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Biomedical subjects

R Docter

Publications and source records attributed to R Docter.

At least 109 records · Page 6Linked to original sources

Serum thyroid hormone concentrations during prolonged reduction of dietary intake.

In nine obese but otherwise healthy subjects the effect of caloric restriction on the serum concentrations of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), urea, uric acid, creatinine, and bilirubin was studied. Blood was obtained before and 2, 4, and 6 wk after the subjects had changed to a chemically defined diet (31 g amino acids, 44 g carbohydrate, and 1.5 g fat; 300 kcal/day). A decline of body weight to 88% and of serum T3 to 70% of the pretreatment values was observed. Creatinine and bilirubin increased to 115% and 163%, respectively. Uric acid and rT3 showed a transient rise to 148% and 180%, respectively. Serum urea was lowest (72%) from the second until the fourth week. There was a highly significant correlation between serum rT3 and uric acid (r = 0.77, p less than 0.001). The time course of the changes seems to indicate that conversion of T4 into T3 and rT3 is mediated by separate processes.

Adult↗

Value of luteinizing hormone-releasing hormone testing in bromocriptine treatment of amenorrhea and hyperprolactinemia in patients with pituitary tumors.

The results of bromocriptine treatment in 13 patients with radiologically evident pituitary tumors are described. A menorrhea was present in all patients, hyperprolactinemia in 12 of the 13 patients, and acromegaly in 3 patients. Five patients have previously been treated surgically and by radiotherapy because of suprasellar extension of the adenoma. Plasma prolactin levels after one single dose of 2.5 mg of bromocriptine were found to have no predictive value as to the dosage needed for treatment, whereas the plasma gonadotropin response after the administration of luteinizing hormone-releasing hormone appeared to be predictive with respect to the return of ovulation during bromocriptine therapy.

Adenoma↗

Lowering of serum 3,3',5-triiodothyronine thyroxine ratio in patients with myocardial infarction; relationship with extent of tissue injury.

Serial measurements of haematocrit (Ht), plasma thyroxine (T4), triiodothyronine (T3) and alpha-hydroxybutyrate dehydroxygenase (alpha-HBDH) were performed in patients following myocardial infarction (MI). Infarct size was estimated by mathematical analysis of the change in plasma alpha-HBDH activity with time. After an initial small increase Ht decreased 12% until day 9 and remained constant thereafter. Serum T4 did not change during the entire study. Serum T3 decreased to 66% at day 9 and then returned to normal within 2 months. These figures are expressed relative to determinations in the first blood sample obtained within 12 h after MI. A significant correlation between the lowest serum T3/T4 ratio and infarct size was observed. These observations suggest that in these patients the peripheral conversion of T4 into T3 is reduced. This was accompanied by an increased production of reverse T3 as evidenced by observations in one patient.

Aged↗

Radioimmunoassay of 3,3'-di-iodothyronine in unextracted serum: the effect of endogenous tri-iodothyronine.

The development of a highly sensitive and specific radioimmunoassay for 3,3'-di-iodothyronine (3,3'-T2) is described. The assay was applied to the measurement of 3,3'-T2 in unextracted human serum and used 8-anilino-1-naphthalene-sulphonic acid to inhibit the binding of 3,3'-T2 to serum transport proteins. The lower limit of detection of the assay was 2 fmol 3,3'-T2 per tube, which corresponded to 10 pmol 3,3'-T2/l serum. The mean concentration of 3,3'-T2 in normal serum was found to be 23 pmol/l, which is considerably lower than most values reported previously. Evidence is presented which suggests that the cross-reactivity of tri-iodothyronine with the antiserum to 3,3'-T2 is an important factor in the measurement of serum concentrations of 3,3'-T2 by radioimmunoassay.

Cross Reactions↗

Response to thyrotrophin-releasing hormone and triiodothyronine suppressibility in euthyroid multinodular goitre.

In twenty-two female patients with euthyroid multinodular goitre of varying size, thyroid suppression of 131I thyroid uptake by triiodothyronine (T3) and thyrotrophin (TSH) release after thyrotrophin-releasing hormone (TRH) administration were compared with thyroid weight, estimated by a planimetric method, and with serum thyroxine (T4) and T3 concentrations. Maximal increment of TSH (deltaTSH) after TRH and per cent T3-suppressibility were inversely related to thyroid weight and not related to basal serum T4 or T3 concentrations. deltaTSH and per cent suppression correlated positively, but deltaTSH was more often subnormal than T3-suppressibility. A practical consequence of our study is that nonconformity of the two tests may occur. This should be kept in mind in the evaluation of patients with thyroid disorders.

Adult↗

Hypothyroidism in an area of endemic goiter and cretinism in Central Java, Indonesia.

In an area of severe endemic goiter in Central Java, Indonesia, clinical overt or mild hypothyroidism appeared to be present in 7 out of 20 cretins and also in 12 out of 94 non-cretinous subjects, all 5-20 years of age, living in the village of Sengi. Hypothyroidism was not found in a control group of 70 subjects of the same age living in Londjong just outside the edemia. In hypothyroid subjects the plasma PBI-concentration was 0.98+/-0.32 mug/100 ml (mean+/-SD) vs. 2.72+/-1.24 mug/100 ml in euthyroid subjects from Sengi and 4.86+/-0.80 mug/100 ml in controls from Londjong. Values for T3 were 56.3+/-3.17 ng/100 ml in hypothyroids, 140.5+/-38.5 ng/100 ml in euthyroids from Sengi and 121.6+/-27.4 ng/100 ml in controls. The TSH levels (geometric mean and range) in these 3 groups were, respectively, 210.1 (108.0-342), 15.6 (3.0-372) and 4.1 (0.8-7.0) muU/ml. The differences between the mean concentration of PBI, T3 and TSH in the hypothyroid and euthyroid groups were highly significant (P less than 0.001). These data strengthen the clinical diagnosis of hypothyroidism in cretins as well as in non-cretinous subjects. All hypothyroid subjects had a PBI less than 1.8 mug/100 ml and T3 less than 120 ng/100 ml and TSH greater than 100 muU/ml. In 8 hypothyroid subjects, restudied 18 months after iodized oil injection, hypothyroidism was either corrected or markedly improved. It therefore appears that iodine deficiency per se in postnatal life may lead to (juvenile) hypothyroidism, which can be corrected by iodine therapy. Our findings have implications for the definition and diagnosis of endemic cretinism. Not all hypothyroid subjects in an area of endemic iodine deficiency should be classified as cretins.

Adolescent↗

Inactivation of thyrotrophin releasing hormone by human and rat serum.

The inactivation of thyrotrophin releasing hormone (pGlu-His-Pro-NH2, TRH) and its deamidated analogue pGlu-His-Pro-OH (TRH-OH) in human and rat serum has been studied using specific radioimmunoassays. No difference was apparent between human and rat serum with regard to proteolytic activity towards TRH and TRH-OH. It was found that the inactivation of both peptides is a saturable process. The disappearance of TRH was clearly inhibited by TRH-OH, luteinizing hormone-releasing hormone and dithiothreitol. The suppressive action of these compounds was observed to be dependent on their concentration. Proline and EDTA showed little inhibiting activity. Proline amide and pyroglutamic acid left the reaction unaffected. In no single instance could any production of TRH-OH from TRH be demonstrated.

Animals↗

Serum gonadotrophins, testosterone and spermatogenesis in subfertile men.

In 210 subfertile men there existed a significant positive correlation between serum FSH and LH (0.41). No correlation was observed between the gonadotrophin levels and testosterone. In contrast to this FSH as well as LH were negatively correlated with the natural logarithm (ln) of the sperm count/ml ejacate (-0.44 and -0.18, respectively). When the positive correlation which existed between FSH and LH was used to calculate partial correlation coefficients, the coefficient between FSH and ln sperm count did hardly change (-0.41) the coefficient between LH and ln sperm count on the other hand became insignificant (-0.05). This suggests that spermatogenesis influences FSH serum levels in subfertile men by a decreased suppression when sperm production is diminished. Testicular biopsies taken from 97 of these patients were used to determine biopsy scores. These scores showed a significant negative correlation with FSH (-0.34) and a positive one with ln sperm count/ml ejaculate (0.45). Interestingly the biopsy score of 16 patients who fertilized their wives, was found to be higher compared with the score of the other patients who did not fertilize. The number of sperm/ml ejaculate and the FSH values of these 2 groups of biopsied patients were, however, not significantly different. This leads to the conclusion that the biopsy score is a better parameter for the evaluation of oligospermic men than either sperm count or FSH serum values.

Follicle Stimulating Hormone↗

Subcellular localization of a rat liver enzyme converting thyroxine into tri-iodothyronine and possible involvement of essential thiol groups.

Experiments with rat liver homogenates showed that on subcellular fractionation the ability to catalyse the conversion of thyroxine into tri-iodothyronine was lost. The activity could in part be restored by addition of the cytosol to the microsomal fraction. Both components were found to be heat labile. The necessity of the presence of cytosol could be circumvented by incorporation of thiol-group-containing compounds in the medium. Optimal enzymic activity was observed in the presence of dithiothreitol and EDTA in medium of low osmolarity. By comparing the distribution of the converting enzyme over the subcellular fractions with a microsomal marker enzyme, glucose 6-phosphatase, it was demonstrated that the former is indeed of microsomal origin. Finally, it was shown that thiol groups play an essential role in the conversion of thyroxine into tri-iodothyronine.

4-Chloromercuribenzenesulfonate↗

Degradation of thyrotropin releasing hormone and a related compound by rat liver and kidney homogenate.

The inactivation of the hypothalamic hormone by rat liver and kidney homogenates was studied, using specific radioimmunoassays for the measurement of thyrotropin releasing hormone, pGlu-His-Pro-NH2 (TRH), and for an analogous peptide, pGlu-His-Pro-OH(TRH-OH), which has been proposed as a major metabolite of TRH [NAIR et al., 1971]. The inactivation of TRH and the free acid was found to be rapid. Heat lability and saturation kinetics suggest the involvement of enzymatic processes. In liver homogenate, TRH-OH production from TRH was observed. The accumulation of TRH-OH was substantial in experiments employing near-saturation concentrations of TRH. The liver and kidney are ascribed as major sites for breakdown of TRH in vivo.

Animals↗

Binding of L-triiodothyronine to isolated rat liver and kidney nuclei under various circumstances.

Triiodothyronine (T3) is specifically bound by nuclei from rat liver and kidney. Binding of T3 at 37 degrees C reaches its maximum at 30 min. In the presence of EDTA (to remove Mg2+) T3 binds to a class of binding sites with an estimated equilibrium association constant (Ka) of 3.3 x 10(10) M(-1) and a maximal binding capacity (MBC) of 3.8 fmol T3/100 mug DNA. In the presence of MgCl2 T3 binds to a second class of binding sites with an estimated Ka of 4.8 x 10(8) M(-1) and a MBC of 123 fmol/100 mug DNA. Among the analogues tested, binding - relative to T3 - of D-T3, triiodothyoacetic acid and desamino-T3 is the same for both classes of binding sites, but relative affinity of thyroxine, D-T4, tetraiodothyroacetic acid and desamino-T4 is 2.5 to 6 times higher for the second class of binding sites than for the first class. The presence of a cytosol binding protein is not a prerequisite for binding of T3 to the nucleus.

Animals↗