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E Macchia

Publications and source records attributed to E Macchia.

48 records · Page 3Linked to original sources
PubMed1983

TSH-displacing activity versus TSH-binding inhibiting activity of immunoglobulins from patients with Graves' disease.

Inhibition of binding of TSH to thyroid plasma membranes by immunoglobulins G (IgG) from patients with Graves' disease has been interpreted as evidence of an interaction with the TSH receptor, but other explanations may account for this phenomenon. Displacement of receptor-bound TSH might be a more direct index of such an interaction. The aim of the present study was to assess TSH-displacing activity (TDA) of Graves' IgG by a newly developed assay and compare TDA to TSH-binding inhibiting activity (TBIA) and thyroid-stimulating antibody (TSAb) activity. TDA was assessed by preincubating 125I-TSH with thyroid plasma membranes and by measuring residual bound 125I-TSH after addition of IgG. TBIA was evaluated by determining binding of 125I-TSH to thyroid plasma membranes preincubated with IgG. Results were expressed as % TSH-displacing or binding inhibition activities of test IgG with respect to normal control IgG. The percent of TDA positive Graves' IgG preparations (72.7%) was greater than that of TBIA positive (48.5%). There was no correlation between TDA and TBIA results, since 11 Graves' IgG preparations were TDA positive but TBIA negative, and 6 were TDA negative but TBIA positive. Hashimoto's or idiopathic myxedema IgG preparations were positive in 2/7 in the TDA and in 1/7 in the TBIA assays, respectively. Neither TDA nor TBIA correlated with TSAb determined by cAMP accumulation in thyroid plasma membrane. The TDA assay developed in this study appeared to be more sensitive than the more widely used TBIA assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1983

A sensitive method for assaying thyroid stimulating immunoglobulins of Graves' disease: use of the guanyl nucleotide-amplified thyroid adenylate cyclase assay.

The purpose of this study was to develop and validate a sensitive method for evaluating adenylate cyclase stimulation by thyroid-stimulating antibodies (TSAb), based on the measurement of thyroid membrane adenylate cyclase activity in the presence of a non-hydrolyzable GTP analogue, guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The addition of Gpp(NH)p (10(-5)M) produced a 10-fold increase of the sensitivity of the system for both TSH and TSAb. Immunoglobulin G preparations from sera of 30 patients with Graves' disease were tested for the adenylate cyclase stimulation either in the presence or in the absence of Gpp(NH)p: a significant stimulation was observed in 27/30 patients when the GTP analogue was added to the system, while only 20/30 patients were positive in the absence of the nucleotide. The advantage of Gpp(NH)p addition was also evident in a large series which included 57 patients with Graves' disease, 15 with Hashimoto's thyroiditis or primary myxoedema and 22 normal subjects. In fact, 88% of patients with Graves' disease resulted positive, while no significant stimulation was elicited by Hashimoto's thyroiditis, primary myxoedema and by normal immunoglobulins. The sensitivity achieved in our system which employs thyroid plasma membranes was similar to that obtained by other investigators with the use of thyroid slices or thyroid cells in primary culture. Furthermore, methods based on thyroid plasma membranes are supposed to have a better reproducibility, since the same tissue preparation, if appropriately stored, may be used in several different tests.

Adenylyl Cyclases↗
PubMed1982

Thyroid-stimulating immunoglobulins.

The presence of thyroid-stimulating immunoglobulins in patients with Graves' disease is well established. Considerable evidence has accumulated that these immunoglobulins are antibodies to a thyroid plasma membrane antigen whose precise nature remains to be identified. The question whether the antigen is related to the TSH receptor is still debated. The causative role of thyroid-stimulating immunoglobulins in the hyperthyroidism of Graves' disease is widely recognized. The use of human specific stimulation assays has circumvented the objection of the relatively low frequency of long-acting-thyroid-stimulator-(LATS)-positive patients. Individual variations in the thyroid response may account for the lack of correlation between the levels of thyroid-stimulating immunoglobulins and most parameters of thyroid function. In this respect, the interference of nonstimulatory thyroid antibodies and of other autoimmune mechanisms may be of importance. An important clinical implication of thyroid-stimulating immunoglobulin determinations is their value in predicting the relapse of hyperthyroidism in treated patients. This clinical application has been so far limited by the technical difficulties of the assays. This emphasizes the need for a simple and reliable test, which can be used for routine measurements of thyroid-stimulating immunoglobulins.

Graves Disease↗
PubMed1982

[Thyroid-stimulating immunoglobulins. The related antigens].

The presence of thyroid stimulating antibodies (TSAb) in patients with Graves' disease is well established. Considerable evidence has accumulated that these are antibodies to thyroid plasma membrane components related to the TSH receptor. The question of whether thyroid stimulation is mediated by a direct interaction with the TSH binding site is still debated. Recent data obtained by the use of monoclonal antibodies to the TSH receptor are consistent with the view that Graves' immunoglobulins comprise antibodies to at least two different components of the TSH receptor complex, one of which is more strictly related to the binding of TSH and the other to the transmission of the hormonal effect. The causative role of TSAb in the hyperthyroidism of Graves' disease is widely recognized. The use of human specific stimulation assays has circumvented the objection of the relatively low frequency of LATS-positive patients. Individual variations in the thyroid response may account for the lack of correlation between levels of thyroid stimulating immunoglobulins and most parameters of thyroid function. In this respect, the interference of non-stimulatory thyroid antibody and of other autoimmune mechanisms may be of importance. An important clinical implication of TSAb and TSH-binding inhibiting antibody determinations is their prognostic value in predicting the relapse of hyperthyroidism in treated patients. This clinical application has been so far limited by the technical difficulty of the assays. This emphasizes the need for a simple and reliable test, which can be used for routine measurements of TSAb.

Antibodies, Monoclonal↗
PubMed1981

Comparison between thyroid stimulating and tsh-binding inhibiting immunoglobulins of Graves' disease.

In the sera of patients with Graves' disease abnormal thyroid 'stimulating' immunoglobulins have been demonstrated by in vivo and in vitro assay systems. Conflicting results have been reported when thyroid stimulating and thyrotrophin (TSH)-binding inhibiting activities have been compared. The present study was performed in forty-nine hyperthyroid Graves' patients to ascertain the relationships among TsH-binding inhibiting immunoglobulins (TBII), measured by a radio-receptor assay, thyroid stimulating antibody(TSAb), assayed by stimulation of adenylate cyclase-cAMP system in human thyroid plasma membranes, and LATS, measured by McKenzie's mouse bioassay.TBII was detected in twenty-one of forty-nine (42.9%), TSAb in thirty-five of forty-nine (71.4%) and LATS in nineteen of forty-nine (38.8%).TBII was also present in four of sixteen (25%) patients with other thyroid autoimmune disorders. When the results obtained with the different techniques were compared, correlation was found between LATS response and TSAb activity ( =0.53, P less than 0.001), while there was no correlation between TSAb and TBII activities and between LATS response and TBII activity. These data conform that TSAb is specific and sensitive marker of Graves' disease and suggest that TBII activity is not necessarily synonymous with thyroid stimulation, and could reflect a different phenomenon concomitantly produced.

Animals↗
PubMed1976

Dissociation of responsiveness to thyrotropin-releasing hormone and thyroid suppressibility following antithyroid drug therapy of hyperthyroidism.

Responsiveness to synthetic thyrotropin-releasing hormone (TRH), thyroid suppressibility by triiodothyronine (T3) and the outcome of hyperthyroidism following prolonged therapy with thionamides were studied in a group of 35 patients with toxic diffuse goiter. TRH and T3 suppression tests were performed 10 days to 24 months (mean 4 months) after withdrawal of antithyroid drugs. Nineteen patients were euthyroid and had a normal thyrotropin (TSH) response to TRH, while 4 were recovering from mild hypothyroidism due to overtreatment and had an exaggerated response. No response was observed in 12 patients with recurrent hyperthyroidism. Positive T3 suppression tests were found only in 10 of the 30 cases examined. Peak and net 2 h secretion responses of TSH to TRH exhibited a significant inverse correlation with the levels of serum thyroxine and serum triiodothyronine, but were unrelated to the degree of thyroid suppressibility. Relapse or recurrence of thyrotoxicosis occurred in at least 9 of the 23 patients having no evidence of hyperthyroidism at the time of TRH test. Each of them was found to be responsive to TRH, while the T3 suppression test was negative in 8 and had to be discontinued in one because of thyrotoxic symptoms. The present data indicate that during the early period after completion of a prolonged course of antithyroid drug therapy responsiveness to TRH in toxic diffuse goiter is: a) correlated with circulating thyroid hormones, b) unrelated to the degree of thyroid suppressibility by T3 and c) of little value in predicting the long-term results of treatment.

Adult↗
PubMedDate not supplied

Thyroid hormone receptors in neonatal, prepubertal, and adult rat testis.

Thyroid hormone (TH) is involved in the differentiation and development of rat testis, whereas its role in adult testis function is still undefined. The aim of our work has been to further analyze the presence in the testis of rats of various ages of messenger RNA (mRNA) coding the different TH receptor (TR) subtypes using a sensitive assay, such as reverse transcriptase-polymerase chain reaction (RT-PCR). To rule out the possibility of an "illegitimate transcription," we have analyzed both T3-binding capacity of adult rat testis and the presence in the same organ of TR proteins by immunohistochemistry, using specific antibodies directed against the various TR isoforms. Messenger RNA coding for TR alpha1 and alpha2 isoforms was clearly visible in gels prepared from RT-PCR samples obtained from the testis of rats of all ages, including adults, whereas mRNA for the TR beta1-beta2 was absent. The T3 maximal binding capacity (Cmax) by nuclear extracts of testicular homogenates gradually decreased from birth to adulthood, still remaining significantly detectable in adult testis, and represented approximately 1% of the Cmax observed in the liver. The immunostaining technique revealed an intense nuclear staining along the basement membrane of testicular tubules prepared from rats of all ages and incubated with an antipeptide antibody specific for TR alpha1 (alpha1-403). Staining with an antipeptide antibody specific for TR beta1 (beta-62) was never present. Our data show that mRNAs coding for the functional TR alpha1, and also for the still undefined alpha2, are present in the testis of rats of all ages. T3-binding activity and immunohistochemical studies confirmed that the message is translated into proteins. The transcriptional activity clearly decreased from birth to adulthood, but it still remained significantly present. The presence of a TR alpha1 message indicates that the adult rat testis may be directly responsive to T3 and, therefore, suggests an action of TH on rat testis that is not only developmental, but also metabolic.

Aging↗