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Biomedical subjects

G Brabant

Publications and source records attributed to G Brabant.

At least 19 recordsLinked to original sources
PubMed1992

In vitro and in vivo regulation of thyrotropin receptor mRNA levels in dog and human thyroid cells.

Regulation of thyrotropin (TSH) receptor (TSHr) mRNA accumulation as compared with two other thyroid differentiation markers (thyroglobulin and thyroperoxidase (TPO] has been investigated by Northern blot. In dogs in vivo, chronic stimulation of the thyroid TSHr mRNA although it increased the levels of thyroglobulin and TPO mRNA. In dogs treated with thyroxin, the quiescent thyroids expressed normal levels of TSHr and TPO mRNA but depressed levels of thyroglobulin mRNA. In primary cultures of dog thyrocytes, dedifferentiation of the cells by treatment with epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate led to decreased TSHr mRNA levels and nearly abolished thyroglobulin and TPO gene expression. However, TSHr mRNA was always present, compatible with the fact that these cells, when treated by TSH, reexpress differentiation. Treatment of the cells with TSH or forskolin transiently increased the TSHr mRNA level after 20 h, an effect inhibited by cycloheximide. This up-regulation was confirmed at the protein level: forskolin-treated cells showed an enhanced cAMP response to TSH and an increased binding of labeled TSH to their membranes. Long term TSH treatment led to a slight down-regulation of TSHr mRNA in dog thyrocytes, but in human thyroid cells no marked down-regulation was observed.

Animals↗
PubMed1992

Early adaptation of thyrotropin and thyroglobulin secretion to experimentally decreased iodine supply in man.

Five healthy male volunteers (aged 25 to 28 years) were studied both after 4 weeks of treatment with 200 micrograms iodine/d orally (PO) and following experimental iodine depletion by treatment with 3 x 300 mg perchlorate/d PO over a 4-week period, in an attempt to better define the early adaptive responses to an alteration in iodine supply in thyroid function. Intrathyroidal iodine, serum triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4), reverse T3 (rT3), thyroxine-binding globulin (TBG), thyroglobulin (Tg), and thyrotropin (TSH) levels (10-minute sampling over 24 hours) were measured at the end of iodine administration and at the end of perchlorate treatment. Thyroid volume was determined by sonography, and iodine content was determined by fluorescence scintigraphy. TSH pulses were analyzed by computer-assisted programs. Comparing both experimental situations, perchlorate treatment significantly reduced intrathyroidal iodine concentration (4.0 +/- 1.3 to 3.0 +/- 1.2 nmol/mL, P less than .05), but thyroid volume and total serum T4, T3, FT3, and TBG levels were not altered. Mean 24-hour serum TSH levels (1.8 +/- 0.3 to 1.0 +/- 0.3 mU/L, P less than .001), amount of TSH secreted/pulse (0.5 +/- 0.1 to 0.3 +/- 0.1 mU/L, P less than .001), and FT4 levels (15.7 +/- 1.7 to 14.3 +/- 1.4 pmol/L, P less than .005) were significantly diminished, whereas Tg levels (18.6 +/- 10.0 to 35.1 +/- 14.0 ng/mL, P less than .01) were significantly increased. Thyroid-specific antibodies were normal and were not altered by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Gene expression of differentiation- and dedifferentiation markers in normal and malignant human thyroid tissues.

Steady state mRNA transcript levels of thyroid differentiation markers such as TSH receptor (TSHR), thyroglobulin (Tg) and thyroid peroxidase (TPO) as well as a potential marker of dedifferentiation, c-myc, marker were investigated in patients with thyroid tumors and in normal controls using Northern blot analysis. Blots were normalized by acridine orange staining whereas analysis of beta-actin mRNA levels revealed highly variable levels already in normal tissue suggesting regulation of this "constitutively" expressed gene. Determination of c-myc mRNA revealed increased steady state mRNA levels in anaplastic carcinomas (ATC) as compared to normal tissues. However, in some patients c-myc transcript levels were lower in the tumor than in the adjacent normal tissue reducing the significance of c-myc as a marker of dedifferentiation. High levels of TSH mRNA were found in control thyroids, whereas in ATC no normal TSHR mRNA was detected. In PTC and follicular thyroid carcinomas (FTC) the transcripts varied from increased to markedly reduced levels. In one patient with FTC 2 independent preparations of the tumor revealed different results, undetectable and clearly detectable TSHR mRNA levels. Xenotransplantation of this tissue on nude rats showed a variable expression pattern in the individual xenotransplantations suggesting heterogeneity of the tumor tissue. Tg and TPO mRNA were strongly expressed in normal tissues and completely lost in all ATC. In differentiated thyroid tumors the transcript levels of Tg and TPO varied from normal to complete loss of expression of either Tg or TPO, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridine Orange↗
PubMed1992

Circadian changes in pulsatile TSH release in primary hypothyroidism.

OBJECTIVE: We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism. DESIGN: In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured. SUBJECTS: Nine patients with overt primary hypothyroidism, seven patients with subclinical hypothyroidism and 16 healthy controls. MEASUREMENTS: Computer-assisted analysis by the Desade and Cluster programs. RESULTS: Both computer-assisted programs revealed an increased TSH pulse amplitude in both overt and subclinical hypothyroidism versus controls (Desade: 36.9 +/- 31.4 (mean +/- SD) (P < 0.001) and 2.8 +/- 1.9 (P < 0.001) vs 0.4 +/- 0.2 mU/l; Cluster: 25.6 +/- 25.1 (P < 0.001) and 2.4 +/- 1.4 (P < 0.001) vs 0.4 +/- 0.2 mU/l). TSH pulse frequency remained unchanged with approximately 10 pulses/24 hours. A highly significant correlation was found between the mean 24-hour TSH concentration and the TSH pulse amplitude in all controls and patients but not to TSH pulse frequency. The nocturnal TSH surge was absent in six out of nine patients with overt primary hypothyroidism. The deficient nocturnal rise of TSH in primary hypothyroidism vs controls (22 +/- 51 vs 82 +/- 41%, P < 0.001), was associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency. CONCLUSIONS: Mean 24-hour TSH pulse amplitude is increased in primary hypothyroidism, but TSH pulse frequency remains unchanged. The decrease of the nocturnal TSH increase in primary hypothyroidism is associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency.

Adult↗
PubMed1992

The pulsatile GH secretion in acromegaly: hypothalamic or pituitary origin?

OBJECTIVE: We studied the effects of different modes of octreotide therapy on the pulsatile pattern of GH release in an attempt to define better its regulation by growth hormone-releasing hormone (GHRH) and somatostatin and its effects on IGF-I plasma levels in acromegaly. DESIGN: In six acromegalic patients not cured by previous treatment we compared the 24-hour GH secretion profiles under basal conditions with subcutaneous (s.c.) bolus injections of 100 micrograms octreotide every 8 hours and with continuous s.c. infusions of the same daily dose. Blood samples were taken every 10 minutes over 24 hours followed by a GHRH test (100 micrograms GHRH i.v.) with blood sampling every 15 minutes for another 2 hours. After a 4-week interval all patients were treated either by the bolus or continuous mode of octreotide application in a randomized cross-over design. On day 4 of treatment blood sampling and GHRH test were repeated. Octreotide treatment was withdrawn for another 4 weeks; all patients then received the alternate application mode and were measured under similar conditions. MEASUREMENTS: Serum GH and plasma IGF-I concentrations were analysed by serial array averaging. IGF-I levels were measured in two different assays with and without previous protein extraction. For GH pulse detection three different algorithms (Cluster, Pulsar, Desade) were applied. RESULTS: With both treatments, the initially elevated basal 24-hour mean serum GH concentrations (58.0 +/- 9.7 mU/l mean +/- SEM) decreased significantly (bolus: 11.5 +/- 4.9 mU/l, P < 0.001 vs basal; continuous infusion: 7.6 +/- 1.9 mU/l, P < 0.001 vs basal) after 4 days. GH suppression was significantly more pronounced following continuous infusion than bolus (P < 0.05). IGF-I plasma concentrations were lowered significantly (P < 0.05) with both forms of treatment which did not differ between themselves. Bolus and continuous infusion treatment significantly inhibited (P < 0.05) the amplitudes of pulsatile GH release, but did not change the pulse frequency. In two of the patients, GHRH stimulation did not increase GH serum levels suggesting a constitutive activation of adenylyl cyclase. CONCLUSION: Continuous subcutaneous octreotide treatment in acromegaly suppresses mean GH levels better than bolus injection. The number of GH pulses remains unaffected by both modes of treatment providing evidence against a somatostatinergic mechanism of pulsatile GH secretion in these patients. The unchanged frequency of pulsatile GH release in the patients unresponsive to exogenous GHRH indicates that this pattern might be independent of hypothalamic GHRH and somatostatin and suggests a pituitary-derived mechanism for GH pulse generation in acromegaly.

Acromegaly↗
PubMed1992

Classification of dynamical diseases by new mathematical tools: application of multi-dimensional phase space analyses to the pulsatile secretion of parathyroid hormone.

The biological importance of dynamic hormonal secretion has been demonstrated. There is good evidence from recent studies that parathyroid hormone (PTH) which plays an important role in bone physiology is secreted in a pulsatile manner. In this study we performed a classification of two 'dynamical diseases' namely osteoporosis and hyperparathyroidism by the visualization of dynamic PTH-secretion in multidimensional phase spaces.

Adult↗
PubMed1992

Temporal pattern of pancreatic insulin and C-peptide secretion and of plasma glucose levels after nutritional stimulation.

The dependency of the secretory pattern of insulin and C-peptide on either oral ingestion of the energy substrates glucose and protein or gastric distension was determined in nine healthy male subjects. To analyze secretion dynamics, high frequency blood sampling, computed estimation of individual hormone half-lives, deconvolution of data, and pulse analysis of the deconvoluted data by the Cluster program were used. After stimulation with oral glucose and protein, baseline insulin, C-peptide, and glucose levels increased in parallel, forming two or three large increases (macropulses), with a mean duration of 63.8 min. The frequency of high frequency insulin and C-peptide pulses was unchanged, whereas a significantly increased amplitude formed the basis of insulin/C-peptide macropulses after both oral stimulations. No changes in baseline insulin/C-peptide concentrations or in amplitude or frequency were observed after a challenge with 400 mL H2O (n = 3). Gastric distension with an equal volume of H2O (400 mL) did not influence pancreatic hormone secretion. Insulin and C-peptide secretions were pulsatile, with a frequency of approximately one pulse per 12 min correlated to C-peptide pulses. When calculated by multiple regression analysis glucose, insulin and C-peptide plasma levels increased simultaneously after the challenge with either glucose or protein, suggesting a neuronal or humoral intestinal-pancreatic regulation of pancreatic hormone secretion. These findings suggest that high frequency insulin and C-peptide pulses form the basis of insulin and C-peptide plasma levels after meal stimulation.

Administration, Oral↗
PubMed1992

The nude rat is established as a model for endocrine studies: regulation of thyroid function and xenotransplantation of a thyroid tumor cell line.

The thyroid physiology of athymic nude rats, rnu/rnu, is characterized and established here as an animal model to study transplanted thyroid tumors. Male rats were catheterized 5 days before experiments were started. The mean thyroid-stimulating-hormone (TSH) plasma concentrations were 2.9 +/- 0.6 ng/ml during infusion of 0.25 ml/h of 0.9% NaCl (n = 12). T3 plasma concentrations were 2.6 +/- 0.4 ng/ml. T4 plasma levels were 22.0 +/- 5.6 micrograms/dl. A bolus of 0.1 mg thyrotropin-releasing hormone (TRH) significantly increased TSH plasma concentrations (P less than or equal to 0.001; from 2.9 +/- 0.6 to 7.8 +/- 1.1 ng/ml, n = 12). No pulsatile TSH secretion was observed in a 2-hour period with blood samples taken every 10 minutes (n = 12) and hourly sampling disclosed no circadian variation of TSH during a 24-hour period (n = 4). Successful xenografting was possible in 12 of 15 cases using a follicular thyroid carcinoma cell line (FTC 133). Measurement of human thyroglobulin (hTg) by a hTg IRMA revealed high levels in rats with functional FTC tumors, whereas no hTg was detected in untransplanted rats or animals with nonfunctional transplants.

Animals↗
PubMed1992

Thyroid hormones influence perceptual processing in a visual search paradigm.

The mechanisms that mediate the effects of thyroid hormones on higher cognitive processes are not well understood. In the present experiments, event-related potentials (ERPs) and behavioral measurements were recorded in a visual search paradigm where a target item had to be detected in a number of distractor items. 10 healthy subjects were given a daily dose 300 micrograms thyroxine (T4) p.o. and recordings were made before and after 3 weeks of treatment. All subjects developed hyperthyroidism with a completely suppressed TSH (1.6 +/- 0.5 mU/l vs. non detectable), a significant increase in T3 (1.5 +/- 0.2 vs. 1.9 +/- 0.2 ng/ml). T4 (6.6 +/- 1.6 micrograms/dl vs 11.9 +/- 2.7 micrograms/dl) and sex-hormone binding globulin (2.9 +/- 1.1 vs. 3.8 +/- 1.3 micrograms/ml; all p less than 0.0005). Compared to the control group (n = 15), thyroid hormones improved controlled serial visual processing, as indexed by changes of the late positive ERP component and target detection hit rate (in both cases p less than 0.01), whereas parallel detection of salient features remained unchanged. The data suggest a differential impact of thyroid hormones on visual information processing.

Arousal↗
PubMed1991

Measurement of intracellular Ca2+ in single aequorin-injected and suspensions of fura-2-loaded ROS 17/2.8 cells and normal human osteoblasts. Effect of parathyroid hormone.

It is known that parathyroid hormone (PTH) activates the cyclic AMP (cAMP) signalling pathway in osteoblasts. In recent years it has been suggested that an elevation of the intracellular free Ca2+ concentration ([Ca2+]i) may also be involved in the regulation of osteoblast function by PTH. However, this remains controversial. Here we investigated the effect of PTH on the [Ca2+]i of ROS 17/2.8 cells and normal human osteoblasts. The [Ca2+]i was measured in single aequorin-injected cells and in suspensions of cells loaded with fura-2. Human PTH-(1-38)-peptide (1-300 nM) had no effect on the [Ca2+]i in single aequorin-injected ROS 17/2.8 cells (n = 17) measured at various times after injection (1-20 h), or in suspensions of fura-2-loaded ROS 17/2.8 cells (n = 9). Ionomycin (1 microM) increased the [Ca2+]i in fura-2-loaded and single aequorin-injected ROS 17/2.8 cells by 285 +/- 60 nM (n = 9) and 312 +/- 99 nM (n = 6) respectively, indicating that both methods detect changes in [Ca2+]i with equal sensitivity. In contrast, human PTH-(1-38) (10-100 nM) markedly stimulated cAMP accumulation in ROS 17/2.8 cells. In single aequorin-injected normal human osteoblasts there was no change in the [Ca2+]i in response to 100 nM human PTH-(1-38) or 100 nM bovine PTH-(1-84) (n = 18). In contrast, in suspensions of normal human osteoblasts loaded with fura-2, an increase in [Ca2+]i in response to human PTH-(1-38) (100 nM) was found (60 +/- 28 nM; n = 6). Considerable variation in the magnitude of the response was observed between individual preparations and donors. These data indicate that PTH activates cAMP accumulation without affecting [Ca2+]i in ROS 17/2.8 cells and that PTH causes a rise in [Ca2+]i only in a small subset of normal human osteoblasts. We suggest that the Ca2+ response to PTH in osteoblasts is limited by the state of differentiation of the cells, and may be due either to the presence of a distinct Ca2(+)-mobilizing receptor or to a cAMP-mediated Ca2+ response.

Aequorin↗
PubMed1991

Frequency and amplitude enhancement of calcium transients by cyclic AMP in hepatocytes.

Interactions between signalling pathways such as the cyclic AMP and the Ca2+/phosphatidylinositol pathway may occur and be of major relevance in the regulation of cell function. We demonstrate here that cyclic-AMP-dependent mechanisms cause a marked increase in frequency and peak free Ca2+ of alpha 1-receptor-induced Ca2+ transients in single hepatocytes and lower the threshold for alpha 1-receptor agonists. Adrenaline at low physiological concentrations generates alpha 1-receptor-induced Ca2+ transients, which requires activation of the beta 2-receptor signalling pathway. We conclude that an interaction between the alpha 1-receptor signalling pathway and cyclic-AMP-dependent mechanisms activated by beta 2-receptor occupation is crucial to elicit a complete adrenergic response to adrenaline at physiological concentrations in rat hepatocytes.

Aequorin↗
PubMed1991

Efficacy and tolerability of a long-acting intramuscularly injectable depot preparation of bromocriptine: the results of a double blind study.

The tolerability and efficacy of a long-acting im applicable form of bromocriptine (Parlodel LAR) was tested in a double-blind approach in 20 patients with hyperprolactinemia or prolactinoma, 17 of them complaining of persistent side effects on oral treatment with dopamine agonists. The study-code revealed similar characteristics for age, sex, weight, clinical symptoms and previous therapy in both groups but prolactin serum levels were higher in the verum group even though the difference was not significant. In all 10 patients receiving Parlodel LAR prolactin serum concentrations were significantly suppressed and tumor size was reduced in 5 of the 9 patients with visible tumors when controlled after 28 days. In contrast, no significant change in serum prolactin levels was observed in the placebo group and tumor size of all visible tumors was not altered. Side effects typically reported for dopamine agonists started 3 h after application in the verum group and were significantly different to the unspecific side effects reported in the placebo group during the first 72 h. Thereafter systemic tolerability was indistinguishable between both groups. The local tolerability at the injection site was excellent for both, Parlodel LAR and placebo.

Adolescent↗
PubMed1991

Human thyrotropin receptor gene: expression in thyroid tumors and correlation to markers of thyroid differentiation and dedifferentiation.

Human thyrotropin (TSH) receptor steady-state transcript levels were analyzed by Northern blot analysis in thyroids of patients with thyroid carcinoma, with hyperfunctioning adenoma and in normal controls. In control tissue and benign tumors expression levels of TSH receptor mRNA were high whereas in anaplastic carcinomas no normal TSH receptor mRNA was detected. In papillary and follicular tumors it varied from normal to markedly reduced levels. Thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA were strongly expressed in normal tissue and in hyperfunctioning adenomas but were completely lost in all anaplastic tumors. In papillary tumors expression of TPO and Tg mRNA varied from normal to a complete loss of expression of either TPO, Tg or both. Tg and TPO steady-state expression did not correlate to TSH receptor transcript levels. C-myc mRNA was highly expressed in anaplastic carcinomas, very variable in normal controls and in differentiated thyroid tumors and low in hyperfunctioning adenomas. In summary, TSH receptor mRNA is persistently expressed in all differentiated thyroid tissues and tumors but lost in undifferentiated carcinomas. Its persistence far along the transformation pathway further supports the concept that this gene which inserts the thyrocytes in the physiological regulatory network is almost constitutively expressed in this cell.

Adolescent↗
PubMed1991

Hypothalamic regulation of pulsatile thyrotopin secretion.

To determine the mechanism underlying pulsatile TSH secretion, 24-h serum TSH levels were measured in three groups of five healthy volunteers by sampling blood every 10 min. The influence of an 8-h infusion of dopamine (200 mg), somatostatin (500 micrograms), or nifedipine (5 mg) on the pulsatile release of TSH was tested using a cross-over design. The amount of TSH released per pulse was significantly lowered by these drugs, resulting in significantly decreased mean basal TSH serum levels. However, pulses of TSH were still detectable at all times. The TSH response to TRH (200 micrograms) tested in separate experiments was significantly lowered after 3 h of nifedipine infusion compared to the saline control value. Nifedipine treatment did not alter basal, pulsatile, or TRH-stimulated PRL secretion. The persistence of TSH pulses under dopamine and somatostatin treatment and the blunted TSH responses to nifedipine infusion support the hypothesis that pulsatile TSH secretion is under the control of hypothalamic TRH. The 24-h TSH secretion pattern achieved under stimulation with exogenous TRH in two patients with hypothalamic destruction through surgical removal of a craniopharyngioma provided further circumstantial evidence for this assumption. No TSH pulses and low basal TSH secretion were observed under basal conditions (1700-2400 h), whereas subsequent repetitive TRH challenge (25 micrograms/2 h to 50 micrograms/1 h) led to a pulsatile release of TSH with fusion of TSH pulses, resulting in a TSH secretion pattern strikingly similar to the circadian variation. These data suggest that pulsatile and circadian TSH secretions are predominantly controlled by TRH.

Adult↗
PubMed1991

Unaltered pulsatile and circadian TSH release in euthyroid patients with endemic goitre.

To evaluate the pathophysiological role of TSH in goitrogenesis we investigated pulsatile TSH secretion in 11 patients with a non-toxic goitre and in 11 healthy controls. Thyroid volume was 40 +/- 10 ml in the goitre group and 15 +/- 4 ml in the controls as measured by ultrasound. Blood was sampled continuously via an indwelling venous catheter at 10-min intervals over 24 h. Neither the mean 24-h serum TSH levels (goitre 1.1 +/- 0.5 vs controls 0.9 +/- 0.4 mU/l) nor the nocturnal surge of TSH were significantly different between the two groups. The average of the TSH pulse frequency (goitre 10.8 +/- 3.7 vs controls 9.6 +/- 3.5 pulses/24-h) and of the TSH pulse amplitude (goitre 0.4 +/- 0.2 vs controls 0.3 +/- 0.1 mU TSH/l) as analysed by DESADE programme (detection of secretory activity by discrete deconvolution) did not differ in the two groups. Furthermore, there was no correlation between the volume of the thyroid gland and the dynamics of the TSH secretion. We conclude that our data do not suggest a relevant pathophysiological role of TSH secretion in the development of non-toxic goitre in man.

Adult↗
PubMed1991

[Evaluation of fetal lung maturity with the measurement of enzymatic activities in amniotic fluid: comparison of three ratios].

Measurement, in amniotic fluid, of gamma-glutamyl-transferase (GGT) alkaline phosphatase and of thermostable and thermolabile (TLAP) isoenzyme allows to anticipate the unexpected risk of hyaline membrane disease. ROC method adapted to three ratio of these enzymatic activities shows that TLAP/GGT is the most performant at the level of 0.9 with a sensitivity of 96% and a specificity of 60%.

Alkaline Phosphatase↗
PubMed1991

[Value of amniotic gamma-glutamyl-transpeptidase assay in the diagnosis of fetal digestive stenosis after 24 weeks of amenorrhea].

In 18 women compared with 1,181 controls, foetal digestive tract stenoses were discriminated, independently of the gestational age, by a more than 50 IU/l level of gamma-glutamyl transpeptidase in the amniotic fluid. This test had a specificity of 99% and a sensitivity of 85% which was accounted for by the inclusion in the study of distal stenoses and oesophageal atresias, all conditions where the gamma-glutamyl transpeptidase level is normal. In cases with ultrasonically detected abdominal wall abnormalities, this test is also useful in the diagnosis of subjacent digestive tract stenosis.

Amniotic Fluid↗