Search PubMed⌕ Search

Biomedical subjects

G Brabant

Publications and source records attributed to G Brabant.

At least 91 records · Page 5Linked to original sources
PubMed1998

Determinants of serum leptin levels in Cushing's syndrome.

Corticosteroids and insulin increase leptin expression in vivo and in vitro. To investigate whether increased serum cortisol influences serum leptin concentrations in humans, we analyzed fasting serum leptin and insulin levels in 50 patients with Cushing's syndrome [34 female patients: 27 with the pituitary form and 7 with the adrenal form; age, 41.6 +/- 2.7 yr; body mass index (BMI), 29.6 +/- 1.2 kg/m2; 16 male patients all with the pituitary form; age, 39.2 +/- 3.1 yr; BMI, 26.3 +/- 2.3 kg/m2] and in controls matched for BMI, age, and gender. Serum leptin levels were higher in female than in male patients in both the Cushing (P < 0.01) and control (P < 0.001) groups. Disease-specific differences in serum leptin levels were only detected in male (106 vs. 67 pmol/L; Cushing's syndrome vs. control, P < 0.05), not female, patients. Multiple stepwise regression analysis of both patient groups revealed insulin as the best predictor of serum leptin concentrations, accounting for 37% of the variance in serum leptin levels, in contrast to BMI or mean serum cortisol (as measured by sampling in 10-min intervals over 24 h). In the subgroup of patients (n = 9) with pituitary adenoma, serum leptin levels were reduced after tumor resection, with concurrent decreases in serum cortisol, insulin, and BMI. In conclusion, chronic hypercortisolemia in Cushing's syndrome appears not to directly affect serum leptin concentrations, but to have an indirect effect via the associated hyperinsulinemia and/or impaired insulin sensitivity.

Adolescent↗
PubMed1998

Coding of time-varying hormonal signals in intracellular calcium spike trains.

In a variety of cell types extracellular hormonal stimuli varying in time are transfered across the cell membrane into repetitive spikes of the intracellular calcium concentration ([Ca2+]i). Distinct temporal patterns of [Ca2+]i spikes are capable of regulating the function and structure of target cells. Here, we investigate the ability of transmembrane signaling to encode time-varying hormonal stimulations (bandlimited Gaussian white noise) in a model of receptor-controlled [Ca2+]i oscillations. The encoding of hormonal signals in [Ca2+]i spike trains is quantified by using an information-theoretic approach allowing to estimate the hormonal stimulus from [Ca2+]i spike trains. Our results suggest that intracellular [Ca2+]i spike trains convey faithful information on temporal variations of extracellular hormonal concentrations at scales of 30-200 sec, corresponding to cut-off frequencies between 5 and 30 mHz of the random hormonal stimulation.

Animals↗
PubMed1998

Coarse-grained entropy rates quantify fast Ca2+ dynamics modulated by pharmacological stimulation.

Calcium (Ca2+) is an ubiquitous intracellular messenger which regulates cellular processes, such as secretion, contraction, and cell proliferation. A variety of cell types respond to hormonal stimuli with periodic oscillations of the intracellular free Ca2+ concentration ([Ca2+]i) which can be modulated in their frequency in a dose-dependent manner. The period of these well-studied oscillations varies normally between 30 sec and a couple of minutes. Here we study [Ca2+]i oscillations in clonal beta cells (hamster insulin secreting cells, HIT) under pharmacological stimulation. Besides the well-known high-amplitude low frequency oscillations we try to analyze for the first time low-amplitude high frequency oscillations of [Ca2+]i under pharmacological stimulation which have not been explored in experimental approaches to date. Using coarse-grained entropy rates computed from information-theoretic functionals we demonstrate differences in temporal complexity of the fast low-amplitude [Ca2+]i dynamics corresponding to different phases of pharmacological stimulation which are additional to the well-known dose-dependent pattern of low-frequency high amplitude [Ca2+]i dynamics.

Algorithms↗
PubMed1997

Impairment of ATP-induced Ca2+ -signalling in human thyroid cancer cells.

Extracellular nucleotides like ATP that activate the Ca2+ -phosphatidylinositol (PI) signalling pathway have been suggested to participate in the regulation of normal human thyroid function. We examined, whether P2y-purinergic receptors are expressed on human thyroid cancer cells and whether post-receptor Ca2+ signalling is altered by malignant transformation. Extracellular ATP caused a biphasic increase in cytosolic free Ca2+ ([Ca2+]i) in normal human thyrocytes and in human follicular (FTC) and papillary (PTC) thyroid carcinoma cells. In FTC and PTC cell lines the dose-response curves for ATP-induced changes in [Ca2+]i were shifted to the right when compared with normal thyrocytes, whereas in undifferentiated thyroid carcinoma (UTC) cells even high concentrations of ATP (500 microM) failed to stimulate a rise in [Ca2+]i. By contrast, ATP stimulated inositol 1,4,5-trisphosphate (IP3) formation and capacitative Ca2+ entry was operational as judged by thapsigargin in normal thyrocytes and all thyroid cancer cells. Thus, P2y-purinergic receptors are expressed on thyroid tumor cells independent of degree of differentiation. In UTC cells, however, impairment in the Ca2+ -phosphatidylinositol (PI) signalling cascade occurs distal to the formation of IP3 and proximal to the activation of capacitative Ca2+ entry. Disturbed ATP-induced Ca2+ -signalling and alterations in the Ca2+ -PI signalling cascade may contribute to decreased expression or loss of specific thyroid functions in thyroid cancer cells.

Adenosine Triphosphate↗
PubMed1997

Immunohistochemical detection of E-cadherin in differentiated thyroid carcinomas correlates with clinical outcome.

A retrospective immunohistochemical analysis of the adhesion molecule E-cadherin (E-CD) was performed in 112 differentiated thyroid carcinomas and 38 synchronous and 20 relapse metastases primarily from operations performed at the Medical School Hanover between 1982 and 1992. E-CD-specific antibody 5H9 was applied to paraffin-embedded tissues. All patients were clinically followed for a maximal period of 12 years. Lack of E-CD expression i.e., <5% of tumor cells positive) occurred in 18 of 112 (16.1%) cases, whereas the majority showed either low (24.1%), medium (35.7%), or high (24.1%) positivity. No difference was found between papillary (n = 88) and follicular (n = 24) carcinomas. Univariate statistical analysis for survival (Kaplan-Meier) showed that lack of E-CD expression (P < 0.024) is an adverse prognostic factor for differentiated thyroid carcinomas. The highest significance was seen among patients without lymph node involvement at first presentation (pN(0); P = 0.0068) and among females (P = 0.0033). Multivariate analysis (Cox model) indicated that E-CD staining is an independent prognostic factor (corrected risk factor, 3.7; P < 0.03) in addition to distant metastasis (pM1) and tumor size. A comparison of E-CD stainings between primary tumors and their metastatic lesions showed similar results in both synchronous and relapse metastases after therapy. In conclusion, E-CD immunostaining is an independent prognostic indicator for differentiated thyroid carcinomas. It may help to uncover the small group of patients with differentiated thyroid carcinomas carrying a high risk of suffering an unfavorable clinical outcome.

Biopsy↗
PubMed1997

A liquid mixed meal or exogenous glucagon-like peptide 1 (GLP-1) do not alter plasma leptin concentrations in healthy volunteers.

Glucagon-like peptide 1 [7-36 amide] (GLP-1) and the obese gene product (leptin) are thought to be involved in the central regulation of feeding. Both may act from the peripheral circulation to influence brain function. To study potential interactions, GLP-1 ([7-36 amide]: 0.4, 0.8 pmol kg-1 min-1 or placebo on separate occasions) was infused intravenously (from -30 to 240 min) into nine healthy volunteers [age 26 +/- 3 years, body mass index: 22.9 +/- 1.6 kg/m2, glycated haemoglobin HbA1c: 5.0% +/- 0.2% (normal: 4.0%-6.2%), creatinine: 1.1 +/- 0.1 mg/dl], and (at 0 min) a liquid test meal (50 g sucrose in 400 ml 8% amino acid, total amino acids 80 g/l) was administered via a nasogastric tube. Plasma leptin (radioimmunoassay, RIA), glucose, insulin (microparticle enzyme immunoassay), C-peptide (enzyme-linked immunosorbent assay) and GLP-1 (RIA) were measured, and statistical analysis was done with repeated-measures ANOVA and Student's t-test. Plasma leptin concentrations were 31 +/- 6 pmol/l in the basal state. They did not change within 240 min after meal ingestion nor in response to the infusion of exogenous GLP-1 [7-36 amide] (P = 0.99 for the interaction of experiment and time) leading to GLP-1 mean plasma levels of 25 +/- 2 and 36 +/- 3 (basal 6 +/- 1) pmol/l. On the other hand, glucose (from basal 4.7 +/- 0.1 to 6.0 +/- 0.2 mmol/l at 15 min, P < 0.05) and insulin (from basal 28 +/- 2 to 325 +/- 78 pmol/l at 45 min, P < 0.05) increased clearly after the meal with placebo. In conclusion, (1) plasma leptin levels in normal human subjects show no short-term changes after feeding a liquid mixed meal and (2) do not appear to be directly influenced by physiological and pharmacological elevations in plasma GLP-1 [7-36 amide] concentrations. This does not exclude interactions at the cerebral (hypothalamic) level or on more long-term temporal scales.

Adult↗
PubMed1997

Immune thyroiditis after transplantation of allogeneic CD34+ selected peripheral blood cells.

A 28-year-old female patient underwent allogeneic PBSCT from her HLA-identical sister for AML in first CR. CD34+ cells were positively selected from PBPC using immunoaffinity columns. She received 8.0 x 10(6) CD34+ cells/kg and 1.74 x 10(6) CD3+ cells/kg body weight (BW). The patient developed acute GVHD III and mild limited chronic GVHD. Thirteen months after transplantation severe thyrotoxicosis requiring plasmapheresis occurred. Immune thyroiditis was confirmed cytologically by lymphocytic infiltration in a fine needle aspirate and by elevated thyroid-Ab-titers. The patient's donor had received thyroid hormone substitution for 10 years for hypothyroidism. The most probable cause of immune thyroiditis after allogeneic BMT is the transfer of antithyroid donor lymphocytes. These lymphocytes can also be transferred with a CD34+ selected peripheral stem cell graft. The transplantation of lymphocyte-depleted autologous bone marrow or PBPC grafts after myeloablative treatment is increasingly considered as potential treatment of severe autoimmune diseases. This case demonstrates that even low numbers of lymphocytes are capable of transferring autoimmune disorders.

Adult↗
PubMed1997

Treatment of macroprolactinoma with cabergoline: a study of 85 patients.

OBJECTIVE: Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY DESIGN AND PATIENTS: Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm. MEASUREMENTS: Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62). RESULTS: Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS: Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Adolescent↗
PubMed1997

Gender-specific differences of serum leptin in obese and normal-weight adolescents: studies in type-I diabetes and Turner syndrome.

The influence of exogenous insulin and estrogen substitution on serum leptin-like immunoreactivity was studied longitudinally in patients with type-I diabetes and Turner syndrome using a specific radioimmunoassay. Prepubertal, pubertal and postpubertal samples of 17 patients (9 girls, 8 boys) with type-I diabetes mellitus developing obesity were compared to those of 17 normal-weight controls matched for gender, age and diabetes duration. Six obese and six normal-weight girls with Turner syndrome were studied without hormone substitution, with ethinylestradiol alone, and with cyclic estradiol/gestagen substitution. The mean leptin levels of the girls with diabetes were two times higher than boys at all times, while insulin doses and glycemic control had no influence. In Turner syndrome estrogen substitution led to increased leptin levels only in the obese group. This study revealed that both body weight above normal and female sex steroids seem to be necessary to elevate leptin concentrations, while exogenous insulin has no effect.

Adolescent↗
PubMed1997

UKPDS 20: plasma leptin, obesity, and plasma insulin in type 2 diabetic subjects.

We measured plasma leptin and insulin concentrations across a spectrum of obesity in 829 white Caucasian, 154 Afro-Caribbean, and 204 Asian type 2 diabetic subjects. Although the leptin concentrations covered a large range, there were no subgroups of diabetic subjects with very high or low leptin levels that would suggest mutations in the leptin gene or leptin receptor gene comparable to the obese diabetic ob/ob and db/db mice models respectively. In all three ethnic groups, leptin concentrations correlated with body mass index (BMI) in a similar manner to nondiabetic patients and were higher in females than males after adjustment for BMI, with no difference between ethnic groups. In a multivariate regression analysis, plasma leptin was associated with gender and BMI, (both P < 1 x 10(-17)) and with fasting plasma insulin concentrations (P = 5 x 10(-9)). Subjects treated with insulin had both raised insulin and leptin concentrations. When matched for different therapies, gender, and BMI, diabetic subjects with high leptin levels also had high insulin levels (P < 0.0009). High leptin concentrations may in part be influenced by hyperinsulinemia or impaired insulin sensitivity.

Aged↗
PubMed1997

Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors.

The mechanisms involved in the rapid glucagon-like peptide-1 (GLP-1) release following glucose ingestion are poorly defined. Besides a direct intestinal stimulation of L cells, humoral and neuronal mechanisms have been discussed. We investigated the temporal pattern of GLP-1 release in five healthy men (aged 27.8 +/- 3.6 yr, body mass index, 23.4 +/- 1.2 kg/m2) after an overnight fast for 60 min under basal conditions and for 60 min after an oral glucose load (OGL; 100 g) in both the presence and absence of atropine (80 ng/kg min, iv). Blood was sampled every 2 min, and data were evaluated for the temporal pattern of GLP-1 secretion by several computer-assisted programs (deconvolution, Pulsar analysis, and Fourier transformation). With all methods a pulsatile pattern of plasma GLP-1 levels with a frequency of five to seven per h was detected; this remained unchanged in the different metabolic states and during atropine treatment. Glucose and GLP-1 plasma levels showed a parallel increase after OGL (OGL without atropine = control: 8.4 +/- 2.9 and 7.9 +/- 3.0 min, respectively). Atropine infusion delayed this increase significantly (16.8 +/- 8.07 and 17.4 +/- 6.61 min, respectively; P < 0.02). In contrast to plasma glucose concentrations (82.7 +/- 0.3% of control; P < 0.05), atropine infusion reduced the integrated GLP-1 pulse amplitude to 56.0 +/- 11.3% of the control levels (P < 0.05). In conclusion, GLP-1 is secreted in a pulsatile manner with a frequency comparable to that of pancreatic hormones. Mean GLP-1 plasma concentrations increase after OGL due to augmented GLP-1 pulse amplitudes but not frequency. The differential effect of atropine on glucose and GLP-1 plasma levels suggest a direct cholinergic muscarinic control of L cells.

Adult↗
PubMed1997

Twenty-four-hour rhythms of plasma catecholamines and their relation to cardiovascular parameters in healthy young men.

Diurnal and ultradian rhythms of plasma norepinephrine and epinephrine and their role in the regulation of cardiovascular parameters were investigated over 24 h of recumbency in a group of five men. Catecholamines were measured at 10 min intervals, and blood pressure and heart rate were recorded continuously. Norepinephrine and epinephrine rapidly fluctuated in each subject, with no obvious diurnal rhythm. Spectral analysis suggested two ultradian rhythms with periods of around 12 h and 50-100 min for both catecholamines. The pulse detection programs PULSAR and CLUSTER revealed 20-30 pulses/24 h for norepinephrine and epinephrine, with a significant correlation between the two rhythms (r = 0.63-0.80, P < 0.001). Neither the frequency nor the amplitude of these rapid fluctuations differed between day and night. Arousal in the morning caused a small increase in plasma catecholamines and getting out of bed a large increase. Thus changes in posture and activity are the main influences on the diurnal variations of plasma catecholamines reported previously, while the ultradian rhythms of sympathoadrenomedullary activity appear to be of intrinsic origin. Blood pressure and heart rate exhibited a diurnal rhythm with a nightly decrease. Arousal and rising from bed increased blood pressure and heart rate significantly. Although the amplitude of the rapid fluctuations of plasma catecholamines at times exceeded those caused by postural changes in the morning, when both plasma norepinephrine and epinephrine levels correlated highly with all cardiovascular parameters, correlations were not significant during recumbency. Thus the intrinsic ultradian fluctuations of plasma catecholamines appear not to be involved in the control of cardiovascular parameters during recumbency, and the increase in blood pressure and heart rate in the morning appears to be controlled by direct sympathetic neural input to the heart and vasculature in response to changes in activity and posture rather than by an endogenous surge of plasma catecholamines.

Adult↗
PubMed1997

Menin mutations in patients with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN-1) is a familial cancer syndrome with parathyroid, pituitary and enteropancreatic tumors. The disease phenotype segregates with markers on chromosome 11q13. Very recently a new gene was cloned from this region and was found to carry mutations in 14 of 15 unrelated MEN-1 patients. The gene was termed menin and is predicted to code for a tumor suppressor protein of 610 amino acids, but its precise function is totally unknown. To confirm this finding we used PCR from genomic DNA and direct sequencing to analyze exons 2 through 10 of the menin gene in eight patients from four pedigrees with MEN-1 syndrome or an affected relative. We identified four different heterozygous mutations, three of them are novel: one nonsense mutation, one large deletion of 32 bp and two insertions, all of them located in exon 2. Our results confirm that patients with MEN-1 carry mutations in the menin gene.

Adult↗
PubMed1997

Altered bone metabolism in inflammatory bowel disease.

UNLABELLED: A reduced bone mineral density has been reported in inflammatory bowel disease (IBD). OBJECTIVE: To assess the mechanisms of bone disease in IBD. METHODS: We studied in 90 patients (61 with Crohn's disease, 22 with ulcerative colitis, 7 with indeterminate colitis) biochemical markers of bone metabolism in serum and bone mineral density by peripheral quantitative computed tomography at the forearm. RESULTS: Forty-five percent of the patients had a reduced bone density (Z score < -1). Serum calcium was normal in most patients, vitamin D deficiency was documented in 17%. Osteocalcin, a serum marker of bone formation, was decreased in 26% (1.2 +/- 0.1 ng/ml), whereas the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a recently described serum parameter of bone breakdown, was stimulated in 38% (10.4 +/- 2.3 microg/L). Of 33 patients with increased ICTP levels, 19 showed a decreased bone density (Z score < -1), and 2 of them never received steroids. An active status of the underlying disease in most patients with increased ICTP levels suggests a direct effect of the underlying IBD. In the whole series of patients with a history of active disease (n = 34), 47% had signs of an increased bone degradation (ICTP > 5 microg/L; mean, 12.9 +/- 4.7 microg/L). Data derived from a retrospective survey of 245 patients with IBD suggest that the prevalence of bone fractures in IBD is unexpectedly high, particularly in patients with a long duration of disease, frequent active phases, and high cumulative doses of corticosteroid intake. CONCLUSIONS: Several mechanisms may be involved in IBD-associated bone disease: (1) a high inflammatory activity directly induces bone degradation via yet unknown pathways, (2) treatment with corticosteroids may exert catabolic effects on the bone, or (3) malabsorption and vitamin D deficiency may activate bone turnover.

Adolescent↗
PubMed1997

Algorithmic complexity of growth hormone release in humans.

Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

Acromegaly↗
PubMed1997

Changes in cardiovascular risk factors and hormones during a comprehensive residential three month kriya yoga training and vegetarian nutrition.

In participants of a comprehensive residential three month yoga and mediation training programme living on a low fat lacto-vegetarian diet changes in cardiovascular risk factors and hormones were studied. Substantial risk factor reduction was found. Body mass index, total serum and LDL cholesterol, fibrinogen, and blood pressure were significantly reduced especially in those with elevated levels. Urinary excretion of adrenaline, noradrenaline, dopamine, aldosterone, as well as serum testosterone and luteinizing hormone levels were reduced, while cortisol excretion increased significantly.

Adolescent↗