Ernest Beutler was one of the preeminent haematologists of the last half of the 20th and the early 21st century. In a career that spanned six decades, his research interests included such diverse areas as red cell metabolism, blood preservation, glycolipid storage diseases, leukaemias and iron metabolism. Indeed, he was quite different from most of his contemporaries in that his knowledge encompassed not only haematology and not only the medical sciences, but the biological sciences as a whole. He was among the first to describe X chromosome inactivation, and he established the critical link between glucose-6-phosphate dehydrogenase deficiency and drug-induced haemolysis. He was a skilled and innovative clinician, and an early advocate of bone marrow transplantation for the treatment of acute leukaemia. He was a prolific author, with over 800 publications; a long time member of the Editorial Board of Blood; founder of the journal Blood Cells Molecules and Diseases; and an editor of Williams Haematology from the time of its inception. He bequeathed $1 million to the American Society of Haematology to recognise and reward outstanding basic research and its clinical application: a pursuit to which he had committed his life. Indeed, he became an extraordinary exemplar of the bench-to-bedside ethos, which holds that even today, an MD researcher, working with limited means and independent of pharmaceutical companies, can have a great impact on the practice of medicine.
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http://dx.doi.org/10.1111/j.1365-2141.2010.08542.x | DOI Listing |
Br J Haematol
November 2009
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hepcidin, the master regulator of enteric iron absorption, is controlled by the opposing effects of pathways activated in response to iron excess or iron attenuation. Iron excess is regulated through a pathway involving the cell surface receptor hemojuvelin (HFE2) that stimulates expression of the hepcidin encoding gene (HAMP). Iron attenuation is countered through a pathway involving the hepatocyte-specific plasma membrane protease matriptase-2 encoded by TMPRSS6, leading to suppression of HAMP expression.
View Article and Find Full Text PDFAnnu Rev Genomics Hum Genet
October 2009
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Genetic testing holds great promise as a screening tool to identify persons at risk for a disease at the presymptomatic stage. However, the complexities of gene-disease associations, even in single-gene diseases, pose important challenges. These challenges include defining the role of screening for mutations that have low penetrance, which cause disease in only a minority of patients with the genotype.
View Article and Find Full Text PDFAnnu Rev Pathol
May 2009
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hepcidin, a 25-amino-acid antimicrobial peptide, is the central regulator of iron homeostasis. Hepcidin transcription is upregulated by inflammatory cytokines, iron, and bone morphogenetic proteins and is downregulated by iron deficiency, ineffective erythropoiesis, and hypoxia. The iron transporter ferroportin is the cognate receptor of hepcidin and is destroyed as a result of interaction with the peptide.
View Article and Find Full Text PDFBlood Cells Mol Dis
August 2009
Department of Epidemiology, University of North Carolina at Chapel Hill, CB#7435, 2106 McGavran-Greenberg Hall, Chapel Hill, NC 27599-7435, USA.
Glucose-6-phosphate deficiency is the most prevalent enzyme deficiency, with an estimated 400 million people affected worldwide. This inherited deficiency causes neonatal hyperbilirubinemia and chronic hemolytic anemia. Although most affected individuals are asymptomatic, exposure to oxidative stressors such as certain drugs or infection, can elicit acute hemolysis.
View Article and Find Full Text PDFBlood
January 2009
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hepcidin plays a major role in the regulation of iron homeostasis. Several bone morphogenetic proteins (BMPs) are strong inducers of hepcidin (Hamp1, HAMP) expression. Hemojuvelin, a protein critical for maintaining appropriate levels of hepcidin, acts as a coreceptor for BMP2 and BMP4, thereby providing a link between iron homeostasis and the BMP-signaling pathway.
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