Differential expression of the neural cell adhesion molecule NCAM 140 in human pituitary tumors

We have analyzed the expression of the intracellular marker protein neuron specific enolase (NSE), synaptophysin (SYN) and of the cell surface marker NCAM (neural cell adhesion molecule) in both normal human hypophysis and in pituitary adenomas in order to explore their potential use as diagnostic tools. All adenomas (4 prolactinomas, 3 growth hormone (GH) producing adenomas and 4 inactive adenomas) showed SYN and NSE immunoreactivity on tissue sections and this was confirmed by immunoblots. NCAM 140 (an isoform of NCAM with molecular mass 140 kDa) was detected by immunoblotting in normal human adenohypophysis, in all GH adenomas, and in three out of four inactive adenomas, but not in prolactinomas. Using highly sensitive techniques, NCAM immunoreactivity was observed by electron microscopy in all adenomas. These data indicate that NCAM 140 is a constituent of the cell surface of endocrine cells in both normal human adenohypophysis and its tumors. Since prolactinomas express very low levels of NCAM 140 compared to other hypophyseal tumors its virtual absence could be used for differential diagnosis. A combined analysis of NCAM, SYN and NSE could be useful to characterize inactive adenomas which are not immunoreactive for pituitary hormones and which may contain no or only low levels of the alpha chain of the glycoprotein hormones

Expression of the neural cell adhesion molecule NCAM in endocrine cells

We examined the expression of the neural cell adhesion molecule NCAM in a number of endocrine tissues of adult rat and in an endocrine tumor cell line. NCAM was found by immunoelectron microscopy to be present on the surface of all endocrine cells in the three lobes of the hypophysis, although staining was relatively less intense in the intermediate lobe, and in pancreatic islets. Pituicytes, hypophyseal glial cells, were also labeled for NCAM. A rat insulinoma cell line (RIN A2) also expressed NCAM as judged by immunocytochemistry. Analysis of NCAM antigenic determinants (Mr 180, 140, and 120 KD) revealed large variations in the relative proportions of NCAM polypeptides present in the different tissues. Although all tissues and cell lines expressed NCAM-140, NCAM-180 was not detected in the adenohypophysis, pancreas, or adrenal medulla, and NCAM-120 was found in none of the endocrine tissues or cell lines except at low levels in the neurohypophysis. The tumor cell line expressed significant levels of NCAM-180, which was most abundant in the neurohypophysis. These results show that NCAM expression appears to be a general property of endocrine cells, although the antigenic composition differs markedly from that in brain tissue. These data are discussed with regard to the embryological origins of the different endocrine tissues, and possible functional implications are suggested

Schnittstelle Notaufnahme: Interdisziplinäre Perspektiven

Zusammenfassung: Die Notaufnahme des Basler Universitätsspitals wird interdisziplinär als "Notfallstation" geführt. Das dort praktizierte "Basler Modell" wird schlaglichtartig beleuchtet. Ethische Fragestellungen, insbesondere die Frage nach dem Sistieren einer Behandlung, sollten frühzeitig und interdisziplinär besprochen werden. Da das Ziel der Versorgung in der präklinischen Phase zumeist der möglichst rasche Transport in ein geeignetes Zielkrankenhaus ist, bietet sich oft erst im Reanimationsraum der Notfallstation erstmals die Chance, diese Fragen überhaupt auszusprechen. Hier können entscheidungsrelevante Zusatzinformationen berücksichtigt werden wie etwa der mutmaßliche Wille des Patienten, aber auch die Prognose. Die unterschiedlichen Standards der präklinischen und der klinischen Phase können an der Schnittstelle Notfallstation zu Konflikten führen. Hier ist die Kommunikation des Teamleaders mit dem Rettungsteam, aber auch mit den Kollegen der anderen Disziplinen von entscheidender Bedeutun

Demographics and prevalent risk factors of chronic subdural haematoma: results of a large single-center cohort study

Chronic subdural haematoma (CSDH) is a typical disease in elderly patients and encountered frequently in neurosurgical practice. With an increasing number of elderly people in the general population, there is a need to investigate risk factors (age, falls, anticoagulant or antithrombotic therapy) which could be pertinent to the development of this disease. We reviewed 354 patients undergoing surgery for CSDH over a period of 7 years (1996-2002), the occurrence being equally distributed over these years. CSDH occurred more often in elderly (≥65 years) than in younger people (69 vs 31%), and in men than in women (64 vs 36%). Falls were reported in 77% of patients. There was a trend towards a higher risk of falls in the elderly. Antithrombotic or anticoagulant therapy was present in 41% of patients, 32% of them having had falls. Overall postoperative mortality was 0% and overall recurrence rate 13.6%. CSDH in the elderly population, especially in men, is frequently associated with falls and anticoagulation or antithrombotic therapy. The indication for these medications, especially in elderly patients at risk for falls, should be carefully evaluated and controlle

3',5'-Cyclic Adenosine Monophosphate- and Ca2+-Calmodulin-Dependent Endogenous Protein Phosphorylation Activity in Membranes of the Bovine Chromaffin Secretory Vesicles: Identification of Two Phosphorylated Components as Tyrosine Hydroxylase and Protein Kinase Regulatory Subunit Type II

Abstract: Membranes of the secretory vesicles from bovine adrenal medulla were investigated for the presence of the endogenous protein phosphorylation activity. Seven phosphoprotein bands in the molecular weight range of 250,000 to 30,000 were observed by means of the sodium dodecyl sulphate electrophoresis and autoradiography. On the basis of the criteria of molecular weight, selective stimulation of the phosphorylation by cyclic AMP (as compared with cyclic GMP) and immunoprecipitation by specific antibodies, band 5 (molecular weight 60,300) was found to represent the phosphorylated form of the secretory vesicle-bound tyrosine hydroxylase. The electrophoretic mobility, the stimulatory and inhibitory effects of cyclic AMP in presence of Mg2+ and Zn,2+ respectively, and immunoreactivity toward antibodies showed band 6 to contain two forms of the regulatory subunits of the type II cyclic AMP-dependent protein kinase, distinguishable by their molecular weights (56,000 and 52,000, respectively). Phosphorylation of band 7 (molecular weight 29,800) was stimulated about 2 to 3 times by Ca2+ and calmodulin in the concentration range of both agents believed to occur in the secretory tissues under physiological conditions

Further Characterization of Dopamine Release by Permeabilized PC 12 Cells

Rat pheochromocytoma cells (PC 12) permeabilized with staphylococcal α-toxin release [3H]dopamine after addition of micromolar Ca2+. This does not require additional Mg2+-ATP (in contrast to bovine adrenal medullary chromaffin cells). We also observed Ca2+-dependent [3H]-dopamine release from digitonin-permeabilized PC 12 cells. Permeabilization with α-toxin or digitonin and stimulation of the cells were done consecutively to wash out endogenous Mg2+-ATP. During permeabilization, ATP was removed effectively from the cytoplasm by both agents but the cells released [3H]dopamine in response to micromolar Ca2+ alone. Replacement by chloride of glutamate, which could sustain mitochondrial ATP production in permeabilized cells, does not significantly alter catecholamine release induced by Ca2+. However, Mg2+ without ATP augments the Ca2+-induced release. The release was unaltered by thiol-, hydroxyl-, or calmodulin-interfering substances. Thus Mg2+-ATP, calmodulin, or proteins containing -SH or -OH groups are not necessary for exocytosis in permeabilized PC 12 cells