subtle functional aypairmen
i
t, was present for ls years following doses of
50, and 100 ne of 131] to animals. It was discovered in these studies that]
thyroids failed to enlarge in response to the administration of thiouracil
spite of the increase in cell height. The bizarre nuclear forms became ap
after the administration of the thiouracil. Such changes were produced in
that had received 5 pic and were accentuated in animals that had received 2
100 pe. The results of these studies were published.

20,

the

Maloof, F., Dobyns, B.M., and Vickery, A.L.: The Effects of Various Doses
Radioactive Iodine on the Function and Structure of the Thyroid of the Rat.
Endocrinol. 50: 612-638, June, 1952.
Morphulogical Changes in the Nucleus of Rat Thyroids Following131 Radiati
One of the primary objectives from very early in this contract has

the nature of the large irregular hyperchromatic nuclei in irradiated

numbers of rats were placed on an iodine deficient diet for a mumber of da

to study

. Large
and then

given various single doses of 131] to study muclear changes in a variety o ways.

previously observed, changes appeared in several months and were accentuat
administration of thiouracil. The impairment to the glandular enlargement
usually produced by the administration of thiouracil, was again evident fo
of isl, which were not large enough to cause architectural distortion.

By

frequent observations it became evident that the impairment to enlargement
in the mildly irradiated gland surprisingly did not occur promptly after 1
been given but occurred after a considerable lapse of time, long after the
vanished from the gland. See attached Figure 5. The appearance of abuncs
nuclear forms and the inability of the gland to enlarge on thiouracil se
temporally related. These opservations supported our belief that the irre
forms represented preparation for but thwarted attempts at cell division.
of hypertrophy was suspected to be a consequerce.
In order to explore this possibility, animals were divided into sev
depending on the radiation which they had received and were given colchici

attempt was made to determine a mitotic index in the previously irradiated

animals treated in various ways with thiouracil and colchicine. Unfortuna
mitoses seemed to be either sufficiently infrequent or unidentifiable so
experiments did not yield conclusive results as to the frequency of mitose
more extensive studies of nuclear change will be described.

AS
by the

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i
doses

ing more

f the gland
T_ had

Sly had

bizarre
to be
nuclear
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-

groups
An

ids of
y the
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Other

Observations on the Biochemical Changes Resulting from a Single Therapeutic Dose of
4917 in Man
Early in this project enormous amounts of time were devoted to collect
detailed data, especially kinetic data, on selected patients who were give
therapy for hyperthyroidism. Only selected patients could be used because

enormous amount of time required for the study of a single patient. The s
clinical effects of 131y therapy have been ultimately measured against a
background of data on each individual patient.

It was hoped that in this

might be possible to find explanations for the great variation in the re
different patients to this therapy. The responsible investigator is in

131+ therapy, as well as other forms of therapy for hyperthyroidism at Cle
Metropolitan General Hospital. There has thus been an opportunity to stud
patient in great detail and to organize all studies in a predetermined fa

the largest amount of information could be obtained from each patient, whe
treated surgically or with 131, .

Select target paragraph3