Search PubMed⌕ Search

Biomedical subjects

L Chiovato

Publications and source records attributed to L Chiovato.

121 records · Page 7Linked to original sources
PubMed1982

Studies on thyroid cell surface antigens using cultured human thyroid cells.

Human thyroid cells in primary culture were used for studies of thyroid cell surface antibodies in patients with thyroid autoimmune disorders. Radioiodinated IgG preparations containing thyroid microsomal antibody (TMAb), thyroid stimulating antibody (TSAb) and/or thyroglobulin antibody (TgAb) were tested for binding to thyroid cells. Binding was observed with radioiodinated IgG from patients with Graves' disease, Hashimoto's thyroiditis and idiopathic myxoedema containing TMAb, irrespective of the presence of TSAb and TgAb, while negative results were obtained with normal IgG. A dose-dependent inhibition of binding to thyroid cells was produced by the addition of the corresponding unlabelled IgG preparations. Evidence for tissue specificity was provided by the absence of binding to human skin fibroblasts used as controls. Preabsorption with human thyroid microsomes completely abolished the binding to thyroid cells of a radioiodinated TMAb positive IgG preparation, while only incomplete removal of the reactivity to thyroid microsomes was produced by preabsorption with thyroid cells. These data suggest that some but not all microsomal antigenic determinants are expressed on the thyroid cell surface. Binding to thyroid cells was also observed with purified TgAb, indicating that thyroglobulin antigenic determinants are present on the surface of thyroid cells. No evidence of binding was obtained with a TSAb positive Graves' IgG preparation with undetectable TMAb and TgAb. Unlabelled IgG preparations containing TMAb from patients with either Hashimoto's thyroiditis or idiopathic myxoedema were shown to inhibit the binding to thyroid cells of radioiodinated TMAb positive Graves' IgG and vice versa. These data indicate that antibodies present in these thyroid autoimmune disorders share common thyroid cell surface antigens. However, the binding of radioiodinated IgG from a patient with idiopathic myxoedema was only partially inhibited by Graves' or Hashimoto's IgG, suggesting that some of the thyroid cell surface antibodies of idiopathic myxoedema may not be detectable in other thyroid autoimmune disorders.

Antibodies↗
PubMed1979

Solubilization of human thyroid microsomal antigen.

The ability of detergents (Triton X-100 and deoxycholate), high ionic strength solution (3 M KC1), and proteolytic enzymes (papain and trypsin) to solubilize human thyroid microsomal antigen was studied. Antigenic activity released from thyroid microsomal preparation into the incubation mixture was separated by centrifugation at 143,000 x g for 90 min and measured using 125I-labeled human immunoglobulin G (IgG) with elevated antimicrosomal (anti-M) and undetectable anti-thyroglobulin antibodies (anti-M IgG). All solubilized materials were shown to bind [125I]anti-M IgG and to inhibit its binding to untreated thyroid microsomes. These effects were specific and dose related. Measurements of specific activity and total amount of solubilized antigen by an absorption technique showed that Triton X-100 was the most effective agent, followed by deoxycholate, papain, trypsin, and 3 M KC1 in decreasing order. Affinity chromatography with the deoxycholate-solubilized material coupled to Sepharose 4B resulted in a 15.6-fold purification of [125I]anti-M antibodies. The present results indicate that thyroid microsomal antigen may be solubilized by several agents and this can provide the basis for its identification and purification.

Antigens↗
PubMed1978

Comparison of radioassay and haemagglutination methods for anti-thyroid microsomal antibodies.

Parallel measurements of circulating anti-thyroid microsomal (anti-M) antibodies by radioassay and haemagglutination were performed on subjects with or without thyroid disorders. Three-quarters (75.4%) of control subjects had undetectable antibody levels (less than 10 u/ml) by radioassay and only 3.1% had concentrations of greater than or equal to 75 u/ml. Abnormally elevated levels (greater than or equal to 75 u/ml) were found in most of the patients with Hashimoto's thyroiditis (94.1%) or idiopathic myxoedema (86.7%), in the majority (75.0%) of those with Graves' disease and only in a minority of those with other thyroid disorders. The percentage of positive sera by haemagglutination was very similar in all groups to that of abnormal values observed in the radioassay. Direct comparison of parallel tests on a total of 631 sera revealed a highly significant correlation (r = 0.91, P less than 0.001) between the two methods, but elevated antibody titres by haemagglutination were found in some sera with negative radioassays. All these sera were from a single patient with thyroid carcinoma associated with Hashimoto's thyroiditis and had elevated levels of anti-thyroglobulin (anti-Tg) antibodies. Evidence that such discrepancies were due to anti-Tg antibodies reacting with microsomal-bound Tg was provided by the demonstration that the haemagglutination produced by these sera could be completely inhibited by the addition of Tg. A similar inhibition was observed with two rabbit antisera to human Tg, but not with sera from patients with thyroid autoimmune disorders containing high levels of anti-microsomal anti-bodies.

Adenoma↗
PubMedDate not supplied

Measurement of thyroid cell surface antibodies by radioassay using human cultured thyroid cells.

The present report describes a sensitive and quantitative binding radioassay for measurement of thyroid cell surface antibodies (TCSAb). Enzyme-dispersed thyroid cells from surgical specimens of human normal thyroid tissue were used after 7 days of culture. 125I-labelled Graves' IgG was shown to bind to cultured thyroid cells. The binding was time-and temperature-dependent and increased linearly with the number of thyroid cells. Evidence for specificity was provided by the lack of binding of radioiodinated Graves' IgG to human fibroblasts and by the negligible binding of 125I-labelled normal IgG to thyroid cells. A dose-dependent inhibition of binding of 125I-labelled Graves' igG to thyroid cells was produced by the addition of graded amounts of the unlabelled original Graves' IgG preparation, but not by normal IgG. Assays for TCSAb were performed on IgG preparations from patients with and without thyroid autoimmune disorders using the original Graves' IgG preparation as reference standard. Results were expressed in terms of arbitrary units/100 microgram IgG, 1 unit corresponding to the minimum amount of the standard IgG producing a significant inhibition of binding. Negative tests were found in most normal subjects (15/18) while low TCSAb levels (less than or equal to 1.8 U/100 microgram IgG) were detected in 3 cases. Increased TCSAb levels were found in the majority of the patients wit Graves' disease (14/21), in most of the patients with idiopathic myxedema (9/10) and in all of those with Hashimoto's thyroiditis (10/10).

Autoantibodies↗
PubMedDate not supplied

Measurement of cAMP accumulation in Chinese hamster ovary cells transfected with the recombinant human TSH receptor (CHO-R): a new bioassay for human thyrotropin.

Circulating TSH bioactivity may vary in several clinical and experimental conditions. Since the reliability of the current methods for the measurement of TSH bioactivity is limited, a new bioassay based on cAMP accumulation in Chinese Hamster Ovary cells transfected with recombinant human TSH receptor (CHO-R) was set up. The sensitivity was 0.3 +/- 0.1, 0.4 +/- 0.1 and 0.01 +/- 0.01 micrograms/L for TSH IRP 80/558, recombinant human TSH and bovine TSH, respectively. Standard curves were parallel, and the intra- and inter-assay coefficients of variation were 13 +/- 1.1% and 22 +/- 1.9%, respectively. LH, FSH, CG and TSH subunits did not stimulate cAMP accumulation up to high concentrations. Circulating TSH was partially purified by immunoaffinity separation and concentrated before being bioassayed. However, plain sera with high TSH levels, such as those from primary hypothyroid patients (PH), could be directly tested in CHO-R bioassay, provided that sera were added at concentrations lower than 10%. TSH from 6 normal subjects had biological to immunological ratio (B/I) ranging from 0.6 to 2.1 (mean +/- SD = 1.4 +/- 0.5). TSH from 6 patients with PH showed bioactivity significantly lower than in normals (B/I = 0.6 +/- 0.3; p < 0.001; range = 0.3-1.1). TSH from 5 patients with central hypothyroidism of hypothalamic origin (CH) had undetectable basal bioactivity (B/I < 0.2), which normalized in only one patient after acute TRH and in all patients after chronic TRH administration. In conclusion, CHO-R cells provide an excellent tool for evaluating TSH bioactivity, owing to high sensitivity, specificity, reproducibility and feasibility of the assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Free thyroxine values in dried blood spots on filter paper in newborns are related to both gestational age and birth body weight.

The results of free thyroxine (FT4) measurements in dried blood spots on filter paper in 744 euthyroid newborns (616 at term, 128 preterm), 10 newborns with congenital hypothyroidism and 4 euthyroid newborns with congenital TBG deficiency are reported. FT4 was measured by column adsorption chromatography of free hormone followed by radioimmunoassay in the eluate. FT4 values averaged 24 +/- 0.2 pmol/L (mean +/- SE) in euthyroid newborns, 23.0 +/- 0.9 pmol/L in euthyroid newborns with TBG deficiency (p = NS), and 5.7 +/- 0.4 pmol/L in hypothyroid newborns (p less than 0.001 vs both groups). Total T4 (TT4) values in newborns with TBG deficiency were not different from those in hypothyroid newborns, but were significantly lower than those in euthyroid newborns without TBG abnormalities. FT4 values were higher in full-term newborns than in preterm newborns (25.2 +/- 0.3 vs 21.2 +/- 0.5 pmol/L, p less than 0.001). In both full-term and preterm newborns FT4 values in dried blood spots increased with birth body weight (bbw), virtually plateauing when bbw was greater than 2,500 g. The cut-off values established on the basis of the bbw (8.0 and 13.1 pmol/L for a bbw of less than or equal to 2,500 g and greater than 2,500 g, respectively) showed higher specificity and predictive value of positive results than the cut-off values based on the gestational age. In any case, the sensitivity, specificity and predictive values of FT4 determinations proved to be higher than those of TT4 and TSH measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMedDate not supplied

Changes of circulating thyroid autoantibody levels during and after the therapy with methimazole in patients with Graves' disease.

The changes occurring in the levels of circulating thyroid microsomal antibody (M-Ab) and antithyroglobulin antibody (Tg-Ab) during antithyroid drug therapy were studied in 32 patients receiving methimazole for Graves' disease. M-Ab was determined by competitive binding radioassay and Tg-Ab by a sandwich radiometric method. Before treatment 25 subjects (78.1%) had abnormally elevated (greater than or equal to 75 U/ml) M-Ab levels. A more than 30% reduction of M-Ab concentration with respect to the pretreatment value was found in 16 (64.0%) of these patients within the first 3-5 months of therapy, in 23 (92.0%) within 8-11 months and in 21 (84.0%) at the end of treatment (16-18 months). No change was found in the 7 patients with initial M-Ab levels less than 75 U/ml. The reduction of M-Ab was more pronounced in the patients with good control of thyrotoxicosis than in those who were still hyperthyroid or were rendered hypothyroid during treatment. Twenty-three patients were followed after completion of the course of methimazole therapy, and 13 of them showed relapse of hyperthyroidism. A significant rise of M-Ab with respect to the values observed at the end of treatment occurred in all relapsing patients who had abnormally elevated M-Ab levels before therapy. With one exception, no M-Ab increase was found in the 10 nonrelapsing patients. However, no difference between relapsing and nonrelapsing patients was observed when the M-Ab changes occurring during treatment were considered. A similar trend during and after withdrawal of therapy was noted for Tg-Ab but, because of the relatively small percentage of positive subjects (25%), the results were less conclusive. The present data indicate that methimazole treatment induces a fall of thyroid antibodies in patients with Graves' disease, and that relapse of hyperthyroidism is associated with an increase of these antibodies. However, the antibody changes occurring during treatment showed no prognostic value in predicting the outcome of therapy.

Adolescent↗
PubMedDate not supplied

Lectin-induced expression of DR antigen on human cultured follicular thyroid cells.

HLA-DR antigens, the human equivalent of mouse I region-associated or Ia products, are polymorphic cell surface sialoglycoproteins involved in initiation of the immune response. Their expression is normally restricted to B lymphocytes, macrophages, dendritic and other antigen-presenting cells and vascular endothelium and possibly some cells of the mucosa lining body cavities. HLA-DR expression can be modified during cell differentiation; B lymphocytes become negative on maturing to plasma cells and human T lymphocytes acquire these antigens when activated in vitro or in vivo. We report here that human thyroid follicular cells which are normally negative for HLA-DR molecules, can be induced to express these antigens when cultured with phytohaemagglutinin (PHA), concanavalin A (Con A) or pokeweed mitogen (PWM). These lectins exert their action directly on the thyroid cells with no concomitant mitogenic effect.

Animals↗
PubMedDate not supplied

Thyroiditis: clinical aspects and diagnostic imaging.

Thyroiditis belongs to a heterogeneous group of inflammatory thyroid diseases. Hashimoto's thyroiditis, has an autoimmune pathogenesis: patients can be euthyroid or develop hypothyroidism, but may also experience transient thyrotoxicosis. Silent and postpartum thyroiditis also recognize an autoimmune origin; their clinical course being characterized by transient thyrotoxicosis occurring either sporadically or post-partum. Subacute thyroiditis is a painful, inflammatory disease of viral origin. Acute thyroiditis is a rare, serious, bacterial inflammatory disease. Riedel's thyroiditis is a rare chronic inflammatory disorder of unknown etiology, characterized by dense thyroid fibrosis. A diffuse thyroid hypoechogenicity is the hallmark of Hashimoto's thyroiditis, due to extensive lymphocytic infiltration of the gland. In postpartum and silent thyroiditis a diffuse or multifocal hypoechogenicity is found, while subacute thyroiditis is characterized by multiple ill-defined and migrating hypoechogenic areas. Both in acute and Riedel's thyroiditis there is marked hypoechogenicity.

Adolescent↗
PubMedDate not supplied

[Occupational exposure to endocrine disruptors: state of the art].

Research into how exposure to "endocrine disrupters chemicals" affects human health is attracting increasing attention among European and international scientists since these contaminants are so widespread in the home and work environment and can have far-reaching effects on mental and physical health. Here we draw a general picture of studies to date on specific occupational exposures to single chemicals such as bisphenol A, styrene, etc., or homogeneous groups such as pesticides, metals, dioxins, phthalates and others. Although the exposure occurs in different ways, the toxic mechanisms of action vary widely, and it is hard to establish precisely the conditions of occupational exposure, significant correlations are nevertheless evident between the potential dose and its effects and further studies are certainly needed. There is still much debate on the epidemiological methods employed, which may overestimate exposure. The "measure" or at least an accurate description of exposure conditions is critical to the whole question and attempts to ensure this involve standardized procedures and statistical tests as the basis for a protocol for assessing the risk of occupational exposure. Investigations to date have focused on the effects on the reproductive system, in males in particular. However, considering the broad range of equilibria and systems on which endocrine destructive compounds can act, the international scientific community needs to persist in its efforts to develop methods for checking the effects on other endocrine organs--particularly the thyroid gland--and on the immune and neurological systems.

Adult↗
PubMedDate not supplied

Thyroid autoimmunity: really an important cause of sporadic congenital hypothyroidism?

The transplacental transfer of maternal antithyroid antibodies has recently been hypothesised as an aetiological factor in CH. In order to test this hypothesis, mothers and newborns identified by neonatal screening as suffering from hypothyroidism were tested for TgAb, MAb and TSHBAb. Significant titres of MAb and TgAb antibodies were found in 5% of the newborns and their mothers. TSHBAb was found in 1 out of 18 newborns and 1 out of 14 mothers. A causal link was found between the transplacental transfer of IgG inhibiting thyroid growth and function induced by TSH from a mother with Hashimoto's thyroiditis a newborn with CH and in her CH newborn. However the present series did not reveal the high percentage of cases with CH and thyroid antibodies reported by others and particularly not among the neonates born to mothers without any kind of maternal thyroid pathology. It therefore seems that the role of autoimmunity in the pathogenesis of CH and TH is yet to be clarified.

Autoantibodies↗
PubMedDate not supplied

[Congenital hypothyroidism. Comparison of neuropsychological development of monozygotic twins].

Early treated congenital hypothyroidism (CH) allows a normal neuropsychological development in many cases, but sometimes light neuromotor, linguistic, behavioural disturbances are described. In this work we compare two 9 year old twins to study the direct influence of CH in the neuropsychological development, eliminating variables linked to environment and the genetic aspects; one of the twins is affected by early treated congenital hypothyroidism, the other doesn't show any somatic, motor, linguistic, cognitive or behaviour affection. Our intention is to value the influence of CH in the neuropsychological development eliminating the variables linked to environment and to the genetic aspects. From this study emerges that both the somatic and neuropsychological development of the two twins are globally identical still, slight differences could possibly be pointed out during the evaluations, in the their neuropsychological performances. The psychomotor development of the hypothyroid twin resulted to be normal, but slower than the normal twin in any time. In the light of these results we can hypothesize that the differences in the global development are linked to the presence of congenital hypothyroidism although early treated in one of them, because the other variables linked to the genetic, environmental and socio-cultural factors are of no relevance whatsoever in this case. The two sisters are actually genetically and phenotypically identical, and both subject to the same familiar dynamics and receive the same education.

Child↗