Myelo-erythroid commitment after burn injury is under ß-adrenergic control via MafB regulation.

Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by ß-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (linneg Sca1+cKit+), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). ß-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB+ cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients' peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective ß1,2-adrenergic blocker) increases MEPs. Also, MafB+ cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that ß-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients.

Perturbed MafB/GATA1 axis after burn trauma bares the potential mechanism for immune suppression and anemia of critical illness.

Patients who survive initial burn injury are susceptible to nosocomial infections. Anemia of critical illness is a compounding factor in burn patients that necessitates repeated transfusions, which further increase their susceptibility to infections and sepsis. Robust host response is dependent on an adequate number and function of monocytes/macrophages and dendritic cells. In addition to impaired RBC production, burn patients are prone to depletion of dendritic cells and an increase in deactivated monocytes. In steady-state hematopoiesis, RBCs, macrophages, and dendritic cells are all generated from a common myeloid progenitor within the bone marrow. We hypothesized in a mouse model of burn injury that an increase in myeloid-specific transcription factor V-maf musculoaponeurotic fibrosarcoma oncogene homolog B at the common myeloid progenitor stage steers their lineage potential away from the megakaryocyte erythrocyte progenitor production and drives the terminal fate of common myeloid progenitors to form macrophages vs. dendritic cells, with the consequences being anemia, monocytosis, and dendritic cell deficits. Results indicate that, even though burn injury stimulated bone marrow hematopoiesis by increasing multipotential stem cell production (LinnegSca1poscKitpos), the bone marrow commitment is shifted away from the megakaryocyte erythrocyte progenitor and toward granulocyte monocyte progenitors with corresponding alterations in peripheral blood components, such as hemoglobin, hematocrit, RBCs, monocytes, and granulocytes. Furthermore, burn-induced V-maf musculoaponeurotic fibrosarcoma oncogene homolog B in common myeloid progenitors acts as a transcriptional activator of M-CSFR and a repressor of transferrin receptors, promoting macrophages and inhibiting erythroid differentiations while dictating a plasmacytoid dendritic cell phenotype. Results from small interfering RNA and gain-of-function (gfp-globin transcription factor 1 retrovirus) studies indicate that targeted interventions to restore V-maf musculoaponeurotic fibrosarcoma oncogene homolog B/globin transcription factor 1 balance can mitigate both immune imbalance and anemia of critical illness.

Occult infiltrating bi-ventricular papillary renal cell carcinoma metastasis found during coronary artery bypass graft surgery.

Metastatic papillary renal cell carcinoma (RCC) to the heart has never been reported. We report the case of a 73-year-old patient with papillary RCC metastatic to the left and right ventricles, found during a triple vessel coronary artery bypass graft surgery.

Twenty-five years of leadership: a look at trends in tenure and appointments of chairs of ophthalmology.

OBJECTIVE: To assess trends in tenure for chairs of academic departments of ophthalmology and to assess characteristics that may be correlated with longevity. DESIGN: Cross-sectional study. PARTICIPANTS: Current chairs from 136 institutions were surveyed. METHODS: Questionnaires mailed to ophthalmology chairs. MAIN OUTCOME MEASURES: Questionnaires assessed demographics along with duration of tenure for current and previous chairs. RESULTS: From 1983 through 2007, 415 individuals (404 men and 11 women) held the position of chair at the 127 responding institutions. The mean duration of tenure for chairs whose tenure included 1980 was 20.3 years, and the mean duration decreased to 14.7 years for chairs whose tenure included 2000. Mean annual turnover changed from 4.8% during the first 5 years of the study to 6.7% during the last 5 years of the study. Departments had an average of 3.3 chairs during this period, with 25 departments having 5 or more new chairs. The number of female chairs increased from 4 in 1983 to 6 in 2007. Length of tenure was not found to correlate with a department's national ranking. CONCLUSIONS: The average turnover rate for chairs of departments of ophthalmology has shown a slight upward trend over the last 25 years with a corresponding decrease in mean tenure length. Although this trend is not particularly alarming compared with those of other disciplines, academic leaders must be aware of this trend to estimate future leadership needs and to take steps to ensure tenure length does not decrease in such a way that it hinders the field.

Industrial-scale synthesis and applications of asymmetric hydrogenation catalysts.

This Account provides an overview of our activities in the area of asymmetric hydrogenation over the last 12 years. We discuss the manufacture of metal-containing precatalysts and their use in asymmetric hydrogenation processes. Many of the metal complexes have been made on a multikilogram scale for our own use and also provided to our customers. In addition, we review some of the applications that we have developed for our asymmetric hydrogenation catalysts, many of which have been operated on commercial scales. This all underlines that asymmetric hydrogenation is a mature technology that has been adopted for use in the pharmaceutical and fine-chemical industries.