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Biomedical subjects

R R Cavalieri

Publications and source records attributed to R R Cavalieri.

At least 73 records · Page 4Linked to original sources

Comparative evaluation of 99mTc GH, 99mTcO4, and 99mTc DTPA as brain imaging agents.

The brain imaging properties of 99mTc glucoheptonate, 99mTc pertechnetate, and 99mTc DPTA are compared. Results demonstrate that optimum images are obtained at 90, 180, and 180 min., for 99mTc GH, 99mTc DTPA, and 99mTc perterchnetate, respectively. The former two images are not affected by prior bone imaging with 99mTc pyrophosphate, while 99mTc pertechnetate images are adversely affected. 99mTc glucoheptonate appears to be the superior agent for brain imaging, followed by 99mTc DTPA and 99mTc pertechnetate.

Brain Diseases↗

Extrathyroidal conversion of thyroxine to 3,3',5'-triiodothyronine (reverse-T3) and to 3,5,3'-triiodothyronine (T3) in humans.

In order to estimate the relative magnitude of the two alternative pathways of monodeiodination of thyroxine (T4) in adult humans, the metabolic clearance rates (MCR) and production rates (PR) of 3,3',5'-triiodothyronine (reverse-T3,rT3) and of 3,5,3'-triiodothyronine (T3) were determined in six euthyroid control subjects (C) and in five hypothyroid patients (H) receiving L-T4 as replacement therapy (0.15-0.3 mg/day). MCR was computed by a non-compartmental method of analysis from the plasma disappearance of 125I rT3 and 131I T3 during 72 h following simultaneous injection of tracers. PR was calculated from MCR and the serum concentration of rT3 and T3, respectively, determined by radioimmunoassay. In the H subjects, rT3 MCR averaged 97.1 +/- 12.8 (SD) 1/day and rT3 PR, 34.3 +/- 12.8 microng/day; T3 MCR was 28.7 +/- 6.1 1/day and T3 PR, 20.3 +/- 6.6 microng/day (all corrected to 70 kg body weight). These results were not significantly different from those in the control group; rT3 MCR 104 +/- 24 1/day, rT3 PR 33.0 +/- 9.2 microng/day; T3 MCR 24.0 +/- 5.9, T3 PR 24.2 +/- 4.1. The proportionof total triiodothyronine (rT3 averaged 62% in H patients and was similar (57%) in the C group. The results obtained in the H subjects indicate that the production of rT3 is a major route of T4 metabolism, equal to or exceeding that of T3. From the close agreement between the mean values for rT3 PR in the C and H groups it is concluded that most, if not all of the rT3 produced in normal humans is derived by extrathyroidal conversion from T4.

Aged↗

Binding of thyroid hormones and their analogues to thyroxine-binding globulin in human serum.

The present study was undertaken to study the binding of several thyroid hormones and structurally related compounds to human serum thyroxine-binding alpha-globulin (TBG). The source of TBG was normal human serum diluted 1:100 in 0.035 M barbital buffer, pH 7.4. In the binding assays, 125I-thyroxine, unlabeled thyroxine, and diluted serum were incubated for 20 h at 37 degrees in Plexiglas equilibrium dialysis units. Two orders of binding sites were discerned: a high affinity, low capacity binding site with an affinity constant of approximately 2.5 X 10(9) M-1, and a low affinity, very high capacity binding site with an affinity constant of less than 10(6) M-1. Studies with purified TBG, serum deficient in TBG, and purified human serum albumin indicated that the high affinity site represented binding to TBG and the low affinity site represented binging to albumin. The ability of several groups of thyroid hormone analogues to bind to TBG was then investigated. As a result of these studies, the following structural features of thyroid hormones were found to be important for optimal binding activity: (a) the L-alanine side chain conformation, (b) the presence of a 4'-hydroxyl group, (c) the presence of two substituents in the inner and outer rings (positions 3, 5, 3', and 5'), and (d) the presence of either bromines or iodines in the inner ring and iodines in the outer ring. Of lesser importance was the presence of an oxygen atom in the ether position.

Alpha-Globulins↗

Compensatory thyroid hypertrophy after hemithyroidectomy in rats.

Thyroid enlargement occurs in association with a variety of circumstances characterized by an impaired capacity of the gland to secrete adequate amounts of hormone. To elucidate the factors responsible for such compensatory thyroid growth, particularly the role of TSH, we have observed the response of the serum TSH, T3 and T4 concentrations following hemithyroidectomy in the rat, and have attempted to correlate changes in these functions with changes in the weight and histology of the thyroid remnant. Hemithyroidectomy was performed in male Sprague-Dawley rats weighing 150 to 370 g, sham-operated animals serving as controls. As compared to findings in sham-operated animals, serum T4 concentrations declined promptly after hemithyroidectomy. In Experiment I serum T4 concentrations remained low for about 10 days and then returned to initial values. In Experiment II serum T4 concentrations remained lower than initial T4 values or values found in sham-operated animals until 34 days after hemithyroidectomy. Serum T3 concentrations were not significantly altered after hemithyroidectomy in either group but tended to be lower in the hemithyroidectomized animals. Serum TSH concentrations increased within 3 days after hemithyroidectomy and, for as long as 21 weeks, remained at values higher than those present preoperatively or those seen in sham-operated animals. Thyroid lobe weight increased following removal of the contralateral lobe and this increase was also sustained throughout the duration of the experiments. Biochemical and histological observations indicated that enlargement of the residual lobe was due to hypertrophy rather than hyperplasia.

Animals↗

Simultaneous measurement of percentage free thyroxine and triiodothyronine: comparison of equilibrium dialysis and Sephadex chromatography.

An equilibrium dialysis technique was used to measure simultaneously the proportion of free thyroxine (%FT4) and free 3,4,5'-triiodothyronine (%FT3) in sera from patients with diverse states of thyroid function and abnormal levels of plasma T4-binding proteins. In general, the correlation between %FT4 and %FT3 values was excellent in the entire group of patients studied. Studies were also conducted to ascertain whether Sephadex columns could be employed to obtain simultaneous measures of plasma binding of T4 and T3. Mixtures of diluted serum and 125I-T4 and 131I-T3 were applied to columns of Sephadex in order to separate "bound" and "free" fractions. The values for percent free T4 and T3 yielded by the Sephadex process (%FT4S and %FT3S), although far greater numerically, correlated closely with 5FT4 and %FT3 measured directly by equilibrium dialysis. When %FT4 and %FT3 were multiplied by their respective serum concentrations, the resulting free T4 and free T3 indices provided good separation of hyperthyroid and hypothyroid groups from the euthyroid group. As in the dialysis method, %FT4S closely correlated with %FT3S.

Chromatography, Gel↗

Preparation of 125-I-labeled human thyroxine-binding alpha globulin and its turnover in normal and hypothyroid subjects.

A protein with the electrophoretic, immunologic, and hormone-binding properties of thyroxine-binding globulin (TBG) has been prepared from human plasma and labeled with radioiodine (125-I) by an enzymatic method of iodination. The [125-I]TBG retained the electrophoretic and immunologic characteristics of unlabeled TBG but exhibited a partial loss of thyroxine-binding activity, as assessed by affinity chromatography. The in vivo behavior of [125I]TBG was studied in six euthyroid subjects (controls) with normal serum levels of TBG as measured both by radioimmunoassay and by determination of maximal T4-binding capacity and in four male patients with untreated primary hyperthyroidism, three of whom had elevated serum TBG. The half-time of the final slope of the plasma disappearance curve averaged 5.0 days plus or minus 1.2 (SD) in the controls and ranged from 3.9 to 109 days in the hypothyroid patients. The distribution volume was similar in the two groups, 6.7 plus or minus 1.3 vs. 7.1 plus or minus 2.1 liters. The catabolic clearance rate averaged 0.99 plus or minus 0.33 liters plasma/24 h in the controls and 0.92 plus or minus 0.46 in the hypothyroids. The absolute turnover rate of TBG, calculated from the catabolic clearance rate multiplied by the serum concentration of radioimmunoassayable TBG, averaged 17.8 plus or minus 2.1 mg/day in the controls and ranged from 14.8 to 33.2 mg/day in the hypothyroids. Among the entire group of subjects there was no correlation between the serum TBG concentration and the absolute turnover rate of TBG.

Alpha-Globulins↗

The distribution kinetics of triiodothyronine: studies of euthyroid subjects with decreased plasma thyroxine-binding globulin and patients with Graves' disease.

The kinetics of distribution of 3,3',5-triiodo-L-thyronine (T(3)) have been studied employing both a single-injection and a continuous infusion of T(3-) (131)I. External monitoring of radioactivity in the liver during the infusion permitted estimation of the hepatic distribution volume (V(H)) and the one-way hepatic clearance (C(H)) of the hormone. Among 10 euthyroid control subjects, V(H) averaged 2.07 liters +/-0.50 (SD), and the mean value for C(H), 231 ml of plasma per min (+/-64). In three euthyroid men whose plasma showed decreased binding capacity by thyroxine-binding globulin (TBG) abnormally high V(H) and C(H) values were found, the increase in C(H) being proportional to the decrease in binding activity by plasma proteins. Among all 13 subjects, there was a high correlation (+ 0.86) between C(H) and the proportion of free hormone in plasma, measured in vitro. In four patients with hyperthyroid Graves' disease V(H) ranged from 3.2 to 4.2 liters and C(H) was elevated in every case, averaging 989 ml/min. The increase in C(H) in this group was out of proportion to the elevation of free hormone fraction in plasma. Seven patients who were either euthyroid or hypothyroid after treatment of Graves' disease showed a slight but significant increase in C(H) compared with the euthyroid controls without Graves' disease. The percentage of free hormone in the plasma of the treated group was normal or low and therefore could not explain the persistent elevation in unidirectional hepatic clearance observed. The rate of accumulation of labeled T(3) in the tissues of the thigh during the interval from 10 to 60 min of the sustaining infusion of tracer was slow compared to the rate of equilibration in the liver and did not differ significantly among the various groups studied. These latter findings suggest that in slowly equilibrating tissues such as the thigh the kinetics of T(3) distribution are relatively insensitive to alterations in hormone-binding activity by plasma proteins.

Graves Disease↗