George Constantin Cotzias, June 16, 1918June 13, 1977 | By Vincent P. Dole | Biographical Memoirs
George Constantin Cotzias
June 16, 1918 June
By Vincent P. Dole
GEORGE CONSTANTIN COTZIAS was
born in the city of Chania on the island of
Crete, the eldest child of Constantin and Catherine Stroumboli Cotzias
and the grandson of George J. Cotzias, a wealthy merchant in Athens. His
father, Constantin George Cotzias, a lawyer and journalist, had recently
been banished from Athens because of political activity in support of
the king. He was arrested by the fascist government of Eleftherios
Venizelos and exiled to Crete to limit his political influence, but he
was able to return to Athens eighteen months later. Soon after returning
he established an influential newspaper and an advertising agency.
Twelve years later, in 1932, he became president of the Greek chamber of
commerce and in 1934 was elected mayor of Athens.
As mayor and later in the expanded role of
governmental minister for all municipal activities in the region of
Greater Athens, Constantin Cotzias shaped the political structure of the
modern city of Athens. He reorganized its government, initiated programs
of health and public works, rebuilt the municipal hospital, paved roads,
created parks, supported young artists, and established a new municipal
This productive period was
terminated abruptly by the invasion of Greece in 1940. After an intense
but brief resistance, the Greek armies were defeated. The prime
minister, Alexandros Koryzis, refusing to acknowledge defeat and
collaborate, committed suicide. In this extremity, King George of Greece
asked Constantin Cotzias to go to the United States as
ambassador-at-large representing the Greek government in exile.
George and his family arrived in New York in August
1941, financially destitute after a desperate four-month journey through
warring countries. They remained in New York until the defeat of the
Axis powers in 1945 made it possible for his parents to return. To
complete this account, Constantin Cotzias was reelected mayor of Athens
by an overwhelming majority in the first postwar election (1951), but he
died shortly afterwards of a heart attack at the age of fifty-nine while
resuming his municipal duties. Cotzias Square, next to the town hall of
the city of Athens, bears his name.
As the eldest
son of a leading citizen of Athens prior to these events, George Cotzias
had a privileged early life, attending the best schools and associating
with the most stimulating intellectuals of the city. Reflecting George's
mother's interest in literature, the Cotzias home was a meeting place
for leading writers of prewar Athens and, of course, as the mayor's
residence, it was at the epicenter of public policy.
At the age of twenty-two, within one year of
graduating from medical school, George apparently was on his way to an
uneventful career as a medical practitioner in Athens, specializing in
surgery. He had become an assistant to the professor of surgery,
Xenophon Kondiades. However, the invasion of Greece changed all plans.
George immediately volunteered for military service, although as a
medical student he was exempt from the draft. At the request of
Professor Kondiades, heading a surgical team at a hospital close to the
Albanian front, he was assigned to this unit, but while he was in
transit the hospital was obliterated by bombing, which killed the entire
staff. Military resistance collapsed before the advancing German army.
George made his way back to Athens, rejoined his family, and left Greece
After arriving in New York in 1942,
George applied for admission to medical school to complete his studies.
The rejection by Cornell was unequivocal; not only was he found to be
deficient in English, he was told that his education in Athens had
provided inadequate training in basic biochemistry, pharmacology, and
physiology. He would need further premedical training even to be
eligible for admission to the first year of medical school. Applications
to Columbia, New York University, Johns Hopkins, and Pennsylvania were
Reminiscing in later years,
George recalled critical advice that his father gave him at this low
point. "When I ran for the office of councilman, I was defeated. So I
ran for mayor and was elected. Choose the leading medical school in the
country and apply there." With this advice George applied to Harvard
Medical School and had the good fortune to be interviewed by Soma Weiss,
a brilliant professor of medicine and himself a refugee a decade earlier
from Nazi oppression. After a long conversation in German, which George
spoke fluently, Weiss recommended that he be admitted conditionally to
the third year of study at the medical school. Two years later he
graduated from Harvard cum laude. He then trained as an intern in
pathology at Brigham Hospital, as an intern in medicine at Massachusetts
General Hospital, and was a resident in neurology at Massachusetts
This brings the story to the
point at which I first knew George Cotzias. During the four years of
World War II, it was my good fortune to be assigned to a naval medical
research unit based at the hospital of Rockefeller Institute (now
Rockefeller University) and to work in the department of D. D. Van
Slyke. With the end of the war and demobilization, I left Rockefeller
and returned to Massachusetts General Hospital, where five years earlier
I had trained in medicine. Shortly afterward to my great surprise and
delight, the director of the Rockefeller Hospital, Thomas Rivers,
invited me to return to Rockefeller. He asked me to form a new
department, replacing that of Van Slyke, who planned to move to
Brookhaven National Laboratory the following year.
My first act was to invite Lewis Dahl to join me;
Dahl, a scholarly physician and friend, who was completing a tour as
senior medical resident at Massachusetts General Hospital, agreed.
Within the hour George burst into my office and announced explosively,
"I'm coming, too." This unusual application could have been
counterproductive, but fortunately Dahl had worked with Cotzias and gave
him an enthusiastic endorsement. Immediately I had two talented
associates with whom to start the department, the only difficulty being
there was no space for the new laboratory immediately available at
Rockefeller. At Rivers's suggestion, my two associates were assigned to
Van Slyke's group during his final year (an invaluable experience for
them), and I started my new career as department head with a year's
sabbatical in Europe.
The five years after my
return were busy ones. We studied hypertensive patients, looking for
clues to the nature of this disorder in disturbances of salt metabolism
and energy balance. George, in addition to loyal work as a team member
in the clinical studies, became interested in the metabolism of amines
in the tissues. He reasoned that catecholamines, diamines, and histamine
have powerful vasomotor effects that might be relevant to hypertensive
disorders. In particular, he directed his attention to the enzymes that
limit their biological activity by oxidizing them.
George thus initiated studies that led him some
fifteen years later to the demonstration that l-DOPA (the amino acid
l-dihydroxy phenylalanine) was effective in giving symptomatic relief to
patients with disabling Parkinsonism. The most important of these
studies were conducted after he left my department in 1954. Dahl left at
the same time, both having outgrown the limited opportunities for
advancement at Rockefeller. They transferred their work to Brookhaven
National Laboratory, where Van Slyke meanwhile had established a strong
medical division and was able to provide space and support for each to
develop an active, independent laboratory.
move to Brookhaven also provided George with a new resource for
metabolic studies, namely a cyclotron. When activated by a beam of
high-energy neutrons, trace metals in samples of tissue and blood can be
determined with unprecedented sensitivity and specificity. George seized
the opportunity. In a series of basic studies over the following decade,
he elucidated the distribution, absorption, elimination kinetics, and
probable function of manganese. At the same time he became interested in
its toxicity, manifest especially in the neurological symptoms of
Chilean miners excavating manganese ore. As a neurologist he was
impressed by the similarity of the symptoms to those of classical
Parkinson's disease (rigidity, retardation of motion, tremors, lack of
coordination), and as a pathologist he was attracted by the opportunity
to correlate specific structural lesions made by a known toxin to
disturbances of brain function. In both disorders the main lesions found
in the brain involve the substantia nigra, a region made conspicuous by
a deposit of dark melanin pigment. It was known that this region of the
brain is rich in the neurotransmitter dopamine and also that both
melanin and dopamine are derived from common precursors. Further, it was
known that this region is deficient in both substances in patients with
A possible remedy, as was
evident to several investigators at the time, is to increase the supply
of dopamine to the neurones in this region. However, dopamine
administered as a medication (orally or by injection) cannot reach the
site in significant concentration because it does not pass the
blood-brain barrier. As an alternative, one can look for precursors of
dopamine that are not excluded by the barrier, administer them in large
doses, and hope that when the molecules arrive at the critical site
enough will be converted into dopamine to have a therapeutic effect.
Other investigators had pursued this idea with little success, although
the validity of the approach was shown by the transient benefit seen
after injection of the precursor, dihydroxy-phenylalanine (DOPA). But
this effect was only of theoretical interest. It was not of practical
value as a treatment because of the severe toxicity associated with the
Cotzias, at this point, made a critical
observation that converted the transient response into a successful,
large-scale treatment. By starting with very small doses of DOPA, given
orally every two hours under continued observation, and gradually
increasing the dose over a period of several weeks as permitted by the
development of tolerance, he was able to stabilize patients on large
enough doses to cause a dramatic remission of their symptoms. He further
improved the treatment by utilizing the active isomer, l-DOPA,
recognizing that the inactive isomer, d-DOPA (which constitutes 50
percent of the dose in a racemic mixture) is responsible for 50 percent
of the toxicity but contributes nothing to the therapeutic result.
The result was soon confirmed by other investigators
and has now become the standard treatment for Parkinsonian symptoms. To
his credit, Cotzias realized that this success was only one step toward
a definitive treatment. After having a remission, many patients show a
disturbing tendency to relapse, even with continued treatment, or to
develop movement disorders. He therefore was engaged during the last
decade of his life in testing supplementary treatments, especially those
utilizing structural analogs of dopamine (like apomorphine) that could
penetrate the blood-brain barrier and substitute for dopamine without
having to be converted by local enzymes. By a remarkable coincidence,
his early interest in the function of bioactive amines in tissues and
his subsequent investigations of the toxicity of manganese converged on
this problem. Cotzias was at work on the development of new medications
when his career was terminated by lung cancer. Like his father, he died
at age fifty-nine, before his work was finished.
George was a large man physically and
intellectually--restless, fiercely loyal, informed, intuitive, quick in
conversation with an infectious laugh that began as a furtive chuckle
and grew into a roar. Basically he remained the intense young medical
resident who burst into my office in 1946 announcing, "I'm coming, too."
He is survived by his widow, Betty, and a son, Constantin George
Among the honors and awards received by
George Cotzias were election to the National Academy of Sciences (1973),
election to the American Academy of Arts and Sciences (1970), the A.
Cressy Morrison Award in Natural Sciences (1954), the Albert Lasker
Award in Clinical Medical Research (1969), the Borden Award of the
Association of American Medical Colleges (1972), and the annual award of
the American College of Physicians (1974). He received honorary degrees
from Catholic University, Santiago (1969); Women's Medical College of
Pennsylvania (1970); St. John's University, New York (1971); and the
National University, Athens (1974).
- With W. H. Sweet, J. Seed, and P.
Yakovlev. Gastrointestinal hemorrhages, hyperglycemia, azotemia,
hyperchloremia and hypermatremia following lesions of the frontal lobe
in man. In The Frontal Lobes, ed. J. F. Fulton, C. D. Aring, and
S. B. Wortis, vol. 27, pp. 795-822. Baltimore: Williams & Wilkins.
- With G. I. Lavin and D. D. Van Slyke. Observations on
normal and pathologic kidney tissue with ultraviolet photomicrography.
Acta Med. Scand. (Suppl.) 196:259.
- With J. H. Baxter. Effects of
proteinuria on the kidney. Proteinuria, renal enlargement and renal
injury consequent on protracted parenteral administration of protein
solution in rats. J. Exp. Med. 89:643-67.
- With V. P. Dole, L. K. Dahl, H. A.
Eder, and M. E. Krebs. Dietary treatment of hypertension. Clinical and
metabolic studies of patients on the rice-fruit diet. J. Clin.
- With V. P. Dole, L. K. Dahl, D. D. Dziewiatkowski, and C.
Harris. Dietary treatment of hypertension. II. Sodium depletion as
related to the therapeutic effect. J. Clin. Invest. 30:584-95.
- With V. P. Dole. A nomogram for the calculation of
relative centrifugal force. Science 113:552-53.
- With V. P. Dole. Metabolism of amines. I. Microdetermination
of monoamine oxidase in tissues. J. Biol. Chem. 190:665-72.
- With V. P. Dole. Metabolism of amines. II. Mitochondrial
localization of monoamine oxidase. Proc. Soc. Exp. Biol. Med.
- With V.
P. Dole. The activity of histaminase in tissues. J. Biol. Chem.
- Monoamine oxidase: substrates and
inhibitors. In Transactions of the Second Conference on Shock and
Circulatory Homeostasis, ed. H. D. Green. New York: Josiah Macy,
- With V. P. Dole, L. K. Dahl, I. L. Schwartz, J. H. Thaysen,
and C. Harris. Dietary treatment of hypertension. III. The effects of
protein on appetite and weight. J. Clin. Invest. 32:185-91.
- With L. K. Dahl and B.
G. Stall III. Metabolic effects of marked sodium restriction on
hypertensive patients; changes in the total exchangeable sodium and
potassium. J. Clin. Invest. 33:1397-1406.
- With H.
A. Eder, H. D. Lauson, F. P. Chinard, R. Greif, and D. D. Van Slyke. A
study of the mechanisms of edema formation in patients with the
nephrotic syndrome. J. Clin. Invest. 33:636-56.
- With I. Serlin and J. J. Greenough. Preparation of soluble
monoamine oxidase. Science 120:144-45.
- With L. S. Maynard. The partition of
manganese among organs and intracellular organelles of the rat. J.
Biol. Chem. 214:489-95.
- With I. Serlin.
Microdiffusion of acetic acid as an assay for acetylcholinesterase.
J. Biol. Chem. 215:263-68.
- With L. S. Maynard.
The study of certain phases of cell dynamic states with short lived
isotopes as exemplified by Mn56 partition studies in organs
and intracellular organelles. In Proceedings of the International
Conference on Peaceful Uses of Atomic Energy, vol 12, pp. 444-46.
Geneva: United Nations.
- With L. K. Dahl and B. G. Stall.
Metabolic effects of marked sodium restriction in hypertensive patients.
Skin electrolyte losses. J. Clin. Invest. 34:462-70.
- With I. Serlin. State
of tissue acetylcholinesterase as determined by Cobalt60
gamma radiation inactivation. Radiat. Res. 6:55-66.
- With J. J. Greenough.
Concomitant analysis for oxygen uptake and ammonia evolution during the
monoamine oxidase reaction. Arch. Biochem. Biophys. 75:15-23.
- With J. J. Greenough. Specificity of the manganese pathway
through the body. J. Clin. Invest. 37:1298-1305.
- With D. C. Borg. Manganese metabolism in man: rapid exchange
of Mn56 with tissue as demonstrated by blood clearance and
liver uptake. J. Clin. Invest. 37:1269-78.
- Manganese in health and disease. Physiol. Rev.
- With A. J. Bertinchamps. Dosimetry of
radioisotopes. Science 128:988-90.
- With D. C.
Borg. Incorporation of manganese into erythrocytes as evidence for a
manganese porphyrin in man. Nature 182:1677-78.
- With A. J. Bertinchamps
and J. J. Greenough. Thirst for bile in rats with bile fistulas.
- With J. J. Greenough.
Quantitative estimation of amineoxidase. Nature 183:1732-33.
- Diagnostic uses of radioisotopes. Symposium and panel
discussion on the uses of radioisotopes in clinical practice. NY
State J. Med. 59:18.
- With J. J. Greenough. Dependence of periodic activation and
inhibition of monoaminoxidase by aliphatic compounds upon chain-length.
- Metabolic relations of
manganese to other minerals. Symposium on Interactions of Mineral
Elements in Nutrition and Metabolism. Fed. Proc. 19:655-58.
- With D. C. Borg and A. J. Bertinchamps. Clinical experience
with manganese. In Metal-Binding in Medicine, ed. M. J. Seven and
L. A. Johnson, pp. 50-58. Philadelphia: Lippincott.
- Manganese versus magnesium: Why are
they so similar in vitro and so different in vivo? Fed.
Proc. pt. II, suppl. 10, 20:98-103.
- With P. S.
Papavasiliou. Neutron activation analysis: the determination of
manganese. J. Biol. Chem. 236:2365-69.
- With D. C.
Borg and B. Selleck. Specificity of the zinc pathway in the rabbit:
zinc-cadmium exchange. Am. J. Physiol. 201:63-66.
- With D. C. Borg and B. Selleck. Virtual absence of turnover
in cadmium metabolism: Cd109 studies in the mouse. Am. J.
- With D. C. Borg, A. J.
Bertinchamps, E. R. Hughes, and P. S. Papavasiliou. Nuclear studies in
medicine: manganese metabolism. In Symposium Nuklear under
Klinike (with special reference to cancer and cardiovascular
diseases) Wissenschaftliche abhandlungen der arbeitsgemeinschaft fur
forschung des landes nordrheinwestfalen, ed. L. E. Farr, et al., vol 18,
pp. 49-58. Koln: Westdeuchen Verlag.
- With D. C. Borg, E.
R. Hughes, A. J. Bertinchamps, and P. S. Papavasiliou. Phenothiazine:
curative or causative in regard to Parkinsonism? In Symposium on the
Extrapyramidal System and Neuroleptics, ed. J-M. Bordeleau, vol. 20,
pp. 193-98. Montreal: University of Montreal.
- With E. R.
Hughes. Adrenocorticosteroid hormones and manganese metabolism. Am.
J. Physiol. 201:1061-64.
- With G. C. Borg and B. Selleck. Specificity of the zinc
pathway through the body: the turnover of Zn65 in the mouse.
Am. J. Physiol. 202:359-63.
- With E. R. Hughes and
E. P. Cronkite. Total body irradiation and manganese metabolism.
- With D. C. Borg. Interaction
of trace metals with phenothiazine drug derivatives. I.
Structure-reactivity correlations. II. Formation of free radicals. III.
Theoretical part. Proc. Natl. Acad. Sci. U.S.A. 48:617-42.
- With P. S. Papavasiliou. State of binding of natural
manganese in human cerebrospinal fluid, blood and plasma. Nature
- Manganese. In Mineral Metabolism: An
Advanced Treatise, ed. C. L. Comar and F. Bronner, vol. II, pt. B,
pp. 403-42. New York: Academic Press.
- With D. C. Borg.
Phenothiazines and manganese. In Ultrastructure and Metabolism of the
Nervous System, ed. S. R. Korey, A. Pope, and E. Robins, vol. XL, p.
337. Baltimore: Williams & Wilkins.
- With P. S. Papavasiliou and S. T.
Miller. Neutron activation analysis: clinical and biological studies of
manganese. In Third Colloque International de Biologie de Saclay,
metals: essential or detrimental to life? Brookhaven Lecture Series,
vol. 26, pp. 1-14.
- With M. H. Van Woert. Manganese
poisoning--new insights. Lima, Peru. Oct. 1963. Revista de
Neuro-Psiquiatria, pp. 392-404.
- With P. S.
Papavasiliou. Primordial homeostasis in a mammal as shown by the control
of manganese. Nature 201:828-29.
- With B. M.
Patten, A. Sakamoto, M. H. Van Woert, and P. S. Papavasiliou. Tremorine
induced tremor versus extrapyramidal disease. Nature 201:929-30.
- With P. S. Papavasiliou and S. T. Miller. Manganese in
melanin. Nature 201:1228-29.
- With P. S.
Papavasiliou. The specificity of the zinc pathway through the body:
homeostatic considerations. Am. J. Physiol. 206:787-92.
- With P. S. Papavasiliou, M. H. Van Woert, and A. Sakamoto.
Melanogenesis and extrapyramidal diseases. Fed. Proc. 23:713-18.
- Der Manganmetabolismus und seine Storungen.
Verhandlungen der Deutschen Gesellschaft fur innere Medizin, 70:327-30.
German Society of Internal Medicine, Wiesbaden.
- Transport, homeostasis and specificity in trace metal
metabolism. In Proceedings of the Sixth International Congress of
Nutrition, pp. 252-69. Edinburgh: E. & S. Livingstone.
- With K. N. Prasad and
H. A. Johnson. A cytoplasmic organelle of melanocytes. Nature
- With K. N. Prasad. A nomogram for the
estimation of microcuries and millimicrograms from cpm. J. Nucl.
- With E. Homsher. Antidiuretic hormone
and bile flow. Nature 208:687-88.
- With M. H. Van
Woert. Possible roles of melanin in some extrapyramidal functions. In
Monographs Biology and Medicine, p. 95. New York: Grunne &
- With M. H. Van Woert and A. R. Nicholson.
Functional similarities between the cytoplasmic organelles of
melanocytes and the mitochondria of hepatocytes. Nature
- Manganese, melanins and the extrapyramidal system. J.
- With M. H. Van Woert. Anion
inhibition of monoamine oxidase. Biochem. Pharmacol. 15:275-85.
- With S. T. Miller and J. Edwards. Neutron activation
analysis: the stability of manganese concentrations in human blood and
plasma. J. Lab. Clin. Med. 67:836-49.
- With A. A.
Britton. Dependence of manganese turnover on intake. Am. J.
- With E. R. Hughes and S. T.
Miller. Tissue concentrations of manganese and adrenal function. Am.
J. Physiol. 211:207-10.
- With P. S. Papavasiliou and
S. T. Miller. Role of the liver in regulating distribution and excretion
of manganese. Am. J. Physiol. 211:211-16.
- With A.
J. Bertinchamps and S. T. Miller. Interdependence of routes excreting
manganese. Am. J. Physiol. 211:217-24.
- Manganese in biological system. In
Encyclopedia of Biochemistry, ed. R. J. Williams and E. M.
Lansford, Jr., p. 506. New York: Reinhold.
- With M. H.
Van Woert and L. Schiffer. Aromatic amino acids and modification of
Parkinsonism. N. Engl. J. Med. 276:374-79.
I. Mena, O. Marin, and S. Fuenzalida. Chronic manganese poisoning:
clinical picture and manganese turnover. Neurology 17:128-36.
- With M. H. Van Woert and A. Nicholson. Mitochondrial
functions of polymelanosomes. Comp. Biochem. Physiol. 22:477-85.
- With A. C. Foradori, A. Bertinchamps, and J. M. Gulibon.
The discrimination between magnesium and manganese by serum proteins.
J. Gen. Physiol. 50:2255.
- Importance of trace
substance in environmental health as exemplified by manganese. Paper
presented at the First Annual Conference on Trace Substances in
Environmental Health, University of Missouri, Columbia.
- Dopa and Parkinsonism (Letter to the Editor) Br. Med.
- With P. S. Papavasiliou. Therapeutic
studies of Parkinsonian patients: long-term effects of D-L and L-dopa.
In Progress in Neuro-Genetics, ed. A. Barbeau, and J-R. Brunette,
pp. 357-65. Amsterdam: Excerpta Medica Foundation.
- With P. S. Papavasiliou, E. R. Hughes,
L. Tang, and D. C. Borg. Slow turnover of manganese in active rheumatoid
arthritis accelerated by prednisone. J. Clin. Invest.
- With K. Horiuchi, S. Fuenzalida, and I.
Mena. Chronic manganese poisoning: clearance of tissue manganese burdens
with persistence of the neurological picture. Neurology
- With A. C. Foradori. Trace metal metabolism.
In The Biological Basis of Medicine, ed. E. E. and N. Bittar,
vol. 1, chap. 3, pp. 105-21. New York: Academic Press.
- L-dopa for Parkinsonism. N. Engl. J. Med. 278-630.
- With P. S. Papavasiliou, R. Gellene, and R. B. Aronson.
Parkinsonism and dopa. Trans. Assoc. Am. Physicians 81:171-83.
- With P. S. Papavasiliou and S. T. Miller. Functional
interactions between biogenic amines, 3´, 5´-cyclic AMP and
manganese. Nature 220:74-75.
- Dihydroxyphenylalanine treatment of Parkinsonism.
- With P. S. Papavasiliou, R. Gellene, R. B. Aronson, and I.
Mena. Long-term effects of dopa on Parkinsonism: a proposal. In Third
Symposium on Parkinson's Disease, ed. F. G. Gillingham and I. M. L.
Donaldson, pp. 178-81. Edinburgh: E. & S. Livingstone.
- With P. S. Papavasiliou and R. Gellene. Modification of
Parkinsonism: dyskinesias accompanying treatment with dopa. In
Psychotropic Drugs and Dysfunctions of Basal Ganglia: A
Multidisciplinary Workshop, Public Health Series Publication 1938,
ed. G. E. Crane and R. Gardner, Jr., pp. 140-47. Washington, D.C.: U.S.
Government Printing Office.
- With P. S. Papavasiliou and
R. Gellene. Modification of Parkinsonism: chronic treatment with L-dopa.
N. Engl. J. Med. 280:337-45.
- With P. S.
Papavasiliou. Autoimmunity in patients treated with L-dopa. JAMA
- L-dopa (L-DOPA) treatment of
Parkinsonism. JAMA 207:1522.
- Parkinsonism and
dopa: an editorial. J. Chronic Dis. 22:297-301.
- With I. Mena, K. Horiuchi, and K. Burke. Chronic manganese
poisoning: individual susceptibility and absorption of iron.
- With P. S. Papavasiliou, R.
Gellene, C. Fehling, and I. Mena. L-dopa in the treatment of Parkinson's
syndrome and of chronic manganese poisoning. In Proceedings of the
Eighth International Congress of Gerontology, vol. I.
- With P. S. Papavasiliou and R. Gellene. L-dopa in
Parkinson's syndrome. N. Engl. J. Med. 281:272.
- Metabolic modification of some neurologic disorders.
- 2-amino-4-hydroxy-6-7-dimethyletrahydropteridine in
Parkinson's disease. JAMA 210:1594.
- Limiting factors in the treatment with
dopa. In L-dopa and Parkinsonism, ed. A. Barbeau and F. H.
McDowell, pp. 3-5. Philadelphia; F. A. Davis.
- With I.
Mena, J. Court, S. Fuenzalida, and P. S. Papavasiliou. Modification of
chronic manganese poisoning: treatment with L-dopa or 5-OH tryptophan.
N. Engl. J. Med. 282:5-10.
- With P. S.
Papavasiliou, C. Fehling, B. Kaufman, and I. Mena. Similarities between
neurological effects of L-dopa and of apomorphine. N. Engl. J. Med.
- Catecholamines in the brain. N. Engl.
J. Med. 282:513.
- With S. Duby, J. Z. Ginos, A.
Steck, and P. S. Papavasiliou. Dopamine analogues for studies of
Parkinsonism. N. Engl. J. Med. 283:1289.
- Levodopa in the treatment of
Parkinsonism. The George R. Minot Memorial Lecture, Chicago, Ill., June
22, 1970, JAMA 218:1903-8.
- With P. S.
Papavasiliou, A. Steck, and S. Duby. Parkinsonism and levodopa. Clin.
Pharmacol. Ther. 12:319-22.
- With P. S. Papavasiliou,
J. Z. Ginos, A. Steck, and S. Duby. Metabolic modification of
Parkinson's disease and of chronic manganese poisoning. Ann. Rev.
- With L. Tang, J. Z. Ginos, A. R.
Nicholson, and P. S. Papavasiliou. Block of cerebral actions of L-dopa
with methyl-receptor substances. Nature 231:533-34.
- With P. S. Papavasiliou. Blocking the negative effects of
vitamin B6 on patients receiving L-dopa. JAMA
- With L. C. Tank, S. T. Miller, and J. Z.
Ginos. Melatonin and abnormal movements induced by L-dopa in mice.
- With I. Mena and J. Court.
Levodopa, involuntary movements and fusaric acid. JAMA
- L-dopa and prognosis. In Developments in
Treatment for Parkinson's Disease, ed. G. C. Cotzias and F. H.
McDowell, pp. 78-84. New York: Medcom Press.
- With S. E.
Duby, A. J. Steck, and P. S. Papavasiliou. Apomorphine versus L-dopa in
Parkinsonism. Fed. Proc. 30:126.
- With S. E. Duby
and L. K. Dahl. Coupling of hypotensive and anti-Parkinson effects with
two dopaminergic drugs. Trans. Assoc. Am. Physicians 84:289-96.
- With P. S.
Papavasiliou, S. E. Duby, A. J. Steck, C. Fehling, and M. A. Bell.
Levodopa in parkinsonism: potentiation of central effects with a
peripheral inhibitor. N. Engl. J. Med. 286:8-14.
- Levodopa-orally or intravenously; negative pyridoxine
effect. JAMA 219:226.
- With W. H. Lawrence, P. S.
Papavasiliou, S. E. Duby, J. Z. Ginos, and I. Mena. Apomorphine and
Parkinsonism. Trans. Am. Neurol. Assoc. 97:156-59.
- With J. Z. Ginos, A. LoMonte, and S. Wolf. Apomorphine: its
dopaminergic action and its spectrofluorimetric determination. Fed.
Proc. 31:269, 312.
- With L. C. Tang, S. T. Miller, D.
Sladic-Simic, and L. S. Hurley. A mutation influencing the
transportation of manganese, levodopa and tryptophan. Science
- With P. S. Papavasiliou, S. E. Duby, A. J.
Steck, and J. Z. Ginos. Some newer metabolic concepts in the treatment
of Parkinsonism. Neurology 22(Suppl.):82-85.
P. S. Papavasiliou, S. E. Duby, A. J. Steck, M. Bell, and W. H.
Lawrence. Melatonin and Parkinsonism. JAMA 221:88-89.
- With L. C. Tank and I. Mena. Effects of inhibitors and
stimulators of protein synthesis on the cerebral actions of levodopa. In
Chemical Approaches to Brain Function, Neurosciences Research,
ed. S. Ehrenpreis and I. J. Kopin, vol. 5, pp. 97-108. New York:
- With S. E. Duby, P. S. Papavasiliou, and
W. H. Lawrence. Injected apomorphine and orally administered levodopa in
Parkinsonism. Arch. Neurol. 27:474-80.
- With W. H.
Lawrence, P. S. Papavasiliou, and S. E. Duby. Nicotinamide ineffective
in Parkinsonism. N. Engl. J. Med. 287:147.
- Limitations of controlled double-blind studies of drugs.
N. Engl. J. Med. 287:937.
- Metabolic responses to
levodopa. N. Engl. J. Med. 287:1302-3.
- With P. S. Papavasiliou and I. Mena.
L-meta-tyrosine and Parkinsonism. JAMA 223:83.
- With N. G. Gillespie, I. Mena, and M. A. Bell. Diets
affecting treatment of Parkinsonism with levodopa. J. Am. Diet.
- Levodopa and related drugs.
Medical Letter 15:21-24.
- With P. S. Papavasiliou
and W. H. Lawrence. Levodopa and dopamine in cerebrospinal fluid.
- With J. Z. Ginos, A.
LoMonte, A. K. Bose, and R. J. Brambilla. Synthesis of tritium-
deuterium-labeled apomorphine. J. Am. Chem. Soc. 95:2991-94.
- With I. Mena and P. S. Papavasiliou. Overview of present
treatment of Parkinsonism with Levodopa. Adv. Neurol. 2:265-77.
- With I. Mena, F. C. Brown, P. S. Papavasiliou, and S. T.
Miller. Defective release of growth hormone in Parkinsonism improved by
levodopa. N. Engl. J. Med. 288:320-21.
- With P. S.
Papavasiliou, I. Mena, and M. Bell. Oxybate sodium for Parkinsonism.
- Levodopa, manganese and degenerations of the brain. In
The Harvey Lectures, series 68, pp. 115-47. New York: Academic
- With P. S. Papavasiliou and I. Mena. Short and
long-term approaches to the "on and off" phenomenon. Adv. Neurol.
- With P. S. Papavasiliou, I. Mena, L. C. Tang,
and S. T. Miller. Manganese and catecholamines. Adv. Neurol.
- With I. Mena, P. S. Papavasiliou, and J.
Mendez. Unexpected findings with apomorphine and their possible
consequences. Adv. Neurol. 5:295-99.
- With I.
Mena, P. S. Papavasiliou, J. Mendez, and F. C. Brown. Chronic treatment
with Levodopa and growth hormone release. Adv. Neurol. 5:471-76.
- With J. S. Mendez, P. S. Papavasiliou, and I. Mena.
"On-off" phenomenon during treatment of Parkinsonism with L-dopa. In
Current Concepts in the Treatment of Parkinsonism, ed. M. D.
Yahr, pp. 151-60. New York: Raven Press.
- With W. G.
Clark, M. K. Menon, L. R. Hines, R. M. Hoar, S. M. Kurtz, P. A. Mattis,
I. Iwai, H. Watanabe, and J. C. Page. The acute toxicity of l-dopa.
Toxicol. Appl. Pharmacol. 28:1-7.
- With S. T.
Miller, A. R. Nicholson, Jr., W. H. Maston, and L. C. Tang. Prolongation
of the life-span in mice adapted to large amounts of L-dopa. Proc.
Natl. Acad. Sci. U.S.A. 71:2466-69.
- With L. C. Tang
and J. Z. Ginos. Monoamine oxidase and cerebral uptake of dopaminergic
drugs. Proc. Natl. Acad. Sci. U.S.A. 71:2715-19.
- With L. C. Tang and M. Dunn. Changing the actions of
neuroactive drugs by changing brain protein synthesis. Proc. Natl.
Acad. Sci. U.S.A. 71:3350-54.
- With J. S. Mendez, I. Mena, and P. S. Papavasiliou.
Diphenylhydantoin: blocking of levodopa effects. Arch. Neurol.
- With I. Mena. Protein intake and treatment of
Parkinson's disease with levodopa. N. Engl. J. Med. 292:181-84.
- With S. T. Miller and H. A. Evert. Control of tissue
manganese: initial absence and sudden emergence of excretion in the
neonatal mouse. Am. J. Physiol. 4:1080-84.
P. S. Papavasiliou, S. T. Miller, H. W. Kraner, R. Hsieh. Sequential
analysis: manganese, catecholamines and L-dopa induced dyskinesia. J.
- With J. S. Mendez, E. W. Finn,
and K. Dahl. Rotatory behavior induced in nigra-lesioned rats by
N-propylnoraporphine, apomorphine and levodopa. Life Sci.
- With P. S. Papavasiliou, J. Z. Ginos, and E.
Tolosa. Treatment of Parkinson's disease and allied conditions. In
The Nervous System, ed. D. B. Tower and T. N. Chase, vol. 2.,
pp.323-29. New York: Raven Press.
- With J. Z. Ginos, E.
Tolosa, L. C. Tang, and A. LoMonte. Cholinergic effects of molecular
segments of apomorphine and dopa-minergic effects of N, N-dialkylated
dopamines. J. Med. Chem. 18:1194-1200.
- With P.
S. Papavasiliou, E. S. Tolosa, J. S. Mendez, and M. Bell-Midura. The
treatment of Parkinson's disease with aporphines: possible role of
growth hormone. N. Engl. J. Med. 294:567-72.
- With L. C. Tang. Modification of the
actions of some neuroactive drugs by growth hormone. Arch.
- With P. S. Papavasiliou, V. F. L. Rosal, and S. T. Miller.
Treatment of Parkinsonism with N-n-propyl norapomorphine and levodopa
(with or without carbidopa). Arch. Neurol. 35:787-91.