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PubMed2001

2001 Torald Sollmann Award lecture. Looking toward the future, using lessons from the past.

It is a privilege and honor to be selected by the American Society of Pharmacology and Experimental Therapeutics for the Torald Sollmann Award. I wish to take this opportunity to comment on my experiences over the last 40 plus years as both a student and a faculty member. I was trained in pharmacology as well as medicine with the goal of entering an academic career that would permit me to engage in teaching and research. The subject of my presentation focuses on the events that helped to shape my career. Attention is given to those who made it possible for me to advance in my learning, teaching, and research. In addition to having been taught by excellent instructors, I have benefitted from having many outstanding undergraduate and graduate students, as well as postdoctoral fellows, without whom much of what I feel I have accomplished would not have been possible. Being surrounded by a supportive environment and accompanied by bright and eager young students gives me reason to look toward the future with enthusiasm. I chose to take the time and space allotted to me to present a brief overview of where I have been and how many individuals played important roles in helping to achieve my goals. In essence, this composition is a tribute to my family, professional associates, and current and former students.

Adrenergic beta-Antagonists↗
PubMed2001

The Jeremiah Metzger Lecture. Hypercoagulable states: challenges and opportunities.

Thromboregulatory physiology is essentially a function of the blood vessel wall. Constitutive endothelial cell activities maintain blood fluidity by down regulating the initiation as well as, the propagation of blood coagulation. The major systems involved include: the Protein C, TFPI, plasmin generating and antithrombin pathways, all of which are focused on the cell membrane. Altered regulation of these endothelial functions forms the basis of the pathophysiologic events associated with the inherited primary hypercoagulable states. Secondary hypercoagulable syndromes occurring in various clinical states with conversion to a vascular thrombogenic phenotype reflect non constitutive activated endothelial cell functions with concomitant down regulation of the constitutive anticoagulant surface activity. So called idiopathic clinical thrombosis in most circumstances represents multi hit events in which specific genetic abnormalities or polymorphisms together with specific acquired alterations in geographically distinct endothelial cell beds culminate in a recognizable coagulation phenotype.

Animals↗
PubMed2001

The Gordon Wilson Lecture: viruses and human disease.

In many ways, Ebola virus infection provides a model for understanding the toxicity of viruses and their causal role in human disease. The highly aggressive course of Ebola virus infection provides a model for understanding the molecular mechanisms of viral cytotoxicity. In addition, the use of animal models and definition of immune correlates, which lead to protection, may provide lessons that are applicable to other viral infections. Perhaps the greatest challenge facing biomedical science today is the containment of the human immunodeficiency virus, the causative agent of AIDS. In many ways the critical obstacles to the development of a vaccine for HIV are similar to those observed with Ebola virus infection. Because the reservoir of infection is not known and human-to-human spread has been documented, vaccines may provide the best opportunity to contain and limit the spread of infection worldwide. Similar to Ebola virus, there are few convincing examples of immune resistance of HIV infection. In addition, it has been difficult to identify broadly neutralizing antibodies that can prevent infection in vitro or in vivo. In defining immune correlates, relevant animal models, and mechanisms of cytotoxicity, it is hoped that similar efforts may lead to effective vaccines for other infectious diseases. In this way, Ebola virus infection provides a useful paradigm for understanding the genetic determinants of viral disease and in facilitating the development of treatments and prevention of viral infections.

Animals↗