Dynamical” Vs“与动态. “Genetic” Disease What Do Complex Rhythms.ppt

“Dynamical” Vs. “Genetic” Disease: What Do Complex Rhythms Reveal About Pathophysiology? Leon Glass Isadore Rosenfeld Chair in Cardiology McGill University, Montreal Quebec, Canada Genetic Disease (40,000 hits) Garrod (1908) – Inborn errors of metabolism show Mendelian inheritance Pauling et al. (1949) – Sickle cell anemia: a molecular disease Ingram (1956) – Chemical difference between normal human and sickle cell anemia hemoglobin Genetic Disease: Implications for Research Identify abnormalities ? Map abnormalities Determine genome (human genome project) ? Develop therapies Genetic Disease: Implications for therapy Prevention Environmental modifications (restrict toxic agents, replace deficient products or organs, remove toxic substances or organs) Gene therapy (increase or decrease expression of genes) Genetic Disease: Limitations of Concept Disease arises from interactions between genetics and environment Complex polygenic diseases are common and still not well understood Gene therapy is of limited utility so far People still get sick and must be treated Disorders are often dynamic (even genetic ones) Dynamical Disease (166 hits) Reimann (1963) – Periodic diseases Mackey and Glass (1977) – Dynamical diseases associated with qualitative changes in dynamics in physiological systems Reimann (1963) Mackey and Glass (1977)  rate of change = production – destruction Dynamical Disease: Implications for Research Collect data from complex rhythms over long times () Develop mathematical models and study effects of parameter changes Develop biological models that display complex rhythms Develop therapies Dynamical Disease: Implications for Research Collect data from complex rhythms over long times () Develop mathematical models and study effects of parameter changes Develop biological models that display complex rhythms Develop therapies Pure Parasystole Rules of Pure Parasystole Modulated Parasystole Modulated Parasystole with Noise Parasystole: Concl