The Albion Walter Hewlett Award (named for Professor of Medicine and Chair of the Stanford Department of Medicine 1916-1925) recognizes a role model, accomplished in discovery of the biological sciences and at the same time a consummate and compassionate physician. In introductory remarks, Dr. Stanley L. Schrier, Professor of Medicine (Hematology), the tenth recipient of the Award, indicated that the person so identified is no longer a viable model in academic medicine. The loss of this sort of person is serious because this appropriately trained physician-investigator was uniquely positioned to study pathophysiology, defined as the processes by which disordered biology produces disease. He used his own studies on the clinical manifestations of the thalassemias to clarify what he meant by pathophysiology. Thus he and his colleagues first defined membrane material properties of alpha and beta thalassemic RBC membranes and the states of hydration of alpha and beta thalassemic RBC and found them to be strikingly divergent. The biochemical counterparts of these alterations proved to be the accumulation of the excess unmatched partially oxidized globin chains on the membrane skeleton. In vitro studies with chemical oxidants selectively oxidized alpha and beta globin chains which then attached to the RBC membrane skeleton and reproduced the membrane material properties characteristic of beta and alpha thalassemia respectively. Many of these alterations had occurred prior to the reticulocyte stage so that pursuit of pathophysiology shifted to studies of marrow erythroid precursors, and it was shown that in beta thalassemia major there was accelerated programmed cell death as well as defective assembly of the membrane skeleton.
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机译:阿尔比恩·沃尔特·休利特奖(以医学教授和斯坦福大学医学系主席的名字命名(1916-1925年))认可了榜样,在发现生物科学方面取得了榜样,同时又是一位精湛而富有同情心的医师。在序言中,该奖项的第十位获得者(血液学)医学教授Stanley L. Schrier博士指出,这样确定的人已不再是学术医学的可行榜样。这种人的流失是严重的,因为这个受过适当训练的医师-研究人员在研究病理生理学方面处于独特的位置,病理生理学定义为无序生物学产生疾病的过程。他利用自己对地中海贫血的临床表现进行的研究来阐明他的病理生理学含义。因此,他和他的同事首先定义了α和β地中海贫血RBC膜的膜材料特性以及α和β地中海贫血RBC的水合状态,发现它们之间存在显着差异。这些改变的生化对应物被证明是膜骨架上过量未匹配的部分氧化的球蛋白链的积累。用化学氧化剂进行的体外研究选择性氧化了α和β球蛋白链,然后将其连接到RBC膜骨架,并分别再现了β和α地中海贫血的膜材料特性。这些改变中的许多发生在网织红细胞阶段之前,因此对病理生理学的追求转移到了对骨髓红系前体的研究,并且表明在β地中海贫血中,严重的程序性细胞死亡加速和膜骨架组装不良。
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