Obituary

Constantine Spiro Anast

ConstantineSpiroAnast(1924-398’13

In Memory of Constantine Spiro Anast

Constantine S. Anast, Professor of Pediatrics at Harvard Medical School (1979-1987) was a world renowned pediatric endocrinologist. Early in his career, he established himself as a scholar and contributor !o the understanding of hormo- nal regulation of mineral metabo!ism especially as it relates to the skeletal system of infants and children. His pioneering investigations led to the recognition of endo- crine related bone disorders and to methods of diagnosis and treatment of a number of pediatric bone diseases. In recognition of many of these si@icsnt contributions in basic research and in clittica! medicine over the lasr three decades, he was awarded the 1987 American Society of Bone and Mineral Research Frederick C. Barter Award.

To commemorate Dr Anast’s legacy to both basic research aod thu trait-dog of a new generation of pediatric endocrinologists, the Constantine S. Anast Lecturership was established and this ‘Symposium on Bone and Mineral Metabo- limt’ was held on May 25,1988, at the Children’s Hospital, Boston, MA. This issue presents those papers contributed by his close associates during his last years and that of Dr Howard Rasmussen, a long time friend and colleague and leader in the field of calcium metabolism who was selected as the First recipient of this award, generously supported by Rarer Piiarmaceuticals. Dr Rasmussen’s paper, ‘Themes- sengerfunction of Cd’: from PTH action to smooth muscle contraction’, describes the conceptualization of the messenger role of Ca”, an area of active investigation for Dr Rasmussen over the last twenty years and is a direction which was seeded by Connie’s studies during his Fellowship in Dr Rasmussen’s laboratory. Dr E Brown’s paper details the interrelotiowhip of ‘Calcium, magnesbm and pamthyroid hor- mone secretkm’, a subject of great interest to Connie Anast. Dr Brown’s laboratory is investigating potential mechanisms by which Ca*+ and MC inhibit PTH release and his insight is shared with us in this paper. Dr T. Carpenter continued his training

in pzdiatric endocrinology as a fellow under Connie’s tutorship and developed his interest in regulation of the vitamin D synthetic pathway. Dr Carpenter reviews cal- cium and phosphoros regulation of la-hydroxylase activity and describes studies carried out in collaboration with Dr Anast examining vitamin D metabolism in mag-

nesium deficiency in his paper, ‘Minend regulation of vitamin D metaboftsm’. In his recent years in Boston, Connie has been leading a team of associates (including L. Key, M.D., F. Shapiro, M.D., J. Greenberger, M.D. and Julie Glowacki, Ph.D.) in studying osteopetrosis, evaluating etiological factors and possible therapeutic

approaches for this disorder, including the use of 1,25-dihydroxyvitamin D in high dosage. Dr Glowacki’s paper. ‘Impaireo osfeoclart differntial’on in ~hcu~~~o~c; impr0nf.s o/Donepartic/es in os~eopeiroricmruana’. descnbrs one important aspect in understanding the -nteoclast abnormality in ostopyci~osis related to the cell biolo- gy of ostcoclhst differentiation.

Corn& Anast tras bou in Chicago. ilbnois. o%\larch 23, 1924. He was :aixd ;; Chicago and attended the University of Chicago School of Medicine where his bfe- long interest in pediatric medicine began. His internship and residency in Pediatrics were at the State University of New York in Syracuse from 1948 to 1952 and his re- search career developed as a fellow with Dr Lytt Gardner from 1954 to 19% Con- nie e.tabbshed his own laboratory at the University of Missouri School of Medicine in 1956 where he remained for 23 years until coaxed by Harvard Medical School and Children’s Hospital in Bostun. Massavhusctts. to join the Division of Endocri- nology. His integration of the endoctinological aspects of mineral and bone metab- olism into the already recognized programs of orthopedic and general surgery in bone research created a new dimension for thou& investigdtions of pmbkms re- lating to the skeletal system. Many postdoctoral fcliowc trained in Connie Anmt‘s laboratory at the Unirersity of Missouri and Harvard Mcdicsl Schools are now in- dependently established.

Although Connie was an exceptionally talented clinician and teacher wittt a hroad interest in pediatric problems, his academic focus from the beginning was the hormonal aspeas of m;neral and bone metabolism. The earliest publications from the laboratory he established at the University of Missouri reported the measure- ment of scnnn levels of magnesium in new5om infants and, in collaboration with others. observations of solfate metabolism iocludiog incorporation into chick bone, transport by small intestine in rat, rabbit hod hamster and definition of its depett- dency upon protein synthesis and Na’ and Y+ transport. The publication on serum magnesium levels in infants was his first introdtiction to the homeostasis of divaknt ions which would prove to be the major focus of his sobsequent research career. Recognizing the importance of this area of research to pediatric medicine, Dr Anast. early in his academic career. spent a sabbatical leave in the laboratory with Dr Howard Rasmussen in 1964 and. with Dr Amaud, obtaitted new understanding of the interrelationships between pamthyroid hormone and vitamin D and in thr nature and mechanism of action of cakitonitt.

During the following decade in Missouri, the interrelationship between these cal- ciotropic hormones in regulating mineral and bone metabolism were strengthened by numerous basic and chemical studies and more detail of mechanisms iovulvcd were added. For example. in collaboration with his associates at the IJniv&*y of Missouri, he investigated the effect of calcitottin on the resf~nse to pamthyroid hormone and of dietary calcium on ultimobranchial and pamthyroid gland in the chicken. Later, with his Missouri associates, be continued to study the relative fail- ure of parathyroid hormone action in vitamin D-deficient animals. In clinical inves- tigations, one of his most signiticant observations on parathyroid gland function was the failure of panthyroid hormone secretion in magnesium deficiency which provided an explanation for the hypocakamia seen in patients with this metabolic

disorder. His interest and work on the interrelationship of magnesium csd c&i- tropic hormones continued until his darh and included the effects of mqnesium on calcitonin secretion and on renal 2Shydroxyvitamin I)-la-hydroxylase activity. In another series of Papers, he helped define the role of calciotropic hormrmes in calci-

um homwstasis in newhom infants. The latter studies led him to examfine the proh- lem of hypocalcemia in the newborn infant and to conclude that the hypocalcemia was not due solely to hypoparathyroidism but was in part due to lack of responsive ness tu pamthyroid hormone and, perhaps, to the increase in calcitonin levels ob- served during the first 96 hours in hypocalcemic infants of all gestational ages.

Connie’s contributions to training in pediatrics and pediatric endocrinology and to basic and clinical research in endocrinology and metabolism are attested to by the successes of his past trainees and by his many published original reports, te- views, chapters and hooks. Most impressive, however, were his love for the puh- lished word and the knowledge it imparts, his disciplined and objective thinking which he generously shared with his students and associates, his fondness for nature and music (especially Beethoven), his love of children and, above all, his love of and devotion to his wife, Fern, their iour sons and their extended families.

We would like to acknowledge contributions to these thoughts from William H. Bergstrom, M.D., Syracuse University, Julius B. Richmond, M.D., Harvard Uni- versity, Thomas W. Bums and Leonard R. Forte7 Ph.D., University of Missouri- Columbia and Harold E. Harrison. M.D., Johns Hopkins University.

John F. Crigler, M.D. Melvin J. Glimcher, M.D. Edward M. Brown, M.D. Jane B. Lian, Ph.D.