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Biomedical subjects

K W Wenzel

Publications and source records attributed to K W Wenzel.

At least 73 records · Page 4Linked to original sources
PubMed1981

Mitogenic response of peripheral blood lymphocytes from patients with Graves' disease incubated with solubilized thyroid cell membranes containing TSH receptor and with thyroglobulin.

Transformation of peripheral blood lymphocytes (PBL) in response to solubilized TSH receptor and to human thyroglobulin (hTG) was carried out in patients with Graves' disease (GD). Mean stimulation index (SI) in response to solubilized TSH receptor was significantly increased only in hyperthyroid GD patients (SI = 3.0 +/- 1.8 SD, n = 13, p less than 0.025) when compared to normal subjects (SI = 1.5 +/- 0.8 SD,n = 14). All other subgroups of GD patients (i.e., euthyroid GD patients after treatment as well as those with/without ophthalmopathy or TSH-displacing antibody [TDA]) showed a tendency to elevated mean SI, which, however, was never significantly increased. In contrast, patients who were suspected of having a "disseminated autonomy" showed a tendency to decreased mean SI compared to GD patients. The mitogenic response of PBLs induced by solubilized TSH receptor could be suppressed by incubation of antigen and PBLs with bTSH. Control experiments with purified protein derivate of tuberculin(PPD) as stimulating antigen revealed, however, that bTSH itself suppresses the mitogenic response of PBLs and that the decrease of SI in this experiment is not due to blockage of the antigenic determinants of the TSH receptor protein. Human thyroglobulin (hTG) produced no significant increase in the SI of PBLs. Only 9 out of 47 GD patients showed an SI higher than the mean of normals + 2 SD. All those patients, however, who showed an elevated SI ( greater than 2.0) also revealed an increased SI with solubilized TSH receptor.

Cell Membrane↗
PubMed1981

Circulating diiodotyrosine: studies of its serum concentration, source, and turnover using radioimmunoassay after immunoextraction.

This report describes the application of a sensitive, specific, and reproducible RIA for diiodotyrosine (DIT) in human serum and metabolic studies on the source and kinetics of circulating DIT. Interference by cross-reactivity of T4 and other analogs was completely eliminated by isolation of DIT from serum with an efficient preparative immunoprecipitation technique. Mean (+/- SD) serum DIT levels were 161 +/- 133 pmol/liter (7.0 ng/100 ml) in 41 normal subjects, 64 +/- 30 pmol/liter in 46 pregnant women, 241 +/- 83 pmol/liter in the cord serum of 48 newborn infants, 542 +/- 494 pmol/liter in 22 hyperthyroid patients, and 101 +/- 71 pmol/liter in 15 hypothyroid patients. Mean values in pregnant, newborn and hyperthyroid subjects were significantly different from the normal mean. Very low DIT serum levels were found in four athyreotic patients during oral T4 substitution therapy, indicating that little DIT is formed by peripheral T4 degradation. In five normal subjects who received a single oral dose of 3 mg T4, serum DIT remained unchanged in one case and decreased in four cases. Radioimmunological measurements of DIT elimination from serum after the iv injection of 1 mg DIT in two normal volunteers gave MCRs of 103 and 133 liters/day and an average extrathyroidal DIT turnover rate of 19 nmol/day (8.2 microgram/day). These data indicate that circulating DIT arises predominantly from the thyroid, suggesting that peripheral formation of DIT is a minor metabolic pathway in the human.

Adult↗
PubMed1979

Amniotic fluid concentrations of 3,3',5'-tri-iodothyronine (reverse T3), 3,3'-di-iodothyronine, 3,5,3'-tri-iodothyronine (T3) and thyroxine (T4) in normal and complicated pregnancy.

Amniotic fluid concentrations of 3,3',5'-tri-iodothyronine (rT3), 3,3'-Di-iodothyronine (3,3'-T2), 3,5,3'-tri-iodothyronine (T3) and T4 were studied in 384 women during normal and complicated pregnancy. An inverse correlation was observed between decreasing rT3 and increasing 3,3'-T2 concentrations in amniotic fluid with gestational age. The mean rT3 level in normal pregnancy was 2.81 nmol/1 at 12-20 weeks and decreased significantly to 1.06 nmol/1 at 36-42 weeks of gestation. The mean 3,3'-T2 concentration was 49.1 pmol/1 at12-20 weeks increasing to 119 pmol/1 at 36-42 weeks. The mean T4 value of 3.83 nmol/1 at 12-20 weeks was about half that of later periods. The T3 concentration in a random sample of 45 amniotic fluids ranged from less than 28 to 370 pmol/1 (mean 102 pmol/1). The mean rT3, 3,3'-T2 and T4 values measured in patients with intra-uterine malnutrition, gestation diabetes, tocolysis, placental insufficiency and rhesus incompatibility at 31-40 weeks of gestation were not significantly different from those in uncomplicated pregnancy. Significantly decreased rT3 and T4 concentrations were found in toxaemia. From the results obtained in complicated pregnancy it may be concluded that measurements of iodothyronines, especially rT3, in amniotic fluid have insignificant diagnostic value in the recognition of intra-uterine lesions with the probable exception of fetal hypothyroidism. The analysis of the dependence of iodothyronine concentrations on the gestational age showed a maximum of rT3 and T4 levels between 20 and 30 weeks of pregnancy. This marked rise of iodothyronine concentrations in amniotic fluid at mid-gestation may be due to the onsetting maturation of the hypothalamic-pituitary-thyroid control system of the fetus.

Adult↗
PubMed1978

[Once-weekly intravenous L-thyroxine replacement in hypothyroidism].

A 58-year-old female patient with gastrointestinal complications also had primary hypothyroidism which proved therapy-resistant against high-dosage oral replacement with L-thyroxine or an L-thyroxine/L-triiodothyronine combination. Administration of four intravenous injections each of 2 mg L-thyroxine given at weekly intervals brought about a clinical and chemical euthyroid state. Thereafter it was possible to adopt an oral L-thyroxine replacement procedure without complications. Intravenous replacement of L-thyroxine and later transfer to oral medication appears a superior and safer method than the daily subcutaneous or intramuscular administration described hitherto.

Administration, Oral↗
PubMed1978

A low T3 syndrome in diabetic ketoacidosis.

The pituitary-thyroid axis was investigated in nineteen euthyroid patients with severe diabetic ketoacidosis. A 'low T3 syndrome' was found, with the following characteristics: lowered serum concentrations of triiodothyronine (T3), increased reverse triiodothyronine (rT3), slightly low thyroxine (T4), normal thyrotrophin (TSH), slightly increased triiodothyronine uptake (RT3U) values, and a blunted TSH response to thyrotrophin-releasing hormone (TRH). These disturbances in thyroid-function tests required several days good control of the diabetes to be corrected, at least partially. The data suggest the presence of an abnormal extrathyroidal T4 metabolism as well as a pituitary defect. Caution is recommended in the interpretation of thyroid-function tests during and several days after the treatment of diabetic ketoacidosis.

Adult↗
PubMed1978

Relationship between thyroid status and Graves' disease-specific immunoglobulins.

The prevalence of TSI in Graves' disease was investigated with a radioligand receptor assay using human thyroid membranes and highly purified labeled porcine TSH or bovine TSH in 110 patients before treatment and in 39 patients after successful treatment with antithyroid drugs. In 11 patients, the assay was performed before, during, and after therapy. The results in the radioligand receptor assay were compared to thyroid function tests (TRH test, free T4 index, serum %3 level, and thyroid suppression test). Normal IgG inhibits nonspecifically, but dose dependently, the binding of [125I]TSH to thyroid membranes. IgG samples from patients were only considered to be positive if they reduced the binding of the labeled hormone below the mean value minus 2 SD of the controls. TSI activity was found in 50% of the patients with untreated diffuse toxic goiter, in 3 out of 27 cases who regained suppressible thyroid function, and in 5 out of 12 cases who were off therapy for more than 6 weeks and showed normal TRH tests and normal hormone levels but in whom the suppression test was not performed. Our data cannot prove the hypothesis that only humoral antibodies are responsible for the thyroid stimulation in Graves' disease, but of course they cannot exclude it; furthermore, they suggest the existence of antibodies which bind to the human thyroid cell membrane without necessarily stimulating thyroid cellular activity.

Antigen-Antibody Complex↗
PubMed1978

Relationships between association state and enzymic activity of human erythrocyte phosphofructokinase.

Human erythrocyte phosphofructokinase has been subjected to active band centrifugation and stability measurements over a broad range of conditions. The enzyme behaves differently in-Tris buffer containing ATP and phosphate buffer containing fructose 6-phosphate. In the first buffer, dissociation is favoured and after prolonged storage of the enzyme tetramers represent the highest state of association. At 4 degrees C the enzyme exhibits the phenomenon of reversible cold-inactivation. This property is attributed to slow dissociation of the active associated states of the enzyme to dimers. The cold-inactivated enzyme can be reactivated by fructose 1,6-bisphosphate. Inorganic phosphate and fructose 6-phosphate have been found to protect the enzyme from cold-inactivation. Under these conditions, the sedimentation coefficient and the specific activity depend on the enzyme concentration only. The specific activity does not change on storage of the diluted enzyme at 4 degrees C. At 20 degrees C, however, a slow activation proceeds during incubation of the diluted enzyme. The correlations between the association state and the enzymic activity are discussed.

Enzyme Activation↗
PubMed1978

Association behaviour of human erythrocyte phosphofructokinase. Dependence of molecular weight on enzyme concentration as analyzed by frontal gel chromatography.

Self-association of human erythrocyte phosphofructokinase has been studied at pH 8.0 and at 4 degrees C in the presence of 2 mM fructose 6-phosphate by means of frontal gel chromatography. Under these conditions the basic associating catalytically active species is the tetramer of the enzyme with a molecular weight of about 330000, the monomers of which having a molecular weight of 83000 as determined by sodium dodecyl sulphate electrophoresis. The experimental data have been compared with various models describing the enzyme association. The mode of association can sufficiently be described by assuming a weakly negative cooperative process in which the association constant of the nucleation step (association of two tetramers to an octamer) is larger than that of the following propagation steps. The geometry of association appears to be approximately spherical.

Chromatography, Gel↗
PubMed1977

Aspects of the absorption of oral L-thyroxine in normal man.

Using a double isotope method, the optimal conditions for the absorption of an L-thyroxine (L-T4) preparation were examined. In particular, the influence of food intake on L-T4 absorption was examined. As distinct from the unfavorable results hitherto obtained with L-T4 lactase mixtures, a tablet similar to a commercial 100 mug L-T4 lactose preparation showed good absorptionof 70.6% +/- 12.9% SD. In the fasting state, the L-T4 absorption of both preparations was significantly better (p less than 0.001) than with simultaneous food intake: 79.3% +/- 7.2% SD versus 63.9% +/- 10.5% SD. The calculated absorption of a 3-mg L-T4 dose in a lactose preparation used in testing thyroid suppressibility was significantly lower (p less than 0.001) than the absorption of a smaller L-T4 dose, and the absorption in the fasting state was again signifiantly (; less than 0.01) higher compared to that with simultaneous food intake: 52.6% +/- 4.3% SD versus 43.9% +/- 5.4% SD. The possibility of retention in the liver in the case of a large 3-mg L-T4 dose is indicated. The data suggest that with L-thyroxine medication simultaneous food intake should be avoided.

Administration, Oral↗
PubMed1977

The thyroidal production of reverse triiodothyronine in autonomous adenoma.

The ratios of reverse triiodothyronine (rT3) to triiodothyronine (T3) concentrations were similar (0.89 +/- 0.09) in twenty-three autonomous thyroid nodules (fourteen decompensated, nine compensated) and paranodular tissues (0.82 +/- 0.08), whereas the serum ratio was significantly lower (0.098 +/- 0.014). This is compatible with the hypothesis that thyroidal rT3 and T3 production from mono- and diiodotyrosine may be a random process in contrast to non-random extrathyroidal rT3 and T3 formation.

Adenoma↗
PubMed1976

Effect of a single dose of dexamethasone on serum concentrations of thyroid hormones.

In ten euthyroid subjects, in whom endogenous thyroid-stimulating hormone (T.S.H.) production was suppressed by oral thyroxine (T4), a single dose of dexamethasone resulted in reduced serum-3,3'5-triidothyronine (T3) concentration and raised serum-3,3',5'-triiodothyronine (reverse T3 or rT3) concentration after 24 h. These changes were not related to changes in free hormones or binding proteins. Adrenal glucocorticoids may have a pathophysiological role in modulating the peripheral metabolism of thyroid hormones in stress.

Adult↗
PubMed1976

Self-association of human erythrocyte phosphofructokinase. Kinetic behaviour in dependence on enzyme concentration and mode of association.

The kinetic behaviour of human erythrocyte phosphofructokinase has been analyzed over a relative wide range of enzyme concentration (0.01 -- 1.7 mug/ml). The kinetic cooperativity which becomes apparent when the enzymic reaction rate is plotted versus the fructose 6-phosphate concentration decreases with increasing enzyme concentration. Simultaneously, a decrease of the half-saturation concentration for fructose 6-phosphate [S]0.5 is observed. Maximum velocity passes through a maximum at increasing enzyme concentrations. Sets of curves representing specific enzymic activity of phosphofructokinase versus enzyme concentration obtained at various fixed concentrations of fructose 6-phosphate and ATP are analyzed. The shapes of these curves are interpreted in terms of an association model of human erythrocyte phosphofructokinase, in which an inactive dimer (Mr 190000) and active multimers of the dimeric form are involved. The conclusion is drawn that the sigmoidal shape of the plots of the enzymic reaction rate versus fructose 6-phosphate concentration is partially caused by a displacement of the equilibrium between different states of association of phosphofructokinase to multimers by this substrate. On the other hand, the inhibition of the enzyme by high concentrations of ATP may be partially caused by a shift of this equilibrium to the state of the inactive dimer.

Adenosine Triphosphate↗