[The simultaneous appearance of three uncommon tumours]. / Synchrones Auftreten dreier seltener Tumoren.

A 70-year-old woman presented with nasal obstruction and pain projecting onto the left cheek. The face seemed asymmetric including exophthalmus on the right side. Nasal endoscopic inspection revealed a sarcomatous tumor located on the middle turbinate. The CT showed that the tumor filled the left maxillary sinus completely and had eroded the maxillary bone. In addition, a round, sharply defined intraorbital neoplasm on the right side was identified in the contrast-enhanced MRI. Histological examination of the extirpated intraorbital tumour showed a neurilemmoma. A tissue biopsy of the intranasal tumour falsely suggested an intestinal adenocarcinoma. Multiple neoplasms suspicious of disseminated lung metastases were detected in the CT of the thorax. One round lesion removed by thoracoscopy revealed a carcinoid. The intranasal tumour was excised completely and the histology proved beyond doubt an inverted papilloma.

Binding proteins for cyclic and linear oligopeptides in plasma membranes and the cytosol of rat hepatocytes.

Using a cyclolinopeptide A analogue, the hydrophobic cyclic peptide c(-Ala-Lys-Pro-Phe-Phe-Ala-Lys-Pro-Phe-Phe-), termed CDP (cyclodecapeptide), as ligand in affinity chromatography, hepatocellular peptide binding proteins were isolated from the integral part of plasma membranes and the cytosol. The sequence of the isolated protein with MW of 50 kDa from the integral part of the plasma membrane fraction was identical to cytochrome P450 II C13 and cytochrome P450 II C22, whereas the sequence of the 54 kDa protein was identical to 3-hydroxyandrogen-UDP-glucuronosyltransferase. These proteins have also been described as binding proteins for bile acids. As shown in earlier studies, bile acids and CDP also compete for uptake into hepatocytes. In the cytosol, a further known bile acid binding protein, the glutathione-S-transferase (G-S-T) subunit Yb1, was isolated and sequenced as binding protein for CDP and also for a further cyclopeptide, the somatostatin analogue OO8, and a linear peptide with renin-inhibiting activity, EMD 55068. As shown in uptake studies using isolated basolateral plasma membrane vesicles, G-S-T was able to increase the uptake of EMD 51921, a linear peptide with renin-inhibiting potency, into the vesicles when the latter were preloaded with G-S-T. The binding of the substrate to the outside of the preloaded vesicles was not different than binding to unloaded vesicles. The maximal transport rate of the carrier-mediated/facilitated diffusion and the rate of permeation, however, were doubled in the presence of G-S-T, pointing to the involvement of intracellular binding proteins such as G-S-T in the unloading of the carrier protein and in the reduction of the free substrate concentration.

Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors.

OBJECTIVE: Circulating leptin, the product of the ob gene, is known to be closely correlated with adipose tissue mass, but it is also subject to short-term regulation by a variety of hormones including catecholamines. The aim of this study was to investigate the contribution of the three beta-adrenergic receptors to leptin secretion from cultured human adipocytes. DESIGN AND METHODS: The model of in vitro differentiated human subcutaneous adipocytes was used in this study. The presence of the beta-adrenoceptor subtypes was studied by RT-PCR. The functional role of the receptor subtypes was determined by stimulation of lipolysis by selective beta-adrenergic agonists and by measuring glycerol release. Leptin secretion into the medium of cultured human adipocytes from young normal-weight females was measured by radioimmunoassay. RESULTS AND CONCLUSION: In a first set of experiments, the expression of the three beta-adrenergic receptor subtypes in cultured human adipocytes was demonstrated. To test their functional activity, the effect of the beta-adrenoceptor agonists isoproterenol (non-selective agonist), dobutamine (beta(1)-selective), fenoterol (beta(2)-selective) and the beta(3)-selective agonists BRL 37344 and CGP 12177 was studied. All agonists exhibited a dose- and time-dependent stimulation of glycerol release into the medium in a rather uniform manner. Isoproterenol rapidly reduced leptin secretion from cultured subcutaneous adipocytes in a dose-dependent fashion. Incubation with 10(-6)mol/l isoproterenol for 24h resulted in a reduction of the leptin concentration by 48% (P < 0.01). A similar, but less pronounced suppressing effect was seen for dobutamine and fenoterol, whereas both BRL 37344 and CGP 12177 were not effective. These data provide evidence that catecholamines are able to suppress leptin release from differentiated human adipocytes, supporting the concept that leptin secretion is acutely regulated by surrounding hormones. This inhibition is obviously mediated via beta(1)- and beta(2)-adrenergic receptors.

Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-alpha and transforming growth factor-beta1.

OBJECTIVE: Leptin, the product of the ob gene, is overexpressed in human obesity and increased serum leptin levels are closely correlated with adipose tissue mass, but the regulation of leptin production is not completely understood. The aim of this study was to characterize the role of tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 in depot-specific secretion of leptin from cultured human adipocytes. DESIGN AND METHODS: We measured the leptin concentrations in the culture medium of omental and subcutaneous abdominal adipocytes taken from severely obese individuals and kept in suspension culture, and studied the effect of TNF-alpha and TGF-beta1 on leptin release. Leptin protein was measured by radioimmunoassay, leptin mRNA was assessed by reverse transcriptase (RT)-PCR relative to a housekeeping gene. RESULTS AND CONCLUSION: Leptin secretion from subcutaneous fat cells was 2- to 3-fold higher than that from omental fat cells after incubation for 2 and 24h respectively. A 2-h exposure of adipocytes to 1nmol/l TNF-alpha and 400pmol/l TGF-beta1 respectively did not significantly affect leptin secretion. Whereas a 24-h incubation with 1nmol/l TNF-alpha also did not influence leptin secretion from fat cells from both depots, exposure of omental fat cells to 400pmol/l TGF-beta1 for 24h resulted in a significant inhibitory effect (by 33%) on leptin secretion (P<0.05). A 24- and 48-h exposure of in vitro differentiated human adipocytes to TNF-alpha led to a significant decrease in leptin mRNA levels to 70 +/- 8% and 49 +/- 13% of controls respectively. Similarly, TGF-beta1 decreased leptin mRNA expression in newly differentiated human adipocytes to 77 +/- 12% after 24h and to 54 +/- 8% after 48h compared with control cultures. These data provide evidence that long-term exposure of human fat cells to TNF-alpha or TGF-beta1 may suppress leptin expression in human adipose tissue. The inhibitory effect of TGF-beta1 appears to be more pronounced in omental as compared with subcutaneous adipocytes.

Effects of leptin on the differentiation and metabolism of human adipocytes.

BACKGROUND: Leptin is an adipose protein regulating food intake in the hypothalamus. Animal studies have suggested that leptin also acts in an auto-/paracrine fashion on adipose cell function. OBJECTIVE: The aim of this study was to investigate the effects of leptin on the differentiation and metabolism of cultured human adipocytes. MATERIAL: Adipose tissue from young healthy, lean women (body mass index (BMI) <27 kg/m(2)) undergoing elective mammary reduction surgery and young obese individuals (BMI>40 kg/m(2)) undergoing laparoscopic gastric banding. METHODS: Human preadipocytes in primary culture were induced to undergo differentiation by defined adipogenic factors. Mature adipocytes were isolated by collagenase digestion and kept in culture suspension. Glycero-3-phosphate dehydrogenase (GPDH) activity was used as a marker of adipose differentiation; glucose uptake, lipolysis and PAI-1 secretion were measured as parameters of fat cell function. RESULTS: Human preadipocytes and adipocytes from lean and obese subjects expressed the long leptin receptor isoform and two of the three short forms as assessed by polymerase chain reaction (PCR). Leptin at a supraphysiological concentration induced a transient increase of GPDH activity, but had no effect on glucose uptake and PAI-1 secretion from human adipocytes. In addition, basal and isoproterenol-stimulated lipolysis as well as the antilipolytic action of insulin in human adipocytes was not significantly affected by leptin exposure. CONCLUSION: In contrast to animal data, the results of our experiments do not demonstrate significant effects of leptin on main metabolic functions of human adipocytes arguing against a local auto-/paracrine action of leptin in human adipose tissue.