PubMed Health⌕ Search

Biomedical subjects

F Raue

Publications and source records attributed to F Raue.

At least 181 records · Page 10Linked to original sources

Sensitive homologous radioimmunoassay for human parathyroid hormone to diagnose hypoparathyroid conditions.

A sensitive radioimmunoassay for human parathyroid hormone (hPTH) to diagnose hypoparathyroid conditions is described. The antiserum was raised in goats against extracted hPTH. Synthetic human PTH fragment (53-84) is used as a standard and 125I-Tyr52hPTH (53-84) as a tracer. After a two-step incubation (24 h + 24 h) at 4 degrees C, the bound and free fractions are separated by a mixture of second antibody and polyethylene glycol solution. The detection limit for hPTH (53-84) is 2 pmol/L hPTH (53-84) (2 mol/tube). The PTH level in 36 healthy subjects was 5-12 pmol/L. Of 14 patients with hypoparathyroidism 11 patients had PTH concentrations below normal, two patients had levels on the lower limit of the normal range (5 pmol/L). The concentration of one patient with pseudohypoparathyroidism was markedly elevated. This assay is suitable for detecting low PTH levels and for studying changes of PTH concentration within the normal range.

Calcium↗

Metastatic C-cell carcinoma: calcitonin and CEA production in monolayer culture.

Mechanically dissociated cells from a surgically removed mediastinal C-cell carcinoma (MTC) were cultured over a period of 4 months. The cells of the monolayer culture consisted of clusters of small epithelial-like cells. Using semithin and ultrathin sections, two different types of cells could be characterized by shape of nucleus and by content and distribution of secretory granules. One type of cell showed a more irregularly shaped nucleus, the other contained a large oval nucleus, similar to the normal C-cell of the human thyroid. Calcitonin (CT) and carcinoembryonic antigen (CEA) were measured in supernatants in duplicate by radioimmunoassays. Radioimmuno-detectable CT levels in the supernatant of culture medium varied between 0.8 and 1.6 ng/ml and CEA levels between 5 and 27 ng/ml during a 2-month period. The present study proves that in monolayer-cultured cells of a MTC, metastases continue to produce radioimmuno-detectable CT and CEA. Whether the two different cell types in culture are relevant for carcinoma needs further investigation.

Adult↗

Inherited thyroxine-binding globulin excess. Study in a kindred.

A three-generation family with hereditary high thyroxine-binding globulin (TBG) serum levels has been studied. All patients were clinically euthyroid and did not have a goiter. Four females of the eleven members of the kindred had elevated TBG (range: 34-56 micrograms/ml), total thyroxine (T4) and total triiodothyronine (T3) levels, but normal free T4 (fT4) and normal response of thyroid stimulating hormone (TSH) to intravenous application of thyrotropin-releasing hormone (TRH). Microheterogeneity of TBG studied by isoelectric focusing showed a normal pattern. No variations of the four main bands as seen in other causes of TBG excess like liver diseases, estrogen therapy or pregnancy could be measured. The changes in TBG concentration seem to be due to an abnormal gene expression controlling synthesis of TBG.

Adolescent↗

Secretion of calcitonin and carcinoembryonic antigen in long-term organ culture of human medullary thyroid carcinoma: biochemical and immunocytochemical studies.

Tissue cultures of four C-cell carcinomas (medullary thyroid carcinoma, MTC) were prepared to study the basal and stimulated calcitonin (CT) and carcinoembryonic antigen (CEA) release. Immunohistological staining of the explants for CT and CEA have been performed after various periods of culture. These MTC explants were able continuously to release CT and CEA for periods up to 157 days. The spontaneous CT and CEA release decreased sharply during the 1st week of culture, then remained nearly constant over the observation period. THE CEA/CT secretion ratio slightly declined during long-term culture; CEA release seems to drop earlier than CT production. CT and CEA could be detected in the same cells by immunocytochemical technique. The septal tissue consisting of dense connective tissue and amyloid produced by tumor cells seemed to increase during long-term culture. CT, but not CEA, was stimulated by pentagastrin (10(-5) M), glucagon (6 x 10 (-6) M), and dose related by calcium (2.5-20 mM) in vitro. The MTC explant organ long-term culture proved to be a useful model for studies of human CT and CEA secretion.

Adolescent↗

Pheochromocytoma in multiple endocrine neoplasia.

Three patients with a surgically confirmed and 1 with suspected pheochromocytoma as part of the syndrome of multiple endocrine neoplasia (MEN) type II are presented. Pheochromocytoma and medullary thyroid carcinoma (MTC) as well as other tumors are part of this heritable entity. Three cases were members of a MEN IIa family and 1 patient has suffered from a sporadic form of MEN IIb. Pheochromocytoma was diagnosed by screening procedures (catecholamine screening, computerized tomography, sonography or selective venous catheterization). In 2 of the patients there was no clinical manifestation of the pheochromocytoma. On three occasions MTC was diagnosed first, the thyroid tumor occurred prior to the pheochromocytoma by 7, 6, and 1/2 years. Pheochromocytoma occurred bilaterally in 2 patients, in 1 it is suspected in both adrenals.

Adrenal Gland Neoplasms↗

Importance of early diagnosis and follow-up in multiple endocrine neoplasia (MEN II B).

Three patients with a sporadic form of multiple endocrine neoplasia (MEN) IIb are presented. MEN IIb is the association of medullary carcinoma of the thyroid (MTC), pheochromocytoma and multiple mucosal neuromata. The age at diagnosis and primary therapy of MTC was relatively late (8, 16, 18 years) although thyroid enlargement (two cases), typical marfanoid habitus (two cases) or multiple mucosal neuromata (one case) had been evident since early childhood. The diagnosis was confirmed by measurements of tumour markers like calcitonin (CT) and carcinoembryonic antigen (CEA) for MTC, measurements of vanillylmandelic acid for pheochromocytoma, evaluation of the thyroid gland by sonography, scintigraphy and fine needle biopsy, and investigation of the adrenals by computer tomography and meta-(I-131) iodobenzylguanidine (I-131-MIBG) scintigraphy. After surgical treatment determinations of tumour markers confirmed relapses of MTC in all cases. Early diagnosis of MEN IIb, which could be made by recognition of the typical clinical appearance, is of special importance because of the poor prognosis of MTC.

Adolescent↗

Different effects of hypercalcemic state induced by Walker tumor (HWCS 256) and 1,25 (OH)D3 intoxication on rat thyroid C cells. An ultrastructural, immunocytochemical, and biochemical study.

Two different models of chronic C cell stimulation by the hypercalcemic state were compared with respect to their morphology, immunocytochemistry, and biochemistry. In the chronic hypercalcemic state due to the HWCS 256 strain of the Walker tumor C cells show signs of degeneration such as vacuolation, on day 7 after tumor implantation. On day 10 tumor induced hypercalcemia leads to irreversible cell damage with karyopyknosis and karyorrhexis. These morphological changes are accompanied by a decline in radioimmunologically measurable calcitonin content of the thyroid and by the loss of response to acute stimulation of C cells. In contrast, in the hypercalcemic state due to 1,25(OH)2D3 intoxication we find an almost complete degranulation of C cells but no signs of degeneration or cell damage, although the thyroid calcitonin content and the calcitonin secretion capacity is greatly reduced. Tumor induced cachexia as a reason for C cell damage in tumor bearing rats could be excluded. Other possible reasons, such as acute overstimulation and tumor factors acting directly on C cells are discussed.

Animals↗

Reversible diminished calcitonin secretion in the rat during chronic hypercalcemia.

A transient increase in serum calcitonin (CT) concentration is induced by an acute iv calcium (Ca) load, whereas in the chronic hypercalcemic state, serum CT levels, as well as CT content of the thyroid, are equivocal. The secretion of CT was tested in three models of hypercalcemia in rats: tumor induced by the hypercalcemic Walker carcinosarcoma 256 (HWCS 256), chronic parenteral Ca administration, and chronic 1,25(OH)2D3 administration. In rats with HWCS 256, serum CT levels increased from basal values of 0.21 +/- 0.11 ng/ml to a maximum of 0.42 +/- 0.20 ng/ml on day 4 after tumor transplantation, 1 day before serum Ca increased. The serum CT levels declined again the following day (day 5). In thyroidectomized, parathyroid autotransplated rats with HWCS 256, serum Ca increased 1 day earlier than in intact rats. Substitution of CT by exogenous CT injections delayed the hypercalcemia for one day. Ca loading was followed by a decreased serum CT level (delta CT); the CT content of the thyroid fell from 9.4 +/- 1.1 ng/mg wet wt to 1.0 +/- 0.3 ng/mg wet wt. While hypercalcemia was present. Also chronic intraperitoneal Ca administration induced a decrease in the CT response to a Ca load (delta CT) and a decrease in thyroid CT content from 9.32 +/- 0.58 ng/mg wet wt to 3.84 +/- 0.33 ng/mg wet wt. These changes were no longer present 4 days after stopping Ca administration. In chronic hypercalcemia induced by 1,25(OH)2D3 administration, basal serum CT levels did not vary significantly, whereas serum Ca increased to 11.8 +/- 0.46 mg/dl on day 4. CT after an acute Ca load was diminished, as was CT content of the thyroid during 1,25(OH)2D3 administration. These changes were reversible after stopping 1,25(OH)2D3 administration. During chronic hypercalcemia a reversible exhaustion of CT content of the thyroid and a diminished CT response to acute Ca stimulation was observed, while basal serum CT levels remained unchanged.

Animals↗

Variations of plasma calcitonin levels measured by radioimmunoassay systems for human calcitonin.

Radioimmunoassay systems of different characteristics are available for routine determination of human calcitonin (hCT). The purity and calcitonin content of the used standards has to be observed, different antisera may yield discrepant absolute values from the same plasma samples. HCT measurements permit blood level control during treatment with this hormone. In most thyroidectomized patients hCT is not measurable--it is supposed that there is no relevant extrathyroidal calcitonin production in man. HCT RIA systems also recognize rat calcitonin. In this species, chronic hypercalcemia first leads to increased calcitonin secretion which is soon followed by a decrease. Presumably, this fall reflects down-regulation of calcitonin secretion which is more a calcium conserving than an anti-hypercalcemic hormone.

Animals↗

[Tumor markers in C-cell cancer].

C-cell carcinoma (medullary thyroid carcinoma) is associated with increased serum calcitonin levels. In addition, increased serum levels of other tumour markers are also found: carcinoembryonic antigen (CEA), adrenocorticotrophic hormone (ACTH) and tissue polypeptide antigen (TPA). The relevance of these tumour markers as compared to calcitonin was evaluated in 46 patients with C-cell carcinoma. With decreasing frequency pathologically increased levels were found: calcitonin 93%, CEA 73%, TPA 17% and ACTH 8%. There was a positive correlation between calcitonin and CEA values. Calcitonin and CEA levels correlated with the clinical tumour stage. In selective venous catheterisation estimation of calcitonin is superior to estimation of CEA. Assessment of CEA supplements calcitonin measurements in follow-up controls and evaluation of success of treatment. As regards specificity and sensitivity calcitonin is superior to all other tested tumour markers in C-cell carcinoma.

Adrenocorticotropic Hormone↗