History of Medicine Schedule 2010-2011

William Osler (1849-1919): America’s Most Famous Physician (Robert E. Rakel) The Assassination of John F. Kennedy: A Neurosurgeon’s Eyewitness Account of the Medical Aspect of the Events of November 22, 1963 (Robert G. Grossman) Making Cancer History: Disease and Discovery at the University of Texas M.D. Anderson Cancer Center (James S. Olson) The History of Pathology as a Biological Science and Medical Specialty (L. Maximillian Buja) “Medicine in the Mid-19th Century America” (Student Essay Contest Winner) (David Hunter) The Achievements and Enduring Relevance of Rudolph Virchow (Nathan Grohmann) Medicine: Perspectives in History and Art (Robert E. Greenspan) What Every Physician Should Know: Lessons from the Past (Robert E. Greenspan) Medicine in Ancient Mesopotamia (Sajid Haque) The History of Texas Children’s Hospital (B. Lee Ligon) Visualizing Disease: Motion Pictures in the History of Medical Education (Kirsten Ostherr)

Isolation and {\it in vitro}-immunosuppressive characterization of a novel cyclosporine metabolite

Cyclosporine (CsA) has shown great benefit to organ transplant recipients, as an immunosuppressive drug. To optimize CsA immunosuppressive therapy, pharmacodynamic evaluation of serial patient serum samples after CsA administration, using mixed lymphocyte culture (MLC) assays, revealed in vitro serum immunosuppressive activity of a CsA-like, ether-extractable component, associated with good clinical outcome in vivo. Since the in vitro immunosuppressive CsA metabolites, M-17 and M-1, are erythrocyte-bound, the immunosuppressive activity demonstrated in patient serum suggests that other immunosuppressive metabolites need exist. To test this hypothesis and obtain CsA metabolites for study, ether-extracted bile from tritiated and nonradioactive CsA-treated pigs was processed by novel high performance liquid and thin-layer chromatography (HPLC and HPTLC) techniques. Initial MLC screening of potential metabolites revealed a component, designated M-E, to have immunosuppressive activity. Pig bile-derived M-E was characterized as a CsA metabolite, by radioactive CsA tracer studies, by 56% crossreactivity in CsA radioimmunoassay, and by mass spectrometric (MS) analysis. MS revealed a CsA ring structure, hydroxylated at a site other than at amino acid one. M-E was different than M-1 and M-17, as demonstrated by different retention properties for each metabolite, using HPTLC and a novel rhodamine B/ $\alpha$-cyclodextrin stain, and using HPLC, performed by Sandoz, that revealed M-E to be different than previously characterized metabolites. The immunosuppressive activity of M-E was quantified by determination of mean metabolite potency ratio in human MLC assays, which was found to be 0.79 $\pm$ 0.23 (CsA, 1.0). Similar to parent drug, M-E revealed inter-individual differences in its immunosuppressive activity. M-E demonstrates inhibition of IL-2 production by concanavalin A stimulated C3H mouse spleen cells, similar to CsA, as determined with an IL-2 dependent mouse cytotoxic T-cell line. ^