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Biomedical subjects

P J der Kinderen

Publications and source records attributed to P J der Kinderen.

11 recordsLinked to original sources

Phosphofructokinase in normal thyroid tissue and thyroid neoplasms.

Phosphofructokinase (PFK; ATP: D-fructose-6-phosphate transferase, EC 2.7.1.11) was studied in human thyroid carcinomas (n = 16), follicular adenomas (n = 31) and normal thyroid tissue (n = 19). The specific activity in carcinomas (0.129 +/- 0.070) is significantly increased (p less than 0.001) in comparison with phosphofructokinase in normal thyroid tissue (0.028 +/- 0.009). No difference in phosphofructokinase activity seems to exist between follicular, papillary and undifferentiated carcinomas. Specific activities of follicular adenomas are rather heterogeneous. When these tumors were divided into three groups of increasing proliferative activity as judged by histopathological criteria, highest specific activities of phosphofructokinase were found in the group with the highest proliferative activity. The latter group resembles the enzyme activities found in carcinomas. On the other hand specific enzyme activities of the least active tissues were comparable to normal and different from carcinomas. Adenomas show the same isozyme composition as found in normal thyroid tissue. All three isozymes of PFK, M-(muscle)type, L-(liver)type and P-(platelet)type, were present. Phosphofructokinase from papillary carcinomas show a lesser degree of precipitation with anti-M antibodies. A higher amount of platelet type isoenzyme is found in papillary carcinomas compared to follicular and undifferentiated carcinomas. The influence of citrate, an inhibitor of phosphofructokinase, is in agreement with the isozyme composition.

Adenoma↗

Analytical evaluation of four sensitive assays of thyrotropin, including effects of variations in patient sampling.

Four immunometric kits for thyrotropin with detection limits below 0.1 milli-int. unit/L were evaluated with respect to accuracy, precision, specificity, matrix effects, and high-dose "hook" effect. We also studied variations of values related to the patients' sex and age and time of the day and season when samples were collected. Correlation among the four methods was excellent, except for a few samples, and the interference in these samples could be abolished by adding mouse serum or "suppression medium." These phenomena can also be expected to occur in other immunometric assays involving monoclonal antibodies. With some modifications all tests are suitable for a clinical study of the usefulness of the thyrotropin assay as a primary test for thyroid function.

Adult↗

Pyruvate kinase in normal human thyroid tissue and thyroid neoplasms.

Pyruvate kinase (ATP: pyruvate-2-O-phosphotransferase, EC 2.7.1.40) was studied in human thyroid carcinomas (n = 9), follicular adenomas (n = 32), and normal thyroid tissue (n = 12). The specific activity in carcinomas (mean 0.94 +/- 0.44) is significantly increased (P less than 0.0001) in comparison with pyruvate kinase in normal tissue (mean, 0.14 +/- 0.05). Specific activities of follicular adenomas are rather heterogeneous. When these tumors were divided into three groups of increasing proliferative activity as judged by histopathologic criteria, highest specific activities of pyruvate kinase were found in the group with the highest proliferative activity. On the other hand, specific enzyme activities of the least active tissues (colloid-containing follicular adenomas) were comparable to normal. The isoenzyme composition of normal thyroid tissue is characterized by the presence of K4, K3M, and K2M2 types of pyruvate kinase. In carcinomas, mainly K4 and K3M are found. Undifferentiated tumors express more K4 type compared with follicular and papillary carcinomas. Follicular adenomas with high specific activity show the same electrophoretic pattern as found in follicular carcinomas. Pyruvate kinase from malignant tumors is more inhibited by the amino acid L-alanine than the enzyme from normal thyroid tissue as a consequence of the presence of more K subunits in the malignant tissues. The K4 type from normal thyroid tissue is not kinetically different from the K4 type of carcinomas.

Adenoma↗

Plasma-exchange in the treatment of severe thyrotoxicosis in pregnancy.

Three female patients with severe thyrotoxicosis, two of them pregnant 22 and 16 wk, respectively, were treated with plasma-exchange (PE) combined with anti-thyroid drugs. In both pregnant patients PE was an effective adjunct to therapy with low-dose carbimazol. They were both delivered of normal babies at 37 and 40 wk, respectively. One newborn was euthyroid, the other had transient neonatal thyrotoxicosis. In the non-pregnant patient an ominous situation of thyrotoxic crisis was rapidly reversed by a single PE. During PE an influx of thyroid hormones occurs from the extra- to the intravascular compartment, which increases the efficacy of PE. The 5% albumin solution derived from human donor plasma, used as replacement fluid, contained substantial amounts of thyroid hormones. A 5% albumin solution from human placental origin lacks these hormones and is therefore recommended as replacement fluid for PE in thyrotoxicosis. There are no valid arguments for advocating replacement with donor plasma.

Adult↗

Thyroid function and bone turnover.

The mechanism of thyroid action on bone was studied in 15 patients with thyrotoxicosis and 14 patients with hypothyroidism. The patients were studied twice: when they were thyrotoxic or hypothyroid and when they had returned to a euthyroid state. Parameters of bone turnover showed a decrease when hyperthyroid patients became euthyroid: serum calcium (2.51 +/- 0.04 vs 2.38 +/- 0.03 mmol/l, P less than 0.05), acid phosphatase (11.7 +/- 0.7 vs 8.3 +/- 0.4 U/l, P less than 0.01), alkaline phosphatase (124 +/- 11 vs 98 +/- 8 U/l, P less than 0.05), the calcium/creatinine ratio (1.03 +/- 0.31 vs 0.43 +/- 0.07, P less than 0.01) and the hydroxyproline/creatinine ratio in the urine (69.9 +/- 12 vs 20.7 +/- 2.4, P less than 0.01). These parameters showed an increase when hypothyroid patients became euthyroid: serum calcium (2.36 +/- 0.03 vs 2.48 +/- 0.04 mmol/l, P less than 0.01), alkaline phosphatase (60 +/- 4 vs 84 +/- 8 U/l, P less than 0.05) and the hydroxyproline/creatinine ratio in the urine (15.9 +/- 4.3 vs 25.3 +/- 3.2, P less than 0.05). Changes in the calcium regulating hormones, parathyroid hormone, calcitonin and vitamin D metabolites, were not observed when hyperthyroid patients became euthyroid. When hypothyroid patients were treated a decrease in serum levels of 1.25-dihydroxyvitamin D (32.6 +/- 4.6 vs 17.9 +/- 2.5 ng/l, P less than 0.01) was observed. Serum growth hormone levels decreased when hypothyroid patients became euthyroid (4.3 +/- 0.5 vs 2.6 +/- 0.4 mU/l, P less than 0.01). The possible mechanisms of thyroid action on bone are discussed. The presented findings are in accordance with a direct effect of thyroid hormones on bone in thyrotoxicosis. An additional factor could be somatomedin, that might also be involved in changes in bone turnover in hyper- and hypothyroidism.

Acid Phosphatase↗

A comparative study of free thyroxine estimations.

Two commercial methods (Immophase, Corning and FT4, Lepetit) for the measurement of free thyroxine (FT4) in serum have been experimentally evaluated. Ease of handling and rapidity were satisfactory. Precision profiles showed intra-assay coefficients of variation not exceeding 5% over the entire measurement range (0-70 pmol/l) for both methods. Interassay coefficients of variation were below 8%. Assay results of both methods correlated well with those obtained with a symmetric dialysis method, with correlation coefficients of 0.95 for the Immophase and 0.93 for the Lepetit method and slopes not significantly different from unity. Comparison with this reference method did not give any indication of serious methodological error in either of the kits in spite of theoretical doubts with regard to one of them.

Female↗

Evaluation of the manual enzyme immunoassay (EMIT) procedure for determination of serum thyroxine.

Our experience with the determination of thyroxine (T4) in serum using a homogeneous enzyme immunoassay technique (EMIT, Syva Corp.) is reported. The intra-assay precision of the EMIT Manual Thyroxine Assay was investigated with 2 different calibrator concentrations and showed coefficients of variation varying from 5--2% for thyroxine concentrations of 40 and 120 micrograms/l thyroxine respectively. The inter-assay precision was investigated with different series of calibrators and serum specimens. Coefficients of variation for the calibrators varied from 35--5% in the range of 20--200 micrograms/l thyroxine and for the serum specimens in the range of 8--232 micrograms/l thyroxine from 50--4%. The recovery of various amounts of thyroxine added to thyroxine-free serum varied between 91--103%. The cross reactivity of structurally related compounds such as: monoiodothyronine, diiodothyronine, triiodothyronine, triiodothyroacetic acid and tetraiodothyroacetic acid was investigated. Serum samples of 100 patients were analysed by EMIT and radioimmunoassay (T4 RIA (PEG), Abbott Lab.). A good correlation was found between the EMIT and RIA assay (r = 0.96, slope = 0.96 and y-intercept = 3.37 micrograms/l).

Cross Reactions↗