C.-E.A. Winslow and the later years of public health at Yale, 1940-1945

This paper is one of a series of papers in which I consider contemporary Yale medical education in general and the Yale Department of Epidemiology and Public Health in particular. It tells of the retirement in 1945 of C.-E.A. Winslow, Professor and Chairman of the Yale Department of Public Health since its inception in 1915; of the committees established by the dean of the School of Medicine and the president of the University, charged with determining the future direction of the department; and of the outcome, which, in 1945, proved favorable to Winslow's public health philosophy in contrast to the medical school's clinical needs and desires.     

"C.-E.A. Winslow and the early years of public health at Yale, 1915-1925"

C.-E.A. Winslow was the first chairman of the Department of Public Health at the Yale University School of Medicine. This paper considers the development and changing agenda of his department, the structure of Yale University, and the maturation of public health as a discipline. Winslow's successes and failures are discussed as they relate to Yale and external societal influences.     

Health departments in the U.S. 1920-1988: statements of mission with special reference to the role of C.-E.A. Winslow.

The mission of local health departments in the U.S. is traced from the 1920s to the present through examination of official promulgations of the American Public Health Association and other organizations. As the communicable diseases came under general control, this mission was conceived more broadly. Nevertheless, in effect their public health role was diminished due to the rapid ascendancy of private and not-for-profit medical care, which consistently sought to keep public health out of potential areas of competition. Thinking both within the public health field (as represented by C.-E.A. Winslow) and outside the public health field (as represented by the American Medical Association), had created boundaries limiting public health's role to preventive medical services. This restriction, in turn, largely excluded the public health field from participation in the tremendous expansion of medical care since World War II. The public health role was further limited in 1970 by the removal of much of environmental pollution from its purview. The sum of these and other forces has left the public health field weakened and in considerable confusion about its role at a time when the resurgence of infectious disease (e.g., AIDS and Lyme disease), environmental hazards, and medical care institutions requires a strong public health presence.     

Distinct biological activities of C3 and ADP-ribosyltransferase-deficient C3-E174Q

Low-molecular-weight GTP-binding proteins of the Rho family control the organization of the actin cytoskeleton in eukaryotic cells. Dramatic reorganization of the actin cytoskeleton is caused by the C3 exoenzyme derived from Clostridium botulinum (C3), based on ADP-ribosylation of RhoA/B/C. In addition, wild-type as well as ADP-ribosyltransferase-deficient C3-E174Q induce axonal outgrowth of primary murine hippocampal neurons and prevent growth cone collapse, indicating a non-enzymatic mode of action. In this study, we compared the effects of C3-E174Q and wild-type C3 in the murine hippocampal cell line HT22. Treatment of HT22 cells with C3 resulted in Rho ADP-ribosylation and cell rounding. The ADP-ribosyltransferase-deficient mutant C3-E174Q did not induce either Rho ADP-ribosylation or morphological changes. C3 as well as C3-E174Q treatment resulted in growth arrest, reduced expression of cyclin?D levels, and increased expression of RhoB, a negative regulator of cell-cycle progression. Serum starvation induced apoptosis in HT22 cells, as determined on the basis of increased expression of caspase-9 and Bax. C3 but not C3-E174Q protected serum-starved HT22 cells from apoptosis. This is the first study separating ADP-ribosyltransferase-dependent from ADP-ribosyltransferase-independent effects of C3. While morphological changes and anti-apoptotic activity strictly depend on ADP-ribosyltransferase activity, the anti-proliferative effects are independent of ADP-ribosyltransferase activity.