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INTRODUCTION |
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 TOP INTRODUCTION The American Physiological...American Society for...American Society for Nutritional...American Association of... |
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A sampling of the multidisci-plinary sessions appears below. The Program and Abstract issue contain considerably more details and are mailed to preregistrants before the meeting. For up-to-date information, visit http://www.faseb.org.
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The American Physiological Society |
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TOPINTRODUCTIONThe American Physiological...American Society for...American Society for Nutritional...American Association of... |
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The ability to regulate body temperature effectively during heat exposure depends on the body’s ability to activate appropriate heat dissipating responses. The two major thermoregulatory response to heat stress are the transfer of heat from the body core to the skin via increased skin blood flow and heat transfer from the skin to the environment by evaporation of sweat. The enormous capacity of humans to dilate blood vessels in the skin during thermal stress is the hallmark event that contributes to cardiovascular strain. Cutaneous vasodilation during heat stress leads to a reduction in central blood volume and reduced venous return. The compensatory cardiovascular adjustments leads to a spiraling positive feedback loop which tends to drive body core temperature to excessive levels and predisposes individuals to a variety of heat related disorders (e.g., heat syncope, heat exhaustion, and heat stroke). The ability to prevent excessive hyperthermia and resist heat related disorders is dependent on a complex interaction between reflexes that regulate heat dissipating mechanisms and reflexes which regulate arterial blood pressure and body pressure and body fluid balance. Understanding the nature of these interactions provides insight into factors that contribute to successful heat tolerance (i.e., exercise training) or intolerance (i.e., elderly individuals).
Physiology of Water Transport
Chair: E.M. Wright
Water homeostasis is essential for life at all levels–from the cell to the whole organism. The recent resurgence of interest in water balance is due to the identification of membrane proteins responsible for water transport in and of cells, aquaporins and cotransporters. This, in concert with advances in molecular biology, has led to the reexamination of some long-standing problems in the physiology of water balance (e.g., the mechanisms and route of water transport across epithelial tissues in the kidney, GI tract, lung, and brain. Participants will discuss the recent advances–from molecules to man, including the structure and function of water transport proteins, the regulation of water transport, and the use of knockout animal and human models to examine the role of water transporters in renal, GI, and pulmonary physiology.
Physiological Genomics, Part I: Cells and Genes and their
Applications for Therapies for the Brain
Chairs: B.L. Davidson and H. Federoff
Developing cell or gene-based therapies holds exciting potential for the treatment of CNS disease. Symposium participants will provide an overview of various therapeutic vehicles being developed, with demonstration of their application in multiple disease models. These include models of recessive inherited disease, of the dominant-disorders such as Huntington’s disease and retinitis pigmentosa, and of human brain cancer. Specific topics include the use of virus-based vectors, with application to cancer and neurodegenerative disease models; on progenitor cell populations and their applications in neurobiology, cancer, and neurodegenerative models.
Physiological Genomics, Part II: Bioinformatics–Analysis from
Sequence to Disease
Chairs: P.J. Tonellato, D. Brown, K. Call, and J. Eppig
Three defining activities of bioinformatics are: 1) collection and categorization of large amounts of biomedical data from high-throughput strategies involving new technology (e.g., expression profiling, gene sequencing, phenotyping); 2) processing of data to identify underlying relationships (e.g., determining homology between rat and human genes); and 3) hypothesis- or discovery-driver analysis to extract hidden information within the data (e.g., construction of genetic circuits from expression profile experiments). For each activity, the amount of data and complexity of analysis generally requires the development and use of databases and computationally intensive processes. Modern approaches to addressing these issues have resulted in the development of sophisticated computer workstation environments that provide informatics databases and tools to the scientific community. This session will provide a forum for discussing recent advances in bioinformatics tools and environments, with special emphasis on emerging strategies designed to advance scientific understanding of data derived from basic science research laboratories.
Physiological Function Explored in Microgravity
Chair: C.E. Wade
Speakers will present examples of how microgravity imparts novel examples, including skeletal muscle, circadian clocks, cardiovascular system control, and cellular cytoskeletal architecture.
Complement Activation and Inhibition in the Cardiovascular System
Chairs: G.I. Stahl and S.A. Rollins
The immune system is involved in many human cardiovascular diseases. Inappropriate activation of one of the mechanisms of the immune system, complement activation, has been shown to play an important role in atherosclerosis, myocardial ischemia, and reperfusion injury. Molecular characterization of the initiating events governing complement activation and development of novel therapeutic modalitites for inhibition of complement activation or its effector components is an active and timely component of basic and clinical research. Several complement inhibitors, including soluble complement receptor type 1 and recombinant anit-C5 therapy, are in Phase II clinical trials. Other promising novel technologies for inhibition of complement activation are in pre-clinical development. This symposium will demonstrate the translation science involved in the development and clinical use of pharmacological inhibitors in cardiovascular disease.
Redox Regulation of Cardiomyocyte Life and Death
Chair: D.K. Das
Many diseases, including ischemic heart disease, are influenced and regulated by changes in the redox system. The role of free radicals and antioxidants in this process has not been well considered in the context of the redox system. Speakers will discuss the probable roles of mitochondria, nitric oxide, and superoxide dismutase in the redox abnormalities and transcription regulation of genes which are redox sensitive.
Involvement of the Cytoskeleton in Regulation of Vascular Smooth
Muscle Contractile Function
Chair: G.A. Meininger
The cellular cytoskeleton of vascular smooth muscle cells is composed of microtubules, actin filaments, and intermediate filaments. Many intracellular processes are regulated or modulated by these cytoskeletal elements. Microtubules have been shown to modulate the generation of contractile force in fibroblasts, cardiac myocytes, and vascular smooth muscle cells. Disruption of the microtubules with drugs that depolymerize microtubule filaments is associated with an increase in cell force production and constriction of arterial blood vessels. In contrast, drugs that stabilize microtubules have reverse. In addition, variations, in microtubular polymerization alter vascular tone, reactivity, and calcium handling. The two major controversial views to explain the actions of microtubules on cell contractile function are participation of microtubules in cell signaling pathways critical to regulation of the contractile apparatus and microtubules influence regulation of the matrix-membrane-cytoskeletal mechanical axis and hence cell mechanical properties.
Capillaries: How Their Structure and Function Can Alter to Meet
Tissue Demands
Chairs: A. Baldwin and V. Huxley
Over the past decade, we have accumulated evidence challenging the notion that the smallest blood vessels, the capillaries, are static, uniform, semipermeable pipes with no function except as a passive barrier marking the boundary between the vascular compartment from the tissue compartment. Instead, capillaries are dynamic structures that participate in the active regulation of water, waste, and nutrient exchange: the formation and destruction of exchange vessels and sites for initiation of signals to regulate the flow of blood into the exchange vascular network. Presenters will consider the varied nature of capillaries and how their functions are coordinated to achieve whole organ exchange.
eNOS Dysfunction in Vascular Disease
Chairs: K.A. Pritchard, Jr. and D.G. Harrison
Endothelial nitric oxide synthase (eNOS) is extensively involved in regulation of the peripheral circulation by producing nitric oxide (NO) in response to the physical and chemical environment of the tissues and blood vessels. This symposium (and an other on a similar topic) will consider normal regulation of eNOS and various pathophysiological conditions that suppress or increase NO formation. Participants will include the effects of hypertension, oxidative stress, atherosclerosis, and diabetes on the function of eNOS and NO.
Regulation of Transporters and Channels by Binding Proteins
Chair: D. Rotin
Protein:protein interaction domains, such SH2, SH3, PH, WW, PDZ and numerous others have been demonstrated to play a key role in regulating signal transduction, intracellular localization of proteins, and cytoskeletal organization. In recent years, it has become apparent that ion channels and transporters also use such protein:protein interaction modules for their function. Presenters will describe the function of PDZ domain-containing proteins, such as NHERF/CAL and InaD in regulation CFTR and the Na/H antiporter, and ion channels in the Drosophila photoreceptor, respectively. The role of WW domains and C2 domains of Nedd4 in regulating ENaC also will be described. These domains are responsible for assembling protein complexes and for localization and targeting of regulatory proteins necessary for function of what appears to be a growing number of ion channels and transporters.
Ion Regulation in Cell Organelles
Chair: T. Machen
Many intracellular organelles maintain steep ion gradients across their membranes. For example, the endoplasmic reticulum actively accumulates Ca (approximately 500 µM) for rapid release into the cytosol. The Ca Content of the ER also controls some aspects of protein processing of the ER as well as the activity of Ca entry channels in the plasma membrane. Regulation of lumenal pH in the secretory pathway is required for proper enzymatic activity and processing and transport functions of the ER (pH 7.2–7.4), Golgi (>pH 6.5), and lysosomes, phagosomes and secretory granules (pH 4.5–5.5). Unique insights into organelle ion transport mechanisms have recently been obtained using new methods that combine digital imaging methods with the use of ion-sensitive, fluorescent molecules that have been targeted to organelles with genetic or specialized accumulation approaches. This symposium will discuss use of these methods for determining how pH and other ion concentrations are regulated so precisely in the ER, Golgi, secretory granules, endosomes and lysosomes and phagosomes. We will also discuss how the ER and mitochondria interact with each other and with the plasma membrane in regulation of cell and organelle Ca.
Neurobiology of the GnRH Neuron
Chairs: D.W. Brann and J.L. Roberts
Participants will update of the field of control and regulation of GnRH neurons, an important topic since GnRH is the preeminent central signal in the control of reproduction. The program will cover several critical aspects of the neurobiology of GnRH neurons, including new methods and animal models for the study of GnRH neurons, identification of transcription factors involved in the control of the GnRH gene, identification of factors that regulate GnRH neuron survival and migrating transmitters and steroid hormone control of GnRH neurosecretion, and aging of the hypothalamic-GnRH neuronal system.
Afferent Regulation of the Stress Response: New Views and New
Approaches
Chair: D. Morilak
Much attention has been focused on afferent regulation of activity in the hypothalamic paraventricular nucleus (PVN) as the integrator and common final output for the endocrine and autonomic responses to stress. In addition, the central noradrenergic neurotransmitter system has been intensively studied as a widespread modulator of neural activity in many brain regions involved in the response to stress, and has been proposed to be essential for the primary activation of the PVN in response to a variety of stressors. The panel will address issues of stressor-specificity in the activation and regulation of the stress response and of the anatomical, molecular and neurochemical mechanisms by which such exquisite specificity may be imposed on what has often been perceived to be a generalized, monolithic and rather non-specific process. Topics will include potential molecular mechanisms underlying the modulatory role of norepinephrine throughout the brain in stress, exploring the relationship between NE receptor activation and induction of c-Fos expression; stressor-specificity in the release of norepinephrine and the induction of immediate early gene expression in brain regions contributing to stress-induced activation of the HPA axis, suggestion that the role of NE in activation of CRH neurons in the PVN is stressor-specific; studies using in situ hybridization to identify cellular post-synaptic targets of adrenergic modulation, and potential interactions of norepinephrine with neuropeptide transmitters that may account for stress-specific differences in the degree to which norepinephrine modulates the stress response in the PVN and associated brain regions; employing immediate-early gene technology in combination with axonal transport and ablation methods, suggesting that hypothalamic neuroendocrine and autonomic responses to so-called physiological challenges are mediated via central autonomic pathways and circumventricular structures, while responses to psychological stressors appear to involve complex interactions between ascending somatosensory/nociceptive projections and the limbic forebrain; and evidence that it is activation of neurons in the nearby dorsomedial hypothalamus rather than the PVN that appears to mediate the cardiovascular response to stress in rats, and also suggests that stress-induced recruitment of the hypothalamic-pituitary-adrenal axis relies upon activation of neurons in the DMH. These results provide a new perspective regarding the possible location of hypothalamic command neurons responsible for the major physiologic changes associated with stress and the process of stress adaptation.
The Metabolic Status of Theropod Dinosaurs: New Insights from
Comparative Physiology
Chair: J.W. Hicks
A major controversy in paleontology concerns the evolution of birds and their relationship to theropod dinosaurs, specifically the analysis and interpretation of anatomical features shared in both birds and theropods. Participants will discuss recent studies of extant vertebrates that provide insights into the metabolic status of dinosaurs and implications about the phylogenetic relationship between theropods and birds. The goal of this symposium is to expose the physiological community, particularly comparative physiologists to this ongoing debate in paleobiology and to stimulate fresh perspectives into the metabolic status of theropod dinosaurs. Speakers will rigorously analyze the morphological and physiological evidence of both extinct and extant vertebrates. The debate over the metabolic status of theropod dinosaurs and their relationship to birds has continued for over two decades and has been argued, primarily, by paleobiologists. For many physiologist, particularly comparative respiratory physiologist, the arguments that characterize the debate, at first glance seem untestable and therefore contributions by physiologist have been rather minimal. Recently, due to newly discovered fossils in Northeastern China and in Northern Italy, the controversy concerning the metabolic status of theropods has received considerable attention in both the scientific and lay press and has been the issue of several recent symposia. These symposia have lacked contributions from physiologists. This symposium will expose comparative physiologist to issues that define this controversy and will present information that illustrates new insights into avian evolution gained by studying the physiology of extant vertebrates.
Intrapituitary Interactions: Another Level of Endocrine
Regulation
Chairs: J. Schwartz and G.V. Childs
Speakers will provide an overview of the extent to which interactions among the cells of the anterior pituitary occur and how they act influence the developmental, biosynthetic and secretory activity of the gland. The program will cover various types of cells, the various classes of intercellular factors and the subcellular mechanisms that are involved in the interactions. Participating scientists investigating a diverse set of pituitary systems tied together by a common theme will use these different systems as models to illustrate the types of intrapituitary interactions and provide a basis for understanding the physiological relevance of these interactions.
Cellular Transport Systems in the Regulation of FFA Metabolism
Chair: L.P. Turcotte
Regulation of FFA utilization is a critical area of research in metabolism. Transport systems are believed to be important factors in the regulation of many cellular mechanisms. Although several transport systems have been identified for FFA, the role of these transport systems in the regulation of FFA metabolism has been generally ignored. Partcipants will present evidence for the presence of cellular transport systems for FFA in muscle cells and for the role of these transport systems in the regulation of FFA metabolism.
Fever: The Role of the Vagus
Chair: A.A. Romanovsky
The recent upsurge of interest in the vagus nerve has been precipitated by a series of studies showing that vagal afferentation is important for the development of several host defense responses, including the febrile, to systemic inflammation. Further, a growing body of evidence suggests that vagal afferents, as well as efferents, may be important to non-febrile thermoregulation, in both health and disease. However, the participation of the vagus nerve in body temperature regulation and the mechanisms of this participation have not been discussed in detail at any recent conference; this will be the objective of this symposium. The conflicting issues that will be addressed are: 1) Does vagal thermosensitivity exist and is it functionally important? 2)Are vagal efferents involved in the thermoregulation, and if so, what are the mechanisms of this involvement? 3) Does vagotomy result in febrile nonresponsiveness? 4) What pyrogenic mediators are responsible for activation of vagal afferents in fever? Speakers will review both structural and functional interactions between the vagus nerve and the thermoregulatory system at different levels. Speakers will discuss topics ranging from molecules to individual organs to the whole organism and analyze wide range of histological, electrophysiological, pharmacological, and thermoeffector activity data.
Molecular and Functional Diversity of Epithelial Chloride Channels
Chairs: C. Fuller and D. Benos
Non-ligand gated anion channels have been among the last channels to be characterized at the molecular level. One consequence of this has been increased controversy in the field of epithelial Cl- transport. The basic problem lies in defining which anion channels contribute to regulated Cl- exit across the apical membrane of an epithelial secretory cell. For the last 10 years, it has been widely accepted that CFTR is the major apical membrane Cl-channel and that other anion channels play minor roles in regulated fluid secretion. Furthermore, the regulation of secretion by mechanisms other than those relying on the cAMP/adenylate cyclase system has been largely attributed to other causes. However, recent findings prompt an urgent re-assessment of the role of CFTR as the only player in epithelial fluid transport; epithelial cells in fact contain a multiplicity of Cl- channels that can participate in fluid secretion. CFTR has itself been show to have a non-traditional role regulating other membrane channels that contribute to the classical CF phenotype, most notably ENaC and a second as yet poorly defined Cl- channel, the ORCC; however, the mechanisms underlying these interactions are for the most part obscure. The ORCC has not yet been cloned; is it truly a separate channel, or could it be an already identified channel operating as an ORCC under certain conditions? Multiple members of the extensive CIC family can also be expressed within a single epithelial cell, and data has begun to emerge that the primary role of these channels may lie in volume regulation. As the epithelial CIC isoforms are considered candidates for alternative Cl- conductance pathways in cystic fibrosis (CF), understanding the regulation of these channels is fundamental to their possible role as therapeutic targets in the treatment of CF. The most recently identified (and the most controversial) family of Cl- channels to be described are those activated by Ca2+, the CaCCs. Ca2+-activated Cl- secretion in epithelia has been hotly debated, as Ca 2+ can increase Cl- and fluid secretion by opening basolateral K+ channels in the absence of a direct effect at the apical membrane. The cloning within the last year of an additional bovine, two human and one mouse cDNA with extensive homology to the original bovine CaCC (bCaCC), has led to the identification of a CaCC channel family expressed in several epithelial tissues including a gut and airway. One of these new family members acts as a cell adhesion molecule and all family members isolated to date are post-translationally processed, something not previously associated with ion channels. Preliminary studies suggest that the original bCaCC is located at the apical membrane of tracheal and sub-mucosal gland epithelial cells, consistent with a direct role for this channel in airway Cl- secretion. Presenters will address issues of Cl- channel diversity in the light of recent data and re-evaluate current concepts concerning the mechanisms of Cl- secretion in epithelia with particular reference to events at the apical membrane.
Epithelial-Microbial Interactions: Lessons in Communication
Chair: M.F. Kagnoff
A single layer of epithelial cells separates the intestinal lumen form the host’s internal milieu. It is now recognized that the epithelium engages in cross-talk with the luminal enteric microbial flora and with microbial pathogens that bind to and invade epithelial cells. These interactions can result in the activation of signaling pathways within epithelial cells that culminate in the activation of epithelial cell genes and products, including those that are key components of the epithelial cell innate immune response, and those that alter epithelial cell function. Products released by epithelial cells can act in an autocrine or paracrine manner on the epithelium and on adjacent and underlying immune and inflammatory cells in the intestinal mucosal. Participants will focus on communication between the commensal bacterial flora and noninvasive bacterial pathogens (e.g., H. pylori) and the intestinal epithelium, the strategies and pathways used by enteroinvasive microbial pathogens that lead to altered epithelial cell gene expression, the role of the epithelium in signaling the onset of innate and acquired host mucosal immunity, and mechanisms by which enteric microbes can alter epithelial cell secretory function.
The History of Organ Transplantation: Physiological
Aspects
Chairs: G.E. Folk, Jr. and H. Brown
This interdisciplinary session will include physiology, pathophysiology, immunology, biochemistry, pathology, medicine, and surgery. Speakers will address the historical background of the need for transplantation and how understanding each of the disciplines had an important part in bringing about successful clinical transplantation; this can now correct the underlying pathophysiology. Present methodology and future directions in understanding xenotransplantation (i.e., between species), is important because of dearth of human organs. The kidney, because of its critical role in clearing the body of waste and its function in regulating blood pressure, was an organ early considered for transplantation, since no known treatment could prolong life when it failed. Artificial dialysis of blood to clear nitrogenous waste in this situation was developed between the 1930s and the 1950s, but it is a cumbersome procedure, fraught with complications, and will maintain life for only about 10 years. After WWII, a group of scientists, interested in transplantation. successfully transplanted a healthy kidney from one identical twin for a failing one of the other twin. Since then, better understanding of the immune system has been very helpful in permitting transplantation of organs from unrelated donors. Immunosuppression mediation, early with azothioprine, has been replaced by cyclosporin and its derivatives and steroids. Participants will also report briefly on the ability of humans to exercise after receiving organ transplants, with additional comments on the capability of animals lower and mammals to receive transplanted organs.
Muscle Research in the 20th Century
Chair: M. Bárány
The later half of the 20th century has witnessed an explosion in our understanding of the mechanisms that control muscle contraction and processes the convert chemical energy into kinetic energy. This symposium will feature investigators in the area of muscle research reflect on the most important breakthroughs in this field during the last century. Specific topics will include the structure and function of muscle, progress in mechanochemistry, processes that regulate contraction, and the excitation-contraction coupling process.
Oxygen Sensing and Signaling: Role of Reactive Oxygen
Intermediates
Chair: H.F. Bunn
During the last two years we have made remarkable progress in understanding the mechanisms whereby cells sense changes in oxygen tension and transduce signals to maintain cardiorespiratory homeostasis during hypoxia. Changes in oxygen tension regulate the transcription and/or the mRNA stability of many physiologically relevant genes (e.g., tyrosine hydroxylase, erythropoietin, and vascular endothelial growth factor). An understanding of adaptation to hypoxia at the molecular level requires creative input from a number of scientific disciplines including classic physiology, pharmacology, and cell and molecular biology. The interdisciplinary nature of the papers presented at this symposium provide a timely and valuable impetus to further advances in the critically important area of research. Participants will focus on the role of reactive oxygen intermediates in oxygen sensing and signaling, including physiological studies on carotid body glomus cells and hepatic cells, supporting a model which a cytochrome b-like heme protein senses oxygen and transduces a signal via reactive oxygen intermediates; new information on a recently cloned candidate oxygen sensor, a cytochrome b5-cytochrome/b5 reductase fusion protein that fulfills many of the criteria implicit in Dr. Acker’s model. Dr. Schumacker, will present an alternate model of oxygen sensing and signaling, based on mitochondria as a source of reactive oxygen species. These presentations on oxygen sensing will provide an appropriate background for a discussion on the mechanism by which low oxygen tension activates HIF-1, the heterodimeric transcription factor, which plays an essential role in the regulation of genes important in adaptation to hypoxia. Finally, the relative importance of reactive oxyen intermediates in carotid body chemoreception and regulation of gene expression will also be discussed.
Hypoxia-Induced Muscle Damage from Reactive Oxygen Intermediates:
From Pathways to Function
Chairs: M.A.P. Brotto and T.M. Nosek
Conditions such as hypoxia, reperfusion, vitamin E deficiency, muscular dystrophy, oxidative stress, and repetitive activation of muscle are associated with increased production of reactive oxygen intermediates (ROI). Further, prolonged exercise is accompanied by increased concentrations of ROI within muscle cells from membrane-associated reactions, involving NADPH oxidase and increased mitochondrial respiration. Strenuous exercise and some pathological conditions may produce so much ROI that they overwhelm the natural intracellular buffering system and denature proteins important in the contractile and excitation-contraction coupling (ECC) processes. Numerous labs have demonstrated that hypoxia has deleterious effects on both cardiac and skeletal muscles. Production of specific ROIs have been proposed to be involved in this response. Speakers will explore the pathways by which ROIs are produced under normoxic and hypoxic conditions and the role of ROIs in the decreased contractile function observed in the ischemic heart and hypoxic skeletal muscle under resting and fatiguing conditions.
Differential Control of Sympathetic Outflow: A Window
into Central Mechanisms Mediating Patterned Autonomic Responses
Chairs: S. Morrison and G. Gebber
The central nervous system is responsible for the elaboration of the patterns of sympathetic outflow to different tissues that is an essential component in the maintenance of homeostasis and in the autonomic support of behaviors, adaptations to changing environment, and responses to disease or injury. Symposium speakers have used multidisciplinary approaches (anatomical, electrophysiological, and neurochemical) to examine the differential regulation of sympathetic outflow to functionally specific targets and will relate this information to the organization and performance of central neural circuits that selectively govern the sympathetic discharge to different tissues. Presentations will illuminate how these data increase our understanding of the neural substrates underlying the generation of the patterns of autonomic activation that support behaviors such as the defense response of thermoregulation. Not only will the variety of target organs and physiological perturbations to be discussed (cardiovascular, thermoregulatroy, metabolic, etc.) broaden the audience interested in this symposium, but also the overlap of sympathetically controlled tissues studied with different approaches will provide a significant cohesion among the presentations, a strengthening of the conclusions that can be drawn from them, and an articulation of areas for future investigation. This symposium addresses a topic that relates to one of the fundamental integrative aspects of central autonomic regulation.
Extracellular ATP and cAMP as Paracrine and Interorgan Regulators
Chairs: L. Bankir and E. Inscho
The field of extracellular nucleotides and purinoceptors has interested investigators probing the physiological and pathophysiological roles of P2 receptors in virtually every organ system. With this renewed interest has come a new appreciation for the roles extracellular adenine nucleotides like ATP and cAMP can play, regulating or modulating many aspects of renal function. In the last 5 years, investigators have provided compelling evidence that extracellular nucleotides, working through activation of P2 purinoceptors, have a significant impact on renal microvascular function, mesangial cell function, and on renal epithelial transport. Evidence has implicated P2 receptor activation by ATP in mediating autoregulation of renal hemodynamics in both the rat and the dog through selective modulation of preglomerular resistance. Locally released ATP has a direct paracrine and/or autocrine effect modulating renal epithelial transporters and tubular epithelial channels to influence tubular fluid composition. Plasma cAMP influences sodium and phosphate reabsorption in the proximal tubule and contributes to the regulation of glomerular filtration rate. Recent studies are beginning to uncover the mechanisms by which extracellular nucleotides evoke these varied physiological and/or pathophysiological events. Purinoceptor research represents a rapidly developing field of organ system research, and the kidney is a major contributor to that progress. Although the specific roles of extracellular nucleotides and their renal receptors to purine nucleotides have not been identified absolutely, it now appears that ATP is not just for energy anymore and that cAMP is not only a "second" messenger. This symposium will bring the renal community up to date on this new and exciting area of investigation. It represents a different focus from the more established areas of renal research and promises to yield many new insights as more work is performed. This is an ideal time to initiate broad- based discussions of the renal implications of extracellular nucleotides.
MAP Kinases: New Implications for Renal Cell Function
Chairs: D. Kültz and D.W. Good
Mitogen-activated protein (MAP) kinases are important mediators of a variety of cellular processes, including adaptations to osmotic and other stresses. Participants will consider cell functions controlled via MAP kinases and their relevance to renal function. In recent years, studies on MAP kinase signaling pathways have extended beyond the biochemical and genetic frontier into the realm of physiology. New advances highlighting the complex role of MAP kinases in cell and epithelial physiology as well as current approaches for studying MAP kinase signaling in the kidney are discussed in this symposium. The symposium will bring together experts on MAP kinase signaling, osmoregulation, and renal cell function and include presentations on the molecular basis of signal transduction by stress-activated MAP kinases, the regulation of MAP kinases by cytokines and other stimuli, the role of MAP kinases in maintenance of renal cell integrity during osmotic stress, the role of MAP kinases in the regulation of renal tubule transport, and MAP kinase function during renal injury and repair.
Apoptosis in Lung Pathophysiology
Chairs: B.D. Uhal and A. Fine
Apoptosis is fundamentally important in all cell types, but its roles in the lung are only recently being identified. Over the last 2 to 3 years, separate bodies of literature suggest both beneficial and detrimental roles for apoptosis in lung pathophysiology, depending on the cell type in question and the timing and location of the apoptotic stimulus. Evidence supports an important role for FAS (APO1,CD95) in a surprising variety of pulmonary cell types, and suggests an involvement of this receptor in the pathogenesis of lung fibrosis and other diseases. These data contrast to other numerous works documenting important positive roles for apoptosis in the resolution of lung injury; therefore, knowledge of the regulation of apoptosis in key lung cell populations is of fundamental importance. Apoptosis in response to highly reactive molecules is believed to be an important determinant in patholgenic processes in the lung, and the signaling pathways induced in specific lung cell subsets are beginning to be elucidated. The role of apoptosis as a regulator of tumor growth is crucial to understanding lung tumorigenesis and its control. Very recently, the concept of local renin/angiotensin systems as key regulators of apoptosis is emerging in investigations of lung pathophysiology and pharmacologic manipulation of pulmonary fibrogenic processes.
Mechanisms Regulating Endothelial Cell Barrier Function
Chairs: T. Stevens and A. Malik
Endothelial cell barrier disruption is a cardinal feature of vascular inflammation. Despite this significance, controversy exists regarding important molecular mechanisms activated by neurohumoral inflammatory mediators that are responsible for barrier disruption. Contribution of transcytotic vesicleswill be discussed. Moreover, it is unclear whether inflammatory agonists principally increase protein permeability by activating myosin light chain kinase-dependent contraction or by decreasing cell-cell and cell-matrix tethering. Finally, increased cytosolic calcium represents an important stimulus for endothelial barrier disruption, but calcium-driven processes contributing to barrier disruption are poorly understood. Speakers collectively provide new information regarding the molecular proceeds activated during the course of inflammation.
Lung Redox Homeostasis: Emerging Concepts
Chairs: M.P. Merker and C.A. Dawson
Significant attention has been focused on the role of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in oxidant induced lung injury. The vast literature featuring these classic protective pathways has sometimes obscured growing interest in other molecular mechanisms involved in regulating lung cellular redox homeostasis. This symposium will be concerned primarily, although not exclusively, with pulmonary endothelium and will consideralternative and emerging research in the area of lung responses to oxidative processes. Presenters will concentrate on the role of endothelial plasma membrane NAD(P)H oxidase in ischemic lung injury, transplasma membrane electron transport systems in regeneration of antioxidant in the blood, protective role of xanthine oxidase lung injury and its regulation by cytokines and oxygen tension, metal homeostasis and metallothionein in lung endothelial responses to oxidant stress, and the regulation of the stress response enzymetheme oxygenase in lung oxidant injury.
Emerging Concepts: Protein Kinase C Isozymes and the Regulation of
Diverse Cell Response
Chairs: E.C. Dempsey and P.A. Insel
This symposium will focus on the importance of heterogeneity within key intracellular kinase cascades, like protein kinase C (PKC), and how individual isozymes of an enzyme family contribute to the regulation of diverse cell responses. Eleven different isozymes of PKC have been described. There have been major advances in our understanding of how these individual isozymes contribute to diverse cell responses and how their activity and expression are regulated, even though many of these concepts are not yet widely appreciated. There have also been many advances in the experimental approaches available for the investigation of PKC isozymes. These are also not well known. This symposium will address two questions: How do individual isozymes of PKC contribute to the regulation of diverse cell responses and what are the best approaches to studying the role of PKC isozymes in different cell responses. Discussions will include knowledge about individual PKC isozymes and cell responses relevant to lung biology (like permeability, secretion, contraction, growth, and apoptosis); new ideas on mechanisms that regulate PKC activity, including the interaction of reactive ox gen species with PKC and the identification of novel PKC kinase that regulates phosphorylation of the enzyme; the concept of targeted translocation of PKC isozymes within the cell and importance of isozyme-specific binding proteins; emerging concepts on the link between individual PKC isozymes and two important cell responses (proliferation and apoptosis); and new research tools recently developed, isozyme-specific knock-out mice. Each speaker will emphasize contemporary approaches to studying PKC isozymes and their role in cell responses.
Teaching Physiology Laboratories in the 21st Century
Chair: D.U. Silverthorn
The traditional physiology student laboratories of the 1960s have almost disappeared due to many factors: animal rights issues, cost, the advent of computers, and the shift in bench research away from whole-animal studies, which created a generation of instructors who lack the expertise to conduct the traditional experiments. But what kinds of hands-on experiences are our undergraduate and graduate physiology students getting to replace those traditional labs? Speakers will describe and discuss laboratories in which students use invertebrates and molecular techniques to answer basic physiological questions; newly renovated undergraduate laboratories that combine computers, physical models, and inquiry; incorporating technology in the laboratory changed the curriculum; and experiences changing from animal laboratories for medical students to simulated lab experiences. There will conclude with a panel-audience discussion regarding the problems and issues involved in implementing the different lab formats.
Role of TGF-b in Renal Disease: Mechanisms and Therapeutic
Prospects
Chair: N.J. Laping
Transforming growth factor-beta (TGF-beta) is perhaps the most important factor in the progression of renal disease. Although its role as a mediator of renal disease has been well established, the cellular and molecular mechanism by which TGF-beta mediates fibrosis are now being elucidated. This symposium highlights the advances made on the mechanistic front and identifies possible modes of therapeutic intervention. Speakers will discuss recent findings on the signal transduction of TGF-beta with a focus on transcriptional mechanism involving smad proteins. Transgenic and induced models of renal disease will illustrate the importance of TGF-beta in progressive renal disease. Small molecule compounds that inhibit the activity of the TGF-beta type I receptor will also be discussed.
Bone Marrow Transplantation in Non-Malignant Diseases.
Chairs: G.C. Tsokos and S. Berney
Many autoimmune diseases are associated with hyper activated T and B lymphocytes that are self-reactive and contribute to disease pathology. Elimination of most of those cells with ablative chemotherapy followed by administration of autologous stem cells is likely to suppress disease, even to the point of remission in some patients. There is published evidence for this dramatic benefit in patients suffering from systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and scleroderma. Leading experts will discuss the immunologic rationale for reinfusing autologous stem cells in patients with autoimmune diseases following ablative chemotherapy. The reinfusion of stem cells is likely to decrease the rate of various complications associated with chemotherapy. The risk of disease reappearance exists, since genetic factors are dominant in the pathogenesis of systemic autoimmune diseases. Emerging lymphocytes may remain tolerant to self antigens or may become autoreactive again, because central and/or peripheral tolerance breaks. Participants will discuss the clinical experience on the treatment of lupus, rheumatoid arthritis, scleroderma and multiple sclerosis, along with "lessons learned" and the financial implications of using transplantation and chemotherapy in the treatment of autoimmune diseases.
Cancer Genetics
Chair: P. Wiernik
It has become clear that genetics plays a more important role in the developmental and clinical course of human neoplasia than previously thought. The history of our understanding of the role of heredity in cancer began long before the modern era of molecular genetics with careful studies of families with multiple cancers. Participants will present some of these landmark studies as well as evidence for a genetic etiology of several hematologic malignancies and prostate cancer, our current understanding of the role of certain genes in the etiology and pathogenesis of kidney cancer, breast and ovarian cance, and unifying themes characteristic of genetically based human neoplasms such as anticipation.. Understanding the genetics of cancer may eventually lead to the development of new methods for preventing and treating cancer targeted at certain genes or gene products.
Chemokines: From Bench to Bedside
Chair: S. Gupta
Chemokines are a superfamily of small related molecules that are secreted by a variety of cells and have pleiotropic functions. The family of chemokines continues to grow; more than 50 members of the family have been identified. They mediate their effects by binding to G-protein-coupled cell surface receptors belonging to the superfamily of seven transmembrane posterior. There have been major advances in the understanding of chemokines’ role in inflammation, autoimmunity, and infections. Our recent progress in understanding the role of chemokines in various human diseases is likely to lead to the development of novel therapeutic approaches. This symposium will highlight the basic functions of chemokines and chemokine receptors and their role in the pathogenesis of inflammatory bowel disease, asthma, and HIV infection.
Host Polymorphisms and Susceptibility to Infectious Diseases
Chair: M. Goldsmith
The development of increasingly sophisticated tools for probing the human genome has promoted the elucidation of human genes that influence the pathogenesis of diverse diseases. Cancer has been a major and productive focus of such research efforts to date, but it is also compelling to apply these approaches to diseases caused by microbial pathogens such as viruses and bacteria. The earlier discovery of major histocompatibility antigens exemplified how host gene products can control the immune response to specific antigens, which can influence the disease outcome of a particular infection. Various genetic strategies increasingly are being implemented to identify other polymorphic genes that influence the pathogenesis of human infections. This symposium will define state-of-the-art methods for "mining" the human genome in order to discover key associations with complex biologic processes including the response to pathogenic organisms. It will also illustrate this paradigm with striking examples in which genetic tools led to the identification of genes and/or polymorphisms that are critical determinants of the natural history of select infectious diseases, including those caused by HIV and mycobacteria. Further exploitation of such approaches should provide highly useful information that may be applied in the molecular characterization, prevention, prognostication and treatment of infectious diseases that affect human populations.
Therapeutic Manipulation of Angiogenesis
Chair: D. Arenberg
Advances in the field of angiogenesis in the last several decades have resulted from techniques in cellular and molecular biology that have defined molecular events involved in normal as well as pathologic angiogenesis. In vivo and in vitro models that allow the study of angiogenesis in the absence of inflammation have permitted the discovery of many factors that directly regulate angiogenesis. Concurrently, we have also gained new insights into the role of angiogenesis in the pathogenesis of many diseases. Obviously, cancer is dependent on angiogenesis, but many investigators are studying "old diseases" by using a new paradigm, which suggests that angiogenesis may be important in non-malignant diseases as well (e.g., pulmonary fibrosis, rheumatoid arthritis, asthma, or coronary artery disease). Speakers will discuss recent advances, especially as they relate to angiogenesis, and the potential application of new angiogenesis-related therapies.
Biochemical Signaling in the Control of Microcirculatory Function
Chair: W.N. Duran
Biochemical signals regulate microcirculatory function, as they are important determinants of blood flow, permeability, angiogenesis, and immunomodulation. Signaling interactions between vascular wall and blood cells provide a unique way of communicating, coordinating and integrating appropriate biologic responses to meet the changing needs of tissues. This symposium will review both intercellular and intracellular signaling interactions as well as the molecular biology of key elements in the signaling cascade.
Microvascular Remodeling: Physical Stimuli and Molecular
Regulation
Chair: T.C. Skalak
The interdisciplinary panel involved in microvessel remodeling will address the role of mechanical stresses in long-term regulation of individual microvessel structure, microvascular network pattern formation, the role of specific molecular signals in the recruitment of smooth muscle cell precursor cells to developing capillaries and arterioles, and two therapeutic topics–the design of tissue-engineered networks for blood supply to artificial tissue constructs, and delivery of exogenous angiopoietin to lung microvessels to prevent hypertensive conditions. How is the development of microvessel networks regulated in vivo by spatially regulated production of growth factors in response to local environmental stimuli? Conflicting issues are the lineage of recruited fibroblasts or smooth muscle cells, molecular guidance of arteriolar pattern by mechanical versus metabolic factors, and the alteration of pattern formation by rational manipulation of stresses or growth factors. The session will combine whole network, single vessel, isolated, and cocultured cell approaches to understanding this problem. This combination of approaches is usually not treated in a single session. Future directions in patterned substrates for guidance, microvessel-specific gene expression systems, inducible cell-specific gene expression, and in vivo lineage techniques also will be discussed.
Integrin Mechanics
Chairs: K-L.P. Sung and G.A. Truskey
This symposium will summarize the recent advances in research on the integrin molecules that mediate cellular adhesion, migration, and tumor cell invasion as well as signal transduction from extracellular molecules to the cytoplasm, so that the physiology and pathophysiology of integrins can be understood at the molecular and cellular levels. Presenters will integrate molecular biology and mechanical approaches to the study of integrin function. Topics include recent advances in integrin structure/function; an overview of the direct influence of alpha V integrins on the processes of angiogenesis and vascular remodeling in the tumor, with specific mention of the mechanistic blockage of angiogensis by alpha-V integrin that disrupts intracellular signaling events in vascular cells leading to the induction of apoptosis; endothelial cells exposed to cyclic mechanical strain and will focus on the role of cyclic strain in modulating endothelial cell morphology, proliferation, and migration function via the focal adhesion proteins focal adhesion kinase (pp125FAK) and paxillin which are tyrosine phosphorylated; kinetics and mechanics of platelet and neutrophil interactions under shear fields, with platelet-neutrophil aggregation studies using high speed/hing resolution DIC imaging will be discussed; the relationship between local deformation of the apical cell membrane and focal contact dynamics; integrin-mediated adhesion/migration/signaling, including the idea that the integrin mediated cell adhesiveness, migration rate and signaling messages can be modulated by growth factors. These interdisciplinary approaches combined with recently developed experimental methods include the use of a flow chamber, confocal microscopy, centrifugation force, atomic force microscopy, and total internal reflection fluorescence microscopy systems. These approaches are at the interface of molecular, cellular, and biophysical sciences and are aimed at elucidating the mechanisms of cell adhesion in health and disease.
Tissue Engineering of Vascular Grafts for the Third Millenium
Chairs: J.A. Francois and N. L’Heureux
From engineering to physiology, from biology to chemistry, tissue engineering intrinsically requires a multidisciplinary approach. Seen by many as one of the most promising fields in biomedical research, tissue engineering will have to merge these different approaches to mature into a full-fledged discipline. One of the most challenging organs to recreate is the artery. Unlike many organs and tissues., the blood vessel has a critical paracrine function as well as a demanding mechanical function. A successful transition from in vitro to in vivo requires not only sufficient mechanical strength but also an appropriate blood compatibility and inflammatory response. The failure of small diameter synthetic vascular grafts has shown that his dual role is critical for long-term patency. Tissue engineers are using natural or synthetic biodegradable materials in an effort to control the inflammatory process. This approach can be combined with the seeding of cultured cells to provide blood compatibility. Cells can also play a role in a well-orchestrated remodeling process that allows the removal of the implanted material while maintaining appropriate mechanical properties. This symposium will present various approaches to design smart tissue engineered vessels working with the body in a remodeling process that will provide long-term patency. From fully synthetic biodegradable prosthesis to completely biological vessel, participants will discuss a full spectrum of issues covering current and future strategies to control the remodeling process.
Adhesion and Motility of Metastic Cells
Chairs: C. Dong and K. Anderson
Cell adhesion and motility are two intimately related biological processes that affect the course of metastasis of cancer cells. These biological processes eventually result in cell interactions with its environments. Recent new developments in the research have focused on cell receptor/ligand interactions related to cancer cell adhesion to endothelium; dynamic cell adhesion to endothelium or actual trapping in smaller capillaries during the process of extravasation; interactions of tumor cells with basement membrane; signal transduction associated with tumor cell migration; cell motility and cytoskeletal dynamics, etc. This symposium will bring together investigators with backgrounds in both engineering and cellular physiology to share the most recent finding relating cancer cell metastasis to adhesion and motility.
Low Saturated Fat, High Carbohydrate Diets: Effects on
Triglyceride and LDL Synthesis, the LDL Receptor and Cardiovascular
Disease Risk
Chairs: R.H. Knopp and W.C. Willett
Saturated fatty acids of dietary or endogenous origin are an important cause of hypercholesterolemia. One of the approaches to the population-wide reduction of plasma cholesterol levels is to restrict saturated fatty acid intake. The most widely endorsed dietary recommendation is to restrict dietary fat in to and with it, saturated fat, substituting carbohydrate. The limitation in this approach is a tendency of the body to manufacture saturated fatty acids form carbohydrate, which can manifest as an increase in plasma triglyceride levels, a reduction in HDL-C levels and a failure of LDL-C levels to fall further. To explore the mechanism and conditions wherein these effects obtain and their potential cardiovascular disease consequences, a panel of experienced clinical investigators will present their latest research relevant to the subject. One possible conclusion from this symposium is that more dietary fat restriction, substituting with carbohydrate, may not necessarily be better, and the approaches to selectively restricting saturated fat intake without augmenting carbohydrate intake beyond a certain point may offer a better opportunity to successfully lower plasma and LDL cholesterol levels without potentially adverse effects on other lipoprotein species.
Refresher Course
Integrating Molecular Biology into the Physiology Curriculum
Chairs: J.C. Schadt and A.J. Lechner
This refresher course will provide a background for molecular biology concepts, techniques, and terminology that will help society members teach contemporary physiology. Presenters will consider with the use of molecular techniques to answer physiological questions or to diagnose and treat phathophysiological conditions. The workshop will consist of 1) four 20-minute oral presentations; 2) poster presentations (viewed before and after oral presentations); and 3) a panel discussion of posters and oral presentations. Discussions will include molecular techniques, the biological basis of these techniques, the associated jargon; the use of molecular techniques (e.g., site-directed mutagenesis, expression systems, etc.) to study channel biology; using gene therapy to study and ultimately correct physiological problems; and using transgenic and knock-out models to answer physiological questions.
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American Society for Investigative Pathology |
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Endothelial nitric oxide synthase (eNOS) plays a critical role in vascular function. Loss of eNOS and its product, nitric oxide, are believed to play a causal role in endothelial dysfunction, atherogenesis, inflammation, and intimal proliferation. Recent evidence suggests that eNOS is capable of generating both nitric oxide and superoxide anion. This symposium will focus on the roles of LDL cholesterol, oxidation, and availability of tetrahydrobiopterin and asymetric-dimethyl arginine in modulating eNOS function. In addition, cholesterol-dependent and independent effects of HMG CoA reductase inhibitors on eNOS expression and activity will be discussed. Signal transduction, mediated by PKC, will be presented as a potential mechanism by which eNOS can be induced to generate superoxide in diabetes mellitus. The regulatory domain of eNOS for the generation of nitric oxide will be presented in terms of physiology and pathophysiology.
Mitochondria and Neurodegeneration
Chair: W.D. Parker
Mitochondria occupy a critical position in maintaining the cellular energy economy. They have unique genetic properties because they contain their own genome. In addition to their bioenergetic role, mitochondria may have a regulatory role in apoptotic cell death. Mitochondrial electron transport chain dysfunction is present in any neurodegenerative disorders, both sporadic and familial. These defects may in turn cause important pathogenic consequences such as oxidative stress through diversion of electrons from their normal pathway leading to generation of cytotoxic oxygen radicals. Mitochondrial gene transfer experiments suggest that these defects arise, at least in part, from mitochondrial DNA which may accumulate errors through inheritance or through oxidative damage secondary to aging. This symposium will discuss the evidence for mitochondrial dysfunction in neurodegenerative disorders, particularly Alzheimer’s disease and Parkinson’s disease, the resulting impact on cellular functioning, and will explore potential avenues for drug therapy of mitochondrial lesions.
Molecular Markers of Cancer
Chair: M.E. Sobel
Participants will discuss three different approaches to understanding cancer cell biology: The history of the discovery of a multifunctional gene that binds both extracellular matrix components and the ribosome, and possible implications for understanding cancer cell pathophysiology; the use of laser capture microdissection to analyze genetic changes in cancer cells; and an example of translational research in which elucidation of specific proteins produced by breast cancer cells that play a role in the pathogenesis of bone metastases may lead to new clinical paradigms for the treatment of metastasis.
Regulation of Vascular Growth by Extracellular Matrix
Chair: E.H. Sage
Vascular morphogenesis and the growth of vessels as a consequence of injury or remodeling are influenced substantially by components of the extracellular matrix. In a broader sense, extracellular matrix connotes not only structural glycoproteins but other classes of regulatory molecules as well, e.g., matricellular proteins, growth factors, cell surface adhesive molecules, and their receptors. This symposium, which addresses the regulation of vascular growth and integrity, will include discussion of four major factors with activities integral to angiogenesis and vascular remodeling. Topics include juxtacrine signaling through Eph-ephrins in vascular cell assembly, VEGF and vascular survival, PECAM-1 and its modulation of vascular cell adhesion, migration and proliferation, and the matricellular protein thrombospondin 2, which regulates collagen fibrillogenesis and vascular growth.
Virology of Neoplasia
Chair: F.V. Chisari
Certain DNA and RNA viruses play an important role in human neoplasia. Participants will focus on the mechanisms by which papillomaviruses, Epstein Barr virus, and retroviruses (transcripitional regulation) and herpesviruses contribute to carcinogenesis. The ability of these viruses to deregulate growth control by inactivating tumor suppressor genes, differentially regulating cellular gene expression, modulating signal transduction pathways and triggering angiogenesis and inflammation will be discussed.
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American Society for Nutritional Sciences |
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Understanding of the inter-relationships between pulmonary insufficiency diseases, nutritional status, and specific nutrient needs of infants and children during critical stages of growth is important for developing strategies for treatment of chronic pulmonary insufficiency in infants and children. Vitamin A may play a role in stimulating epithelial cell growth in pulmonary disease. Increased work of breathing, dyspnea, or steroid drugs used to treat some types of pulmonary insufficiency contribute to elevation in energy expenditure. This symposium will explore the evidence for the role of specific nutrients in the treatment of pediatric pulmonary disease, and approaches to improved dietary management and need for specialized nutritional products in affected populations.
Obesity in Developing Countries
Chairs: B. Caballero and N. Mokhtar
Speakers discuss data documenting the emerging problem of obesity and its complications in developing countries. Global health projections anticipate that in 20 years, more than 60% of the disease burden attributed to chronic non-communicable diseases will occur in the developing world. The unique combination of poverty and undernutrition with obesity poses a challenging public health problem.
Is Sustained Calcium Supplement Use Required to Retain the
Benefits of the Higher Calcium Intake
Chair: B. Dawson-Hughes
Increasing calcium intake to recommended levels increases bone mass in children and reduces rates of bone loss and fractures in the elderly. Despite many demonstrations of efficacy, however, dietary calcium intakes in the United States remain far below recommended levels. Supplement use has become more prevalent, but many people who take calcium supplements do not take them consistently over the long term. This symposium will address the value and limitations of "stop-start" calcium supplement use. The participating scientists will explore and integrate available evidence, consider possible mechanisms, and suggest preferred approaches to optimizing the effect of dietary and supplemental calcium on the skeleton in children and adults.
Preventing Obesity: Public Health Strategies
Chairs: S. Fried and B. Moore
There is a global epidemic of obesity and over 50% of Americans are overweight (body mass index 25kg/m2). Obesity increases risk for cardiovascular disease, diabetes, stroke, and certain cancers. Most experts agree that the recent rise in the prevalence of obesity results primarily from environmental factors, including a sedentary lifestyle and an abundance of easily available, calorically dense food in our society. Recent attention has focused on the need for major innovative public health initiatives to change the environment conducive to the development of obesity. Experts will discuss available evidence as to which strategies may be effective, the needs of high-risk groups such as African American women, and the epidemic of childhood obesity.
Oxidative Stress in Aging and Diabetes
Chairs: N. Fukagawa and S. Nair
"Oxidative stress" is a disturbance in the balance between pro-oxidants (reactive oxygen and nitrogen species) and antioxidants in favor of the pro-oxidant state. It is thought to be one of the mechanisms leading to the initiation or progression of specific diseases as well as the general process of aging. Mitochondria continuously produce oxygen free radicals by a variety of reactions under normal conditions, and mitochondrial DNA (mtDNA) has been demonstrated to be more susceptible to mutations than nuclear DNA. In the past decade, the role of mitochondria and mtDNA mutations in the pathogenesis of diseases has been defined and extensively investigated. Changes in mitochondrial function and accumulation of mtDNA mutations have been associated with the aging process per se. Furthermore, oxidative stress has been implicated in the pathogenesis of diabetes mellitus and a number of complications associated with the disease, such as teratogenesis, retinopathy, neuropathy, cataracts, and vasculopathy. Topics will include mitochondria and oxidative stress in human disease; the influence of oxidative stress on the aging process; diabetes mellitus and its effects on vascular disease; and muscle mitochondria in aging and Type II diabetes.
Cereal Grains: An Evolutionary Perspective
Chair: J. Hallfrisch
This will examine the effects of grains in the American diet, both beneficial and not. Speakers will consider the mechanisms underlying the effects and the components of grains responsible for them.
Calorie Restriction: Effects on Body Composition, Insulin
Signaling, and Aging
Chairs: B. Hansen and H. Ortmeyer
Calorie restriction is used for its anti obesity, its anti aging, and its anti disease properties. Significant reduction in the development of diabetes, prevention of the development of much of the Metabolic Syndrome X, and prevention of kidney disease have been demonstrated. Aging processes have been slowed and mortality postponed through dietary restraint. Recently, outstanding progress has been made in identifying the mechanisms underlying these effects of reduced calorie intake. Profound changes in metabolism have been identified, together with important changes in gene expression. This symposium will examine the newest data in this field with the goal of highlighting the wide array of processes that show sustained alterations with calorie restriction (without malnutrition), and which slow aging.
Leucine as a Nutritional Signal
Chairs: S. Hutson and R. Harris
Although the anabolic effects of amino acids from dietary protein and on protein synthesis and cell function were first reported more than 20 years ago, until recently the molecular basis for many of these observations had remained elusive. Now there is convincing evidence that amino acids are actually participants in signal transduction pathways, activating in some cells the same signaling cascades as the anabolic hormone insulin. In many instances, the indispensable branched chain amino acid leucine can exert the same effects as amino acid mixtures. This symposium will feature new developments in understanding the molecular mechanisms by which leucine metabolism is regulated, how this nutrient functions in the central nervous system, and how leucine activates signaling pathways that regulate protein translation and growth.
Functional Foods for Health Promotion: Modifiers of
Efficacy
Chairs: J. Milner and P. Anderson
Research continues to provide compelling evidence about the critical role that diet has in health promotion and disease prevention. The concept that foods, or their components, may offer benefits beyond basic nutrition is of increasing interest to those involved with health care including the consumer. However, the interrelationship between diet and health is not simple but reflects a myriad of factors that may promote or hinder the response. This program will provide insights on aspects that influence the physiological response to biologically active compounds in foods. Speakers will focus on the variation in content of bioactive components in foods, key factors influencing their physiologic bioavailability, the effect that elucidation of the human genome will have on the molecular targeting of food components, and the food safety/regulatory scheme in light of factors that can influence the variability in the physiologic response of food components.
Molecular Mechanisms of Protective Effects of Vitamin E in
Atherosclerosis
Chairs: M. Meydani and M. Traber
This symposium covers signal transduction and gene expression pathways in which vitamin E has a regulatory role, and probably not as an antioxidant! These newly discovered mechanisms for vitamin E provide a scientific rationale for understanding the epidemiological and clinical findings and potential role of dietary vitamin E in modulating inflammatory process associated with the risk of developing atherosclerosis beyond its antioxidant protection of LDL oxidation.
Fatty Acids in Human Milk and Formulas: Assessing Functional
Outcome for the Infant
Chairs: K. Michaelsen and C. Lammi-Keefe
The scientific, particularly the nutrition, community continues to be plagued by its inability to relate to nutrient adequacies or deficiencies with relevant measures of functional outcome. In the past decade, investigators and clinicians have begun to question and assess adequacy of the essential fatty acids and their long chain polyunsaturated fatty acid derivatives during the perinatal period. Significant evidence exists that improvement in fatty acid status of the neonate through breastfeeding or formulas can be beneficial. Modulation of content of the fatty acids for these modes of feed via either the mother’s diet or fortification, respectively, remains controversial and not completely resolved. Investigators continue to come back to the "so what" question; i.e., what functional outcome measure should be assessed? What instruments can be further explored? This symposium will review our current level of understanding regarding instruments that may be sensitive indicators of infant fatty acid status and discuss methodologies that theoretically are potential indicators of functional integrity and that may be sensitive to subtle differences in nutriture, especially as it relates to the fatty acids that are crucial to growth and development of the central nervous system.
Adipocyte Function, Differentiation, and Metabolism
Chairs: N. Moussa and J. N'tambi
Obesity is currently recognized as a major health problem, with 97 million adults in the United States being overweight or obese and thus at increased risk of morbidity and mortality from several diseases including diabetes and coronary heart disease. A significant part of the development in obesity research should be credited to the progress in adipocyte metabolism and differentiation research. Adipose tissue has been considered for a long time as metabolically inactive and primarily serving as a fat storage tissue. Participants will review the new role of fat cells as an endocrine tissue and highlight the function and regulation of major secreted proteins that play a key role in obesity. Two of the obesity genes (agouti and leptin), cloned in the past 8 years, are primarily produced by fat cells. Discovery of these genes led to a better understanding of mechanistics of obesity and in particular the role of the adipocyte-hypothalamus interaction in regulation of energy balance. Studies of cultured adipocytes and their differentiation made a major contribution to understanding adipose tissue development and regulation. The role of major transcription factors and adipogenic markers in fat cell differentiation and regulation and recent advances in the genetics of brown fat and its contribution to regulation of energy balance will be reviewed. Overall, speakers will document how increased understanding of the molecular mechanisms of adipocyte differentiation and metabolism is enabling us to manipulate fat deposition and to control metabolic disorders associated with fat cell dysfunction.
Accomplishments in Child Nutrition During the Twentieth Century
Chairs: B. Nichols and F. Greer
This symposium celebrates the dramatic progress in child nutrition and health in the U.S. during the past century. Infant mortality fell as health and food safety and security were improved. Speakers will highlight the roles of the food industry in the provision of safe foods and the federal government in providing food security and examine the importance of the resurgence of breastfeeding at the end of the 20th century.
Nutritional and Metabolic Diversity: Understanding Biologic
Variance in the Obesity/Diabetes/Cardiovascular Disease Connection
Chairs: B. Tobin and G. Miller
At present, 58 million Americans have one or more types of cardiovascular disease, which claims more lives each year than the next seven leading causes of death combined. However, the incidence of coronary heart disease is not evenly distributed throughout the population. The co-morbid-associated conditions of obesity and diabetes lend strong evidence for the existence of nutritional and metabolic individuality as an explanation for population variance. This symposium is for scientists and clinicians who wish to understand genetic molecular, subcellular, whole body, and statistical approaches to identify and understand nutritional and metabolic variance in relation to obesity, diabetes, and cardiovascular disease.
Probiotics in Health and Disease
Chair: W.A. Walker
Probiotics defined as "organisms belonging to the natural flora with low or no pathogenicity but with functions of importance to health and well being of the host," has become an important functional food in the alternative treatment of gastrointestinal disease. We know that "natural" intestinal flora when present in an appropriate balance can supplement important gastrointestinal protective functions. This symposium will address the communication between bacteria and the gut epithelium ("cross-talk") and the resultant up-regulation of intestinal defenses. Participants will consider the role of probiotics in mucosal immune function, the prevention of human disease, and current clinical studies to show efficacy in the treatment of humans and speculate on their potential use of the future prevention/treatment of gastrointestinal inflammatory disease states. This symposium will help provide treatment options to patients non-responsive to the conventional use of antibiotics.
Probiotics in Health and Disease
Chair: W.A. Walker
Probiotics defined as "organisms belonging to the natural flora with low or no pathogenicity but with functions of importance to health and well being of the host," has become an important functional food in the alternative treatment of gastrointestinal disease. We know that "natural" intestinal flora when present in an appropriate balance can supplement important gastrointestinal protective functions. This symposium will address the communication between bacteria and the gut epithelium ("cross-talk") and the resultant up-regulation of intestinal defenses. Participants will consider the role of probiotics in mucosal immune function, the prevention of human disease, and current clinical studies to show efficacy in the treatment of humans and speculate on their potential use of the future prevention/treatment of gastrointestinal inflammatory disease states. This symposium will help provide treatment options to patients non-responsive to the conventional use of antibiotics.
Does Diet Have an Important Role in Colon Cancer?
Chairs: W. Willett and M. Forman
The topic of diet and colon cancer has been of interest for at least three decades. Recently, new data has become available from large prospective studies and randomized intervention trials. This symposium will evaluate the consistency of these findings with earlier work, including animal studies and mechanistic investigations, and determine the degree to which a clear picture of the relation between diet and colon cancer has been achieved.
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American Association of Anatomists |
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Most anatomists teach one or more of the anatomic disciplines (gross anatomy, histology, neuroanatomy, and embryology) to first-year professional students (medical students, dental students, etc.). There is a need, however, for anatomy teaching outside of this constraint. Participants will describe successful programs that expand opportunities for anatomists to include teaching undergraduate students, professional students at a stage other than first year, residents in clinical training programs, and anatomic teaching to the community at large.
Building a Cortex
Chair: V. Casagrande
The cerebral cortex contains a large proportion of the brain’s neurons and is probably the repository of most of our remembered knowledge of the world, as well as being the source of planned behavior, perception, and consciousness itself. Appreciating how the cortex develops to support these capacities has been a major scientific challenge. The discovery of genes that regulate brain development has opened new doors to our understanding of cortical development. Participants will present new data on how genes build a cortex. Specific discussions will include how genes control cortical size and specify functional areas; evidence demonstrating that the cortex can be regionalized by the differential expression of gradients of genes in the absence of input from the thalamus; data on the regulation of genes involved in thalamocortical pathfinding and cortical areal specification; and how cortical wiring molecules determine connections within the cerebral cortex.
Cell-to-Cell Interactions in the Vascular Wall
Chair: G.C. Schatteman
Cell-cell interactions help regulate a variety of processes in the vascular wall. In this symposium, speakers will discuss newly emerging ideas on how cells of the blood and the vasculature interact to repair injuries in the vascular wall and to create new blood vessels; how cell interactions between the heart and the pro-epicardium influence the formation of the coronary vasculature; the way interactions between the cells of the vascular wall and the extracellular matrix can affect angiogenesis; and the ways in which endothelial cell-smooth muscle cell interactions influence vascular remodeling and blood flow.
Chronic Remodeling During Asthma
Chair: C.G. Plopper
Chronic pulmonary diseases, such as allergic asthma, which are characterized by airways hyperreactivity, also involve significant reorganization of surface epithelium and changes in the immune cell populations resident in the walls of conducting airways. Defining the mechanisms by which chronic airway pathobiology contributes to the severe airways contractility associated with allergic asthma relies on a clear understanding of the trophic interactions between all the components of the airway wall, including epithelium, glands, fibroblasts, smooth muscle, nerve processes, and inflammatory and immune cell populations. Participants will focus on the compartmental changes in epithelium and immune cells and compare changes detected in humans with those observed in a nonhuman primate species, the rhesus monkey, in which allergic asthma has been induced experimentally by exposure to house dust mite.
Craniofacial Development
Chair: D.M. Noden
Numerous cell and molecular interactions and regulatory genes that are necessary for normal craniofacial development have been discovered recently. Some of these genes and signaling systems also operate elsewhere in the embryo, but many are unique to the facial, branchial, or calvarial regions. Disruptions of many of these produce both severe and subtle dysmorphologies of the head. Speakers will update the fates of and interactions among neural crest and mesodermal cells, discuss the genes and gene families that are essential for mammalian head development, and consider the genes and signaling systems necessary for morphogenesis of the face and histogenesis of the inner ear.
Development of the Senses: The Power of the Zebrafish Model
Chair: S.J. Moorman
The zebrafish has become a popular vertebrate model in a variety of different scientific disciplines, including neuroscience and developmental biology. The versatility of the zebrafish as a model has been enhanced by recent advances in molecular biology and genetics. This symposium, organized around the development of the sensory systems, has been designed to illustrate the depth and breadth of techniques that are typically used in research involving zebrafish.
Gap Junctions: Anatomical and Pathological Considerations
Chair: C. Naus
This session reviews the current status of the family of connexin genes that code for gap junction proteins, providing insight into the possible roles of this diversity of intercellular channels; examines the cellular aspects of connexin synthesis and trafficking and association with other intercellular junctions; examines the role of gap junctions in development and recent evidence implicating these channels in calcium signaling and apoptosis; and reviews the gap junctions in growth control.
Histology Education and Assessment
Chairs: D.L. Desha and J.P. Naftel
This symposium will deal with a variety of ways to execute the laboratory component of the course. Topics range from the necessity of maintaining the use of the microscope to eliminating its use entirely and will include a talk on current trends in teaching histology in Japan and discussion regarding changes occurring in histology teaching around the world.
Imaging: Living Systems
Chairs: R.D. Specian and S. Erlandsen
Recent advances in imaging approaches allow novel views of living cells and tissues. Approaches will include imaging of cell trafficking in vivo and ex vivo as well as intracellular trafficking of labeled proteins in cells.
International Approaches to Biomedical Graduate and Postdoctoral
Training Programs in the 21st Century
Chairs: R.R. Cardell and R.L. Drake
Several international experts will discuss topics important for the development of biomedical graduate and postdoctoral programs in the new century. Panelists will focus on common problems related to graduate and postdoctoral training programs and the approaches taken in different countries to solve these problems.
Misregulation of the Basement Membrane in Human Disease
Chair: M. Gordon
Symposium participants will highlight regulatory roles of extracellular matrix, including the structural properties of fibrillin in basement membranes and the molecule’s function in sequestering growth factors; the role of fibronectin and focal adhesion kinase (FAK) in the survival of anchorage dependent cells; how gelatinase B serves to release sequestered VEGF to promote angiogensis in both endochondral bone formation and in tumor progression; and emmprin, a molecule on the surface of tumor cells that stimulates neighboring cells to synthesize matrix metalloproteinases, and its role in tumor progression.
Neuroendocrinology at the Beginning of the 21st Century
(Refresher Course)
Chairs: C.A. Blake and S.A. Miller
During the 20th century, neuroendocrinology emerged as a multidisciplinary field. Great strides have been made in understanding the neurosecretion of posterior pituitary hormones and the neurosecretory neuronal systems involved in the secretion of the adenohypophysial hormones. Study of the effects of hormones and the environment on the development and maintenance of neuroendocrine systems and the feedback effects of hormones at the brain and pituitary have not only increased our knowledge, but also opened new avenues of research. Experts will review their work and the current status of different areas of current neuroendocrine research. Specifically, the will discuss hormone-dependent structural brain differences as well as the possible roles of gonadal hormones and non-hormonal genomic factors in sexual differentiation of the brain; the identification of homeobox transcription factors controlling pituitary development and the roles of hypothalamic neuromodulators and adenohypophysial autocrine and paracrine secretions controlling pituitary secretions; updates of the recent status of leptin, a hormone secreted by adipocytes; and advances in neuroendocrinology resulting from the employment of techniques enabling assessment of gene expression and peptide secretion from single cells as well as knockout or overexpression studies will be covered.
Recent Advances in Muscle Cell Biology
Chair: E. Engvall
The maintenance and regeneration of skeletal muscle is of major importance in muscle disease and in normal aging. The most recent advances in these areas will be presented: identification of factors that regulate myogenesis; what muscular dystrophy genes may tell about muscle function; how muscle regenerates; and alternative sources of cells for muscle regeneration.
Signaling During Angiogenesis
Chair: M.A. Stepp
A better understanding of the molecules that regulate blood vessel growth will impact the quality of life for patients with diseases ranging from cancer and heart disease to diabetes. Signal transduction pathways and how they regulate angiogenesis is the topic of this symposium featuring four prominent researchers in this rapidly moving field. From The Scripps Research Institute, David Cheresh will talk about how integrin-mediated events and Src-family kinases affect endothelial cell apoptosis mediated by growth factors. Martin Schwar
