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About Charles T. Ambrose

I. My four recently published reviews of the literature on senile dementia and aging have emphasized the importance of the microcirculation in both -- including Alzheimer’s disease. Capillary density in the brain, muscles, and elsewhere in the body is reduced with aging in man and animals and results from age-linked declining levels of angiogenic factors. I have proposed therapeutic angiogenesis with recombinant forms of these factors as treatment for the lesser ailments of aging and senile dementia. 1) Aging Research Reviews 2015, in press. 2) J. Alzheimer’s Dis. 2015; 43: 1-17. 3) American Scientist 2013: 101: 194-274.
II. My earlier researches at Harvard Medical School and at INSERM, Paris are summarized below in A-D.
A. My immunological studies from 1959 through 1975 employed an organ culture system involving lymph nodes & spleen fragments from rabbits, rats, and guinea pigs in which the secondary antibody could be elicited in vitro and examined over the course of a month or more. My early studies showed that this response was readily inhibited by chloramphenicol (1) and salicylic acid (2), both at non-toxic, pharmacological levels 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, & 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 and embryo extract could be replaced by dialyzable components of serum, which proved to be physiological levels of corticosteroids & insulin. kk(3) J. Exp. Med., 1964; 119: 1017-49.
C. One unexpected effect observed during dose response experiments with chloramphenicol was the enhancement of the 2º Ab response in vitro when very low levels of various inhibitor agents (e.g., chloramphenicol, actinomycin D, mitomycin C, etc.) were added to the medium. To explain this paradoxical effect, in 1968 I postulated an antibody inhibitory material (AIM). At low levels of an inhibitor agent, AIM was suppressed, allowing increased antibody production. At higher levels of the agent, antibody production was suppressed, as expected. An inhibitory factor was isolated. (4) J. Exp. Med. 1969; 130: 1003-29. (5) Annale d’Immunologie 1975; 126: 3-13. Later, other investigators characterized this phenomenon as due to factors released by newly recognized suppressor cells.
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. This was an early intimation of epigenetic control. (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.
III. Since coming to the College of Medicine, University of Kentucky in 1973, I have focused on teaching pathogenic microbiology to medical students and have offered elective courses in the histories of medicine and microbiology, medical ethics, & humanistic medical literature. My non-scientific publications have concerned historical, humanistic, and ethical issues relevant to medicine. A peripheral interest has been the Dept. of Medicine (1799-1859) of Lexington’s historical Transylvania University, founded in 1780. Parenthetically, the 35 papers listed below were all single-authored by me.

Positions

Present Professor, University of Kentucky College of Medicine
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Honors and Awards

  • T. Cook Smith Lecture, Innominate Club, Louisville, KY, 10 May 2012
  • Locus Grove talk, Louisville, 7 April l 2011
  • Transylvania University Honoree at the National Philanthropy Day, 10 Nov. 2010
  • Honorary Degree (Doctor of Humane Letters, honoris causa), Transylvania University, 23 May 2009


Contact Information

University of Kentucky
College of Medicine
Department of Microbiology, Immunology and Molecular Genetics
MN457 Medical Science Building
Lexington, KY 40536-0298
(859) 233-6200

Email:


Angiogenesis in Senile Dementia and Aging (9)

Cellular Immunology (14)

Priority of Discovery and Plagiarism (6)