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A Pinchera

Publications and source records attributed to A Pinchera.

At least 415 records · Page 23Linked to original sources
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↗
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A new solid-phase immunoradiometric assay for anti-thyroglobulin autoantibody.

A newly developed sensitive and quantitative immunoradiometric assay (IRMA) for anti-thyroglobulin (anti-Tg) autoantibody is described. Serum samples to be tested are added to wells of polyvinyl microtiter plates coated with human thyroglobulin. After removal of the unbound material, anti-Tg antibody is determined by adding purified 125I-anti-human immunoglobulin G antibody. Using 1.0 microliter of serum anti-Tg antibody was detected in 81.2% of patients with Hashimoto's thyroiditis or idiopathic myxedema (n = 32), in 46.4% of those with Graves' disease (n = 28), in 11.9% of subjects with other thyroid disorders (n = 42) and in 4.2% of normal controls (n = 71). Similar percentages of positive tests were observed by passive hemagglutination (PH) and a good correlation was found between the antibody levels determined by the two techniques. Using larger amounts of serum (100 microliters) detectable anti-Tg antibody by IRMA was found in the majority of patients with thyroid autoimmune disorders who had negative PH tests. Quantitative measurements of anti-Tg antibody by IRMA could be obtained by using purified anti-Tg antibody as standard reference. The minimum detectable amount of anti-Tg antibody was 0.5 ng. The present method is proposed as a simple and convenient technique for quantitative measurement of any antibody, using wells coated with the appropriate antigen.

Antigen-Antibody Complex↗
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Expression of calcitonin gene-related peptide in medullary thyroid cancer.

We studied the expression of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in 18 patients with medullary thyroid cancer (MTC) in the neoplastic (primary or metastatic) tissue by immunohistochemistry and in the plasma by radioimmunoassay. CT immunoreactivity was found in 100% of the primary and metastatic MTC, CGRP was expressed in 66% of the primary tumors and in 73% of the metastases. Both the number of positive cells and the degree of staining were always higher for CT than for CGRP staining. While plasma CT concentrations were always increased in patients with metastases, 3 patients with metastases had undetectable plasma CGRP levels. A positive correlation was found between plasma CT and CGRP levels. These data indicate that CGRP is frequently expressed in MTC sections and that plasma CGRP measurement is an additional marker for MTC, although has no advantage with respect to CT measurements in monitoring the progression of the disease.

Adolescent↗
PubMedDate not supplied

Graves' disease and Turner's syndrome.

A case of a 17-year-old female with Turner's syndrome and Graves' disease is reported. The karyotype analyzed in peripheral blood lymphocytes showed a 45,X0 pattern without mosaicism. The diagnosis of Graves' disease was based on the presence of diffuse goiter and appropriate laboratory data, including elevated thyroid radioiodine uptake, increased serum thyroxine and free thyroxine index, detectable thyroid-stimulating antibody and elevated thyroid microsomal antibody titer. Hyperthyroidism was first recognized when the patient was 13-year-old and treatment wih carbimazole was instituted for 18 months. Relapse of hyperthyroidism occurred 9 months after withdrawal of therapy, and a second course of antithyroid drug treatment was given for two yr. Ovarian dysgenesis has been described with a relatively high frequency in patients with Hashimoto's thyroiditis, while the association with Graves' disease has been only occasionally encountered. This finding is surprising in view of the etiopathogenetic and genetic relationships between these two thyroid autoimmune disorders. Some possible explanations are offered to clarify this problem.

Adolescent↗
PubMedDate not supplied

Age- and sex-related variations of serum thyroxine binding globulin.

Measurements of serum thyroxine binding globulin (TBG) by a ligand partitioning sandwich assay were performed in 173 healthy subjects between three months and 92 yr of age. Significant sex-related differences were observed in subjects aged 21 to 50 yr. In males, serum TBG declined progressively reaching a nadir in the fourth decade and then increased with advancing age. In contrast, no significant age-related variation was observed in females.

Adolescent↗
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Graves' IgG stimulation of continuously cultured rat thyroid cells: a sensitive and potentially useful clinical assay.

A continuously cultured line of normal rat thyroid (FRTL) cells can be stimulated by immunoglobulin preparations from patients with Graves' disease as measured by increases in intracellular cAMP levels. Responsiveness is concentration-dependent but is delayed in time relative to thyrotropin. Additionally, the cells respond to Graves' immunoglobulins which have no long-acting thyroid stimulator (LATS) activity and are negative when adenylate cyclase stimulation in human thyroid membrane preparations is assayed. No correlation exists between the stimulation activity and the ability of a Graves' immunoglobulin preparation to inhibit thyrotropin binding; cells are responsive even in the presence of such inhibitor activity.

Adenylyl Cyclases↗
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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

Effects of the antileukemic drug L-asparaginase on sex hormone-binding globulin: studies in vivo and in vitro.

L-asparaginase, an antineoplastic drug used in the treatment of acute lymphoblastic leukemia (ALL), has been previously shown to inhibit the hepatic synthesis of thyroxine-binding globulin (TBG). In two children treated by this drug for ALL, a dramatic decrease in serum sex hormone-binding globulin (SHBG) concentrations was also observed. Serum SHBG levels were still below normal 10 days after L-asparaginase withdrawal. To ascertain whether this reduction was due to the inhibition of SHBG synthesis, SHBG was measured by an immunoradiometric assay (IRMA) in the medium from human hepatoblastoma-derived cells, Hep G2 cells, grown in the absence or presence of graded amounts of the drug from 0.1 nM to 0.1 mM. The results showed a dose-dependent inhibition of SHBG synthesis, with a 50% reduction of SHBG in the medium, assayed by IRMA, using 250 nM L-asparaginase. Furthermore, a time-dependent inhibition was observed using a fixed concentration of the drug (50 nM) added for variable time intervals (1-4 days). These data suggest that the changes observed in vivo are likely due to the inhibitory effect exerted by the drug on SHBG synthesis. This action is not specific, but is part of a general effect at the hepatic level.

Antineoplastic Agents↗
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Use of surgical gamma probe for the detection of lymph node metastases in differentiated thyroid cancer.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131I therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical reintervention when the nodal lesions persist after two 131I treatments. AIM: Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. METHODS AND RESULTS: After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131I doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. CONCLUSIONS: We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.

Adult↗
PubMedDate not supplied

Insulin-like growth factor II (IGF-II) immunohistochemistry in breast cancer: relationship with the most important morphological and biochemical prognostic parameters.

Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.

Adult↗
PubMedDate not supplied

Circulating neuron-specific enolase in medullary thyroid cancer.

The utility of determining circulating neuron-specific enolase (NSE) in medullary thyroid carcinoma was assessed in 25 patients followed up for a mean period of 45.6 months. In 5 patients tested before any treatment serum NSE concentrations were in the normal range. After total thyroidectomy abnormally high serum NSE concentrations (more than 9.8 ng/ml) were found in 1/3 patients with normal calcitonin (CT) in remission, in 2/10 with elevated CT levels but no evidence of disease and in 9/12 with elevated CT levels and documented metastases. The mean (+/- SD) NSE value in this last group was 12.0 +/- 12.6 ng/ml, significantly higher than in the other groups (p less than 0.005). The time course of serum NSE in patients with long follow-up seems to indicate that serum NSE rises when a large tumor mass is present and usually parallels the pattern of circulating CT. Effective treatment of the metastases is usually followed by reduction of serum NSE. Thus, serum NSE can serve as an additional humoral marker for medullary thyroid carcinoma, its elevation being associated with important metastatic involvement and with a poor prognosis of the tumor.

Adolescent↗
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Value of ER-D5 immunocytochemical determination in routine tissue sections of human breast cancer.

ER-D5 is a recently identified protein related to estrogen receptors (ER). Generally ER measurement requires fresh frozen tissue and for ER-D5 assay ethanol (E) fixation of the specimen is recommended. We evaluated the possibility of immunocytochemical detection of ER-D5 in routine formalin-fixed (F) sections in 51 breast cancers comparing the results with those obtained in the same specimens using E as fixative. The results of ER-D5 assay were expressed by the staining index (SI) taking values greater than or equal to 5 as positive. In all tumors ER was also assayed by a biochemical method (DCCA). The sensitivity of ER-D5 detection in F was only 33.3%, while the specificity was 94.4%. A lower cut-off value of SI for F sections (greater than or equal to 2) increased the sensitivity to 66.6%, leaving the specificity unchanged. A strong correlation was found between the SI of ER-D5 in E and F (p less than 0.001). The SI of ER-D5 in F sections was also well correlated with ER concentrations (p less than 0.001). These results suggest that immunocytochemical determination of ER-D5 in routine sections may be useful in retrospective studies of hormone dependence in breast cancer.

Adult↗
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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↗
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Orbital decompression for severe Graves' ophthalmopathy. Results of a three-wall operative technique.

Nine patients out of more than 300 with severe Graves' ophthalmopathy followed in this institution were submitted to orbital decompression carried out on 16 eyes by a three-wall procedure consisting of a transfrontal approach with the removal of the roof, the lateral wall and part of the floor of the orbit. All patients had been previously unsuccessfully treated by orbital radiotherapy and/or systemic corticosteroid administration. The main indications for surgery were marked proptosis or sight-threatening optic neuropathy. Results of treatment were evaluated on clinical grounds and by the variation of the ophthalmopathy index (OI). A significative reduction of proptosis was observed in all eyes, with a mean decrease in the Hertel reading of 3.2 mm, from 22.6 +/- 1.8 mm to 19.4 +/- 1.4 mm (p less than 0.001). A complete regression or improvement of inflammatory signs, corneal lesion and, with one exception, extraocular muscle dysfunction was obtained in all cases. Loss of visual acuity and other manifestations of optic neuropathy were present in 11 out of 16 eyes before surgery. A complete restoration or a marked improvement of optic neuropathy was obtained in 7 cases: failure occurred in the two patients (4 eyes) with longstanding sight loss. The OI decreased in all patients after surgery, from a mean pretreatment value of 8.6 to a mean posttreatment value of 3.8 (p less than 0.001). The clinical response to surgery was excellent in 4 cases, good in 3 and slight in 1; no changes were observed in the remaining patient. Bacterial meningitis which resolved with no sequelae occurred in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Thyroiditis as a model of organ specific autoimmune disease.

In the last few years a great deal of information on the etiopathogenetic aspects of organ-specific autoimmune diseases has been obtained from the extensive study of both animal models of experimental or spontaneous thyroiditis and of human thyroid autoimmune diseases. It has been clearly shown that genetic factors play a fundamental etiologic role. They are responsible for the dysregulation of the immune system and for the target organ susceptibility which favor the onset of the disease. Environmental factors are presumed to act as initiating or precipitating events, leading genetically predisposed individuals to thyroid autoimmunity. A number of immune mechanisms able to trigger autoimmune responses, such as antigenic cross-reactions and the aberrant expression of HLA class II molecules, have been suggested, but the definition of why and how they become operative requires further investigation. Data obtained from experimental models and from human thyroid diseases clearly indicate that the ongoing expansion of autoreactive T cells with specificity for thyroid autoantigens represents the main immunological event responsible for induction and maintenance of thyroid damage. Such autoreactive T cells can induce tissue lesions through activation of different effector systems and secretion of different combinations of lymphokines. In overt thyroid autoimmune diseases autoantibodies directed against functional molecules or cellular receptors can also be involved in the pathogenesis of tissue lesions. However, the pathogenesis of inflammatory destructive lesions of the thyroid is more complex and not yet fully elucidated. It is worthy of note that a large proportion of T cells present in inflammatory human thyroid infiltrates are apparently not directed against the thyroid autoantigens recognized so far.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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Radioimmunoassay for human thyroxine-binding prealbumin.

A radioimmunoassay (RIA) for human thyroxine-binding prealbumin (PA) is described. It employs highly purified PA, anti-human PA serum at 1:30,000 final dilution, normal bovine serum as a carrier, and polyethyleneglycol to precipitate the immune complexes. This assay is extremely sensitive (limit of detection less than 0.2 micrograms per dL or less than 3.6 X 10(-15) moles per tube), accurate (recovery = 98.7 +/- 9 percent, mean +/- S.D.) and reproducible (intra- and inter-assay coefficients of variation = 3.6 to 6.3 percent and 7.2 to 9.5 percent, respectively). There was a highly significant correlation when the RIA was compared with radical immunodiffusion or with PA maximal binding capacity for thyroxine (r = 0.944 and r = 0.724, respectively, p less than 0.001). Concentration of PA in sera from normal subjects (age range = 20 to 88 years) averaged 27.7 +/- 0.5 mg per dL (mean +/- S.E.M.), with significantly higher values in males than in females in all age groups with the exception of the older subjects (20 to 50 years: males = 26.5 to 37 mg per dL; females = 23.1 to 33.8 mg per dL). Levels of PA progressively declined after the fifth decade of life. Pregnancy, hyperthyroidism, chronic liver diseases, cystic fibrosis, cancer and other non-thyroidal illnesses were associated with decreased levels of serum PA. Untreated hypothyroidism and chronic renal diseases showed widely scattered values of PA. Inherited thyroxine-binding globulin (TBG) abnormalities and bisalbuminemia had no apparent effect on concentrations of serum PA.

Adult↗