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Biomedical subjects

H Schleusener

Publications and source records attributed to H Schleusener.

At least 37 records · Page 2Linked to original sources
PubMed1990

Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis.

Cytotoxic activity in sera of patients with Hashimoto's thyroiditis was measured with an antibody-dependent cell-mediated cytotoxicity assay. Cytotoxicity was determined in a 51chromium release assay using human thyroid cell targets incubated with heat-inactivated serum or IgG from patients with Hashimoto's thyroiditis. Effector cells were obtained from peripheral mononuclear cells of normal subjects. Cytotoxicity was significantly increased in patients with Hashimoto's thyroiditis (median specific lysis 20.2%, range 2.1-58.8) compared with normals (median specific lysis 8.1%, range 0-19.5; p less than 0.00001). The amount of percent specific lysis did not correlate with the titres of microsomal antibodies determined by different methods: passive hemagglutination technique (r = 0.2), enzyme immunoassay with microsomal antigen (r = 0.16), and radioimmunoassay for thyroid peroxidase antibody (r = 0.02). The cytotoxic activity was located in the IgG fraction, both in microsomal antibody positive and negative sera. After pre-incubation of microsomal antibody/thyroid peroxidase antibody positive or negative sera with purified thyroid peroxidase followed by analysis in the antibody-dependent cell-mediated cytotoxicity assay, cytotoxicity decreased in only 2 cases but was unchanged in the remaining sera. Western blot experiments with solubilized thyroid membranes and immunoblotting with cytotoxic-positive/microsomal antibody negative sera showed no binding to thyroid peroxidase. Our data suggest that cytotoxicity in sera from patients with Hashimoto's thyroiditis is not mediated by antibodies against thyroid peroxidase, but by antibodies not yet identified.

Adult↗
PubMed1989

Cytotoxic antibodies in congenital hypothyroidism.

Antibody-dependent cell-mediated cytotoxicity was determined in serum samples from 61 patients with congenital hypothyroidism (CH) and 46 of their mothers, using a 51chromium release assay with human thyroid cells. Such cytotoxic antibodies were found in 31% of the children and 24% of their mothers. In the 12 (of 37) newborn infants with hypothyroidism (group 1) who had positive tests, the median cell lysis was 20.1% compared to 4% in healthy newborns. In the 7 (of 29) mothers who had positive tests, the median lysis was 21.3%. In 24 older children with CH (group 2), cytotoxic activity was found in 6, and in them the median lysis was 19.7%; 4 of their mothers had increased lytic activity (median, 20.6%). In 96% of the mother-infant pairs concordance existed between the cytotoxic activity in mothers and their children. Increased thyroid cell lysis was found in 6 of 20 children with athyrosis (30%) and in 6 of 23 children with an ectopic gland (50%), but in only 1 of 14 children with a normal gland. Thyroglobulin antibodies were detected in 2 and antithyroid microsomal antibodies in 3 children-mother pairs. TSH receptor antibodies were present in 5 children and 3 of their mothers. The results indicate that intrauterine autoimmune thyroiditis could be involved in the pathogenesis of CH in some patients.

Autoantibodies↗
PubMed1989

Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease.

Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective [corrected] and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P less than 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P less than 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P less than 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

Follow-Up Studies↗
PubMed1989

Appearance of thyroid diseases using colour-coded duplex sonography.

One hundred and seventeen patients with various thyroid diseases were examined with colour-coded duplex ultrasonography permitting simultaneous real-time display of soft tissue and blood flow. Twenty-four out of 25 patients with an autonomous adenoma, all six patients with thyroid carcinoma and five out of 61 patients with simple nodular goitre showed increased vascularity. Absence of increased vascularity would seem an important parameter for the exclusion of autonomous adenoma and thyroid carcinoma in patients with nodular goitre.

Adolescent↗
PubMed1988

[Etiology and pathogenesis of autoimmune diseases of the thyroid gland].

As for other autoimmune diseases it is discussed also for immune hyperthyroidism (Basedow's disease) and immune thyroiditis, whether factors such as stress and infections with viruses and bacteria may lead to a disturbance of the immune tolerance in persons genetically predisposed. In Basedow's disease antibodies against the TSH-receptor cause an uncontrolled stimulation of the function of the thyroid gland. One year after the end of an antithyroid drug treatment, e.g. with thiamazol, a recidivation rate of circa 50% develops. There are no criteria which may predict the clinical development of an individual after the end of the treatment with a sufficient reliability. This applies particularly also to the measurement of the TSH receptor antibodies and the suppression test at the end of treatment (Alexander's test). According to the experiences of author moreover patients with small and large goitres and with different degrees of Basedow's orbitopathy do not show any difference in the frequency of the recidivations. In the immune thyroiditis a series of antibody-dependent and lymphocyte-dependent processes may lead to a decreased function of the thyroid gland. This includes the interaction of antibodies with the complement system or with the killer cells (ADCC), the direct decomposition of the cells of the thyroid gland by certain subgroups of lymphocytes and the occurrence of blocking antibodies against the TSH receptor. In patients in whom antibodies were made evident may develop a hypothyroidism. But many patients also for ever remain euthyroid. These observations and experimental data suggest that the cell of the thyroid gland also itself must be "susceptible" to the destruction by the antibodies and lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1988

Interferon-gamma protects human thyroid epithelial cells against cell-mediated cytotoxicity.

Interferons have been shown to have antagonistic effects on cell-mediated cytotoxicity. In the present study, we investigated various types of immunologically mediated cytotoxic reactions with a 51chromium release assay, using human thyroid cells as targets, which were cultured in the presence and absence of interferon-gamma (IFN-gamma). Antibody-dependent cell-mediated cytotoxicity (ADCC), natural killer (NK) cell-mediated cytotoxicity, and autologous lymphocyte-mediated cytotoxicity (ALC) were measured utilizing thyroid tissue, sera and lymphocytes from patients with autoimmune thyroid disease as well as from normal subjects. ADCC, determined with sera from patients with Hashimoto's thyroiditis, was reduced by 70% when the thyroid target cells were cultured in the presence of 1000 U human IFN-gamma/ml culture medium. Similarly, natural killer cell-mediated cytotoxicity, as well as autologous lymphocyte-mediated cytotoxicity, was significantly reduced after pretreatment of thyroid target cells with 500-1000 U IFN-gamma/ml culture medium. Although it is known that IFN-gamma renders target cells resistant to NK cell-mediated lysis, this is the first report on this effect using human epithelial cells, which may have major implications for the suggested role of IFN-gamma in the induction and perpetuation of autoimmune thyroid disease.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

[Clinical aspects of hyperthyroidism in areas of different supplies of iodine. Results of a European prospective study].

Clinical aspects of 924 unselected patients with hyperthyroidism from 17 thyroid centres of 6 European countries were investigated in a prospective study for exactly 1 year. Serum samples were centrally assayed for thyroid hormones, thyroid autoantibodies and TSH-binding inhibiting immunoglobulins (TBII), and urine samples for iodine. 26 items of information per patient were computerized and evaluated. Forming 2 groups from iodine-deficient areas (IDA) and iodine-sufficient (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. The most important findings were: 1. Three types of hyperthyroidism were described: Graves' disease was defined as hyperthyroidism with eye symptoms and/or the presence of measurable TBII; autonomous adenomas were defined by a single hot nodule in the thyroid scan; the remainder included TBII negative hyperthyroid patients as well as non-immunogenic forms of hyperthyroidism (toxic multinodular goiter and other multifocal autonomies). These were termed "non-classifiable" patients. Graves' patients, representing an average of 60% of the patients, have an age peak between 40 and 49 years; they are 10 years younger than unclassified hyperthyroid patients and 20 years younger than patients with autonomous adenoma, who represented 9.2% of the patients. Surprisingly, there was no difference in the prevalence of Graves' disease between IDA and ISA. 2. An unexpectedly high rate of 10.5% of hyperthyroid patients (Graves' disease 8.5%, non-Graves' disease 14.2%) had no goiter, a figure increasing in the elderly to almost 17%. In IDA the thyroid was larger and the goiter more often nodular than in ISA. IDA are characterized by significantly higher rates (11.3%) of autonomous adenoma than ISA (3.2%). 3. 59.4% of 507 patients with Graves' disease had eye symptoms, 44.6% of at least grade II or higher using the Werner classification. There was no difference between patients from ISA and IDA. We found unilateral ophthalmopathy in 6.7% of Graves' patients. 4. The median iodine excretion was calculated from urinary iodine after exclusion of values over 250 micrograms iodine/g creatinine, arbitrarily defined as iodine contamination. In IDA the median iodine excretion was 63.6, and in ISA 105 micrograms/g of creatinine. 5. Surprisingly, proven iodine contamination was as frequent in IDA (14.5%) as in ISA (15.2%). In the survey protocol, however, this was noticed less often by physicians in ISA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Cellular and antibody mediated cytotoxicity in autoimmune thyroid disease.

Antibody-dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell-mediated cytotoxicity was measured in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) using a cytotoxicity assay against thyroid target cells. In the ADCC assay, mean +/- SD specific lysis produced by sera from patients with HT was 21.7 +/- 10% compared t 6.2 +/- 3.9% from normal subjects. In the NK assay, cytotoxicity was significantly increased using lymphocytes from HT patients as effector cells. At effector: target (E:T) cell ratios of 50:1 and 25:1, mean specific lysis +/- SD was 18.3 +/- 14.3% and 14 +/- 11.6%, respectively, compared to 3.7 +/- 2.1 and 3.1 +/- 2.1, respectively, for normals. In Graves' disease, 9 of 19 patients had elevated cytotoxicity, whereas no significant changes of ADCC could be found either, as determined in thyrotoxic patients, after 6 months and at the end of a one-year antithyroid drug treatment. Eight of 19 patients showed normal cytotoxicity (mean % specific lysis 2.5 +/- 3.1% compared to 2 +/- 2.9% in normal controls) and low titres of microsomal antibodies (Mab), 3 patients had significantly increased cytotoxicity (mean specific lysis 27.6 +/- 10%) in the presence of high titres of Mab, whereas 8 patients evidenced high values for cytotoxicity (mean specific lysis 24.5 +/- 14.1%) but low titres of Mab. NK cell activity, determined in euthyroid Graves' disease patients either under antithyroid drug therapy or in remission, was not significantly different than that of normal subjects at all E:T cell ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Do HLA-DR-typing and measurement of TSH-receptor antibodies help in the prediction of the clinical course of Graves' thyrotoxicosis after antithyroid drug treatment?

In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.

Antithyroid Agents↗
PubMed1987

Pharmacokinetics and urinary excretion of orally administered diiodotyrosine.

Serum levels of diiodotyrosine (DIT) and urinary excretion rates of DIT and iodine were measured in 10 normal subjects after oral administration of 1.57 mumol of DIT corresponding to 400 micrograms of iodine. Serum DIT concentrations rose promptly from a mean endogenous basal level of 0.23 nmol/l to maximum values between 6.0 and 20 nmol/l within 30 min to 1 h after DIT ingestion. Decreasing DIT levels were found in all subjects 2 h after DIT intake. Urinary excretion of intact DIT was low, being less than 1% of the administered dose of exogenous DIT within 2 days. In contrast, 52% of the iodine administered in the form of DIT was excreted in the urine in the same time interval. The rapid absorption of DIT from the gastrointestinal tract combined with rapid and almost complete metabolic degradation by deiodination make orally applied DIT seem a suitable iodine carrier compound for therapeutic purposes.

Administration, Oral↗
PubMed1984

10 years experience with consecutive measurement of thyrotropin binding inhibiting antibodies (TBIAb).

In the present study we reviewed 230 patients in whom thyrotropin-binding inhibiting antibodies (TBIAb) follow-up determinations had been performed up to 10 yr after hyperthyroidism had first developed. In 104 patients, Graves' ophthalmopathy occurred at some time in the course of the observation period. Fourty-four of these patients with Graves' ophthalmopathy had at least one, and up to four relapses after each one-year course of antithyroid drug therapy with methimazole. The addition of TBIAb-positive results over an observation period of 1-10 yr showed positive cumulative findings in 95% of the 44 patients with recurrences of Graves' disease. A single TBIAb determination during hyperthyroidism showed positive results in 70%. A detailed breakdown showed that TBIAb was detectable during all hyperthyroid phases in 48% of the patients with ophthalmopathy. Thirty-four per cent of the patients had sometimes positive, sometimes negative TBIAb findings in the various hyperthyroid states. In 18% of the patients, TBIAb was not detected in any of the hyperthyroid phases. However, some of these patients became TBIAb-positive for the first time during antithyroid drug therapy or during a remission confirmed by a suppression test. Only 2 of the 44 patients never had TBIAb positive results at any time during the observation period. In those patients without ophthalmopathy during the observation period, the "cumulative" frequency of TBIAb was 74% for patients with diffuse goiter and 52% for patients with diffuse-nodular goiter. However, in patients with ophthalmopathy, there was no difference in TBIAb detectability between those patients with a diffuse and those with a diffuse-nodular thyroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1984

Methodological aspects and clinical results of an assay for thyroid-stimulating antibodies: correlation with thyrotropin binding-inhibiting antibodies.

Several methodological aspects concerning the measurement of thyroid-stimulating antibodies (TSAb) were examined using a 5000-g particulate fraction from human thyroid tissue. TSH displayed maximal stimulation at 32 C. An ATP-regenerating system had no influence at ATP concentrations greater than 0.67 mM. Theophylline did not influence cAMP concentrations in the incubation medium after stimulation with increasing dosages of TSH, suggesting the absence of active phosphodiesterases in the membrane preparations. Sera dialyzed against Tris-HCl were as suitable as immunoglobulin G preparations for determination of TSAb. One hundred and nineteen patients with ophthalmic Graves' disease, 42 of whom were hyperthyroid at the time of study, were investigated for TSH binding-inhibiting antibodies ( TBIAb ) and TSAb. In 76% of these patients, concordance between the presence and absence of both activities was found independent of whether they were untreated, treated, or in remission. When gradations of potency in the two systems were compared, linear regression revealed a correlation coefficient of 0.59. The coefficient correlation increased when TBIAb and TSAb were each determined in a single assay using identical thyroid membrane preparations. In four other patients, both TSAb and TBIAb were measured repeatedly during the course of the disease. In three patients, both activities were parallel, whereas in one patient, dissociation of the two activities was found. The data suggest the presence of antibodies with varying stimulating and binding-inhibiting properties. However, in hyperthyroidism of Graves' disease, both activities usually were present in similar quantities.

Adenylyl Cyclases↗
PubMed1984

Antibody-dependent cell mediated cytotoxicity against human thyroid cells in Hashimoto's thyroiditis but not Graves' disease.

Antibody-dependent cell-mediated cytotoxicity (ADCC) against human thyroid cell targets was measured in a chromium release assay, using serum from patients with autoimmune thyroid diseases. The source of effector cells was peripheral blood mononuclear cells from normal subjects. Mean (+/- SD) specific lysis produced by serum from patients with Hashimoto's thyroiditis was 27.3 +/- 6.1%, compared to 10.6 +/- 4.7% produced by serum from normal subjects and 13.3 +/- 10% using serum from patients with Graves' hyperthyroidism. Cytotoxicity using serum from hyperthyroid patients was not different after treatment. Thyroid cell targets from histologically different thyroid cell preparations (Graves' disease, multinodular goiter, normal thyroid) were equally sensitive to killing, although cells from a benign thyroid adenoma were much less sensitive. A strong positive correlation was found between percent specific lysis and titers of serum microsomal antibody. By addition of patients' immunoglobulin to normal serum, we found that microsomal antibodies were responsible for the cytotoxic effect, whereas thyroglobulin antibodies did not mediate cytotoxicity. These results demonstrate that ADCC plays an important role in the thyroid cell destruction of chronic (Hashimoto's) thyroiditis. Although cytotoxic activity was associated with the antimicrosomal-, but not antithyroglobulin-, positive immunoglobulin G fraction, it is not clear whether the microsomal antibody itself, or an unidentified antibody occurring in the same antibody fraction, is the mediator of cytotoxicity in this disorder.

Adolescent↗
PubMed1983

Radioligand receptor assay for TSH and TSH-binding-inhibiting antibodies using solubilized TSH-receptor.

A radioligand receptor assay (RRA) for TSH and TSH-binding-inhibiting antibodies (TBIAb) using solubilized receptor is presented. Introducing charcoal for separation of bound and free hormone has made the assay easier to handle. The detection limit for TSH is 30 microU/ml as measured by RIA. TBIAb was found in the sera of 19 of 26 hyperthyroid patients. Only 16 sera were positive when the RRA using membrane fragments was applied.

Charcoal↗