American Society for Bone and Mineral Research Awards

CITATION OF DR. CLAUDE D. ARNAUD FOR THE 1991 WILLIAM F. NEUMAN AWARD OF THE AMERICAN SOCIETY FOR BONE AND MINERAL RESEARCH

Dr. Claude D. Arnaud is the 1991 recipient of the William

F. Neuman Award of the American Society for Bone and Mineral Research. The award is given annually to an individual who is not only a creative scientist but also has I f m’ been responsible for training and fostering the careers of young scientists in our field. Dr. Arnaud was born in New York City. He received his B.S. degree from Columbia College in 1951 and his M.D. degree from New York Medical College in 1955. He then served 4 years in the U.S. Navy Intelligence Corps. He was captured by the Vietcong and made a daring and dangerous escape, surviving in the deep jungle for several weeks without supplies. Upon discharge, he completed his house staff training in medicine and endocrinology at Marquette University School of Medicine. In 1962, he became Howard Rasmussen’s first postdoctoral research fellow in the Department of Biochemistry at the University of Wisconsin and subsequently at the University of Pennsylvania. There, he participated in the exciting early studies on the chemistry and actions of parathyroid hormone and calcitonin. While in Philadelphia, he commuted at night to pipette assays with Berson and Yalow, and this experience allowed him subsequently to develop one of the first and most important radioimmunoassays for parathyroid hormone (PTH). In 1%7, Claude joined the research staff of the Mayo Clinic and Foundation and entered into one of the most productive periods of his scientific career. Using the abundant clinical material there, he used his new radioimmunoassay for parathyroid hormone to define the abnormalities in parathyroid function in a number of diverse diseases, including primary hyperparathyroidism, renal osteodystrophy, vitamin D-resistant rickets, oncogenic osteomalacia, benign familial hypercalcemia, and osteoporosis. Using immunochemical techniques, he provided the first data demonstrating that some factor other than PTH was the cause of malignancy-associated hypercalcemia. He also

demonstrated that part of the immunologic heterogeneity of circulating PTH was due to degradation of PTH within the parathyroid glands. In 1974, Claude transferred his appointment to the division of endocrinology as the first head of the endocrine research unit and laid the foundation for its development into an outstanding research group, a process that he would repeat again in San Francisco. In 1974, Claude left Mayo to become chief of the newly formed endocrine research unit at the Veterans Administration Hospital, University of California at San Francisco. He quickly built that unit into a world class group in bone and calcium research. In San Francisco, he continued his research on the pathogenesis of malignancy-associated hypercalcemia, working with Nissenson and Strewler. This culminated in 1987-in a virtual dead heat with the groups at Melbourne and Yale-with the identification of a new PTH-like hormone as the mediator of the syndrome. Claude also set up a system for culturing parathyroid cells and was the first to show that osteoblasts rather than osteoclasts contained PTH receptors, suggesting that the action of PTH on osteoclasts may be indirect. He also demonstrated that cultured human bone cells underwent rapid changes in shape when exposed to PTH. More recently, he has served as a leader in studies on osteoporosis and, along with Chris Cann, has organized experiments on humans during manned space shuttle flight. Recently, he has been appointed as Head of Research in Osteoporosis and Bone Biology at the University of California at San Francisco. Claude was one of the founders and was the third president of the American Society for Bone and Mineral Research. During his presidency, he played a pivotal role in the crucial reorganization that ensured the subsequent growth and preeminence of the Society. As with Bill Neuman, perhaps his most enduring contribution will be the young investigators whom he has recruited into bone and calcium research, nurtured, and helped to develop their independent research careers. Few senior investigators have given themselves so generously to the development of young investigators as Claude. Characteristically, he has removed his name from their publications and, had he not followed this practice, his own bibliography would be at least twice as large. These young scientists-Oldham, Fischer, Heath, Nissenson, Strewler, Bikle, Halloran, Karpf, and Shoback, to name only a few -are continuing to make major contributions to the field of bone and mineral research.

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CITATION OF DR. DEAN T. YAMAGUCHI FOR THE 1991 FULLER ALBRIGHT AWARD OF THE AMERICAN SOCIETY FOR BONE AND MINERAL RESEARCH

ASBMR AWARDS

of the counterbalancing, dual-control mechanism by which prostaglandins regulate bone cell metabolism. His later studies demonstrated three classes of prostaglandin receptor-effector systems in osteoblastic cells: two separate PLC-calcium-linked systems activated by distinct groups of prostaglandins and an adenylate cyclase-linked receptor shared by all prostaglandins. The results of this unique approach to prostaglandin receptor analysis based on signal transduction represent an important contribution to understanding the mechanisms of the actions of prostaglandin in all cells. In parallel, Dr. Yamaguchi undertook a series of original studies of the mechanisms of intracellular hydrogen ion regulation in osteoblasts. He first demonstrated the presence of, and fully characterized, a plasma membrane Na',H+-exchanger system regulated by changes in cell size. These findings have important implications for the mechanisms of local control of osteoblast function. He was also the first to describe a calcium-regulated plasma membrane Cl-/HCO,- exchanger in the osteoblast. Most recently, he has identified and characterized a sodium-dependent, carrier-mediated plasma membrane phosphate transport system in UMR-106-01 cells. This system was shown to be closely regulated by plasma membrane potential and may play an important role in osteoblast control of bone mineralization. His current research is focused on the mechanisms that regulate ion translocation in osteoblast-derived matrix vesicle. Dr. Yamaguchi's innovative work has opened new research areas in osteoblast physiology and signal transduction and has provided a number of important new insights into the mechanisms by which hormones and local factors regulate bone cell function. The American Society for Bone and Mineral Research has fittingly recognized his exemplary record of creative scholarship by conferring upon him the prestigious Fuller Albright award at its 1991 national meeting.

Dr. Dean T. Yamaguchi was presented the 1991 Fuller Albright Award of the American Society for Bone and Mineral Research in recognition of his outstanding contributions to the field of bone cell metabolism and intracellular ion regulation. Dr. Yamaguchi was born in Honolulu, Hawaii and received his B.A. degree from Northwestern University. He received his M.D. degree and a Ph.D. in anatomy from Tulane University, where he was elected to AOA. He served as a house officer at the Tulane University Hospitals and completed a combined UCLA-Wadsworth VA Renal Fellowship in 1984. Dr. Yamaguchi then joined the department of medicine of the UCLA School of Medicine, where he currently serves as an associate professor, is director of the membrane physiology laboratory at the Wadsworth VA Medical Center, and holds a highly prestigious VA Clinical Investigatorship Award. He is a member of the American Federation for Clinical Research, the American Physiological Society, and the American Society of Nephrology. Dr. Yamaguchi's research has focused on defining the processes that regulate transmembrane ion fluxes and intracellular ion concentrations in the osteoblast. He is widely regarded as one of the leading investigators in this field. His initial studies, which provided the first description of parathyroid hormone (PTH)-activated plasma membrane calcium channels in osteoblastic cells, characterized PTH and second-messenger regulation of separate dihydropyridine-sensitive and CAMP-dependent PTH-actiCITATION OF DR. EDUARDO SLATOPOLSKY vated plasma membrane calcium channels in UMR-106 FOR THE 1991 FREDERIC C. BAR'ITER cells. His subsequent studies in these cells defined an addiAWARD OF THE AMERICAN SOCIETY FOR tional calcium channel controlled by protein kinase C BONE AND MINERAL RESEARCH (PKC), demonstrated the existence of depolarization-activated calcium channels, and characterized a new volumeactivated calcium channel system. These studies provided Dr. Eduardo Slatopolsky is important new insights into the mechanisms by which PTH the sixth recipient of the regulates osteoblast function. Moreover, this body of work Frederic C. Bartter Award. He essentially established a new field of investigation. is the Joseph Friedman ProfesIn a subsequent series of highly innovative studies, Dr. sor of Renal Diseases in MediYamaguchi explored the mechanisms by which prostaglancine at Washington University dins regulate the osteoblast phospholipase C (PLC)-calSchool of Medicine and is a cium and adenylate cyclase signaling pathways. He demongraduate of the University of strated that the UMR-106 cell has two distinct prostaglanBuenos Aires Medical School. .+ din receptor-effector systems: (1) a PGF2,-activated PLCHe trained in nephrology at linked system associated with intracellular calcium regulaWashington University under tion and PKC activation, and (2) an adenylate cyclase systhe tutelage of Dr. Neil tem activated by PCEI. Stimulation of the adenylate cy- Bricker and has been on the faculty of that institution clase system inhibited cell proliferation, an effect shown to since 1965. During his training, Dr. Slatopolsky developed an interbe opposed by PGF2, activation of the PLC-calcium stimulatory system. Thus, he provided the first demonstration est in the pathogenesis and management of renal osteodys-

ASBMR AWARDS trophy, the arena where his scientific career has focused and one in which he has become one of the world’s leading figures. Early in his career Dr. Slatopolsky raised an antibody against parathyroid hormone that ultimately enabled him to delineate the metabolism of the peptide and its impact on the skeleton. Using this probe he observed that phosphorus retention in chronic renal failure is mirrored by the development of hyperparathyroidism and that control of phosphate ingestion and/or absorption prevents the skeletal complications of parathyroid excess in this state. These observations were accompanied by development of a radioimmunoassay for parathyroid hormone that has remained the standard by which other such assays have been judged. Dr. Slatopolsky went on to detail the metabolism of parathyroid hormone in uremia, documenting that alterations of clearance lead to the accumulation of circulating carboxyl-terminal fragments that, although nonbiologically active, may be recognized by radioimmunoassay. Dr. Slatopolsky also detailed differences in parathyroid hormone metabolism by kidney, liver, and bone and, in the last instance, studied the impact of uremia on skeletonmediated parathyroid hormone extraction. Typical of his career as an outstanding clinical investigator, these observations made in the laboratory were continuously brought by Dr. Slatopolsky to the bedside, where he showed that restriction of phosphate ingestion or absorption and/or vitamin D therapy, through control of parathyroid hormone secretion, ameliorates development of severe renal osteodystrophy . As the role of aluminum in the pathogenesis of renal osteodystrophy became apparent, Dr. Slatopolsky turned to the pathophysiology of the cation’s effect on the skelton. He showed that aluminum suppresses parathyroid hormone secretion, thereby establishing a major mechanism by which aluminum indirectly impacts on the skeleton. Dr. Slatopolsky demonstrated that the aluminum-induced bone lesion may be reversed by desferroxamine and aluminum withdrawal. Most importantly. he played a pivotal role in establishing that calcium carbonate, particularly in association with reduced dialysate calcium concen-

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trations, is an effective means of preventing uremic hyperparathyroidism, thereby reducing dependence on aluminum-containing compounds. With the continued unfolding of the pathogenetic mechanisms of renal osteodystrophy, it became apparent to Dr. Slatopolsky that vitamin D insufficiency, as well as parathyroid hormone excess, plays a pivotal role in its development. He thus detailed the metabolism of 1,25-dihydroxyvitamin D [ 1,25-(OH),D,] by normal and uremic bone. He also demonstrated that the presence of circulating 1’25(OH)& in end-stage uremia and even the anephric state represents extrarenal production of the metabolite by macrophages, which are particularly effective in uremia. Dr. Slatopolsky also established that by altering setpoint sensitivity to calcium, 1,25-(OH)1D3 directly suppresses parathyroid hormone secretion, laying the foundation for the development of steroid analogs, which he later demonstrated may control secondary hyperparathyroidism without generating hypercalcemia. In a series of critical papers, Dr. Slatopolsky documented that the noncalcemic analog of 1,25-(0H),D,, 22-oxacalcitriol, suppresses parathyroid hormone mRNA levels and secretion of the hormone. These studies open a novel avenue of treatment of uremic hyperparathyroidism with vitamin D in which hypercalcemia is not a complicating factor. He also showed that control of parathyroid hormone secretion by 1.25(OH),& may be physiologically important because eucalcemic uremic dogs develop secondary hyperparathyroidism, which in turn is prevented by administration of the steroid. This is merely a sketch of the remarkable contributions Dr. Slatopolsky has made to our discipline. He has impacted profoundly on our understanding of the pathogenesis of renal osteodystrophy and its ultimate treatment. Although his efforts at the bench have attracted international acclaim, he has never left the bedside and functions to this day as director of the Washington University Dialysis Center. He is thus a paradigm of the clinical investigator. Most importantly, he has left his mark on numerous trainees, found in universities throughout the world.

Citation of Dr. Claude D. Arnaud for the 1991 William F. Neuman Award of the American Society for Bone and Mineral Research.

American Society for Bone and Mineral Research Awards CITATION OF DR. CLAUDE D. ARNAUD FOR THE 1991 WILLIAM F. NEUMAN AWARD OF THE AMERICAN SOCIETY F...
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