in various tissues. Clinical pharmacologists will discuss current clinical trials based on these earlier findings.
Physiological and pathophysiological regulation of cytochrome P450
Chair: E.T. Morgan
It has been known for some time that hormones and cytokines regulate the expression of cytochrome P450, a family of enzymes that is central to the metabolism of drugs and toxins. It is also known that physiological pathways activated by these agents can regulate the induction of P450s by chemical agents and physiological processes. To facilitate our understanding of commonalities and differences in these regulatory events, this symposium will bring together the current knowledge of the mechanisms by which growth hormone, cytokines and growth factors regulate basal P450 expresssion; the signaling pathways that modulate induction of P450; and knowledge about basal transcription factors and development.
Implications of combinatorial chemistry on pharmacological sciences
Chairs: J.S. Lazo and R.W. Ruddon
Combinatorial chemistry has revolutionized the process of drug discovery by making it possible to synthesize and screen vast numbers of potential compounds in the same time it traditionally has taken to study one compound. This symposium will outline how this approach is being used to perform structure-activity analyses of cyclopeptide natural products, to study modulators of protein-protein interactions, to design protein ligand mimetic drugs, and how the concept is being applied to cell biology and drug screening.
Anandamide, endogenous cannabinoid receptor ligand
Chair: C.J. Hillard
Although the N-acylethanolamines were first detected in biological samples 30 years ago, recent discovery of biological functions for these agents has refocused attention on these novel lipids. Anandamide, or arachidonylethanolamide, was extracted from brain and identified as an endogenous ligand for the cannabinoid receptor. This elevates the cannabinoid binding site to the status of a receptor that has its own ligand and, presumably, is part of one or more pathways in the brain. This symposium will focus on the mechanism of anandamide synthesis and catabolism, and the physiological and pathophysiological roles of the cannabinoid receptor.
LPS and NO in the human lung
Chair: P.S. Tobias
Participants will go from the basic biochemistry of lipopolysaccharide interaction with cells to some of the eventual pulmonary physiological consequences, with particular attention to nitric oxide.
Structure-function of cytochromes P450 and flavin-containing monooxygenases-implications for drug metabolism
Chair: J.R. Halpert
In the past decade, much information has been obtained about the structural basis of the specificity of individual drug metabolizing enzymes. Progress has been especially rapid with the cytochromes P450 and flavin-containing mono-oxygenases. Results of site-directed mutagenesis and molecular modeling studies have enabled the development of 3-D models of bacterial and mammalian P450s that allow predictions of new substrates, design of novel inhibitors, and rational redesign of enzyme specificity. The technology in this field is developing rapidly, and the goal of the symposium is to present some of the complementary approaches being used to probe the molecular basis of enzyme specificity.
K+ channels in cardiovascular pharmacology
Chairs: R.S. Kass and R. Levi
Talks will highlight the molecular biology and pharmacology of K+ channels in heart; the relationships between drug binding domains on the K+ channels and their function; the role of K+ channels in inherited heart disease, long QY syndrome; the role of sex hormones in regulation of K-channel expression and drug response; and developmental changes in K+-channel expression in heart.
Mechanism and regulation of neurotransmitter release
Chair: W.A. Catterall
Discussion will include the functions of SNARE proteins in neurotransmitter release as well as the interactions of presynaptic calcium channels with SNARE proteins in neurotransmitter release. The role of presynaptic receptors for nicotine in modulating neurotransmitter release and mossy fiber LTP, a presynaptic form of plasticity will also be discussed.
Prostanoid receptors: molecular biology, pharmacology, and therapeutics
Chairs: J. Jasper and E. Goetzl
The symposium will include an overview of prostanoid receptors-molecular biology and knockout mice studies, a summary of the second messengers involved in prostanoid receptor signal transduction, the way in which a single prostaglandin may have multiple effects depending on the cell type and receptor subtype expression. This molecular overview will be related to the clinic by an overview of the therapeutic areas served by these new prostaglandin receptor ligands.
Phantom free radical metabolites: implication of futile metabolism for toxicity and drug testing
Chair: R.P. Mason
Many free radical metabolites of toxic chemicals and drugs react in such a way that the parent compound is re-formed and oxygen is reduced to superoxide. Such futile cycles are known to occur in vitro for free radical metabolites formed either by one-electron oxidation or reduction of the parent compound. Anti-cancer quinones exemplify superoxide generation through drug reduction. Phenolic drugs, which, upon one-electron oxidation, form phenoxyl radicals that react with GSH and NADPH to form superoxide generating radicals, are another example. The biological consequences of these phantom free radical metabolites will be discussed. An analog of this futile metabolism to toxic transition metal will be developed.
Genetic and epigenetic regulation of monoamine transporters
Chairs: N.R. Zahniser and R.D. Blakely
Topics in this symposium include: vesicular neurotransmitter transportfrom bioenergetics to synaptic transmission; a channel-like model for the plasma membrane serotonin transporter; protein kinases and regulated trafficking in the control of monoamine clearance; and the consequences of spontaneous and engineered genetic alterations in the serotonin transporter on physiology and behavior in humans and other species.
Molecular determinants of protein phosphatase specificity in cell signaling
Chair: M.C. Mumby
Speakers will address protein tyrosine phosphatases as specific regulators of cellular signaling events in vivo; the role of protein tyro-sine phosphatases in regulating signal transduction mechanisms; spatial determinants of the hormonal regulation of protein phosphorylation; and the role of protein-protein interactions in the control of specificity of protein phosphatase 2A in cell signaling.
Mitochondria as targets for drug toxicity
Chair: E.P. Brass
An understanding of the molecular basis of drug toxicity is critical for rational drug design to avoid toxicity, the development of preclinical screens, assessment of adverse events during clinical development, and for monitoring large populations exposed to the agent. Advances in the cellular and molecular biology of mitochondria have made an understanding of mitochondrial-xenobiotic interactions possible. Also, the role of mitochondria in cellular homeostasis has expanded to include potential regulatory functions in processes such as apoptosis. This symposium will review the basic science foundations of this understanding and review three paradigms for mitochondrial-based drug toxicity.
Herbal medicine: current status of use and research in the United States
Chair: C.N. Gillis
This topical symposium will include an overview of the current use and regulation of herbal preparations in the U.S., the pharmacologic principles underlying the efficacy of certain herbal preparations, and scientific studies of specific examples, i.e., anticancer compounds, St. John's Wort, Ginkgo biloba, and pine bark.
Genetically engineered mice as models for signaling and regulation in the cardiovasuclar system
Chair: K.R. Chien
CRE-Lox-based systems and gene targeting in the mouse have been developed to study signaling pathways for complex cardiac phenotypes such as cardiac development and failure. Many transgenic and gene-targeted mice have recently been developed to address issues related to natriuretic peptide receptor signaling in the heart and cardiovascular system. Double knockouts of the G9/G11 genes have provided clear evidence of the redundant role these genes play in the control of cardiac muscle growth and development. A series of novel animal models have been generated to study the role of G-protein-coupled receptor kinases in the control of cardiovascular physiology and disease. Their developers will discuss the use of these cutting-edge models to study cardiovascular regulation.
Colloquium (honoring Anthony Y.H. Lu with a Plenary Lecture by Dr. Lu)
Drug metabolism in the new millennium
Chair: G.T. Miwa
The colloquium will showcase the most recent research advances in the areas of drug and xenobiotic biotransformations and the regulation of drug metabolizing enzymes, emphasizing the relevant biochemistry, biology, chemistry, and pharmaceutical science. Speakers will articulate their vision of the future of this field.
Short Course
Apoptosis
Chairs: J.S. Lazo and J.A. Hickman
Sessions include: A Primer on In Vitro Methods to Detect Cell Death, Intracellular Proteases and Apoptotic Signaling, Cell Death In Vivo, Cell Death in Immunological Disorders and Apoptotic Signaling Molecules, and Cell Death in Neurons: For Better or Worse.
Workshop
Utilizing the resources of the Genome Project
Chairs: F.S. Collins and S.E. Old
The Human Genome Project is rapidly providing a rich array of resources, including biological materials, informatics, technologies, and methodologies. These resources have tremendous potential for identifying candidate loci for complex diseases and relating these findings to the study of gene structure and function. This workshop will provide a forum to enable researchers to take advantage of the opportunities contributed by the Human Genome Project.
ASPET/ASCPT Teaching Institute
Computer and electronic media in pharmacology education: the agony and the ecstasy
Chairs: R.D. Schwartz-Bloom, D. Abernethy
Speakers, including pharmacology educators, have developed computer-based pharmacology material that can be accessed on the Web by medical school students, clinicians, and other interested audiences. Demonstrations of the programs will be given, which will include animation that can be integrated into both Web-based and computerized classroom-based teaching material.
Graduate Student Convocation
Scientific communicationeffective mechanisms and ethical obligations
Chair: G.M. Stancel
Topics include lecture and seminar presentations with special emphasis on job interviews, poster and platform presentations at scientific meetings, and mechanisms for the preparation of manuscripts and grants. The workshop will discuss methods for effective oral and written presentations as well as the responsibilities and ethics of professional communications.
Burroughs Wellcome Fund Lecture
Novel K+ channel families and their pathophysiological implications
Speaker: M. Lazdunski
| American Society for Investigative Pathology |
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Invited speakers will describe their latest work on the cellular and molecular basis of heart and blood vessel development. Emphasis will be on identiying transcriptional controls that link critical morphogens such as BMPs, Wnts, activin, and sonic hedgehog with the onset of structural and contractile protein gene expression that marks cardiac and vascular smooth muscle differentiation. The molecular basis of left-right asymmetry in specification of cardiac chamber identity and aortic arch artery development will be discussed as will the transcriptional controls underlying vascular smooth muscle diversity.
Emerging Mechanisms for HIV Pathogenesis: The `Ins' and `Outs' of Candidates for Therapeutic Targets
Chairs: S.C. Peiper and R.W. Doms
Recent scientific advances have provided tremendous insight into the pathogenesis of infection with the human immunodeficiency virus that will have a direct impact on our understanding of AIDS. These insights may well open new avenues for therapy of this disorder. The symposium will include an overview of contemporary perspectives on HIV infection and in-depth discussions of recently elucidated mechanisms in viral entry and packaging.
Trends in Experimental PathologyDisease Models Through Gene Targeting
Chairs: J.D. Locker and M.B. Prystowsky
Animal model systems are the cornerstone of experimental pathology, but many important processes for which appropriate model systems are not available. Now, however, the ability to target gene function has enabled a more focused approach in which animal genomes are altered to create disease model systems. Both abnormal expression (through transgenes) and abnormal lack of expression (through gene disruption) can be studied in the intact mouse. Four speakers will address a variety of fundamental questions of disease biology based on novel experimental animals. 1) Knockouts and transgenics as model systems to study the genesis of brain cancer have focused on the p53 gene and studies have shown that altered p53 modifies control of both the cell cycle and apoptosis; surprisingly, these fundamental pathways are tissue-specific, because the mechanisms in the brain are distinctive from other sites. 2) A critical switch during the process of carcinogenesis, the induction of angiogenesis (targeting of oncogenes to specific tissue sites, e.g., pancreatic islets, dermal fibroblasts, and epidermal squamous epithelium, has led to model systems in which the early stages of tumor progression can be observed and experimentally manipulated; animal models demonstrate the timing of the angiogenic switch and enable study of growth factors and drugs that sustain or modify angiogenesis). 3) Another fundamental question in cancer biology, the two levels of the relationship of the peroxisome to liver carcinogenesis: a) the peroxisome is regulated by a nuclear receptor (the PPAR); and b) reactive oxygen is a byproduct of normal metabolism of the peroxisome. Targeting genes to the peroxisome can either stimulate or repress generation of reactive oxygen and the resultant carcinogenesis, thus directly establishing the relationship of the two processes. However, knockout of the peroxisomal acyl CoA oxidase gene leads to a full sequence of liver damage and carcinogenesis. This enzyme is part of a pathway that appears to eliminate natural ligands that activate the PPAR. The abnormal activation mimics the activity of carcinogenic drugs that also activate this receptor. 4) A unique perspective on the problem of animal models: When studies are built around a distinctive problem in pathogenesis, transgenic and knockout mice allow certain specific kinds of manipulations. Even this approach is too limited, because many such processes cannot be properly studied in the mouse. Nevertheless, spontaneous models in other species can overcome this limitation. Resources for finding out about these systems are thus an important complement to direct experimental manipulation of the mouse genome.
Chemokines in Inflammation
Chairs: R.M. Strieter and J.J. Oppenheim
Five speakers will discuss the structure-function relationships of the burgeoning families of chemokine and virokine receptors and their activating ligands; the structure-function relationships of new chemokine ligands and new chemokine subfamilies; how the degranulating effects of neutrophil chemoattractants such as interleukin-8 generate the release of molecules such as defensins and cathepsin G with leukocyte chemoattractant as well as in vivo adjuvant effects; the potential antiinflammatory effects of molecules, such as HIV-1 gp120, that suppress receptors for chemoattractants; the pivotal role of CXC chemokines in regulating angiogenesis in the context of tumor growth; and evidence of the pivotal inducing role of chemokines in the development of TH1- and TH2-dependent cytokine responses and the consequent effects of this on the pathogenesis of autoimmune diseases such as experimental allergic encephalomyelitis. These presentations are intended to communicate that chemokines and receptors, by influencing cell homing, angiogenesis, inflammatory and immune responses, are vital contributors to host defense. Furthermore, pathogenic viruses, by preempting or inhibiting these chemokine-dependent processes, have learned to circumvent host defenses.
Genomic Instability in Cancer
Chair: T.D. Tlsty
Genomic integrity is maintained by a network of cellular activities that assess the status of the genome at a given point in time and provides signals to proceed with or halt cell cycle progression. Mutations in any part of these cellular pathways can have the ultimate effect of disrupting chromosomal integrity. This session will address these issues in different ways. Participants will also present insights into the mutagenic mechanisms that underlie cancer and how they arise.
President's Symposium
Angiogenesis and Microcirculation
Chair: H.F. Dvorak
The topic of this year's ASIP President's Symposium, "Angiogenesis and Microcirculation," is of considerable current scientific interest. Recent progress has elucidated the mechanisms of how new blood vessels are formed under normal and pathological circumstances. It is expected that this new information will lead to the development of novel therapeutic approaches that will allow, as appropriate, both positive and negative modulation of new blood vessel formation. Such modulation will be important in the treatment of many diseases in which angiogenesis plays an important role, particularly cancer, but also inflammatory diseases such as rheumatoid arthritis, wound healing, etc. Well-known speakers will review the latest work on VPF/VEGF, the pathogenic mechanisms underlying new blood vessel formation, functional properties of the newly formed blood vessels that supply tumors, and various new approaches to control tumor growth by means of anti-angiogenesis.
| American Society for Nutritional Sciences |
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Short stature, i.e., stunting, is a significant problem throughout the developing world, affecting about 43% of children. Most stunting occurs before age 3 years, and stunted children usually become stunted adults. The consequences of becoming and remaining stunted are increased morbidity, mortality, delays in motor and mental development, and decreased work capacity. The causes and etiology of stunting are much less understood than are its timing and consequences. There is little understanding of why and how stunting occurs extensively in environments that are poor, but not desperately so, and in environments that seem to be improving. This symposium reviews and synthesizes our understanding about why and how young children become stunted, emphasizing new knowledge gained over the past 5 years; considers the implications of this understanding for efforts to improve child well-being, and highlights new ideas about the causes and etiology of stunting that especially warrant further investigation.
Fat Distribution During Growth and Later Health Outcomes
Chairs: M.I. Goran and R.M. Malina
Body fat distribution has been hypothesized to play an important role in the link between obesity and risk of related diseases such as non-insulin-dependent diabetes mellitus (NIDDM) and cardiovascular disease. In particular it has been suggested that the development of adipose tissue around the organs (visceral fat) may lead to increased disease risk related to obesity. This clustering of obesity and related disease risk is not limited to adults. Evidence now suggests that the development of body fat pattern and its relationship to increased disease risk emerges early in life. This symposium will review evidence for the accumulation of visceral fat early in life and its relation to risk factors for NIDDM and cardiovascular disease. Speakers will also review the roles of genetics, hormones, diet, gender, maturation, ethnicity, and physical activity in the development of body fat distribution during growth.
Advances in Measuring Food Insecurity and Hunger in the U.S.
Chairs: C.M. Olson, E.A. Frongillo, Jr. and D. Rose
Beginning with the landmark report, "Core Indicators of Nutritional State for Difficult-to-Sample Populations," and the "Ten Year Comprehensive Plan for National Nutrition Monitoring and Related Research," the Food and Consumer Service of USDA and the National Center for Health Statistics of DHHS launched a major effort to develop measures of food insecurity and hunger. Through the work of the Federal Interagency Working Group for Food Security Measurement and a substantial public/private partnership involving many individuals, a state-of-the-art food security survey questionnaire was developed and administered by the U.S. Bureau of the Census as part of its regular Current Population Survey in 1995, 1996, and 1997. Prevalence estimates are now available for 1995. Information on who is at risk and the health and nutritional consequences of food insecurity is rapidly becoming available.
Assembly and Physiology of Apolipoprotein B-Containing Lipoproteins: Not Just for Heart Disease Anymore!
Chairs: R.L. Walzem and R.L. Hamilton
What do the yolk sacs in mammals and birds, human hearts and avian kidneys have in common? In addition to intestine and liver they are now known to assemble and secrete Apolipoprotein B- containing lipoproteins (ApoB-LP). Novel roles of ApoB-LP in tissue- and whole-animal nutriture represent an exciting new area of research. ApoB-LP assembly is a premier example of gene and nutrient interaction because unlike proteins, individual lipid species are not single-gene products. Variation in cellular lipid status renders ApoB-LP assembly responsive to cellular physiology and whole animal nutrition. Nascent ApoB-LP diameter and lipid composition are regulated during the multi-step ApoB-LP assembly process. This level of control provides the means to achieve targeted lipid-nutrient delivery. This symposium will describe the molecular strategies being used to document ApoB gene expression, protein physiology, and ApoB-LP assembly processes and provide up-to-date information on newly identified nutritional purposes of ApoB-LP.
Steroid Hormone Receptor and Nutrient Interactions: Implications for Cancer Prevention
Chairs: D.F. Birt and M.A. Belury
Steroid hormone receptors have critical roles in the regulation of transcription to alter gene expression. It is clear that several nutrients function through interactions with members of the steroid hormone receptor family. Furthermore, several influences of nutrients on cellular processes that are important in cancer are being demonstrated to be mediated through steroid hormone receptors. Therefore, this symposium will present the latest findings on the role of dietary influences on gene expression and carcinogenesis. Nutrients known to be important players in carcinogenesis and known to interact with steroid hormone receptors include retinoids, vitamin D, fatty acids, estrogenic compounds and dietary energy. Steroid hormone receptors that will be discussed include the retinoic acid receptors (RAR, RXR), vitamin D receptor, peroxisome proliferator-activated receptors (PPARs), estrogen receptor, and the glucocorticoid receptor. This session will interest a broad audience of nutritionists, biochemists and cell biologists interested in the area of dietary influences on gene expression and carcinogenesis.
Do Doctors Know When Food Is Medicine?
Chair: B.J. Moore
The American public is increasingly aware of the importance of nutrition in health maintenance and disease prevention and treatment. Physicians are expected to provide their patients with accurate information and guidance concerning overall diet, as well as specific foods and nutrients and their relationship to health. How well prepared are physicians to supply or even evaluate this type of information? The PIC symposium for 1998 will focus on the nutrition education of medical and dental students in the United States. In 1985, the Institute of Medicine published a report on the quality and quantity of nutrition education in a large sampling of U.S. medical and dental schools. That report documented the widespread inadequacy of nutrition education programs in U.S. medical schools, and there is more recent evidence that the situation has not improved since then.
The PIC symposium will address whether and how future physicians and dentists are prepared to guide their patients who seek counsel regarding: 1)discordant messages from the media on vital nutrition issues; 2) confusing nutrition recommendations from highly reputable scientific bodies (RDA's, DRI's, etc.); 3) treatment for the most common nutritional problem in American todayobesity; and 4) the role of nutrition in both the prevention and treatment of disease. Participants will describe and discuss different models reflecting the current nutrition education practices on medical and dental school campuses will be described and discussed. Our goal is to identify key administrative and other barriers to increasing both the quantity and quality of nutrition education. A CD-ROM-based approach to nutrition education offers students the opportunity to pursue nutrition education independently and at their own pace. But providing such technology does not resolve the issue of competing demands on the time of medical and dental students. Nor does it address the relationship between what students feel compelled to study in order to pass examinations and their genuine desire to acquire more training and education in nutrition. The symposium will offer innovative suggestions as to what medical students might do to increase the quantity and quality of nutrition in their medical and dental schools.
Nutrition, Biochemistry, & Molecular Biology of Biotin
Chairs: D.M. Mock and H. Said
The theme of this symposium will be new developments in the physiology, biochemistry, and nutritional science of biotin. Spurred on by observations suggesting that mild to moderate biotin deficiency occurs much more frequently than previously appreciated, the intestinal, renal and hepatic biotin transporters have been identified and characterized, and the regulation has been probed. Biotinidase has recently been cloned and sequenced. Exciting new insights into the regulation of the synthesis of biotin-dependent carboxylases have been gained from studies conducted in prokaryotes. Important analogies to mammalian holocarboxylase synthetase have been made, and conserved sequences have been identified. The first studies examining some putative indices of biotin status have been conducted in human subjects, establishing the presence of substantial amounts of biotin metabolites in both human blood and urine. Recent studies have confirmed the identity of several biotin metabolites, including one that was not identified until 1996.
Interactions of Diet and Nutrition with Genetic Susceptibility in Cancer Epidemiology
Chairs: J. Freudenheim and R. Sinha
Increasingly there is evidence that individual differences in metabolism may be of importance in understanding cancer. In particular, the effect of diet and nutrition as well as other environmental exposures may be modified by genetic differences in the activity of enzymes important in the metabolism of carcinogens or enzymes important in terms of nutrient function. This symposium will include presentations regarding epidemiologic investigations of the interrelations of exposures, genetic susceptibility, and cancer risk. For example, there is evidence that drinking alcoholic beverages is related to risk of breast cancer. One presentation will examine whether genetic differences in one of the enzymes important in the metabolism of alcohol affect the association between alcohol consumption and breast cancer risk such that some individuals are more affected that others despite similar intake.
The Importance of Dietary Essential Fatty Acids in Brain Development and Function
Chairs: J.D. Fernstrom and J. Edmond
The lipid composition of neuronal (and other) membranes is readily influenced by dietary essential fatty acid composition during prenatal and postnatal development. Differences in dietary fatty acid composition do not only affect brain membranes, but also modify brain functions, including behavior. The underlying biochemical and neurophysiologic mechanisms for these effects are not well understood, but are probably related to the role of essential fatty acids as precursors for intraneuronal second messengers (e.g., the prostaglandins). An understanding of the impact of dietary essential fatty acid composition on the chemical and functional aspects of brain development is important, since essential fatty acids are present in breast milk in well-defined proportions, and are currently being added to infant formulas. This symposium will consider whether and how neuronal membrane structure and second messenger functions are influenced by dietary essential fatty acid composition, and the impact of variations in essential fatty acid intake on cognitive and behavioral and visual function in animal and human infants. Consideration will be given to the issue of how much and at what levels essential fatty acids should be included in infant formulas to optimize brain function.
The Nutrition Societies Presidents' Forum: Animal Models in the Advancement of Nutrition Science
Chairs: G.L. Blackburn, M.R.C. Green- wood, R.B. Rucker, and J.S. Stern
The Presidents' Forum delivers cutting-edge knowledge on key topics for current and future scientists in bionutrition. This year, it will focus on state-of-the-art animal models, including those required to test innovative, multidisciplinary experimental biology. A particular focus is the need for core facilities to support local, regional, and national investigations in need of these animal facilities to bridge the gap between molecular and human experimentation. These animal facilities are important to the National Science Technology Center effort to advance an integrated, multifield research initiative that includes how diet causes such profound consequences for health. The President's Office of Science and Technology has identified the science of nutrition as a pivotal research field in America's efforts to minimize the risk of diet-related disease and optimize its health and productivity. The 1998 Forum will explore that role, and the newest ideas and concepts we can bring to it.
Workshops
Applications of the Revised NCHS/CDC Growth Charts (honoring Dr. Alex F. Roche)
Chair: S.S. Guo
The current NCHS/CDC growth charts were developed in 1977. Since then, these charts have been used widely in the United States and have been adopted by the World Health Organization as international charts for assessing growth and nutritional status of infants, children, and adolescents. This timely workshop is organized to describe the revised NCHS/CDC growth charts and discuss their applications. The workshop will discuss: 1) the general guidelines for using and interpreting growth charts; 2) an overview of the NCHS/CDC growth chart revision project; 3) the anthropometric techniques, data quality and reliability across surveys; 4) the statistical development of the revised growth charts; 5) the application of the revised growth charts for monitoring infant growth and nutrition; and 6) effects of maturation on growth assessments. The workshop will interest clinicians, epidemiologist, nutritionists, health practitioners, and public health policy makers.
Medical-Nutrition Education: Bringing Physician Nutrition Specialists into the Mainstream
Chairs: D.C. Heimburger and V.A. Stallings
Nutrition training in undergraduate and graduate medical education has long been recognized as inadequate. The most prominent factor responsible for this inadequacy is the paucity of physician nutrition specialists on medical school faculties who can effectively advocate for change in medical school and residency curricula and serve as role models for incorporating nutrition into patient care. The professional nutrition societies have not always worked together to insure that clinical nutrition achieves increasing recognition and is integrated into medical education and medical care. Yet, it is clear that no single group or society can tackle these complex issues alone. To unify the nutrition societies in order to address these issues, the Intersociety Professional Nutrition Education Consortium (IPNEC) was founded in 1997 with the support of the societies and funding from NIH and industry. This workshop will highlight the current state of training and certification of physician nutrition specialists. Specifically, particpants will highlight the need for physician nutrition specialists to serve as advocates for and teachers of nutrition in medical schools, and the hindrances to increasing their numbers; introduce the Intersociety Professional Nutrition Education Consortium (IPNEC) and delineate its objectives; and relate IPNEC's progress in developing training standards and a unified certification mechanism for physician nutrition specialists.
Conferences
Milk Fat and Mammalian Development: A Comparative Approach
Chairs: O.T. Oftedal and S.J. Iverson
The pattern of nutrient transfer from mother to young varies tremendously among mammals. Although human babies ingest only modest amounts of milk fat, in other taxa the ingestion and utilization of substantial amounts of lipids are critical to neonatal survival. The packaging of milk fat in milk lipid globules presents a specific digestive challenge to the young. This symposium will review recent research on the context, physiological mechanisms, and functional importance of lipid transfer and utilization during the lactation period. Speakers will emphasize extreme examples, such as bears and marine mammals, as a means of reevaluating our understanding of nutrient utilization in early postnatal life, and will assess patterns of lipid intake by suckling young, mechanism of lipid digestion and utilization, lipid deposition, and the significance of milk lipids to the metabolic economy of the mother, especially when she is fasting.
Functional Foods for Health Promotion: A Public Health Opportunity?
Chairs: J.A. Milner and F.A. Coletta
The expanding body of scientific research in recent years linking diet and health has fostered increased attention on the role of nutrition in health promotion and disease prevention. Nutritive and nonnutritive food components, including traditional foods, known nutrients, and phytochemicals that may offer potential health benefits are being studied by scientists in academia, government, and industry. However, the relationship between diet and health is complex and the data are often difficult to interpret. As in many areas of nutrition, scientific consensus does not exist, and there is not a single, accepted definition of functional foods. There is a need for solid scientific data and adherence to scientific principles to ensure not only the scientific validity of statements made about the health effects of food, but also about safety, functional effect, and consumer trust. Participants will discuss these issues in order to increase scientific understanding of the role of physiologically active food components in human health promotion.
Update
Nutrition and Food Safety Initiative
Chair: J.E. Vanderveen
The President of the United States announced on January 25, 1997, a new initiative to improve the safety of the nation's food supply. Details of this initiative, which involves a joint effort by the six federal government agencies having primary responsibilities for food safety, were released in May 1997. In October, the President also directed a special initiative concerning the safety of both domestic and imported fresh produce. Congress appropriated $45 million to fund these special programs in FY 1998 and additional resources are expected to be requested in the future. This session will update the current plans of federal agencies to implement this special initiative, including the role of new techniques and fundamental research findings.
| American Association of Immunologists |
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NIAID 50th Anniversary Symposium: Contemporary Topics in Immunology
Disease Effects on the Immune Response Chairs: F. Brodsky and M. Spriggs
Molecular Regulation of Lymphocyte Migration and Lymphoid Tissue Development Chairs: T.F. Tedder and S. Shaw
Immunoglobulins: From Biology to Design Chairs: H. Schroeder and G. Wu
Cell Life and Death Chairs: V.M. Dixit and D.R. Green
Antigen Presentation: Structure and Mechanisms Chairs: J. Monaco and J. Yewdell
Influence of Innate Immunity on Adaptive Immunity Chairs: R. Locksley and A. Tenner
HIV Day Chairs: S. Lard and S. Bridges
Tolerance to Non-Self: Fetal, Allo- and Xenoantigens Chairs: M. Sykes and T. Mosmann
Special Symposia
Autoimmunity Chairs: B. Kotzin and R L. Coffman
Advances in the Immunology of Aging Chair: R. Hodes
Crosslinking and Conformational Change in Immune System ReceptorsPresidential Symposium Chair: C.A. Janeway
Presidential Address
The Road Less Traveled By: The Role of Innate Immunity in the Adaptive Immune Process C.A. Janeway
| American Association of Anatomists |
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Pathological Oscillation in the Nervous System: Clues for Understanding Normal Brain Organizer: J. Welsh
Gene Knockouts: the Rebirth of Histology Organizer: K.S. O'Shea
The Normal Aging Primate Brain Organizer: D. Rosene
Mechanisms of Vasculogenesis and Angiogenesis During Development Organizer: R. Tomanek
Signals from the Cell Membrane to the Nucleus Organizer: K. Svoboda
Signaling at Cell Junctions in Epithelia Organizers: B. Grove and C. Roskelly
Interactions of Neutrophils and Epithelial Cells in the Lung Organizer: D. Hyde
Organogenesis-common Mechanisms Underlying Differentiation Organizer: B. Carlson
Glutamate and Energy Metabolism Organizer: K. Miller
The Assembly of Myofibrils in Striated Muscle Organizer: D. Fischman
Adhesion Mechanisms and Regulation Organizer: K. Pfenninger
Minisymposia
Trends in Morphological Imaging Organizer: R. Specian
Integrating Computer-aided Instruction Organizers: C. Plopper and K. Rarey
Growth Factors and Development Organizer: R. Runyan
The Role of Mitochondria in Neuroprotection Organizer: J. Hutchins
Cerebral Vasospasms, Ischemia and Subaracnoid Hemorrhage: Adding Insult to Injury Organizer: D. Bernanke
Cardiovascular Development Organizers: M. Watanabe and K. Linask
Signal Transduction and Differentiation Organizer: M.A. Stepp
Lung Development Organizer: J. Tomasek
The Secretory Pathway in Health and Disease Organizer: B. Vertel
Teaching Innovation in Anatomical Education Organizer: R. Drake
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