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Biomedical subjects

R D Hesch

Publications and source records attributed to R D Hesch.

At least 181 records · Page 10Linked to original sources
PubMed1976

Radioimmunoassay of thyroxine-binding globulin in human plasma.

A highly specific and precise radioimmunoassay for thyroxine-binding globulin (TBG) has been developed. Crossreactivity with albumin and prealbumin was excluded. The normal range in young adults was 0.97 mg/100 ml. In childhood TBG was elevated (1.34 mg/100 ml) also in old age (1.28 mg/100 ml). In normals and in childhood there was a good correlation of TBG with thyroxine (T4). T4 did not correlate with TBG with regard to age. Triiodothyroxine (T3) did not correlate with TBG in any group. T4 and T3 exhibited a progressive decrease with age. No correlation between age and TBG was found. In mild thyrotoxicosis (T3 : 4.5 ng/ml, with normal T4 and negative TRH-test) TBG was slightly increased (1.20 mg/100 ml), whereas in more severe hyperthyroidism (T3 : 6.4 ng/ml, T4 : 16.3 mug/100 ml) TBG concentration was not significantly different from normals. In hypothyroidism TBG was elevated (1.26 mg/100 ml). The conclusion from these data is that TBG does not follow the progressive decrease of T4 and T3 with age. Thus, age-dependent euthyroid ranges for thyroid hormone concentration, including TBG concentration, must be established for better clinical discrimination of thyroid function. Possible dependence of TBG on the nature of thyroid hormone concentration must be considered in the production and peripheral kinetics of thyroid hormones.

Cross Reactions↗
PubMed1976

Total and free triiodothyronine and thyroid-binding globulin concentration in elderly human persons.

Total thyroxine (TT4) and triiodothyronine (TT3) were found to be low in healthy elderly subjects with a preferential decrease of triiodothyronine. In order to determine the importance of these findings 22 healthy elderly subjects were examined. Free triiodothyronine (FT3), thyroid binding globulin (TBG) concentration and basal thyroid stimulating hormone (TSH) were measured by radioimmunoassay. Liver enzymes, cholesterol and total protein concentration were also assayed. TBG was significantly increased compared to a middle-aged group and did not correlate with TT4, TT3 and TSH. Basal TSH values were in the normal range and could be detected in all the elderly subjects in contrast to undetectable values in 40% of the younger subjects. FT3 determined directly did not correlate with the values calculated according to the law of mass action. According to the FT3 values the elderly subjects could be subdivided into three groups independent of their TT4, TT3, TBG and TSH values. FT3 was undetectable in one group, in the low normal to normal range in another and elevated in the third group. Our results suggest that 1) there is no correlation between TT4, TT3, elevated TBG and FT3 determined directly or by calculation, 2) basal TSH values seem to indicate possible hypothyroidism in elderly persons which is correlated with elevated cholesterol levels and 3) FT3 measured directly subdivides this metabolic state into three groups possibly depending on the intracellular concentration of T4.

Aged↗
PubMed1976

Characterization of the parathyrin receptor in renal plasma membranes by labelled hormone and labelled antibody binding techniques.

The parathyrin receptor in renal cortex has been investigated by studying the binding of 125I-labelled parathyrin, or of unlabelled parathyrin detected with 125I-labelled antibodies, to a partially purified plasma membrane fraction. The kinetics of hormone uptake demonstrated a biphasic response in both systems at 22 degrees C but this phenomenon was not detectable at 37 degrees C. Specific displacement of lactoperoxidase labelled 125I-labelled parathyrin occurred with 8 ng unlabelled bovine parathyrin. The apparent affinity constant was 2.3-10(8) M(-1) and the apparent binding capacity of the membranes 1.25 pmol/mg protein. Using the labelled antibody technique the receptor showed maximal binding at pH 7.0-7.5. As little as 80 pg bovine parathyrin produced a significant increase in binding of labelled anti-bovine parathyrin antibody and saturation of binding sites was demonstrated at 2.5 pmol/mg protein. Oxidized hormone showed undetectable binding. Treatment of membranes with phospholipases A or D, or Trypsin greatly reduced subsequent hormone binding. Prior incubation of membranes with 1-34 synthetic parathyrin decreased the binding of intact hormone whereas gastrin, insulin and glucagon had no effect. Growth hormone and calcitonin slightly increased parathyrin binding.

Animals↗
PubMed1976

The stimulation of growth hormone release by ACTH and its inhibition by somatostatin.

The rapid injection of 0.5 or 1.0 mg of tetracosacitid (Synacthen¿) was followed by a distinct increase of plasma growth hormone (GH) within 30 or 45 min in 5 of 7 normal volunteers. A second control test was performed in 3 of the 5 "responders" and 1 "non-responder" and showed a consistent reaction in all of them. The tests were then repeated in the 5 "responders" during an infusion of somatostatin (150 mug/h) and the GH response was totally abolished (3 subjects) or markedly reduced (2 subjects). Thus the ACTH induced GH release behaves in a manner similar to most other physiological or pharmacological stimuli of GH release. The cortisol output after ACTH was not altered by somatostatin.

Adrenocorticotropic Hormone↗
PubMed1976

[Calculation of radioimmunochemical determinations by "spline approximation" (author's transl)].

A simplified method, based on the "spline approximation", is reported for the calculation of the standard curves of radioimmunochemical determinations. It is possible to manipulate the mathematical function with a pocket calculator, thus making it available for a large number of users. It was shown that, in contrast to the usual procedures, it is possible to achieve optimal quality control in the preparation of the standard curves and in the interpolation of unknown plasma samples. The recaluculation of interpolated values from their own standard curve revealed an error of 4.9% which would normally be an error of interpolation. The new method was compared with two established methods for 8 different radioimmunochemical determinations. The measured values of the standard curve showed a weighting, and there was a resulting quality control of these values, which, according to their statistical evalution, were more accurate than those of the others models (Ekins et al., Yalow et al., (1968), in: Radioisotopes in Medicine: in vitro studies (Hayes, R. L., Goswitz, F.A. & Murphy, B. E. P., eds) USA EC, Oak Ridge) and Rodbard et al. (1971), in: Competitive protein Binding Assys(Odell, W. D. & Danghedy, W. H., eds.) Lipincott, Philadelphia and Toronto). In contrast with these other models, the described method makes no mathematical or kinetic preconditions with respect to the dose-response relationship. To achieve optimal reaction conditions, experimentally determined reaction data are preferable to model theories.

Computers↗
PubMed1975

Thyroid hormones in the elderly sick: "T4 euthyroidism".

Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital.

Aged↗
PubMed1975

[Value of radioimmuno-assay of triiodothyronie and thyrotropic hormone in the diagnosis of thyroid disease (author's transl)].

Results of a purely in-vitro test were compared with previously available methods in 425 patients. For triiodthyronie, a normal range must be differentiated from the so-called euthyroid range (0.8-2.0 ng/ml) for patients with euthyroid goitre. The accuracy for triiodothyronine is then more than 95% and in hyperthyroidism 97.5%. It is, therefore, superior to other in-vitro measurements. But a disadvantage is that it is easily influenced by thyroid and extrahyroid factors. Similar accuracy is obtained for the TRH function test (thyrotopine-releasing hormone). Noteable is a negative TRH test in 20% of patients with euthroid goitre. The significance of triiodoathyrone determination is decreased in autonormous adenoma, in which the TRH test has an accuracy of 96.5%. In rare diseases of the thyroid all diagnositc possibilities must be taken into account. In ordinary practice stepwise course is suggested. RT-3U, T-4, T-3 and thyroid scan with 99mTc pertechneate are useful as basic tests. PBI is still thought to be important. The second step involves the TRH test rather than 131I function test. Triiocothyronine determination is best for therapeutic and follow-up perposes, a situation in which TRH test is of limited value.

Adenoma↗
PubMed1975

New aspects of radioimmunochemical measurement of human parathyroid hormone using the labelled antibody technique.

Two forms of heterogeneity of parathyroid hormone (PTH) have given rise to conflicting results: one due to the heterogeneity of the secreted species from the gland and their peripheral metabolism and the other representing the immunochemical heterogeneity of the available antibodies. We have developed sequence specific assays using the technique of labelled antibodies. Therefore, results of assays measuring the C-terminal part and the (1-34)-N-terminal part of the molecule could be compared to those of an assay for hormone bearing both N- and C-terminal antigenic determinants. This assay is supposed to detect predominantly (1-84)-intact hormone. The immunoradiometric assay of (1-34)-PTH has a sensitivity of 0.04 ng/ml. This technique avoids the critical iodination of the hormone fragment containing no tyrosine. There is the expected overlap between normal subjects and patients with primary and secondary hyperparathyroidism. The most important finding are results from patients undergoing neck catheterization. We demonstrated nonuniform secretion of different species of PTH by parathyroid adenomata and normal glands. This supports the hypothesis of cleavage of the (1-84)-molecule in the gland.

Antigen-Antibody Reactions↗
PubMed1975

The TRH test in the course of treatment of hyperthyroidism.

In nine patients with thyrotoxicosis (three patients with ophthalmopathy, one patient with T3 thyrotoxicosis) we followed plasma levels of triiodothyronine (T3) and thyroxine (T4) and the TRH induced TSH release before and under treatment with propythiouracil (PTU), carbimazole or methimazol. The patients were observed for 2-8 months and did not receive any thyroid hormones during this time. Before treatment the TSH responses to TRH were absent in all patients. After commencement of antithyroid drug therapy the T3 and T4 plasma values decreased to normal (T3) or subnormal levels (T4) within 1-5 weeks and the patients became euthyroid, but at that time the TRH test was still negative in all patients. Moreover, there was a lag between 2 weeks and 4 months in five of the patients before the TRH test became positive. The duration of this lag could not be correlated with any data of the history or the clinical signs. Several possible explanations for this observation are discussed. Our results suggest that the TRH-test is not suited for the control of the therapeutic effect of antithyroid drug therapy.

Adult↗
PubMed1975

Calcitonin production by rat thyroid tumours.

Immunolocalization techniques have been used to study 16 rat thyroids containing C cell tumours and ten rat thyroids in which no tumours or hyperplasias were found. All rats in these groups were at least 2 years old. An indirect ('sandwich') technique was used which involved rabbit or goat anti-human calcitonin antiserum and either fluorescein or peroxidase-labelled anti-rabbit or anti-goat IgG. Plasma calcitonin levels were measured in these animals and ina further group of ten young normal rats by means of an immunoradiometric assay using goat antiserum against synthetic human calcitonin. Both normal C cells and C cell tumours showed either apple-green fluorescence or positive peroxidase staining. The intensity of staining in the tumours vaired from one cell to another but was ingeneral less than that found for normal C cells. Calcitonin in the blood was detectable in most animals. The mean concentration found in young normal animals was 265 pg/ml (range less than 100-600 pg/ml), in old normal animals 160 pg/ml (range less than 100-400 pg/ml) and in rats with small C cell tumours 470 pg/ml (range 100-1200 pg/ml). The mean concentration in this latter group differed significantly from those of both normal groups (P less than 0-05). One animal with an invasive C cell tumour had a greatly increased calcitonin concentration (greater than 5 ng/ml) in the circulation. The results showed that calcitonin was present in normal rat C cells and that C cell tumours both contained and secreted calcitonin, underlining the similarity between these tumours and human medullary carcinomata.

Animals↗