Uptake of macromolecules by the thyroid.
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Biomedical subjects
Publications and source records attributed to R Hoffenberg.
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Rats treated with 131I and propylthiouracil were shown to develop thyroid tumours 7--9 months after treatment. In this group, the levels of total thyroxine and tri-iodothyronine, and free thyroxine and tri-iodothyronine in the serum were low, and that of TSH was raised. In a group of rats treated with 131I and then propylthiouracil and thyroxine, thyroid tumours were found despite normal concentrations of total and free thyroxine and tri-iodothyronine in the serum. The level of TSH in the serum was significantly raised in this group. Thyroid tumours were not found in the various control groups of rats.
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In ten euthyroid subjects, in whom endogenous thyroid-stimulating hormone (T.S.H.) production was suppressed by oral thyroxine (T4), a single dose of dexamethasone resulted in reduced serum-3,3'5-triidothyronine (T3) concentration and raised serum-3,3',5'-triiodothyronine (reverse T3 or rT3) concentration after 24 h. These changes were not related to changes in free hormones or binding proteins. Adrenal glucocorticoids may have a pathophysiological role in modulating the peripheral metabolism of thyroid hormones in stress.
A radioimmunoassay for the measurement of l-3,3',5'-triiodothyronine (reverse TO, rT3) has been developed for use with unextracted serum. The highly specific antiserum showed no cross-reactivity with l-3,3'5-triiodothyronine (T3) or tetradiodothyroacetic acid (T4A) and cross-reaction with L-thyroxine (T4) was low enough to be discounted for routine assay purposes. If a normal amount of rT3 was added to serum T4 cross-reactivity decreased considerably. Serial dilutions of hyperthyroid sera gave dose-response curves which were parallel to the rT3 standard curve. Serum concentrations of rT3 (mean+/- SEM) were 0-68 +/- 0-02 nmo1/1 in sixty-seven normal subjects, 0-19 +/- 0-02 nmo1/1 in twelve hypothyroid patients and 1-18 +/- 0-12 nmo1/1 in seventeen hyperthyroid patients. In sixteen patients with TO-toxicosis rTO was 0-42 +/- 0-04 nmo1/1 and eighteen patients with high circulating TBG had a mean rT3 of 0-54 +/- 0-03 nmo1/1.
Serum-triiodothyronine (T3) concentrations fell rapidly after surgery in six out of seven initially euthyroid patients. Simultaneous increases in reverse triiodothyronine (rT3) concentrations suggested that the peripheral monodeiodination of thyroxine (T4) proceeds by an alternative pathway in the postoperative period.
A mathematical model was constructed to define the dynamics of incorporation of radioactivity into urea carbon and the guanidine carbon of arginine in plasma albumin after the rapid intraportal-venous administration of Na214CO3 in the isolated perfused rat liver. 2. The model was formulated in terms of compartmental analysis and additional experiments were designed to provide further information on subsystem dynamics and to discriminate between alternative model structures. 3. Evidence for the rapid-time-constant of labelling of intracellular arginine was provided by precursor-product analysis of precursor [14C]carboante and product [14C]urea in the perfusate. 4. Compartmental analysis of the dynamics of newly synthesized urea was based on the fate of exogenous [13C]urea, endogenous [14C]urea and the accumulation of [12C]urea in perfusate water, confirming the early completion of urea carbon labelling, the absence of continuing synthesis of labelled urea, and the presence of a small intrahepatic urea-delay pool. 5. Analysis of the perfusate dynamics of endogenously synthesized and exogenously administered [6-14C]arginine indicated that although the capacity for extrahepatic formation of [14C]-urea exists, little or no arginine formed within the intrahepatic urea cycle was transported out of the liver. However, the presence of a rapidly turning-over intrahepatic arginine pool was confirmed. 6. On the basis of these subsystem analyses it was possible to offer feasible estimations for the parameters of the mathematical model. However, it was not possible to stimulate the form and magnitude of the dynamics of newly synthesized labelled urea and albumin which were simultaneously observed after administration of [14C]carbonate on the basis of a preliminary model which postulated that both products were derived from a single hepatic pool of [16-14C]arginine. On the other hand these observed dynamics could be satisfied to a two-compartment arginine model, which also provided an explanation for discrepancies observed between albumin synthesis measured radioisotopically and immunologically. This was based on a relative overestimation of [14C]urea specific radioactivity resulting from the rapid dynamics of [14C]carbonate and the [14C]urea subsystem relative to the labelled albumin subsystem. The effects of arginine compartmentalization could be minimized in the model by minor slowing of the rate of [14C]carbonate turnover or by constant infusion of [14C]carbonate, both of which permitted valid determination of albumin-synthesis rates.
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