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Biomedical subjects

S Mariotti

Publications and source records attributed to S Mariotti.

At least 163 records · Page 9Linked to original sources

Effect of indomethacin on phytohemagglutinin-stimulated peripheral blood lymphocytes in thyroid autoimmune diseases.

Suppressor lymphocyte function was evaluated in control subjects and in patients with autoimmune thyroid disease, utilizing an assay in which indomethacin was added to lymphocyte cultures to inhibit prostaglandin-producing suppressor cells. This assay is based on the observation that the addition of indomethacin, a potent prostaglandin synthesis inhibitor, to phytohemagglutinin-stimulated peripheral blood lymphocytes should cause an increase in the incorporation of iododeoxyuridine in control subjects and a smaller increase in diseases with reduced prostaglandin-producing suppressor cells. The addition of indomethacin, 1 microgram/ml, stimulated iododeoxyuridine incorporation in phytohemagglutinin-stimulated cultures in control subjects to an index value of 1.43 (i.e., the increment in iododeoxyuridine incorporation with both indomethacin and phytohemagglutinin was 43% greater than the incorporation with phytohemagglutinin alone). The stimulation index was significantly lower in patients with Graves' disease who were toxic and untreated (1.18 +/- 0.25, mean +/- SD; P less than 0.003). Patients who were toxic while receiving antithyroid drugs or after radioiodine therapy or patients euthyroid after treatment had a mean stimulation index in the normal range, although the spread of data was very large in these groups. Responses in patients with Hashimoto's thyroiditis were also quite variable. The average response was 1.74 +/- 0.72, with 40% of the patients showing a high stimulation index. This study supports our previous investigations in which we used different assay systems for measuring suppressor-cell function in patients with thyroid autoimmune diseases and indicates that a defect in suppressor lymphocyte function is measureable by another technique. The abnormality persists in some cases after metabolic control has been achieved, but usually returns toward normal over months or years.

Adolescent↗

Evaluation of risk factor variations in relation to their baseline values in a controlled preventive trial. Application to the Rome Project of CHD Prevention.

This paper proposes a method for separating intervention impact, regression to the mean and spontaneous evolution effects in a controlled preventive trial. Variation dependence on baseline values is estimated by means of corresponding regression lines. Regression line slopes are adjusted to eliminate bias due to the difference between observed and 'true' values. Intervention impact is then evaluated using the control group as reference. Possible differences in factor baseline values are adjusted for. The method is used to analyse variation patterns for body mass index, serum cholesterol, systolic blood pressure, diastolic blood pressure and cigarette smoking in four years in the Rome Project of Coronary Heart Disease Prevention cohorts. All regression lines of variations vs baseline values show a negative slope. A highly significant improvement due to treatment is observed for blood pressure and body mass index, a less substantial but significant improvement is observed for serum cholesterol, and no effect is observed for cigarette smoking.

Adult↗

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↗

Immunoglobulin binding of thyroid hormones in a case of Waldenstrom's macroglobulinemia.

This paper describes a case of hypothyroidism in a patient with Waldenström's disease in which the evidence of thyroid failure was accompanied by an abnormal binding of thyroid hormones in the gamma-globulin fraction. A 68-yr-old patient with Waldenström's disease appeared to be hypothyroid by clinical and laboratory criteria. Serum TSH was elevated; serum T3 (measured by RIA) was low, while T4 levels were undetectable or very high according to the method used. Serum free thyroid hormones were in the hypothyroid range, and both antithyroglobulin and antimicrosomal thyroid antibodies were undetectable. The thyroid gland was normal at autopsy. Elevated binding of radiolabeled thyroid hormones by the patient's serum gamma-globulins was demonstrated by reverse flow electrophoresis and cellulose acetate electrophoresis. This binding could be inhibited by preincubation of serum samples with unlabeled T4 and T3, but not with human thyroglobulin, rT3, DIT, or MIT. Immunoprecipitation of the patient's serum incubated with [125I]T4 or [125I]T3 showed that 56% of T4 and 30% of T3, respectively, were precipitated using an antihuman immunoglobulin M(IGM) serum; only [125I]T4 was precipitable (22%) by the addition of an antihuman immunoglobulin G(IgG) serum. The binding of the thyroid hormones by IgM and IgG, which reduced T4 and T3 availability for their metabolic action at the tissue level, could have contributed to the clinical picture.

Aged↗

A new solid-phase radioimmunoassay to measure IgG secreted by cultured human lymphocytes.

We describe a simple solid-phase radioimmunoassay (RIA) to detect IgG based on competitive binding between radiolabeled and unlabeled IgG for anti-IgG antibody physically adsorbed to the wells of polyvinyl microtiter plates. The assay is sensitive (1 ng), rapid, and is particularly suited for studies of in vitro IgG secretion by human peripheral blood lymphocytes, since such studies require large numbers of cultures. Conditions which permit measurement, by means of this assay, of helper and suppressor T cell effects on IgG production by human B cells in culture are described.

Animals↗

Coronary risk factors predicting coronary and other causes of death in fifteen years.

A multivariate analysis employing the multiple logistic function model has been performed for the prediction of coronary heart disease (CHD) deaths and of other causes of death as function of 14 coronary risk factors measured at entry examination in the pool of two Italian rural population samples, made of 1712 men aged 40-59 at entry and followed for 15 years. A limited number of factors--namely age, serum cholesterol, blood pressure, smoking habits, forced expiratory volume, diabetes--yielded significant coefficients variously associated each other in the different solutions. They were able to provide a satisfactory discrimination between cases and non cases, not only for CHD but also for other end-points including strokes, cancer and lung cancer in particular, chronic bronchitis, and all causes of death. A suggestive prediction of violent causes of death was possible thank to a significant coefficient attributable to blood pressure. Serum cholesterol was significantly contributory only in the prediction of CHD. The multipotentiality of some factors is stressed in view of the planning of community prevention programs directed towards several chronic conditions at the same time.

Adult↗

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↗

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↗

[Identification of subjects at high coronary risk in the Roman Project of Coronary Heart Disease Prevention (author's transl)].

In the Roman Project of Coronary Heart Disease Prevention two different techniques were employed for the identification of individuals at high coronary risk within the treatment groups of the Project. The "risk score" is a simple additive system developed by the working groups of WHO, while the "multiple logistic function" is a complex mathematical model of multivariate analysis. Both of them consider 5 risk factors (age, systolic blood pressure, serum cholesterol, smoking habits and physical activity at work) and are applied for the identification of individuals belonging to the upper 20% of a risk rank list. The two techniques apparently provide similar predictive performances when applied to epidemiological prospective material collected in other studies where the morbid events are already known. When employed in the study population groups they identify, as high risk individuals, different subgroups of population, which overlap only partially. On the basis of theoretical and practical considerations, it has been decided to employ both techniques and to extend, as a consequence, the proportion of high risk individual, eligible for individual treatment, from 20% to about 30% of the total.

Adult↗

[The prediction of coronary heart disease. A mathimatical model applied to Italian field studies (author's transl)].

The multiple logistic function (MLF) was applied for the estimation of coronary heart disease (CHD) - "hard criteria" in 5 years as a function of several risk factors in two rural Italian areas belonging to the "Seven Countries Study". CHD was estimated with solutions including 4, 5 and 11 factors respectively. Only serum cholesterol showed a statistically significant contribution; but other factors, like age and physical activity, very likely contributed to a better discrimination between "cases" and "non-cases". By increasing the number of factors the discrimination tends to improve anyway. In the solution with 11 factors, 46% of the observed cases was found in the upper 10% of the estimated risk probabilities; 57% in the upper 20%; while no cases were found in the lowest 20% of the same rank probability list. For practical purposes of selecting high risk individuals for preventive action, a simple 5 factor solution, including age, systolic blood pressure, serum cholesterol, consumption of cigarettes and physical activity is suggested.

Adult↗