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M Hüfner

Publications and source records attributed to M Hüfner.

At least 19 recordsLinked to original sources

Is soluble CD25 antigen (interleukin-2 receptor) a useful parameter for differential diagnosis of thyrotoxicosis?

Soluble CD25 antigen was measured in 28 patients with Graves' disease and 20 patients with thyroid autonomy in order to address the question of whether this parameter could be used in the differential diagnosis of thyrotoxicosis. Soluble CD25 was significantly elevated in active Graves' disease (2430 +/- 442 U/ml, mean +/- SEM) compared to patients with thyroid autonomy (1295 +/- 225 U/ml, mean +/- SEM). However, compared to normal controls (mean 605 +/- 49 U/ml), both groups of patients had significantly elevated CD25 plasma levels. Investigations in thyroidectomized thyroid cancer patients on and off T4 suppressive therapy showed no influence of T4 on the CD25 level. Soluble CD25 concentrations did not differ in thyroid cancer patients compared to normal controls. We conclude that soluble CD25 may indicate a stimulation of the immune system with high sensitivity; however, due to the low specificity of elevated CD25 levels, its usefulness for differential diagnosis of thyrotoxicosis is limited.

Diagnosis, Differential

An autoimmuno-dominant thyroglobulin epitope characterized by a monoclonal antibody.

It has become evident in recent years that autoimmune thyroglobulin (Tg) antibodies of Graves disease and Hashimoto's thyroiditis show a restricted epitope repertoire compared to Tg heteroantibodies. We have produced monoclonal antibodies (Mab) against human Tg by the hybridoma technique and the epitope specificity was determined by crossblocking experiments. Six noncrossreactive Mabs were used in a double determinant IRMA system for plasma Tg measurements. Sensitivity of the assays was between 1 and 2 ng/ml, intraassay variation less than 5%. Recovery experiments with added Tg were performed in 25 Graves sera with elevated Tg autoantibodies. Monoclonal antibody Tg13 showed an unusual strong interference with autoantibodies resulting in a very low recovery in all sera (median: less than 10%). In further studies Tg was digested by trypsin and after Western blotting, the resulting fragments were incubated with different Mab antibodies, a polyclonal antibody and 10 different Graves sera with high Tg autoantibodies. In contrast to all other mabs only Mab Tg13 showed several low molecular weight bands between 17 and 50 KD. The major bands recognized by Mab Tg13 corresponded to bands obtained by the autoimmune sera, which showed a very homogeneous band pattern. We conclude that Mab Tg13 is specific for an autoimmunodominant B cell epitope of human Tg.

Antibodies, Monoclonal

Description of a variably expressed and labile epitope of thyroglobulin and its occurrence in different thyroid diseases using a monoclonal antibody.

A new category of epitopes of human thyroglobulin is being described defined by a monoclonal antibody (TuTg 1). The epitope shows a very variable expression in normal individuals as well as in different thyroid diseases. According to gel filtration data the epitope is located at the intact molecule and is very sensitive to tryptic digestion. The monoclonal antibody was used in an IRMA system for plasma measurements in the follow-up of thyroid cancer patients. In individuals with high epitope expression the sensitivity to detect recurrency during T4 treatment was higher than a sensitive commercial TG IRMA.

Antibodies, Monoclonal

[Thyroglobulin, 131I-whole body scintigraphy and risk factors in the follow-up of differentiated thyroid cancer].

Results of 131I whole body scans and measurements of thyroglobulin (Tg) in the follow-up of 85 patients with differentiated thyroid cancer were analysed in a retrospective study. All patients were assumed to be tumor-free after therapy. During follow-up, cancer recurrence was observed in 11 patients. Out of 24 131I scans performed for suspected recurrence, cancer was localized in 5. Out of 71 routinely performed 131I scans and Tg measurements during hormone withdrawal, new pathologies were observed in each of two cases one year after the last therapy. 10 out of 11 tumor recurrences were observed in a high-risk group of 40 patients with follicular histology or stage III or IV (UICC 1987). One recurrence occurred in a low-risk group of 41 patients with papillary histology and UICC stage I or II. Later than one year after therapy no recurrence was observed in any patient who belonged to the low-risk group. These results indicate that 131I scans and Tg measurements under endogenous TSH stimulation are necessary in cases of suspected recurrences and probably on a routine basis one year after the last therapy in all patients. In the event of an inconspicuous further course this diagnostic procedure should be restricted to special high-risk groups. Using a cut-off level of 5 ng/ml as compared to 10 ng/ml, the number of false-negative Tg results under suppressive therapy decreased clearly whereas that of the "false-positive" results increased less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Evidence for an osteoblast-activating factor in a patient with peripheral T-cell lymphoma and osteosclerosis.

A patient with peripheral T-cell Lymphoma and acquired, systemic osteosclerosis is described. Bone histology showed a spectacular activation of osteoblasts accompanyed by massive new bone formation. Alkaline phosphatase in serum was elevated and increased to greater than 2000 U/l when the lymphoma became refractory to chemotherapy. In the patient's serum an osteoblast-activating factor could be demonstrated using a rat osteogenic osteosarcoma cell line (ROS 17/2.8). The factor was absent during remission of the tumor. We conclude that osteosclerosis was a paraneoplastic syndrome in this patient due to the secretion of an osteoblast-stimulating factor by the T-cell lymphoma. This situation is similar to the secretion of osteoclast-activating factors described in B-cell lymphomas, particularly multiple myeloma. The characterization of such a factor could be of therapeutic relevance.

Adult

Evidence for immunological differences between circulating and thyroid tissue-derived thyroglobulin in men.

The expression of six antigenic epitopes on plasma Tg and tissue-derived Tg was investigated using mouse mabs in immunoradiometric assays. The sensitivity of the assays ranged between 0.5 and 1.5 micrograms l-1. Plasma thyroglobulin of 15 normal individuals and 18 patients with metastatic, differentiated thyroid cancer was analysed. Whereas five monoclonals produced values comparable to the conventional RIA system, the monoclonal antibody Tg 158 did not detect any Tg in the normal individuals and only low levels in two of the cancer patients with the highest Tg levels. In contrast, dilutions of extracts of three different euthyroid goitre samples and three different samples of differentiated thyroid cancer revealed no difference in the antigenic expression of all six epitopes, including the Tg 158 epitope. Papain digestion of purified Tg resulted in a 76 kD fragment which showed immunoreactivity for Tg 158 as well as for Tg 11. No interference of the binding of Tg 158 by T3, T4 or DIT could be detected. We conclude that the monoclonal antibody Tg 158 detects an epitope which is present in thyroid tissue-derived Tg but not in circulating thyroglobulin. This antibody might be useful for the investigation of the secretory process of thyroglobulin from the thyrocytes into the circulation.

Antibodies, Monoclonal

Development of immunoradiometric assays for human thyroglobulin using monoclonal antibodies and the biotin/avidin system.

Monoclonal antibodies against human thyroglobulin were produced by the hybridoma technique. Using three non-crossreactive monoclonal antibodies, an IRMA system was developed, with a polyclonal rabbit antibody fixed on microtiter plates as first extracting antibody. The monoclonal antibodies were used as second antibody, while anti-mouse IgG-biotin from goat and [125I]streptavidin served as the indicator system. The source of the monoclonal antibodies was diluted culture medium without purification. Sensitivities of 3-4 micrograms/l were obtained with all 3 monoclonal antibodies; interassay variation was about 5%. This test system will be used for further immunological characterization of circulating thyroglobulin in different thyroid diseases.

Antibodies, Monoclonal

Iodothyronine deiodination in rats with severe non-thyroidal illness.

To investigate the iodothyronine metabolism in non-thyroidal illness (NTI), thyroidectomized male Wistar rats bearing the hypercalcemic Walker sarcoma 256 were substituted with, respectively, 2.3 and 11.5 mumol T4/100 g body weight by daily ip injection. Serum T4 and T3 concentrations of euthyroid and hyperthyroid tumor-bearing animals markedly decreased to a nadir at day 8 after tumor implantation: serum T4 fell to, respectively, 43% (euthyroid) and 26% (hyperthyroid) of initial values, serum T3 to 19% (euthyroid) and 26% (hyperthyroid). A measurable serum rT3 concentration could not be detected before and after tumor implantation. In vitro deiodination of T4 to T3 in liver homogenates of the sacrificed animals was not significantly reduced in Walker rats compared with control animals. The activity of T4 deiodinase was significantly induced in hyperthyroid controls (180%) as well as in hyperthyroid Walker rats (155%) in spite of low serum concentrations of T4 and T3. This enzyme induction was even more pronounced in animals whose treatment with high T4 doses was started after tumor implantation. In these rats the serum concentrations of free fatty acids were increased to about 200% of controls. Our data suggest that 1. the fluctuations of iodothyronine serum concentrations in NTI are mainly independent of thyroidal secretion, and 2. the intracellular iodothyronine levels in livers of severely sick animals with different thyroid function are not greatly altered by NTI, in spite of markedly decreased total serum levels.

Animals

Comparative plasma thyroglobulin measurements with three non-cross-reactive monoclonal antibodies in metastatic thyroid cancer patients.

In 12 normal individuals and 25 patients with metastases of differentiated thyroid cancer, plasma thyroglobulin (Tg) concentrations were measured simultaneously with three immunoradiometric assays. Each of the three systems used a different, non-cross-reactive monoclonal Tg antibody as second antibody. In general, there was a very close correlation between the results of the three different systems in the cross-sectional study of the 25 cancer patients as well as in longitudinal follow-up studies in selected patients. The monoclonal antibody Tg 40 produced values about 30% higher than the two other systems. The difference was, however, not statistically significant owing to the large scatter. The monoclonal antibody Tg 13 appeared to be very sensitive to interference with thyroglobulin autoantibodies. In conclusion, the monoclonal antibodies against the three epitopes tested produced very similar Tg values in normal individuals and 25 patients with metastatic thyroid cancer; however, before more is known about epitope specificity of Tg autoantibodies and heterogeneity of tumour Tg, monoclonal antibodies should be used for routine measurements only with caution.

Antibodies, Monoclonal

Increased heterogeneity of serum thyroglobulin in thyroid cancer patients as determined by monoclonal antibodies.

We investigated the immunological heterogeneity of plasma Tg in thyroid cancer patients using monoclonal antibodies in an immunoradiometric assay and a conventional RIA system with a polyclonal rabbit antibody. The results were compared with measurements of plasma Tg in patients with nonmalignant disease. We can demonstrate an increased immunological heterogeneity in tumor patients compared with patients with non-malignant thyroid diseases. In one case the Tg value measured by a monoclonal test system exceeded the value obtained by a polyclonal RIA system in the same sample by a factor of 25. It has to be further investigated whether this increase in heterogeneity is of diagnostic value in the follow-up of thyroid cancer patients.

Adenocarcinoma

[Computed tomography in follow-up of differentiated thyroid carcinoma].

The importance of computed tomography in follow-up aftercare and therapy planning in differentiated carcinoma of the thyroid is examined on the basis of the authors' experiences in a group of about 600 patients. The individual indication ranges are discussed and demonstrated by means of examples.

Adenocarcinoma