Demystifying Medicine

Course Materials for 2012

January 10 – Global Infections: The Great Challenge

• Anthony Fauci (NIAID) - Presentation Handout
• John Coffin (NCI) - Presentation Handout
• Readings
  • Anthony S Fauci: The expanding global health agenda: a welcome development. Nature Medicine, Volume 13, Number 10, October 2007, xxi-xxiii.
  • David M Morens, Gregory K Folkers, Anthony S Fauci: Emerging infections: a perpetual challenge. Lancet Infect Dis 2008; 8: 710–19.
  • Anthony S. Fauci: AIDS: Let Science Inform Policy. Science, v333, 1 July 2011.
  • B. Fenton Hall and Anthony S. Fauci: Malaria Control, Elimination, and Eradication: The Role of the Evolving Biomedical Research Agenda. Perspective. JID. 2009:200 (1 December). 1643.
  • Gary J Nabel & Anthony S Fauci: Induction of unnatural immunity: prospective for a broadly protective universal influenca vaccine. Nature Medicine. v16, n12, December 2010.

January 17 - Stem Cells: The New Frontier in Biology and Medicine

• Mahendra Rao (ICRM)
• Ronald Gress (NCI)
• Readings:
  • Concise review: cord blood banking, transplantation and induced pluripotent stem cell: success and opportunities. Rao M, Ahrlund-Richter L, Kaufman DS. Stem Cells. 2012 Jan;30(1):55-60. doi: 10.1002/stem.770. PMID: 22069231 [PubMed - in process]
  • Cell-based therapy for neural disorders--anticipating challenges. Chiu AY, Rao MS. Neurotherapeutics. 2011 Oct;8(4):744-52.PMID: 21901585 [PubMed - in process]
  • Gene targeting in human pluripotent stem cells. Liu Y, Rao M. Methods Mol Biol. 2011;767:355-67. PMID: 21822888 [PubMed - indexed for MEDLINE]
  • Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Swistowski A, Peng J, Liu Q, Mali P, Rao MS, Cheng L, Zeng X. Stem Cells. 2010 Oct;28(10):1893-904.

January 24 - Parkinson's Disease: From Genes to Surgery

• Codrin Lungu (NINDS)
• Kareem Zaghloul (NINDS)
• Readings
  • Ponce FA, Lozano AM. The most cited works in Parkinson's disease. Mov Disord. 2011;26(3):380-90.
  • Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(21 Suppl 4):S1-136
  • Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181-4
  • Braak H, Del Tredici K, Bratzke H et al. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J Neurol. 2002;249 Suppl 3:III/1-5
  • Witt J, Marks WJ Jr. An update on gene therapy in Parkinson's disease. Curr Neurol Neurosci Rep. 2011;11(4):362-70.
• Win Arias - Introduction
  • 1817 “An essay on shaking palsy”
  • Prevalence: 2% of pop. >50 yrs
  • Insidious, progressive – Example: tennis partner
  • History: George Kotzias discovers dopamine deficiency in substantia nigra….and does something about it
  • Parkinson’s in the genomic era

January 31 - Genomics and Undiagnosed Disease

• Eric Green (NHGRI)
• William Gahl (NHGRI)
• Reading
  • 2011 NHGRI Strategic Plan
  • NT5E Mutations and Arterial Calcifications. Cynthia St. Hilaire, Ph.D., Shira G. Ziegler, B.A., Thomas C. Markello, M.D., Ph.D., Alfredo Brusco, Ph.D., Catherine Groden, M.S., Fred Gill, M.D., Hannah Carlson-Donohoe, B.A., Robert J. Lederman, M.D., Marcus Y. Chen, M.D., Dan Yang, M.D., Ph.D., Michael P. Siegenthaler, M.D., Carlo Arduino, M.D., Cecilia Mancini, M.Sc., Bernard Freudenthal, M.D., Horia C. Stanescu, M.D., Anselm A. Zdebik, M.D., Ph.D., R. Krishna Chaganti, M.D., Robert L. Nussbaum, M.D., Robert Kleta, M.D., Ph.D., William A. Gahl, M.D., Ph.D., and Manfred Boehm, M.D. N Engl J Med 2011;364:432-42.
  • The NIH Undiagnosed Diseases Program: Lessons Learned. Gahl WA, Tifft CJ.
  • The National Institutes of Health Undiagnosed Diseases Program: Insights into rare diseases. Gahl WA, Markello TC, Toro C, Fajardo KF, Sincan M, Gill F, Carlson-Donohoe H, Gropman A, Pierson TM, Golas G, Wolfe L, Groden C, Godfrey R, Nehrebecky M, Wahl C, Landis DM, Yang S, Madeo A, Mullikin JC, Boerkoel CF, Tifft CJ, Adams D; for the NISC Comparative Sequencing Program.
  • Genomics Reaches the Clinic: From Basic Discoveries to Clinical Impact. Teri A. Manolio and Eric D. Green. Cell 147, September 30, 2011, page 14.

February 7 - Stuttering: A Medical Disease?

• Dennis Drayna (NIDCD)
• Donna Krasnewich (NIGMS)
• Penny Friedman (CC)
• Readings:
  • Genomewide Significant Linkage to Stuttering on Chromosome 12. Naveeda Riaz,1 Stacy Steinberg,2,* Jamil Ahmad,3 Anna Pluzhnikov,2 Sheikh Riazuddin,3 Nancy J. Cox,2 and Dennis Drayna1. Am. J. Hum. Genet. 76:647–651, 2005.
  • Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering. Changsoo Kang, Ph.D., Sheikh Riazuddin, Ph.D., Jennifer Mundorff, M.A., Donna Krasnewich, M.D., Ph.D., Penelope Friedman, M.D., James C. Mullikin, Ph.D., and Dennis Drayna, Ph.D.. N Engl J Med 2010;362:677-85.
  • Analysis of Mannose 6-Phosphate Uncovering Enzyme Mutations Associated with Persistent Stuttering*. Wang-Sik Lee‡, Changsoo Kang§, Dennis Drayna§, and Stuart Kornfeld‡1. The Journal of Biological Chemistry VOL.286,NO.46,pp.39786–39793,November18,2011.
• Win Arias - Introduction: Famous Stutterers
  • Demosthenes
  • Moses
  • Emperor Claudius
  • Emperor Caligula
  • Isaac Newton
  • King George V
  • Winston Churchill
  • Lewis Carroll

February 14 - Legionella: More than Only Veterans

• Matthias Machner (NICHD)
• Tara Palmore (NIAID)
• Win Arias - Introduction
  • Pneumonia (8th Cause of Death)
  • BACTERIAL; Strep (Pneumococcal), Staph (MRSA), Strep, Klebsiella, Hemophilus, Mycoplasma, Pneumocystis (HIV), Chlamydia Legionella, plus many others (rarer)
  • VIRAL: adeno-, rhino-, influenza, para-flue, resp. Interstitial virus ,
  • FUNGAL: histoplasmosis, crypto-, blasto-, aspergillus, others
  • OTHERS: Toxin (chemicals, berylium), aspiration, drug (paraquat), radiation, others
• Readings
  • The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Ralph R. Isberg*‡, Tamara J. O’Connor‡§ and Matthew Heidtman‡§. Nature. Volume 7, Page 15, Year 2009.
  • An Outbreak of Legionnaires Disease Associated with a Decorative Water Wall Fountain in a Hospital. Thomas E. Haupt, MS;1 Richard T. Heffernan, MPH;1 James J. Kazmierczak, DVM;1 Henry Nehls-Lowe, MPH;1 Bruce Rheineck, MS;1 Christine Powell, BS;2 Kathryn K. Leonhardt, MD;3 Amit S. Chitnis, MD;1 Jeffrey P. Davis, MD1. Infection control and hospital epidemiology february 2012, vol. 33, no. 2.
  • Legionnaires’ Disease: Clinical Differentiation from Typical and Other Atypical Pneumonias. Burke A. Cunha. Infect Dis Clin N Am 24 (2010) 73–105.

February 21 - Taste: Good and Bad

• Nicholas Ryba (NIDCR)
• Robert Henkin (Taste and Smell Clinic)

February 28 - No Lecture

March 6 - Aging Gracefully

• Toren Finkel (NHLBI)
• Luigi Ferrucci (NIA)
• Readings
  • Harrison's Online: Chapter 72. Clinical Problems of Aging by Luigi Ferrucci, Stephanie Studenski.
  • Finkel T. and Holbrook N. (2000). Oxidants, Oxidative Stress and the Biology of Aging, Nature 408:239-247.
  • Balaban R., Nemoto S., and Finkel T. (2005). Mitochondria, Oxidants and Aging, Cell 120:483-495.
  • Finkel T., Deng C., and Mostaslavsky R. (2009). Recent progress in the biology and physiology of sirtuins. Nature 460:587-591.
  • Finkel T. (2011). Signal Transduction by Reactive Oxygen Species. J. Cell Biol. 194:7-15.
  • J Am Geriatr Soc. 2012 Jan 27. doi: 10.1111/j.1532-5415.2011.03833.x. [Epub ahead of print]
  • Protein Intake and Muscle Strength in Older Persons: Does Inflammation Matter? Bartali B, Frongillo EA, Stipanuk MH, Bandinelli S, Salvini S, Palli D, Morais JA, Volpato S, Guralnik JM, Ferrucci L. Source Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Of Greek heroes, wiggling worms, mighty mice, and old body builders. Ferrucci L, de Cabo R, Knuth ND, Studenski S. J Gerontol A Biol Sci Med Sci. 2012 Jan;67(1):13-6. Epub 2011 Nov 23. No abstract available.
  • Memory Shaped by Age Stereotypes over Time. Levy BR, Zonderman AB, Slade MD, Ferrucci L. J Gerontol B Psychol Sci Soc Sci. 2011 Nov 4. [Epub ahead of print]

March 13 - Hepatocellular Cancer: A Global Disease

• Jean Pierre Gillet (NCI)
• Win Arias (NICHD)
• Readings
  • Jordi Bruix and Morris Sherman. Management of hepatocellular carcinoma: an update. Hepatology 2011  53;1020-1022
  • Kai Breuhakn, Gregory Gores and Peter Schirmacher Strategies for hepatocellular carcinoma therapy and diagnostics: lessons learned from high throughput and profiling approaches.  Hepatology 2011 53:2111-2120
    

March 20 - Head and Neck Cancer: New Paradigms and Treatment

• Silvio Gutkind (NIDCR)
• Barbara Conley (NCI)
• Readings
  • Early Tumor Progression Associated with Enhanced EGFR Signaling with Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer. Athanassios Argiris, Austin G. Duffy, Shivaani Kummar, et al. Clin Cancer Res 2011;17:5755-5764. Published OnlineFirst July 12, 2011.
  • Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States. Anil K. Chaturvedi, Eric A. Engels, Ruth M. Pfeiffer, Brenda Y. Hernandez, Weihong Xiao, Esther Kim, Bo Jiang, Marc T. Goodman, Maria Sibug-Saber, Wendy Cozen, Lihua Liu, Charles F. Lynch, Nicolas Wentzensen, Richard C. Jordan, Sean Altekruse, William F. Anderson, Philip S. Rosenberg, and Maura L. Gillison. J Clin Oncol 29:4294-4301.
  • Update of prognostic and predictive biomarkers in oropharyngeal squamous cell carcinoma: a review. Carolin M. Grimminger · Peter V. Danenberg. Eur Arch Otorhinolaryngol (2011) 268:5–16.
  • Identifying the risk factors for late-stage head and neck cancer. Maria Worsham. Expert Rev. Anticancer Ther. 11(9), 1321–1325 (2011)

March 27 - Inflammatory Bowel Disease: New Biologic and Therapeutic Players

• Warren Strober (NIAID)
• Michael Yao (NIAID)
• Readings
  • Conventional Medical Management of Inflammatory Bowel Disease. Daniel Burger & Simon Travis. Gastroenterology 2011;140:1827–1837.
  • Future Therapeutic Approaches for Inflammatory Bowel Diseases. Scott E. Plevy & Stephan R. Targan. Gastroenterology 2011;140:1838–1846.
  • The role of IL-13 and NK T cells in experimental and human ulcerative colitis. IJ Fuss and W Strober. Nature. Volume 1 Supplement 1, November 2008, S32.
  • Proinflammatory Cytokines in the Pathogenesis of Inflammatory Bowel Diseases. Warren Strober & Ivan J. Fuss. GASTROENTEROLOGY 2011;140:1756–1767.
  • NOD2, an intracellular innate immune sensor involved in host defense and Crohn’s disease. W Strober and T Watanabe. Mucosal Immunology. Volume 4, Number 5, September 2011.

April 3 - Addictions: Are They All the Same?

• Antonello Bonci (NIDA)
• David Goldman (NIAAA)
• Readings
  • Optogenetic Modulation of Neural Circuits that Underlie Reward Seeking. Garret D. Stuber, Jonathan P. Britt, and Antonello Bonci. Journal of Biological Psychiatry. 2011 December 22.
  • AMPA Receptor Synaptic Plasticity Induced by Psychostimulants: The Past, Present, and Therapeutic Future. M. Scott Bowers, Billy T. Chen, and Antonello Bonci. Neuron 67, July 15, 2010, Page 11.
  • A population-specific HTR2B stop codon predisposes to severe impulsivity. Laura Bevilacqua, Stephane Doly, Jaakko Kaprio, Qiaoping Yuan, Roope Tikkanen, Tiina Paunio, Zhifeng Zhou, Juho Wedenoja, Luc Maroteaux, Silvina Diaz, Arnaud Belmer, Colin A. Hodgkinson, Liliana Dell’Osso, Jaana Suvisaari, Emil Coccaro, Richard J. Rose, Leena Peltonen, Matti Virkkunen6, & David Goldman. 23/30 December 2010, Volume 468, Nature 1061.
  • The Genetics of Addictions: Uncovering the Genes. David Goldman, Gabor Oroszi and Francesca Ducci. NATURE REVIEWS | GENETICS. VOLUME 6 | JULY 2005 | 521.
  • A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. L. Elliot Honga, Colin A. Hodgkinson, Yihong Yang, Hemalatha Sampath, Thomas J. Ross, Brittany Buchholz, Betty Jo Salmeron, Vibhuti Srivastava, Gunvant K. Thaker, David Goldman, and Elliot A. Stein. PNAS, July 27, 2010, vol. 107, no. 30, 13509–13514.
  • Patient Testimony - The patient who described her alcohol addiction so powerfully, sent the followjng additional messages she wanted to convey:
    
    "As always, the experience probably was better for me than the audience.  Certainly, it placed my daily frustrations in perspective. I only wish that I had done a better job of organizing my thoughts, or of keeping time!  I realized after the event that I had missed several points that could have been important to your audience.  Among them:
    
    (1) I wish that I had described the many intersections with the medical community in which my symptoms (high blood sugar, all the behavioral symptoms, probably other labs) should have evoked an admonition about drinking, but did not. Two psychiatrists treated me at different times for depression; at least, one of them had the perception and good sense to tell me that that my symptoms resembled those of alcoholics he treated.  That planted a seed--one among a handful of similar seeds planted by family members, my then-husband, one friend, across more than a decade of active alcoholism.  Fortunately, today, I think docs and family are more knowledgeable and less reticent, but I like to encourage people medical and otherwise to speak up when they perceive a problem in someone they care about. How else to break down the addict's singular defenses against self-knowledge?
    
    (2) Among my reasons for staying well, I should have credited research.  Proximity for 20 years to advances in alcohol research was and remains a mainstay of my recovery.
    
    (3) It's interesting to be where I am on the lifespan and anticipating cognitive decline associated with   normal aging, mixing with any consequences of past alcohol abuse, mixing with any so-far-unrealized diagnosis such as Alzheimer's.  I like speaking that message to younger audiences who probably have not considered how the disease looks, even 30 years into recovery, to the drinker."

April 10 - Diarrheal Diseases: Deadly Events

• Roger Glass (FIC)
• Mark Donowitz (Johns Hopkins)
• Readings
  • New Hope for Defeating Rotavirus. Scientific American. Roger I. Glass. April 2006. Page 47.
  • Oral Rotavirus Vaccines: How Well Will They Work Where They Are Needed Most? Manish Patel,1 Andi L. Shane,2 Umesh D. Parashar,1 Baoming Jiang,1 Jon R. Gentsch,1 and Roger I. Glass1,3. JID 2009:200 (Suppl 1) • S39.
  • Rotavirus: realising the potential of a promising vaccine. DOI:10.1016/S0140- 6736(10)60896-3.
  • Translational Approaches for Pharmacotherapy Development for Acute Diarrhea. Mark Donowitz, David Alpers, Henry J. Binder, Thomas Brewer, Jill Carrington, and Michael J. Grey. Gastroenterology 2012; 142:e1-e9.
  • Magic Bullet: The History of Oral Rehydration Therapy. Joshua Nalibow Ruxin. Medical History. 1994. 38: 363-397.
  • D-Glucose Acts via SGLTI to Increase NHE3 in Mouse Jejunal Brush Border by a NHERF2-Dependent Process. Rong Lina, Rakhilya Murtazina, Boyoung Cha, Molee Chakraborty, Rafiquel Sarker, Tian-e Chen, Zhihong Lin, Boris M. Hogema, Hugo R. de Jonge, Ursula Seidler, Jerrold R. Turner, Xuhang Li, Olga Kovbasnjuk, and Mark Donowitz. Gastroenterology. 2011 February; 140(2): 560-571.

April 17 - Autism: Progress Continues

• Susan Swedo (NIMH) - Joint Presentation
• Audrey Thurm (NIMH) - Joint Presentation
• Readings
  • Gene Studies of Autism Point to Mutations and Parent's Age by Benedict Carey. Published April 4, 2012 by The New York Times.
  • Study Links Autism to Maternal Obesity by Abby Ohlheiser. Posted Monday, April 9, 2012 at 10:06am ET.
  • History of Autism. WebMD website http://www.webmd.com
  • Autism Fact Sheet. NINDS website http://www.ninds.nih.gov

April 24 - Gluten Enteropathy: An Expanding Disease

• Bana Jabri (U of Chicago)
• Irwin Rosenberg (Tufts)
• Readings
  • How Doctors Think by Jerome Groopman - Review Pages 1-25 for a written description of a case of celiac disease which illistrates all of the problems in diagnosis and management.
  • Willem-Karel Dicke: Pioneer in Gluten-Free Diet in the Treatment of Celiac Disease by Jefferson Adams. May 14, 2010.
  • Gluten- and Casein-Free Diets for Autistics Spectrum Disorder. Millward C, Ferriter M, Calver SJ, Connell-Jones GG. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD003498. DOI: 10.1002/14651858.CD003498.pub3.
  • Farrell RJ, Kelly CP: Celiac sprue. NEngl J Med 346:180, 2002.
  • Anderson RP, Degano P, Godkin AJ, et al: In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant α-gliadin T-cell epitope. Nat Med 6:337, 2000.
  • Madara JL, Trier JS: Structural abnormalities of jejuna epithelial cell membranes in celiac sprue. Lab Invest 43:254, 1980.
  • Integration of Genetic and Immunological Insights into a Model of Celiac Disease Pathogenesis. Valerie Abadie, Ludvig M. Sollid, Luis B. Barreiro, and Bana Jabri. Annu. Rev. Immunol. 2011.29:493-525
  • Tissue-mediated control of immunopathology in coeliac disease. Bana Jabri and Ludvig M. Sollid. Nature Reviews Immunology. page 858 December 2009, Volume 9.

May 1 - Finale: Present and Future Status for Careers in Biomedical Sciences

• Michael Gottesman (NIH)
• Katheryn Zoon (NIAID)
• Irwin Arias (NICHD)

This web page was last modified on May 1, 2012. For questions about the course, please contact ariasi@mail.nih.gov.