Release Of 125I Research Articles

Radioactivity Release versus Probability for a Steam Generator Tube Rupture Accident

A calculation of the probability distributions for the radioactive releases of 131I and 133Xe in a steam generator tube rupture accident is given; the effects of iodine spiking are included. The accident sequence considered involves loss of off-site power after the steam generator tube rupture. Two models are considered for iodine release, one of which yields upper bound releases, and the other of which is our best-estimate model. With the best-estimate model, the probability of a 131I release >2 Ci is 1 × 10−6 per reactor-year. With the upper bound model, the probability of a 131I release >66 Ci is 1 × 10−6 per reactor-year. The probability of a release exceeding 600 Ci of 133Xe is 2 × 10−6 per reactor-year.

The effect of mercuric chloride on thyroid function in the rat

Oral administration of 3 mg of mercuric chloride for 6 consecutive days increases thyroid function as noted by an increase in thyroid 131I release rate. Administration of 2.5 mg of mercuric chloride daily for 40 days enhanced thyroid weight, thyroidal 125I uptake, and serum PB125I. Chromatographic analysis of thyroid pronase hydrolysates of mercury-treated rats displayed a pattern of distribution in thyroid labeling which demonstrated an increased percentage of labeled monoiodotyrosine (MIT), no alteration in percentage of labeled diiodotyrosine (DIT) or T4, but a significant reduction in percentage of labeled T3 indicating perhaps a coupling defect in synthesis of T3 exerted by mercury. Administration of mercuric chloride at 100 ppm for 3 months results in a decrease in thyroidal 131I uptake and depression in the thyroidal 131I release rate which were permanent and irreversible. These findings indicate that the influence of mercuric chloride ingestion on thyroid function probably reflects the quantity of mercuric chloride administered and the length of time during which exposure to mercury persists.

Retention of clostridial collagenase by primary cultures of parenchymal cells prepared from adult rat liver

Significant levels of collagenase activity have been found in extracts of isolated rat hepatocytes, but not in extracts of rat liver. Hepatocytes prepared by perfusion of liver with 125I-clostridial collagenase and washed repeatedly retained significant amounts of the radiolabeled proteases. During the first 24–48 hours of primary culture of the hepatocytes, the contaminating clostridial collagenase was rapidly inactivated and degraded as judged first, by loss of collagenase activity from both cell extracts and culture medium; and second, by release of 125I into the medium largely in the form of iodinated small peptides.

The characteristics of fission gas release from uranium dioxide during irradiation

Release rates for the unstable rare gases 88Kr, 87Kr, 85mKr, 133Xe, 135Xe, 138Xe were measured for samples of polycrystalline and large-grained uranium dioxide in the temperature range 700–1550°C. Interpretation is in terms of simple diffusion of gas atoms and their halogen precursors. Derived diffusion coefficients for iodine are compared with those obtained from direct measurements of 133I, 131I release from the same experiment and show good agreement. Diffusion coefficients calculated for krypton, xenon and iodine are similar in their magnitudes and temperature dependences, but magnitudes for bromine are much (≈ 200 times) higher.

Direct Effects of Trypan Blue on Thyroid Secretion

Trypan blue directly inhibited in vitro thyroid secretion (butanol soluble 125I release to the media) induced by both thyroid stimulating hormone (TSH) and dibutyryl cAMP. Intracellular colloid droplet counts were also decreased. Inhibition was directly proportional to dye concentration and could be overcome by supramaximal TSH and dibutyryl cAMP. Inhibition could be observed as early as 20 min of incubation, was not increased by preincubation, and could even be demonstrated after TSH in vivo. Trypan blue, in vivo, produced similar inhibition of thyroid secretion. Incubation of 125I-thyroglobulin with lysosomal enzymes revealed inhibition with much lower concentrations of dye. Inhibition of lysosomal enzyme(s) would not appear to explain the marked decreases in colloid droplets, and this may represent two separate effects of trypan blue on thyroid secretion.

Hormonal secretion by hyperactive thyroid cells is not secondary to apical phagocytosis.

Hyperactive dog thyroids were prepared by repeated TSH stimulation in vivo. Butanol-extractable 125I (BE125I) release in vitro from slices and hormonal secretion in vivo in the thyroid vein was enhanced. Apical pseudopods and colloid droplets were very infrequent in such hyperactive thyroids. Moreover, BE125I release was insensitive to cytochalasin B, to inhibitors of microtubules, and to metabolic inhibitors, and decreased only with temperature. Our data demonstrate that hormonal secretion by hyperactive thyroids is not secondary to apical phagocytosis (i.e. macropinocytosis). Micropinocytosis or intraluminal hydrolysis of thyroglobulin are suggested as first step of the secretory process.

In vitro investigations on thyroid metabolism in the crested newt (Triturus cristatus carnifexLaur.). TSH and TRH effects

Abstract In the crested newt the effect of synthetic TRH was tested “in vitro” on cultures of thyroid associated with pituitary glands. The results seem to confirm also in the Urodele Amphibians the activating effect of TRH; the action of this hormone — like that of TSH used under the same conditions — is suggested by the more rapid release of 131I metabolized by the thyroid. Moreover, our observations seem to attest that prolactin is not directly responsible for the activation of thyroid metabolism.

Alterations in cyclic AMP, intermediary metabolism, and ultrastructure in dog thyroid gland induced by synthetic double-stranded RNA

The effects of in vivo administration of polyriboinosinic-polyribocytidylic acid [poly(rI:rC)], an interferon inducer, on cyclic AMP levels, [1- 14C]glucose oxidation, [ 32P]orthophosphate incorporation into phospholipids, release of 131I-labeled thyroid hormones, and ultrastructure were studied in the dog thyroid gland. After in vivo treatment with poly(rI:rC), the responsiveness of these parameters to TSH was evaluated in vitro. In poly(rI:rC)-treated animals, basal cyclic AMP levels were not significantly changed and basal [1- 14C]glucose oxidation was significantly inhibited. TSH increased cyclic AMP levels somewhat less in poly(rI:rC)-treated animals than in controls and stimulated [1- 14C]glucose oxidation in controls, but not in poly(rI:rC)-treated dogs. 32P Incorporation into phospholipids, on the other hand, was stimulated after poly(rI:rC) and it was further stimulated by TSH. In studies of specific phospholipid incorporation, both poly(rI:rC) and TSH responses were most prominent in the phosphatidylinositol and phosphatidylserine fractions. Poly(rI:rC)-treated thyroids showed increased basal release of total 131I with a marked relative increase in T 3 release. The responsiveness of I −, T 4, and T 8 release to TSH remained intact. Ultrasructural response to poly(rI:rC) included a marked dilatation and development of the rough endoplasmic reticulum and an increase in lysosome formation. After exposure to TSH, thyroid slices from poly(rI:rC)-treated dogs partially failed to develop pseudopods and colloid droplets. Poly(rI:rC) effects were present in normal dogs as well as in dogs in which endogenous TSH was suppressed. These findings suggest that poly(rI:rC) directly affects the dog thyroid gland.

On the Mechanism of Cell Membrane Damage by Complement: Evidence on Insertion of Polypeptide Chains from C8 and C9 into the Lipid Bilayer of Erythrocytes

The preceding paper (Hammer, C.H., A. Nicholson, and M. M. Mayer, 1975, Proc. Natl. Acad. Sci., 72:5076) presented evidence on insertion of polypeptide chains from the C5b and C7 subunits of C5b, 6, 7 complex into the phospholipid bilayer of erythrocyte membranes. In the present study, EAC1-8 and EAC1-9 (sheep erythrocytes carrying rabbit antibody and complement proteins C1 through C8 or C9, respectively), prepared with either 125I-C8 or 125I-C9, were incubated with trypsin or chymotrypsin and the release of 125I was measured. Only 9 to 19% of the specifically bound radioactivity was released. In addition, elution experiments were performed with 0.02 M EDTA-1.0 M NaCl. This solution did not elute C9 from EAC1-9. By contrast cellbound C9 was recovered from erythrocyte membranes with sodium dodecyl sulfate (SDS). Thus, enzymatic stripping and elution experiments indicate that cellbound C9 behaves like an integral membrane protein, presumably due to insertion into the lipid bilayer. EAC1-9 membranes that had been subjected to extended digestion with trypsin or chymotrypsin were extracted with SDS to recover the enzyme-resistant part of the C9 molecule from the membrane. Even though this domain of C9 carried 90% of the radioiodine associated with native C9, its m.w. was found to be only 18,000 daltons by analysis on SDS-PAGE. This represents one-quarter of the native C9 molecule.

Myasthenic immunoglobulin accelerates acetylcholine receptor degradation.

Degradation of acetylcholine receptors by cultured rat skeletal muscle cells was determined from the release of 125I from bound 125I-labeled alpha-bungarotoxin. Addition of immunoglobulin from patients with myasthenia gravis to the culture medium accelerated the degradation rate to a mean of 8.51 +/- 0.44 percent per hour, compared with the mean control rate of 3.97 +/- 0.14 percent per hour (P less than .001). A similar mechanism may possibly be involved in the autoimmune pathogenesis of myasthenia gravis in man.

Quantitation of antibody-complement mediated lysis of tumor cells

An assay for quantitating antibody-complement mediated killing based on the release of 125I from 125IUdR labelled target cell is described. The temporal delay between antibody—complement damage and the release of nuclear material was shortened by treatment of the cells with a combination of trypsin and DNase. This treatment increased the rate of release of the labelled nuclear material from damaged cells without causing labelled nuclear material to be released from undamaged cells. The low level of spontaneous release of 125I from the target cells allows this assay to be used for experiments carried out over long time periods or in experiments involving extensive manipulations of the cells.

Thyroid Function and Basal Metabolism in the Ground Squirrels Ammospermophilus leucurus and Spermophilus spp.

The function of thyroid glands of ground squirrels, maintained under conditions of constant illumination and temperature as measured by the release of radioiodine (125I), varied from one time of the year to the next and differed among species. The maximum release rate was 2.476% per day and was observed in the high altitude species, Spermophilus lateralis, while the slowest release rate was 0.029% per day and was observed in the desert species, S. townsendi. The periods of slowest release tended to coincide with late summer and early fall, though individual animals of the eight species in which 125I release rates were studied varied considerably among themselves. The variation within species was thought to reflect the free-running circannual rhythm of thyroid secretion which eventually became out of phase with natural conditions. The reason for differences among species is unknown, though it may be related to water balance. The rhythm of thyroid activity is not a function of body temperature rhythms, but reflects primary rhythms such as TSH (thyroid-stimulating hormone) secretion or release of TSH. Although the time of year when the thyroids are least active overlaps the period of hibernation, thyroid inactivity cannot be a causal factor, since exogenous thyroxine does not prevent torpor and the period of reduced thyroid activity is not precisely correlated with hibernation. Increased thyroid activity typically occurs during the winter and early spring, times when animals may still be in hibernation, at least in nature. This is interpreted to mean that their glands become active during the hibernation period in preparation for reproduction and molting. All of the nine species of ground squirrels in which body temperature and metabolism were measured had basal metabolic rates which could be described by the equation: cm3O2 · g-1 · h-1 = 3.24 W-0.23, although the only nonhibernator in the group, Ammospermophilus leucurus, had a metabolic rate 4%-13% above the level expected from this equation. Removal of the thyroid gland did not change the metabolism of S. mexicanus, while it lowered the metabolism of A. leucurus and S. townsendi 13%-15%, which is far less than expected for animals such as the white rat, in which the thyroid gland contributes a significant amount of thermogenesis. This is consistent with the hypothesis that ground squirrels in general have a low metabolism due to a relatively inactive thyroid. The effect of thyroidectomy on metabolism is related to the time of year in which the gland is removed, so that removal during periods of slow release rate of 125I does not lead to a reduction in metabolism. In general, metabolism declined seasonally independent of whether the thyroid was present or absent. The seasonal changes in metabolism are not due to changes in body weight. In general, body temperature tended to decline when metabolism declined and vice versa.

The dehalogenation of the 5-halo-5,6-dihydrouracils: Uracil formation from 5-iodo- and 5-bromo-5,6-dihydrouracil

The elimination of halide ion from either 5-bromo- or 5-iodo-5,6-dihydrouracil to yield uracil is a slow reaction which, in the case of 5-iodo-5,6-dihydrouracil, is 400 times slower than the enzymatic release of 125I − from 5-[ 125I]iodouracil. The elimination of HBr from 5-bromo-5,6-dihydrouracil is subject to general base catalysis by tris(hydroxymethyl)aminomethane ( k 2 Tris base = 11 × 10 −4 M −1 min −1, 37°C, ionic strength 1.0 M). At pH values near and above physiological, both the bromo- and iododihydropyrimidines are subject to hydrolysis of the dihydropyrimidine ring, a reaction which parallels halide elimination to yield uracil. The resulting 2-halo-3-ureidopropionate then cyclizes via intramolecular attack of the ureido oxygen atom to yield halide ion and 2-amino-2-oxazoline-5-carboxylic acid as final products. In dilute hydroxide ion, the kinetics of 5-bromo-5,6-dihydrouracil hydrolysis (25°C, ionic strength 1.0 M) show a change in rate-determining step as a function of increasing hydroxide ion concentration, a result which, as in the case of 5,6-dihydrouracil, can be explained in terms of the formation of a tetrahedral addition intermediate. The data are discussed relative to enzymatically catalyzed halopyrimidine dehalogenation.

Thyroid iodine uptake, thyroid iodine secretion and plasma TSH levels in male rats during the day and night.

Experiments were performed to assess whether the diurnal changes in thyroid 131I metabolism are paralleled by variations in endogenous iodine. The uptake of iodide by the thyroid gland was determined by a double isotope technique. The T/S iodine ratio and the rate of 131I and 127I secretion from the thyroid gland were determined in rats fed LID during 20 days. The accumulation of iodine by the thyroid gland was prevented by CK1O4 and organic iodine formation was blocked by PTU. The absolute uptake of iodide by the thyroid gland was twice as high during the night than during the day. The thyroid/serum iodide ratios were highest during the night. The rate of release of 131I and 127I from the thyroid gland was augmented in the afternoon. The concentration of TSH in the plasma, measured by radioimmunoassay, was elevated in the afternoon as compared to other times during the day and night. The close association between the diurnal changes in thyroid iodine secretion and plasma TSH concentrations suggest that TSH may be responsible for the differences in iodine secretion observed during the day and night. On the other hand, the intake of iodine in the diet and the urinary clearance of iodine showed diurnal rhythms; the highest values occurred during the night. In addition, about twice as much iodine was available to the thyroid gland at night than during the day. These factors might also contribute to the diurnal variations observed in thyroid iodine metabolism.

Thyroid function in a hibernator, Spermophilus tridecemlineatus

Thyroid hormone secretion (assessed as thyroid 125I release rate) was monitored in Spermophilus tridecemlineatus from summer to winter (July-December) in 1973. The average release rate in July was 2.3% per day, but in August this rate decreased significantly and remained at an average 0.52% per day until December. This low rate (being similar to that of hypophysectomized rats), and the absence of any change in oxygen consumption following thyroidectomy, suggested hormone secretion was "turned off" during this period. During the period August-December, four S. tridecemlineatus showed normal thermoregulatory responses to anterior hypothalamic cooling but no thyroidal response whether restrained, unrestrained, or anesthetized. Thyroid 125I uptake (and presumably hormone manufacture) continued during the period August-December and 24-h uptake averaged 27.0% in December. Possible reasons for "turning off" thyroid hormone secretion are discussed, and it is concluded this is to allow the membrane fatty acids to revert to a less-saturated condition in preparation for low body temperatures during hibernation.

Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism?

We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 mug/rat and 0.6 mug/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2 1/2 days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14C02 and [3H] leucine incorporation into protein in rat thyroid. In the mouse T4 or T3 pretreatment (0.25-25 mug daily) caused dose-related inhibition of both thyroidal ODC activity and 131I release induced by TSH in vivo. In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and 131I release. When LID or RD mice were pretreated with 12.5-125 mug of T4 or T3 over 2 1/2 days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a "short-loop" negative feedback regulating thyroid function.

Thyroid activity of spontaneous hypertensive rats.

Thyroid activity of both male and female spontaneous hypertensive (SH) rats was studied by measurements of uptake and rate of release of 131-I, urinary excretion of 131-I, and thyroxine secretion rate (TSR). In addition, thyroid glands were removed at death and weighed. Radioactivity of the thyroid gland of male rats measured at intervals after administration of 131-I revealed a significantly reduced maximal uptake at 21.5 hr after injection and a reduced rate of release. The mean biological half-life of 131-I for the control group was 37.8 plus or minus 3.1 (SE) hr compared to 54.8 plus or minus 7.2 hr for hypertensives (P less than 0.05). Similar results were observed for females in that biological half-life of 131-I was 32.2 plus or minus 1.2 hr compared with 84.1 plus or minus 4.1 hr for hypertensives (P less than 0.01). Urinary excretion of 131-I by hypertensive rats at 24, 48, and 72hr after injection of 131-I did not differ from control in either experiment. Thyroid weight at autopsy was increased significantly above that of normotensive controls. TSR was measured indirectly in a third group of male spontaneously hypertensive and normotensive rats. TSR of control rats was estimated to be 0.97 mug T4/100 g body wt/day and 1.35 mug T4/100 g body wt/day for SH RATS. The results are consistent with the suggestion that the method for measurement of TSR in hypertensive rats gives an artifactually high value because TSH secretion is elevated.

A study of thyrotropin stimulated 131I release in vitro by thyroid glands obtained from normal and protein deficient rats

The role of anterior pituitary in regulation of thyroid function in protein malnutrition has been investigated in normal and protein deficient rats by an indirect TSH assay method. The release of 131I from the prelabeled thyroid glands was studied in the in vitro model. Exogenous TSH was added to the system in two selected doses and the release was followed for the next 30 minutes. The results indicate a progressive release of radioiodine from the thyroid gland in both the groups. The resting release is significantly enhanced by the addition of TSH to the system. The increase in release was almost to the same extent in the two groups. Thus, the thyroid from the protein deficient rat responds normally to TSH stimulation in the in vitro system. The higher dose of TSH inhibited the release of 131I to some extent, as compared to its one-tenth dose.

A Study of Thyroid Activity in Dwarf and Non-Dwarf Female Chicks During Key Physiological States of Growth and Reproduction

Thyroid function, as indicated by the maximum percent uptake of iodine-131, was measured in non-dwarf and recessive, sex-linked dwarf White Leghorn female chickens at different ages. The rate of uptake and release of 131I by the thyroid gland was closely monitored over a period of eight days after the injection of the isotope. No significant differences were observed in thyroid uptake value of dwarf chicks in one-week-old group (≈ 11.5% for each group). At the age of four weeks the maximum uptake was only 5.58% in dwarfs compared to 10.11% in non-dwarf chicks. Potassium thiocyanate treatment caused a significant reduction in the uptake of iodine-131 by the thyroid glands of both 4-week-old dwarf and non-dwarf chicks although there was no difference in the response pattern of either group to the treatment. Dwarf laying-hens had a significantly lower maximum thyroid uptake (1.4.%) when compared to non-dwarf laying hens (2.48%). A consistantly slower rate of uptake by the thyroid glands of dwarf chickens was observed for all age groups than equivalent non-dwarfs but there were no apparent differences in the release rates of 131I by dwarfs when compared to non-dwarfs. No significant differences were observed between the 131I uptake by the ovaries or eggs of both dwarf and non-dwarf laying hens. A gradual decrease in thyroid activity was observed in both dwarf and non-dwarf chickens with increased age. From this study it was evident that the dwarf bird had significantly lower thyroid activity but with normal organification. The defect in thyroid function in the dwarf bird apparently was not at the level of synthesis but at the level of uptake of iodine.

Relation of thyroid hormone secretion rate (TSR) in rats and fowl to hormone content of their thyroid glands

By the determination of thyroid hormone secretion rate (TSR), the amount of l-thyroxine ( l-T 4) secreted each 24 hr has been estimated. An attempt has been made in this study to determine by bioassay the relation of the daily TSR to the amount of stored hormone (thyroglobulin) in the thyroid of the rat and chicken in terms of l-T 4 equivalents. The individual TSR of 28 rats and 36 chickens was determined. Two animals having the same TSR were grouped as the donor and recipient of the thyroid homogenate. To bioassay the l-T 4 equivalents of donor thyroids, recipient rats and chickens were injected with graded levels of the thyroid homogenate until release of thyroidal 131I was blocked according to the technique used in the estimation of TSR. Mean l-T 4 equivalents in the thyroids of donor rats and chickens were 13.9 and 154.4 μg with a daily secretion of 3.58 and 27.98 μg, respectively. The amount of l-T 4 equivalent in the thyroid homogenate was 3.82 ± 0.35 times the daily TSR in rats and 5.56 ± 0.23 times in chickens ( P < 0.001). The data suggest that in rats and chickens there is a significant difference in the magnitude of bioassayable l-T 4 equivalents stored in the thyroid in terms of daily TSR.