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Biomedical subjects

S Filetti

Publications and source records attributed to S Filetti.

At least 55 records · Page 3Linked to original sources
PubMed1981

Insulin receptor down-regulation, prevention at a post-receptor site.

Nicotinamide (50mM) prevented insulin-mediated down-regulation of insulin receptors in IM-9 lymphoblastoid cells. Half-maximum effectiveness was between 10 and 33mM. Nicotinamide did not influence insulin binding to the cells, cell viability, insulin degradation or protein synthesis. A variety of inhibitors of ADP-ribosylation reactions besides nicotinamide, most of them pyridine analogues, similarly prevented insulin-induced receptor loss. Spermine decreased the number of insulin receptors in IM-9 cells, but this effect was not inhibited by nicotinamide.

Cells, Cultured↗
PubMed1981

Studies on the bioactivity of radioiodinated highly purified bovine thyrotropin: analytical polyacrylamide gel electrophoresis.

Highly purified bovine TSH (stored in solution at -70 C) was radioiodinated by the stoichiometric chloroamine-T method. The iodinated material ws subjected to analytical polyacrylamide disc gel electrophoresis. TSH was eluted from gel slices (1 mm width) and was analyzed for radioactivity and bioactivity. The latter was determined using the cultured thyroid cell cAMP response assay. Radioactivity in the TSH preparation migrated separately from bioactivity, but concordant with the protein bands observed in gels run in parallel. Further studies performed on bovine TSH purified in our laboratory, as well as on a different TSH preparation of exceptionally high potency (both stored as lyophilized powder) revealed a different pattern, with TSH bioactivity and radioactivity eluting concurrently. Iodination of TSH did not alter its electrophoretic migration on disc gel electrophoresis. In all preparations polymorphism of TSH bioactivity was observed, with at least four separate protein bands containing TSH bioactivity being present in our preparation. The relationship between the degree of iodination and retention of TSH bioactivity was examined. Incorporation of 125I into TSH was greatly different at two different concentrations of chloramine-T. Despite this, however, the progressive loss of TSH bioactivity was similar at both concentrations, indicating that incorporation of iodine into the TSH molecule is not itself responsible for the decrease in bioactivity. These studies indicate variability among different TSH preparations in terms of their retention of bioactivity. Significant loss of TSH bioactivity appears to occur during storage in solution. The damage to the biological activity of TSH during the iodination procedure is more likely related to the oxidation process than to the incorporation of iodine.

Adenoma↗
PubMed1981

Serum thyroglobulin levels in the newborn.

To study the pattern of thyroglobulin (Tg) serum concentrations in the first days of life, Tg, TSH, T3, and T4, were measured in both maternal and cord blood at delivery and 1, 6, 12, 24, 48, 72, and 96 h after birth in 16 newborns. Tg levels at birth wee higher in cord blood than in maternal blood. After birth, a prolonged Tg rise occurred. The increased levels became significant at 6 h and were maintained throughout the study. Tg levels were not correlated with serum levels of T3, T4, and TSH. We conclude that either a reduced Tg MCR or an increased thyroidal secretion of Tg after endogenous TSH stimulation in the newborn is a possible explanation for the elevated Tg levels occurring during the first days of life.

Female↗
PubMed1981

Thyroid-stimulating immunoglobulin bioassay using cultured human thyroid cells.

Modifications are described in the cultured thyroid cell cAMP assay for TSH which make it suitable for the measurement of thyroid-stimulating immunoglobulins. Comparison was made between this assay and two others measuring cAMP responsiveness in human thyroid tissue, namely the thyroid slice and thyroid plasma membrane adenylate cyclase assays, all performed with the same tissue sample. Of immunoglobulin G (IgG) samples from 7 unselected patients with untreated hyperthyroidism associated with Graves' disease, 5 produced significant stimulation of cAMP content in cultured thyroid cells when compared to pooled normal IgG. None of these 7 produced a statistically significant increase in thyroid slice cAMP content when assayed in triplicate, the same replicate number used in the cultured thyroid cell assay. Similarly, none of the same Graves' IgG samples produced significant stimulation (vs. control IgG) in the membrane adenylate cyclase assay, in which sensitivity to TSH stimulation was very poor. With a scaled-down modification of the assay using microtiter wells and acetylation to enhance detection of cAMP in the RIA, significant TSI activity was observed in 15 of 18 (83%) IgG samples from patients with untreated Graves' disease. The data indicate the excellent sensitivity and precision of the thyroid cell cAMP assay, as well as its convenience.

Biological Assay↗
PubMed1980

Measurement of reverse triiodothyronine in dried blood spot: methodology and clinical application as a screening procedure for detection of congenital hypothyroidism.

A new sensitive radioimmunoassay method for measuring reverse triiodothyronine (rT3) concentrations in dried blood samples, designed to screen newborn infants for congenital hypothyroidism, has been developed. Paper strips are impregnated with cord blood and dried. Duplicate 5-mm diameter discs are punched from the paper strips and added directly to the radioimmunoassay reaction mixture. After incubation, bound and free hormone are separated by dextran-coated charcoal. The disc remains in the solution throughout the procedure and the assay can be completed within 24 hr. Recovery of rT3 is greater than 95% and coefficients of variation are 9.4% (intraassay) and 12.2% (interassay) at an rT3 concentration of 220 ng/dl. At very low rT3 concentrations (25 ng/dl), coefficients of variation are 14.2% (intraassay) and 18.7% (interassay). The method readily detects 12.5 ng/dl of rT3. With this paper disc method, rT3 was measured in 38 newborns and compared with serum rT3 measured in the same subjects by a standard radioimmunoassay method. The correlation between rT3 values measured in dried blood disc and in serum was very high (r = 0.918). The rT3 in dried blood discs from the cord blood of 745 normal newborns was 228.9 +/- 76.0 ng/dl (mean +/- SD). In contrast, two infants with proven congenital hypothyroidism had rT3 values of 35 and 75 ng/dl, respectively. This study indicates that rT3 can be easily measured in dried blood discs and suggests that the described method may be a useful screening procedure in a program for the detection of neonatal hypothyroidism.

Congenital Hypothyroidism↗
PubMed1980

Thyroid-pituitary function in eight anencephalic infants.

The function of the thyroid pituitary axis was investigated in 8 anencephalic infants with no hypothalamus. Thyrotrophin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyrone (reverse T3 and rT3) were measured in the cord blood in 5 cases and during the first 4 h of life in 3 cases. TSH response to synthetic thyrotrophin-releasing hormone (TRH) (200 microgram iv) was carried out in two cases and thyroid hormone response to bovine TSH (5 IU iv) was evaluated in 3 cases. The following results wre obtained: 1) The pituitary gland was found in all infants and the thyroid was normal both grossly and by microscopic sections. 2) TSH levels at birth were normal but there was no spontaneous post-delivery surge. 3) T4 and T3 values at delivery were within normal range, but no T3 increase was present after birth. rT3 levels at birth were higher than normal in 3 cases. 4) Administration of TRH caused a marked and rapid TSH release. 5) Thyroid hormone response to TSH was normal. The present findings suggest that in the anencephalic foetus both pituitary TSH-secreting cells and the thyroid gland do develop despite the absence of the hypothalamus and are able to function if adequately stimulated.

Anencephaly↗
PubMed1978

Increased serum thyroglobulin levels in patients with nontoxic goiter.

Thyroglobulin (Tg) levels were found to be elevated in 30 to 35 patients with euthyroid sporadic goiter and in 15 of 37 patients with euthyroid endemic goiter. The elevated Tg levels in the goitrous patients did not correlate with either goiter size, TSH levels, or urinary iodine excretion, but did correlate with the triiodothyronine to thyroxine ratio. It was concluded, therefore, that in both sporadic and endemic euthyroid goiters, factors other than goiter size and TSH, such as hypoiodination of Tg may be responsible for the elevated Tg secretion.

Adult↗
PubMed1977

A radioimmunoassay for human thyroglobulin: methodology and clinical applications.

A specific double-antibody radioimmunoassay with a sensitivity of 2.5 ng/ml has been developed for measuring thyroglobulin (Tg) in human serum. As endogenous anti-Tg antibodies in serum interfere in the assay, only sera with a negative tanned red cell (TRC) test are suitable for analysis. Tg was detectable in 84.7% of the euthyroid subjects, with a mean value of 6.1 (values ranging from nondetectable to 43.0 ng/ml). Values were significantly higher in women than in men. Tg release by the thyroid appears to be under pituitary control, as suggested by TSH stimulation and T3 suppression tests. Elevated Tg levels were found in hyperthyroidism, simple goitre, and differentiated thyroid carcinoma. The significance of circulating Tg and the possible application of the Tg RIA are discussed.

Adolescent↗
PubMed1977

Thyrotropin and prolactin response to intraspinal TRH administration in man.

The effect of intraspinal (i.s.) TRH administration of Prolactin (Prl) and thyrotropin stimulating hormone (TSH) serum levels was studied in order to verify the existence of a ventricular route in man for releasing factor delivery to the anterior pituitary, which has been previously reported in rats. Ten young male subjects were given 200 microgram thyrotropin releasing hormone (TRH) i.s. injections and Prl and TSH were measured by radioimmunoassay (RIA) before and at various times after TRH administration. In the same subjects, an i.v. TRH test was also performed. After i.s. TRH, a prompt Prl increase (peak values at 10-30 min and return to baseline within 150 min) and a delayed increase (3-5 h following TRH injection) were observed in 7 and 5 subjects respectively, while an early elevation in serum TSH occurred in 6 subjects and a late one in other 6. In two subjects, a biphasic response of both tropins was present. Prl and TSH response to i.v. TRH was within the normal range in all cases; no late rise of the 2 hormones was observed. A kinetic experiment with 125I-TRH was also carried out to elucidate the mode of i.s. vs i.v. TRH action. These results confirm in man data reported in animals which suggest that TRH can be transported from the cerebrospinal fluid (CSF) to the portal system and the hypophysis.

Humans↗
PubMed1976

Growth hormone levels in diabetes. Correlation with the clinical control of the disease.

We carried out contemporaneous daytime blood sugar and growth hormone (HGH) determinations in eight juvenile and six middle-aged diabetics under both poor and good metabolic control. A continuous blood sampling technic was used. The following results were obtained: 1. HGH values in poorly controlled diabetics were higher and more fluctuating than in normals of a corresponding age. 2. After good control was reached, a significant HGH decrease was observed in all patients but one. In this condition HGH levels were normalized in middle-aged diabetics but not in juvenile ones. In the latter group HGH values, even if decreased, were persistently higher than in controls of the same age. 3. No difference was observed between newly diagnosed diabetics and patients known to have had diabetes for some years. Our data support the suggestion that HGH abnormalities in diabetes are a consequence of the metabolic disturbance.

Adolescent↗
PubMed1975

Effect of dexamethasone on thyroid hormone response to TSH.

The effect of short-term dexamethasone administration (8 mg daily for 3 days) on thyroid hormone response to exogenous TSH (bovine TSH, 5 IU i.m.) was studied in 16 euthyroid volunteers. Serum T3 and T4 concentrations were measured by radio-immunoassay prior to and 2, 6, 12, 24, and 49 hr after bTSH injection, both under basal conditions and during dexamethasone treatment. In all subjects bTSH administration raised both T3 and T4 concentrations significantly. Dexamethasone treatment induced a slight depression of endogenous TSH (m +/- SEM = 2.0 +/- 0.4 versus 1.6 +/- 0.3 muU/ml) and T4 (6.8 +/- 0.4 versus 6.1 +/- 0.2 mug/100 ml) basal values and a significant decrease in T3 value (1.16 +/- 0.09 versus 0.64 +/- 0.06 ng/ml, p = 0.005). The mean increment of both T3 and T4 after bTSH injection was percentually unchanged during dexamethasone treatment but, due to lowered basal value, T3 levels at each time interval after TSH + dexamethasone were significantly lower than the corresponding values observed after TSH alone. The present data show that high dexamethasone doses decrease T3 serum levels significantly without inhibiting T3 response to TSH stimulation. Only a slight lowering was observed in T4 levels.

Adolescent↗
PubMed1975

The effect of short-term triiodothyronine administration on thyroxine response to exogenous TSH in man.

In order to examine whether thyroid hormone concentration interfere with the thyroid gland responsivity to TSH, paired studies on the effect of short-term T3 treatment on T4 response to exogenous TSH ( 5 I.U. i.m.) were carried out in 10 euthyroid volunteers. During T3 administration ( 120 mcg/day for 4 days starting 48 hr before TSH injection) a significant decrease in T4 concentrations was observed both prior to and after TSH, with an inhibition of the T4 response ranging from 36-77% as calculated from the area under the response curve. The present data are in agreement with the existence of a "short-loop" thyroid-thyroid regulatory mechanism in man. In fact, the decreased percent rise of T4 after TSH suggests an inhibitory effect of T4 release following TSH, even though a modification of T4 kinetic parameters during T3 administration may account for a portion of the lowering of T4 blood concentrations.

Adult↗