Charles T. Ambrose, M.D.

Professor

Research statement:

I have no current research program. My earlier researches & recent teaching efforts are summarized below.

A. My immunological studies from 1959 through 1975 employed an organ culture system involving lymph nodes & spleen from rabbits, rats, and guinea pigs in which the secondary antibody (2^oAb) could be elicited in vitro and examined over the course of a month or more. My early studies showed than this response was readily inhibited by chloramphenicol (1) & salicylic acid (2), both at non-toxic, pharmacological levels commonly encountered during clinical therapy. 1) J. Exp. Med. 1963; 117: 1035-51.  2) J. Exp. Med. 1966; 124: 461-82.

B. In the early 1960s completely synthetic media had not yet been devised and most cell cultures depended on the medium composed of a balanced salt solution, placental cord serum, & even embryo extract. Culture results sometimes varied with different lots of serum & embryo extract.  This problem was resolved in my organ culture system with the discovery that the serum could be replaced by dialyzable components of serum, which proved to be physiological levels of corticosteroids & insulin.  3) J. Exp. Med., 1964; 119: 1017-49.

C. One unexpected effect observed during dose response experiments was the enhancement of the 2º Ab response in vitro when very low levels of various inhibitor drugs were added to the medium -- e.g., actinomycin D (4, 5). I postulated an antibody inhibitory material, whose synthesis was itself suppres-sed by low levels of the drug, which at higher levels caused the expected inhibition of Ab production. An inhibitory factor was isolated. Later investigators characterized the phenomenon as due to sup-pressor cells.  4) J. Exp. Med. 1969; 130: 1003-29.  5) Annale d’Immunologie 1975; 126:3-13.

D. I studied the binding of actinomycin D to rabbit thymus chromatin & its DNA in a sub-cellular system as measured by optical rotary dispersion (6). Cortisol (but not chemically related corticosteroids) enhanced AD’s binding to chromatin but not to DNA. I postulated that physiologically active corticosteroids mediate their permissive effect in cells by unmasking DNA sites in chromatin for attachment  of natural signals or inducers.  6) “The Essential Role of Corticosteroid …” in Hormones & the Immune Response, Ciba Foundation Study Group No. 36, London: J. & A. Churchill, 1970, pp. 100-125.

Since 1975 at this College of Medicine I focused mainly on teaching pathogenic microbiology to medical students and offered elective courses in the history of medicine & of microbiology, medical ethics, and medical literature in fiction.  Below are some recent representative publications of mine.

Selected recent publications:

1. Felix Platter, a 16^th-century Medical Student.  The Pharos  2004; 67: 8-13.
2. Osler and the Infected Letter. (A History of the Disinfection of Mail).  Emerging Infectious Diseases 1005; 11: 689-93.
3. The Secret Kappa Lambda Society of Hippocrates (Origin of the AMA’s Principles of Medical Ethics).  Yale J. Biol. & Med. 2005; 78: 45-56.
4. Robley Dunglison, 1798-1869.  The preeminent medical author of mid-19^th-century America. The Pharos 2006; 69: 1-11.
5. The Osler Slide.  A Demonstration of Phagocytosis from 1876 and other Reports of Phagocytosis before Metchnikoff’s 1880 Paper.  Cellular Immunology 2006; 240: 1-4.
6. Immunology’s First Priority Dispute.  An Account of the 17^th-century Rudbeck-Bartholin Feud. Cellular Immunology 2006; 242: 1-8.
7. Ambrose, C.T. The Priority dispute over the function of the lymphatic system and Glisson’s ghost (the 18th-century Hunter-Monro Feud) Cellular Immunology 2007; 245: 7-15.
8. Ambrose, C.T. Osler and the Black Corpuscles: profiles of three early students of phagocytosis. J. Med. Biography 2007; 15 (Suppl. 1): 39-45.
9. Ambrose, C.T. Rudbeck’s Complaint – A 17th-century Latin Letter Relating to Basic Immunology, Scandinavian J. Immunology, 2007; in press.