U.S. Physician-Scientist Workforce in the 21st Century: Recommendations to Attract and Sustain the Pipeline.

The U.S. physician-scientist (PS) workforce is invaluable to the nation's biomedical research effort.

Career outcomes of the graduates of the American Board of Internal Medicine Research Pathway, 1995-2007.

Purpose: In 1995, the American Board of Internal Medicine (ABIM) formalized an integrated residency curriculum including both clinical and research training (the Research Pathway), designed to develop careers of physician-scientists. Individuals who completed Pathway training between 1995 and 2007 were surveyed to determine the extent to which graduates established research-oriented careers.

Method: In 2012, the authors used a Web-based, 56-question, multiple-choice electronic survey of 813 participants in Research Pathway programs who completed their residency training between the years of 1995 and 2007.

Mary Allen Engle Award: The glue of life--a career retrospective.

The author was privileged to be an early contributor to the concept that cell adhesion molecules, the leukocyte (β2) integrins, play a pivotal role in the acute inflammatory process. For the author, this began with the development of a monoclonal antibody (anti-Mo1) that identified a differentiation antigen on the surface of human myeloid cells (including neutrophils, monocytes, and natural killer (NK) cells). Serendipitously, it was discovered that the Mo1 antigen was the heterodimeric glycoprotein (gp155,95) absent from the surface of neutrophils isolated from patients with adhesion defects in vitro and a syndrome characterized by chronic, life-threatening infections in vivo (a syndrome now termed leukocyte adhesion deficiency, type 1) (LAD-1).

Pericellular proteolysis by leukocytes and tumor cells on substrates: focal activation and the role of urokinase-type plasminogen activator.

Previous studies have shown that the urokinase-type plasminogen activator receptor (uPAR) is localized to the adherence sites of leukocytes and tumor cells suggesting that pericellular proteolysis may accompany focal activation of adherence. To assess for focused pericellular proteolytic activity, we prepared two-dimensional substrates coated with FITC-casein or Bodipy FL-BSA. These molecules are poorly fluorescent, but become highly fluorescent after proteolytic degradation.

Subspeciality training in hematology and oncology, 2003: results of a survey of training program directors conducted by the American Society of Hematology.

A survey of directors of adult and pediatric hematology/oncology subspecialty training programs in the United States and Canada was conducted to assess the environment in which recruitment and training is conducted in these medical disciplines. A total of 107 program directors responded to the survey, representing 66% of internal medicine and 47% of pediatric subspecialty programs in hematology or hematology/oncology. Specific areas covered in the web-based questionnaire included the type and demographics of the training program, profile of the training program director, characteristics of the applicant pool and existing trainee recruits, characteristics of the training program environment and curricula, research productivity of trainees, and the career pathways taken by recent training program graduates (including dominant areas of clinical interest).

Human RPE cell lysis of extracellular matrix: functional urokinase plasminogen activator receptor (uPAR), collagenase and elastase.

Age-related macular degeneration (ARMD), proliferative vitreoretinopathy (PVR) and uveitis are characterized by RPE motility through the ECM of retinal lesions. The purpose of this study was to test the hypothesis that multiple proteolytic systems are functionally intact at the HRPE surface and peri-cellular region and that these activities are differentially modulated by IL-1beta. HRPE cells were evaluated: (1).

Binding of urokinase-type plasminogen activator receptor (uPAR) to the mannose 6-phosphate/insulin-like growth factor II receptor: contrasting interactions of full-length and soluble forms of uPAR.

Urokinase-type plasminogen activator receptor (uPAR) binding by the mannose 6-phosphate/insulin-like growth factor II receptor (Man-6-P/IGF2R) is considered important to Man-6-P/IGF2R tumor suppressor function via regulation of cell surface proteolytic activity. Our goal was to map the uPAR binding site of the Man-6-P/IGF2R by analyzing the uPAR binding characteristics of a panel of minireceptors containing different regions of the Man-6-P/IGF2R extracytoplasmic domain. Coimmunoprecipitation assays revealed that soluble recombinant uPAR (suPAR) bound the Man-6-P/IGF2R at two distinct sites, one localized to the amino-terminal end of the Man-6-P/IGF2R extracytoplasmic domain (repeats 1-3) and the other to the more carboxyl-terminal end (repeats 7-9).

Function of the lectin domain of Mac-1/complement receptor type 3 (CD11b/CD18) in regulating neutrophil adhesion.

A lectin function within CD11b mediates both cytotoxic priming of Mac-1/complement receptor type 3 (CR3) by beta-glucan and the formation of transmembrane signaling complexes with GPI-anchored glycoproteins such as CD16b (FcgammaRIIIb). A requirement for GPI-anchored urokinase plasminogen activator receptor (uPAR; CD87) in neutrophil adhesion and diapedesis has been demonstrated with uPAR-knockout mice. In this study, neutrophil activation conditions generating high-affinity (H-AFN) or low-affinity (L-AFN) beta(2) integrin adhesion were explored.

Interactions of integrins with their partner proteins in leukocyte membranes.

Integrins participate in many aspects of immunologic and inflammatory responses, especially those involving cell migration, adherence, and activation. Although leukocyte integrins such as complement receptor type 3 (CR3) are known to carry out certain functions without the intervention of other plasma membrane receptors, many plasma membrane proteins are now known to physically interact and functionally cooperate with integrins. Several of these interactions are highly dynamic within cell membranes; thus integrin-partner protein interactions change during certain physiological processes.

Hematology Grants Workshop-2000.

This year the Hematology Grants Workshop, chaired by Dr. Robert Todd, includes a comprehensive listing of available NIH, VA, and non-federal grants applicable to fellows and junior faculty as well as to established investigators. In Section II, Dr.