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Biomedical subjects

S Mariotti

Publications and source records attributed to S Mariotti.

At least 145 records · Page 8Linked to original sources
PubMed1987

Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies in thyroid diseases.

Recent evidence indicates that human thyroid peroxidase (TPO) has most of the characteristics of the thyroid microsomal antigen. The question of whether TPO accounts for part or all of the antigenic activity recognized by circulating anti-microsomal antigen autoantibody (anti-M Ab) remains to be determined. The availability of an anti-TPO monoclonal antibody and of a highly purified TPO preparation allowed the development of specific and sensitive radioassays for anti-TPO autoantibody (anti-TPO Ab). In this study we compared anti-M Ab and anti-TPO Ab levels in serum from 128 subjects, including patients with Hashimoto's thyroiditis (n = 31), idiopathic myxedema (n = 11), hyperthyroid Graves' disease (n = 45), miscellaneous nonautoimmune thyroid disorders (n = 9), and normal subjects (n = 32). Anti-M Ab and anti-TPO Ab were measured by radioimmunological methods employing two different assay designs: 1) competitive radioassay (CR), based on the inhibition of radioiodinated antibody binding to human thyroid microsomes coated on microtiter wells, using a) [125I]immunoglobulin G (IgG) containing a high anti-M Ab titer (for anti-M Ab determinations), or b) [125I]anti-TPO monoclonal antibody (for anti-TPO Ab); and 2) sandwich immunoradiometric assay (IRMA) using microtiter wells coated with thyroid microsomes (for anti-M Ab determinations) or immunoaffinity-purified TPO (for anti-TPO Ab determinations) and [125I]anti-human IgG antibody. Anti-M Ab also was measured by passive hemagglutination. Anti-M Ab titers by PH closely correlated with anti-TPO Ab levels whether assayed by IRMA (r = 0.905; P less than 0.00001) or CR (r = 0.922; P less than 0.00001). Even closer correlations were found when anti-M Ab and anti-TPO Ab both were measured by the same type of radioassay procedure (IRMA, r = 0.945 and P less than 0.00001; CR, r = 0.957 and P less than 0.00001). No differences in the correlation between anti-M Ab and anti-TPO Ab results were found when the data in patients with different autoimmune thyroid disorders were analyzed separately. Further and more direct evidence for the identity of anti-M Ab and anti-TPO Ab was provided by the ability of purified TPO to completely inhibit the binding to thyroid microsomes of radioiodinated IgG preparations containing high anti-M Ab titers. In conclusion, our results provide strong support for the concept that TPO accounts for virtually all of the antigenic determinants reacting with the autoantibodies commonly termed anti-M antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens↗
PubMed1987

Cellular localization of the microsomal antigen and the thyroid peroxidase antigen.

Evidence has been accumulated that human thyroid microsomal/microvillar autoantigen (M) is expressed both in the cytoplasm and on the surface of thyroid follicular cells. The availability of this autoantigen to the immune system, possibly associated with abnormally expressed HLA-DR antigens may be relevant both to the triggering and to maintenance of thyroid autoimmune reactions. Preliminary biochemical characterization of M suggested that it was a glycoprotein with a mol. wt. of about 100-110 kD. recent studies carried out in our laboratories taking advantage of monoclonal antibodies provided evidence that the structure presently referred as M-Ag is represented by thyroid peroxidase (TPO). The identity between TPO and M is further supported by four-layer immunofluorescence analysis showing a complete overlap of the two antigens both in the surface and in the cytoplasm of thyroid cells and by the observation that the expression of M and TPO is similarly modulated by TSH, possibly through a cAMP-dependent mechanism.

Cells, Cultured↗
PubMed1987

Enhanced production of gamma-interferon by thyroid-derived T cell clones from patients with Hashimoto's thyroiditis.

T lymphocytes from thyroid infiltrate and peripheral blood (PB) of four patients with Hashimoto's thyroiditis (HT) were analysed at clonal level for their ability to secrete interleukin 2 (IL-2) and gamma-interferon (gamma-IFN). As controls, T cell clones from PB of four normal donors and from spleen of two trauma victims were used. While no abnormality was found in the capacity to produce IL-2, the proportion of gamma-IFN-producing (IFN-P) T cell clones derived from HT infiltrates was significantly higher (P less than 0.0005) than that of IFN-P clones derived from normal or patient PB. Most of CD4+ and CD8+ IFN-P clones from thyroid infiltrates, as well as a proportion of CD4+ PB-derived clones of patients with HT, released higher amounts of gamma-IFN than control clones. A relationship could be demonstrated between high gamma-IFN production and natural killer (NK) activity in T cell clones from thyroid and PB of HT patients. In fact, the percentage of IFN-P clones with NK potential (NK+) was remarkably higher (P less than 0.0005) in thyroid infiltrates than in normal spleen or PB. The proportion of IFN-P NK+ clones from patient PB was also significantly increased (P less than 0.02) but, unlike thyroid-derived clones in which the majority of IFN-P NK+ clones were CD8+, most PB-derived IFN-P NK+ clones from the same patients expressed the CD4+ phenotype. Almost all thyroid NK+ clones could be triggered to produce more gamma-IFN, while gamma-IFN synthesis by NK-negative thyroid clones was comparable to that of control clones. In view of the multiple effects ascribed to gamma-IFN in the cascade of events leading to immune responses, the abnormal potential to gamma-IFN secretion shown by intrathyroidal T lymphocytes may be of importance in the pathogenesis of autoimmune thyroiditis.

Adult↗
PubMed1986

L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibodies in idiopathic myxedema and in hypothyroid, but not in euthyroid Hashimoto's thyroiditis.

Thyroid microsomal (MAb) and thyroglobulin (TgAb) antibodies were sequentially measured by sensitive and quantitative radioassays in 17 patients with goitrous Hashimoto's thyroiditis (9 hypothyroid, 8 euthyroid) and in 19 patients with idiopathic myxedema before and at various time intervals up to 24-48 months after the institution of L-thyroxine therapy. Thyroid antibodies were also determined in 5 euthyroid subjects with Hashimoto's thyroiditis maintained without treatment for a similar period. During L-thyroxine administration a reduction of MAb with respect to the pretreatment level was found in 6 of the 9 (67%) hypothyroid patients with Hashimoto's thyroiditis and in 16 of the 19 (84%) patients with idiopathic myxedema. The decrease of MAb was highly significant in both groups (p less than 0.001 and p less than 0.0001, respectively). A fall of TgAb occurred in 2 of the 3 patients (75%) with hypothyroid Hashimoto's thyroiditis and in 9 of the 10 (90%, p less than 0.001) patients with idiopathic myxedema having abnormally elevated pretreatment TgAB levels. No consistent pattern of MAb and TgAb changes was observed in the euthyroid subjects with Hashimoto's thyroiditis, whether treated or untreated. In the hypothyroid patients with Hashimoto's thyroiditis a significant association was found between the decrease of MAb and the reduction of goiter size (p less than 0.05) occurring during L-thyroxine administration. Moreover, the decrease of MAb and TgAb in idiopathic myxedema was greater (p less than 0.05) in the patients with normalized serum TSH (less than or equal to 4 microU/ml) than in those showing only a partial reduction of serum TSH (greater than 4 microU/ml) under L-thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Treatment of amiodarone associated thyrotoxicosis by simultaneous administration of potassium perchlorate and methimazole.

Amiodarone iodine induced thyrotoxicosis occurs frequently in patients residing in areas of mild iodine deficiency and in patients with preexisting goiter. Drug therapy of the hyperthyroidism is often unsuccessful. Twenty-three patients with amiodarone induced thyrotoxicosis were either not treated, treated with 40 mg methimazole daily or with methimazole and 1 gm potassium perchlorate daily for up to 40 days and then with methimazole alone. Thyrotoxicosis was more likely to spontaneously remit in patients without goiter. Therapy with methimazole alone was unsuccessful in inducing euthyroidism in 5 patients with goiter. However, combined therapy with methimazole and potassium perchlorate rapidly alleviated hyperthyroidism in almost all patients with goiter. This drug combination is successful because perchlorate inhibits the active transport of iodine into the thyroid and methimazole blocks the intrathyroidal synthesis of thyroid hormones.

Adult↗
PubMed1986

Age, period, cohort and geographical area effects on the relationship between risk factors and coronary heart disease mortality. 15-year follow-up of the European cohorts of the Seven Countries study.

The effects of three major risk factors (i.e. serum cholesterol, systolic blood pressure and smoking habits) on prediction of coronary heart disease (CHD) mortality in relation to three nuisance variables--i.e. geographical location, age of subject at examination and period of examination--are analyzed using data from three different 5-year apart examinations of the Seven Countries Study and observations on CHD mortality in the corresponding 15-year follow-up period. First, a cross-classification exploratory analysis including both CHD-free subjects at entry and prevalence subjects, by different geographical areas, age classes and examination times is presented. Secondly, a logistic regression including the three major risk factors and the three nuisance variables, regarded both as confounders and effect modifiers is discussed. The prevalence status of the subjects is also considered as a nuisance variable in this second analysis. Results showed that: (a) there is a highly significant (p less than 0.001) marked decrease in the association between cholesterol level and CHD mortality with increasing age of subject; (b) a decreasing association with coronary heart disease mortality as age increases also holds for smoking habits (p less than 0.05). This association, however, tends to be reinforced with time (p less than 0.05), i.e. the relative risk of heavy smokers vs non-smokers is four times bigger in the period 1970-75, than in the period 1960-65, age and all other factors being equal; (c) a possible dependence of the association between systolic blood pressure and CHD on geographical area is suggested, although this finding could be the result of chance with a 10% probability.

Adult↗
PubMed1986

Cytolytic T lymphocytes with natural killer activity in thyroid infiltrate of patients with Hashimoto's thyroiditis: analysis at clonal level.

T Lymphocytes from thyroid infiltrates and peripheral blood (PB) of 3 patients with Hashimoto's thyroiditis (HT) were cloned using a microculture system previously shown to allow the clonal expansion of virtually all PB T lymphocytes from normal individuals. The phenotypic and functional features of a total number of 153 clones from thyroid infiltrates and 206 clones from PB were examined and compared with those of 272 clones derived from normal PB and spleens. The majority of clones derived from thyroid infiltrates of patients with HT had the cytotoxic/suppressor (T8+) phenotype, whereas the majority of clones from PB expressed the helper/inducer (T4+) phenotype. In addition, a consistent proportion (25%) of clones derived from PB of one patient had a phenotype (T3+T4-T8-) that was only occasionally found on clones obtained from PB or spleens of normal subjects. Most clones derived from both PB and thyroid infiltrates of the patients with HT had cytolytic activity, assessed by a lectin-dependent cytolytic assay against the murine P815 tumor cell line. The high frequency of cytotoxic T cells in thyroid infiltrates was related to the increased proportion of T8+ cells, whereas enhanced percentages of cytotoxic cell precursors with T4+ and T3+T4-T8- phenotypes primarily accounted for the high frequency of cytolytic T cells in the PB of the same patients. Many cytolytic T cell clones derived from thyroid infiltrates also had natural killer activity against human K562 and MOLT-4 target cells. These data provide the first functional analysis of T lymphocytes infiltrating the thyroid gland in patients with HT and suggest that the high proportions of cytolytic T cell precursors found in both thyroid infiltrates and PB of these patients may be of importance in determining the tissue damage in thyroid autoimmune disease.

Antibodies, Monoclonal↗
PubMed1986

Thyroid function modulates thymic endocrine activity.

The thymus produces humoral factors that induce proliferation and differentiation of T-cells, which are responsible for cell-mediated immunity. Recent data in animals suggest that such thymic hormone activity is modulated by the neuroendocrine network and, in particular, by thyroid hormones, but no information is presently available in humans. To study this question, we measured the circulating thymic factor called thymulin (Zn-FTS) in hyperthyroid and hypothyroid patients. Thymulin levels were higher in hyperthyroid patients than in normal subjects, whereas hypothyroid patients had lower thymulin levels than normal subjects. A significant correlation was found between circulating thymulin and serum T4 and T3 levels. Thymulin changes could be reversed by appropriate treatment in both groups of patients. Recent data indicate that zinc is required to confer biological activity on thymic hormone molecules. This raised the question of whether the influence of thyroid status on thymulin activity could be mediated by changes in serum zinc concentrations. No support for such an explanation was obtained by thymulin measurements by a modified bioassay using an optimal zinc concentration in the assay system. In conclusion, thyroid status modulates thymic endocrine function in humans. Whether and to what extent such modulation is relevant to the function of the immune system remain to be established.

Adolescent↗
PubMed1986

Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism.

We studied the effect of potassium perchlorate (KClO4) in patients with hypothyroidism due to amiodarone. The short term administration of KClO4 to six such patients led to prompt restoration of euthyroidism, while the three untreated patients remained hypothyroid for 2-6 months. Since KClO4 inhibits thyroid iodide transport, thereby blocking further entrance of iodide into the thyroid and decreasing intrathyroidal iodide content, amiodarone-associated hypothyroidism is probably secondary to the inhibitory effect of excess intrathyroidal iodine on thyroid hormone synthesis.

Adult↗
PubMed1986

Serum thyroid autoantibodies as a risk factor for development of hypothyroidism after radioactive iodine therapy for single thyroid 'hot' nodule.

Hypothyroidism is often observed after radioiodine treatment in Graves' disease, but it is considered a rare complication in single hyperfunctioning thyroid nodule ('hot' nodule). This concept has been recently challenged, but the available data are conflicting. In the present study we therefore assessed the development of permanent hypothyroidism in 126 patients with thyroid hot nodule treated with 131I (180 muCi/g of estimated nodule weight, total dose 5.5-28.9 mCi). Follow-up ranged between 1 to 11 years. Hypothyroidism was observed in 5 (4%) patients, corresponding to a cumulative incidence by life-table analysis of 4.8% ten years after treatment. No relationship was found between the development of hypothyroidism and the size of the nodule or the total amount of administered dose. Fifty-six patients with euthyroid hot nodule at the time of treatment had higher cumulative incidence of hypothyroidism after 10 years (9.7%) than those with toxic adenoma (1.5%) (0.1 greater than P greater than 0.05 by logrank test). When the patients were analyzed according to the presence or absence of serum antithyroglobulin and/or antithyroid microsomal autoantibodies, the prevalence of hypothyroidism after 131I treatment was higher (4/25 = 16%) in patients with significant serum antibody titres (greater than or equal to 1/400 by passive haemagglutination), when compared to that observed in subjects with negative antibody tests (1/101 = 1.0%). Life-table analysis showed in antibody positive patients a cumulative incidence of hypothyroidism after 10 years of 18.0% vs 1.4% in antibody negative patients (P less than 0.001 by logrank test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

In vivo activated cytotoxic T cells in the thyroid infiltrate of patients with Hashimoto's thyroiditis.

High proportions of T8+ cells with inverted T4/T8 ratio were found in freshly isolated thyroid lymphocytes from patients with Hashimoto's thyroiditis. In addition, about one third of thyroid infiltrating cells expressed the TAC antigen, whereas in patient peripheral blood (PB) or normal lymphocytes from PB or lymphoid organs the percentage of TAC-positive cells was consistently lower than 10%. Following negative selection with OKT4 or OKT8 monoclonal antibodies and complement, TAC+ T cells were enriched in the T8+ cell population. Thyroid infiltrating T cells from two patients underwent two different cloning procedures. In the first, single T cells were initially activated with phytohaemagglutinin (PHA) and interleukin 2 (IL-2), in the other with recombinant IL-2 (rIL-2) alone. The majority of T cell clones obtained by initial PHA-stimulation (55-65%) had the T8+ phenotype, but the frequency of T8+ clones obtained by stimulating T cells with rIL-2 alone was even higher (78 & 71%, respectively). The majority of T8+ clones elicited by PHA (35/37 & 36/38) and all the T8+ clones (36/36 & 22/22) obtained from thyroid infiltrates with initial stimulation by rIL-2 displayed cytolytic activity. Most of cytolytic T8+ clones obtained from thyroid infiltrates with both cloning procedures, displayed NK activity against human K562 and MOLT-4 target cells, but not against a NK-resistant target, such as Raji cells. These data suggest that in Hashimoto's disease a considerable proportion of thyroid infiltrating T cells are in vivo activated T8+ cytolytic T cells with NK activity, which may be of importance in determining or maintaining the tissue damage of the target gland.

Adult↗
PubMed1985

Ciliary dynein conformational changes as evidenced by the extrinsic fluorescent probe 8-anilino-1-naphthalenesulfonate.

The binding of 8-anilino-1-naphthalenesulfonate (ANS) to ciliary dynein ATPase leads to a marked increase in the dye's fluorescence intensity, accompanied by a blue shift in the observed fluorescence emission maximum. We found that dynein has 37 +/- 3 ANS binding sites and that experimentally applied ANS concentrations failed to alter enzyme activity. The fluorescence properties of the enzyme-dye complex were used to learn more about the binding characteristics of dynein substrates and effectors and to probe for possible conformational changes of the enzyme. The fluorescence of the dynein-ANS complex is increased by a number of substrates, including ATP, GTP, and UTP. The transfer of excitation energy from dynein chromophores to adsorbed ANS was also investigated. Our findings indicate that dynein appears to undergo a localized conformational change in its interaction with ATP. Native dynein was also found to be conformationally different from heat-activated or NEM-modified enzyme as evidenced by the emission and excitation spectra of the various enzyme-ANS complexes.

Adenosine Triphosphatases↗
PubMed1984

Cutaneous metastasis of a radiation-associated thyroid medullary carcinoma.

The rare event of a single cutaneous metastasis occurred in a 37-year-old white man two years after a subtotal thyroidectomy for sporadic medullary carcinoma is reported. The endocrine nature of the tumor is revealed by the ultrastructural study, and the type of secretion by the biochemical assay of calcitonin (CT) in the serum and in the tumor tissue extract and by the PAP (peroxidase-anti-peroxidase) technique with anti-CT antibodies on paraffin sections. The cytological and histological findings are described. Some peculiar ultrastructural aspects are presented in details. The fact that the patient received a course of Rx therapy (3,000 rads) on the neck for cervical syringomyelia at the age of 20 years is stressed.

Adult↗
PubMed1984

Surface markers and function of circulating thyroid autoantibody-producing cells.

The in vitro synthesis of antithyroglobulin (anti-Tg) and antithyroid microsomal (anti-M) autoantibodies by peripheral blood mononuclear cells (MNC) from patients with autoimmune thyroid diseases was investigated using sensitive immunoradiometric assays. Cultures were carried out in the presence or in the absence of pokeweed mitogen (PWM). Thyroid autoantibodies were undetectable in supernatants of MNC cultures from 9 normal subjects. Supernatants of MNC cultured without PWM had detectable levels of anti-Tg and anti-M in 5 (19.3%) and in 2 (7.7%) of 26 patients with autoimmune thyroid diseases, respectively. In the presence of PWM, a marked increment in the antibody concentrations occurred in all but 1 of these cultures, and the number of positive cultures increased to 13 (50.1%) for anti-Tg and to 15 (57.7%) for anti-M. Studies of MNC fractions depleted of T lymphocytes (non-T cells) were carried out on selected patients showing antibody synthesis only after PWM stimulation. Autoantibody production was not found with non-T cells, but the effect of the mitogen was restored by readdition of T cells. Irradiation (1000 rad) of T cells before coculturing significantly enhanced autoantibody production. With this model no significant functional difference was found between autologous and allogenic T cells from thyroid autoimmune disease patients or from normal subjects. The cells involved in PWM-driven thyroid autoantibody synthesis, as defined by depletion studies, were lymphocytes bearing DR antigens and surface immunoglobulin G (IgG) without detectable surface immunoglobulin M (IgM). Depletion from MNC suspensions of Tg-binding cells abolished PWM-stimulated anti-Tg production, but did not alter the synthesis of anti-M. Further studies were carried out on MNC from a single patient with Hashimoto's thyroiditis, whose non-T cells consistently produced large amounts of anti-M and total IgG in the absence of PWM. The addition of PWM to these unfractionated MNC slightly increased the production of anti-M, but inhibited antibody synthesis after depletion of T lymphocytes. Interestingly, the addition of autologous T lymphocytes to non-T cells inhibited the spontaneous synthesis of anti-M. These data indicate that in vitro synthesis of anti-Tg and anti-M by MNC may be frequently induced by stimulation with PWM in patients with thyroid autoimmune disorders. PWM-stimulated synthesis of thyroid autoantibodies appears to be T-cell dependent and modulated by radiosensitive T lymphocytes. The cells responsible for PWM-dependent thyroid autoantibody synthesis are B lymphocytes with surface membrane IgG and have receptors specific for the autoantigen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

A solid phase immunoradiometric assay for gastric parietal cell antibodies.

We recently described a solid phase immunoradiometric assay (IRMA) for anti-thyroglobulin and anti-thyroid microsomal antibodies. In the present study a similar IRMA for gastric parietal cell antibodies (PCA) has been developed. Samples to be tested are incubated within wells of polyvinyl microtitre plates coated with solubilized gastric microsomal antigen. After removal of unbound material, PCA is detected by adding purified 125I-anti-human IgG antibody. A good correlation was found with the results of PCA assays obtained by indirect immunofluorescence. In contrast, negative PCA by IRMA were consistently obtained in sera containing high titres of several other organ specific and non-organ specific autoantibodies. PCA determinations by IRMA were than carried out in a series of normal controls and patients with autoimmune or non-autoimmune thyroid disorders. Positive results were obtained in three of 70 (4.3%) apparently normal subjects, in 16 of 87 (18.4%) patients with Hashimoto's thyroiditis, in 10 of 48 (20.8%) with idiopathic myxoedema, in 25 of 95 (25.6%) with Graves' disease and in five of 64 (7.8%) with other non-autoimmune thyroid disorders. Preliminary results showed that quantitative measurements of PCA by IRMA could be performed using a serum containing high levels of PCA as standard reference. In conclusion, PCA may be easily and specifically detected using the same IRMA procedure previously developed for anti-thyroid antibodies. We therefore suggest that the present IRMA may be proposed as a general technique for the detection of different organ specific autoantibodies.

Autoantibodies↗
PubMed1983

[Our experience with the effectiveness and tolerance of ibuproxam in rheumatology].

The tolerance and effectiveness of Ibuproxam were investigated in 54 patients with arthrosis, R.A., ankylosing spondylitis, and fibrositis. Statistically significant reduction of pain at the end of the treatment was accompanied by decreased limitation of joint movement and morning stiffness. Simultaneous investigation of clinical and biological tolerance showed that the drug is infrequently responsible for side-effects that are always of negligible importance. Oesophagogastroduodenoscopy in subjects with a prior history and/or signs of active pathology of the upper digestive tract did not reveal exacerbation or recrudescence of lesions, nor the appearance of acute lesions.

Arthritis, Rheumatoid↗
PubMed1983

A new solid phase immunoradiometric assay for antithyroid microsomal antibody.

A new sensitive, quantitative, and specific immunoradiometric assay (IRMA) for antithyroid microsomal (anti-M) antibody has been developed. Samples to be tested are incubated within wells of polyvinyl microtiter plates coated with solubilized thyroid microsomal antigen. After removal of unbound material, anti-M antibody is detected by adding purified [125I]antihuman immunoglobulin G (IgG) antibody. Using 1.0 microliter serum, anti-M antibody was found by IRMA in all of the patients with Hashimoto's thyroiditis or idiopathic myxedema (n = 19), in 86% of those with Graves' disease (n = 42), in 10.9% of subjects with other nonautoimmune thyroid disorders (n = 37), and in 8.4% of normal controls (n = 71). A good correlation was found with the results obtained in anti-M antibody tests by passive hemagglutination. Using larger volumes of serum (up to 100 microliters), anti-M antibody detectable by IRMA was found in some patients with Graves' disease and negative passive hemagglutination tests. Quantitative measurements of anti-M antibody by IRMA could be performed using a standard IgG preparation containing high levels of anti-M antibody. The minimal detectable amount ranged between 1-2 ng IgG, corresponding to a sensitivity 15-30 times greater than that of the competitive binding radioassay. We suggest that the present IRMA may be proposed as a general technique for the detection of different organ-specific autoantibodies.

Animals↗