PubMed Health⌕ Search

Biomedical subjects

H Scherübl

Publications and source records attributed to H Scherübl.

At least 55 records · Page 3Linked to original sources
PubMed1997

A 7-year-old child with primary tumour localisation in the distal duodenum--new imaging procedures for an improved diagnosis.

UNLABELLED: Duodenal gastrinomas in childhood are extremely rare and often missed at first medical consultation. We report on a 7-year-old child with sporadic gastrinoma of primary localisation in the distal duodenum. Small metastases in the liver and regional nodes were detected pre-operatively by somatostatin receptor scintigraphy (SRS) but not by other conventional imaging procedures. Diagnostic procedures include pre-operative SRS, endoscopic ultrasound and intra-operative endoscopic transillumination. CONCLUSION: Gastrinomas are rare abdominal tumours in childhood. Pre-operative tumour-specific diagnosis is possible by 111indium pentreotide SRS.

Biomarkers, Tumor↗
PubMed1997

Electrophysiological properties of human carcinoid cells of the gut.

BACKGROUND & AIMS: Because of their diffuse distribution, neuroendocrine cells of the gut have not been isolated successfully for electrophysiological characterization. We therefore established primary cell cultures from surgically resected human carcinoids and investigated them electrophysiologically. METHODS: The neuroendocrine identity of the isolated gut tumor cells was determined immunocytochemically. The electrophysiological properties of the cells were studied by the patch-clamp technique. RESULTS: The primary cell cultures expressed neurofilament proteins, cytokeratins, and key proteins of the secretion machinery. Spontaneous action potentials were observed in most cells. Using the whole-cell mode of the patch-clamp technique, tetrodotoxin-sensitive voltage-gated sodium currents as well as voltage-gated calcium currents were identified. Calcium channel currents were carried mainly by dihydropyridine-sensitive, L-type calcium channels. The L-type calcium channel currents were also partially blocked by the omega-conotoxins GVIA and MVIIC. Moreover, omega-agatoxin IVA reversibly reduced a component of the calcium channel currents, indicating that neuroendocrine gut tumor cells express different types of voltage-gated calcium channels. In addition, somatostatin was found to inhibit partially the voltage-dependent calcium channel currents and thus calcium-dependent hormone release. CONCLUSIONS: Carcinoid cells of the human gut are electrically excitable cells. They express voltage-dependent sodium and calcium channels as well as somatostatin receptors.

Action Potentials↗
PubMed1996

Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system.

Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration.

Gastrointestinal Neoplasms↗
PubMed1996

gamma-Aminobutyric acid secretion from pancreatic neuroendocrine cells.

BACKGROUND & AIMS: Neuroendocrine cells and tumors derived therefrom contain hormone-storing large dense core vesicles and neuron-like small synaptic vesicle analogues with unknown function. The aim of this study was to characterize the small synaptic vesicle pathway in detail. METHODS: In human pancreatic neuroendocrine tumors and corresponding mammalian cell lines, the expression of key proteins if regulated secretion were detected by immunofluorescence microscopy. Using 3H-gamma-aminobutyric acid (GABA), uptake and release by small synaptic vesicle analogues were studied. RESULTS: Tumor tissues obtained from 14 patients expressed key proteins of neurosecretion such as synaptobrevin, syntaxins, and SNAP 25. These proteins were also found in the cell lines AR42J, BON, RIN, and INR. The cell lines specifically transported GABA by low-affinity plasma membrane transporter and showed an adenosine triphosphate-sensitive GABA uptake into an intracellular compartment. Stored GABA was released upon stimulation by regulated exocytosis. Electrophysiological analyses suggested that calcium-dependent secretion was mediated by activation of voltage-dependent calcium channels of mainly the L type, but also of the N and probably the T type. CONCLUSIONS: Small synaptic vesicle analogues in neuroendocrine cells and tumors can store and secrete GABA and probably other amino acid transmitters by regulated exocytosis comparable with neurons.

Adult↗
PubMed1996

Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2.

Somatostatin receptor scintigraphy (SRS) is positive in approximately 75% of all patients with neuroendocrine gastroenteropancreatic tumours. This study aimed to identify specific somatostatin receptor (sstr) subtypes, which are responsible for the in vivo binding of the widely used somatostatin analogue, octreotide in human neuroendocrine gastroenteropancreatic tumours. Twelve patients underwent SRS with radiolabelled octreotide. After surgical resection, tumour tissues were analysed in vitro for somatostatin and octreotide binding sites by autoradiography. In addition, for the first time, sstr subtype mRNA expression was examined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Tumour tissues from all SRS positive patients were positive by autoradiography. Semiquantitative RT-PCR revealed most prominently sstr2 expression in scintigraphically positive tumours. Two SRS negative tumours contained in vitro octreotide binding sites as well as high levels of sstr1 and sstr2 mRNAs. Positive SRS is mainly due to sstr2. sstr1, 3, 4, and probably 5 are less important for in vivo octreotide binding. False negative scintigraphic results seem to be influenced by factors independent of the expression of specific sstr.

Adult↗
PubMed1995

Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C-cells.

The effect of the adenosine A1 receptor activation on calcitonin secretion was studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin was determined by radioimmunoassay, intracellular cAMP by protein binding assay, intracellular calcium in fura-2 loaded single cells using microspectrofluorimetry, and calcium channel activity by patch clamp technique. The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion. These effects were partly abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(-6) M) also suppressed extracellular calcium-stimulated calcitonin secretion, rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml) pretreatment again partly abolished this inhibitory effect. The addition to the medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our results suggest that in calcitonin-secreting cells A1 receptors couple to adenylate cyclase and calcium channels via PT-sensitive G proteins and thus inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine factor in calcitonin-secreting cells.

Adenosine↗
PubMed1995

Extracellular calcium sensitivity and voltage-dependent calcium channels in C cells.

An essential function of C cells is to monitor [Ca2+]e and to increase CT secretion in response to small increments in [Ca2+]e. CT, in turn, decreases [Ca2+]e via its effects on bone and kidney. [Ca2+]e-dependent CT secretion is known to be mediated by corresponding changes in [Ca2+]i. The [Ca2+]e-sensing of C cells is mediated by DHP-sensitive, voltage-dependent Ca2+ channels, which allow Ca2+ influx even at the resting membrane potential. An increase of [Ca2+]e stimulates transmembrane Ca2+ influx via DHP-sensitive Ca2+ channels, thereby increasing [Ca2+]i and consequently CT secretion. Moreover, [Ca2+]e and cAMP-dependent oscillations of [Ca2+]i are observed in C cells. Various neuropeptides and hormones involved in the control of CT secretion act by regulating Ca2+ channel activity via G proteins. One of these endogenous modulators is SS, which is produced by the C cells themselves and tonically inhibits CT secretion by inhibiting voltage-dependent Ca2+ channels.

Animals↗
PubMed1994

Electrical activity and calcium channels in neuroendocrine cells.

Similar to neuronal cells, neuroendocrine cells express voltage-dependent ion channels and fire action potentials. Ca2+ influx through voltage-dependent Ca2+ channels couples changes in membrane potential to Ca(2+)-dependent cellular processes, such as hormone release. Using the patch-clamp technique, we studied the spontaneous electrical activity as well as voltage-dependent Ca2+ channels in cholecystokinin-producing pancreatic cells (RIN 1056E cell line), in prolactin-secreting pituitary cells (GH3 cell line), and in calcitonin-secreting cells of the thyroid (rMTC 44-2 cell line). All three cell types displayed spontaneous electrical activity, that is, they spontaneously produced action potentials. RIN 1056E cells, GH3 cells, and rMTC cells exhibited (various types of) voltage-dependent Ca2+ channels that were regulated by various neurotransmitters and hormones, such as somatostatin.

Action Potentials↗
PubMed1994

[Significance of false-positive findings of somatostatin receptor scintigraphy in diagnosis of neuroendocrine tumors of the gastroenteropancreatic system].

Localization of gastroenteropancreatic neuroendocrine tumors with conventional imaging techniques can be difficult. With the advent of the somatostatin-receptor scintigraphy the diagnosis of these could be improved. In this study 76 patients with immunohistologically proven neuroendocrine tumors were analysed by comparing somatostatin-receptor scintigraphy with conventional imaging techniques. Somatostatin-receptor-positive lesions were observed in 61 of all patients. Conventional imaging techniques (transabdominal ultrasonography, computerized tomographic scanning of the abdomen, magnetic resonance imaging of the abdomen) revealed neuroendocrine tumors in 42 patients (69%). A follow up of 19 patients with initially false positive somatostatin-receptor scintigrams showed that at least 6 patients had escaped the initial diagnosis by conventional techniques. All in all, our data support previous findings and demonstrate that somatostatin-receptor scintigraphy is a safe and sensitive procedure for in vivo imaging of gastroenteropancreatic neuroendocrine tumors. In addition, in certain cases, somatostatin-receptor scintigraphy is able to detect tumors that had escaped conventional imaging techniques.

Combined Modality Therapy↗
PubMed1993

Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins.

Various heterotrimeric guanine nucleotide-binding proteins have been identified on the basis of the individual subtypes of their alpha subunits. The beta gamma complexes, composed of beta and gamma subunits, remain tightly associated under physiological conditions and have been assumed to constitute a common pool shared among various guanosine triphosphate (GTP)-binding (G) protein heterotrimers. Particular alpha and beta subunit subtypes participate in the signal transduction processes between somatostatin or muscarinic receptors and the voltage-sensitive L-type calcium channel in rat pituitary GH3 cells. Among gamma subunits the gamma 3 subtype was found to be required for coupling of the somatostatin receptor to voltage-sensitive calcium channels, whereas the gamma 4 subtype was found to be required for coupling of the muscarinic receptor to those channels.

Animals↗
PubMed1993

Dihydropyridine binding and Ca(2+)-channel characterization in clonal calcitonin-secreting cells.

1,4-Dihydropyridine-sensitive voltage-dependent Ca2+ channels play a crucial role in the extracellular Ca(2+)-sensing of calcitonin-secreting parafollicular cells of the thyroid (C-cells). To characterize the Ca2+ channels in C-cells, we studied 1,4-dihydropyridine binding and performed electrophysiological experiments with Ca(2+)-sensitive C-cells (rat C-cell line rMTC 44-2) in comparison with 'defective' Ca(2+)-insensitive C-cells (human C-cell line TT). In membranes of rMTC cells, we detected a high-affinity, stereoselective and Ca(2+)-dependent binding site for the Ca(2+)-channel-blocking 1,4-dihydropyridine, (+)-[3H]PN 200-110. Radioligand binding was saturable (Bmax. = 18 +/- 2 fmol/mg of protein), reversible [Ki for (+)-PN 200-110 = 37 +/- 1 pM) and allosterically modulated by the phenylalkylamine (-)-desmethoxyverapamil [(-)-D888] as well as the bis-benzylisoquinoline alkaloid (+)-tetrandrine. Thus the 1,4-dihydropyridine binding in rMTC cells featured all characteristics of binding to the alpha 1-subunit of L-type Ca2+ channels. In contrast, in membranes of TT cells, which are known to lack Ca(2+)-sensitivity, no Ca(2+)-channel-specific (+)-[3H]PN 200-110 binding was detected. In voltage-clamp experiments, rMTC cells exhibited slowly inactivating Ca2+ currents which proved sensitive to (+)-PN 200-110, (-)-D888 and (+)-tetrandrine. These L-type Ca(2+)-channel blockers did not affect the Ca2+ currents in TT cells. The numbers of 1,4-dihydropyridine-sensitive Ca2+ channels in rMTC cells as calculated from both the binding studies and the whole-cell/single-channel recordings were 2000 and 7000/cell respectively. Thus qualitative and quantitative detection of 1,4-dihydropyridine-sensitive Ca2+ channels by radioligand-binding in Ca(2+)-sensitive rMTC cells, but not in Ca(2+)-insensitive TT cells, reflects the electrophysiological detection of functional Ca2+ channel in rMTC cells, but not in TT cells.

Alkaloids↗
PubMed1993

Somatostatin-receptor imaging of neuroendocrine gastroenteropancreatic tumors.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors are often difficult to localize. This study was conducted to examine the value of somatostatin-receptor scintigraphy for visualization of gastroenteropancreatic neuroendocrine tumors. METHODS: Applying the recently developed indium-labeled somatostatin analogue 111In-pentetreotide to 40 patients with gastroenteropancreatic neuroendocrine tumors, the diagnostic power of pentreotide-receptor scintigraphy was evaluated in comparison with conventional imaging techniques. RESULTS: Expression of somatostatin receptors was observed in the majority of patients (11 of 17 in the foregut, 14 of 16 in the midgut, and 7 of 7 in metastatic neuroendocrine tumors with unknown primary). Comparative imaging by computerized tomography, magnetic resonance imaging, and transabdominal ultrasonography yielded false-negative results for somatostatin-receptor scintigraphy in 8 of 40 patients; however, in 16 patients, tumor tissue that had escaped conventional imaging techniques was detected by 111In-pentetreotide scintigraphy. CONCLUSIONS: 111In-pentetreotide scintigraphy is a practical, safe, and sensitive procedure for in vivo imaging of gastroenteropancreatic neuroendocrine tumors.

Adolescent↗