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

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

Manganese containing copper aluminate catalysts:Genesis of structures and active sites for hydrogenation of aldehydes

Copper aluminate spinel (CuO.CuAl2O4) is the favoured Cr-free substitute for the copper chromite catalyst (CuO.CuCr2O4) in the industrial hydrogenation of aldehydes. New insights in the catalytic mechanism were obtained by systematically studying the structure and activity of these catalysts including effects of manganese as a catalyst component. The hydrogenation of butyraldehyde to butanol was studied as a model reaction and the active structure was characterised using X-ray diffraction, temperature programmed reduction, N2O chemisorption, EXAFS and XANES, including in-situ investigations. The active catalyst is a reduced spinel lattice that is stabilised by protons, with copper metal nanoparticles grown upon its surface. Incorporation of Mn into the spinel lattice has a profound effect on the spinel structure. Mn stabilises the spinel towards reduction of CuII to Cu0 by occupation of tetrahedral sites with Mn cations, but also causes decreased catalytic activity. Structural data, combined with the effect on catalysis, indicate a predominantly interface-based reaction mechanism, involving both the spinel and copper nanoparticle surface in protonation and reduction of the aldehyde. The electron reservoir of the metallic copper particles is regenerated by the dissociative adsorption and oxidation of H2 on the metal surface. The generated protons are stored in the spinel phase, acting as proton reservoir. Cu(I) species located within the spinel and identified by XANES are probably not involved in the catalytic cycle

NCAM: a surface marker for human small cell lung cancer cells

Immunocytochemical and immunochemical techniques were used to study the expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopic levels on small cell lung cancer cells. The NCAM polypeptide of Mr 140000 (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer cell lines: it was not detected in cell lines obtained from one patient with a mesothelioma, in two cases of adenocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by immunoblotting in all the lung cancer cell lines tested and synaptophysin in all but the adenocarcinoma cell lines. These antigens were localized intracellularly. The specific expression of NCAM 140 by human small and large cell lung carcinomas suggests its potential as a diagnostic marker

Endokavitäre Brachytherapie als Therapieoption bei vorbehandelten Malignomen der Nasennebenhöhlen.

Einleitung: Die etablierte Behandlung für Malignome mit Wachstum in den Nasennebenhöhlen besteht in der radikalen Operation und perkutanen Radiatio. Im Falle einer erneuten Tumormanifestation ist eine kurative chirurgische Behandlung meist nicht mehr möglich. Aus diesem Grund stellt die Brachytherapie eine Möglichkeit dar, trotz erfolgter Vorbestrahlung eine radiotherapeutische Tumorreduktion zu erzielen.Methode: Zwischen 01/96 und 04/04 wurden 15 Patienten wegen Malignomen mit Wachstum in den Nasennebenhöhlen brachytherapeutisch behandelt. In 9 Fällen handelte es sich um im Intervall aufgetretene Rezidive nach vorangegangener Operation und perkutaner Bestrahlung, in den anderen Fällen um Patienten mit Tumorpersistenz nach demselben Therapieansatz. Zum Einsatz kam eine endokavitäre Moulagetechnik, bei der die Bestrahlungsapplikatoren für die HDR-Brachytherapie unter Verwendung von Ausgussmaterial in die Operationshöhle eingebettet wurden. Es erfolgte die CT-gestützte 3D-konforme Bestrahlungsplanung zur maximalen Schonung des umgebenden, vorbelasteten Gewebes.Ergebnisse: In 14 von 15 Patienten konnte eine lokale Tumorkontrolle erreicht werden. Die das Zielvolumen umfassende Referenzisodose betrug median 14 Gy (Fraktionierung mit 7x2 Gy). Das Zielvolumen umfasste das Tumorbett plus einen Sicherheitssaum von 1 cm. Die einzige Patientin, die lokal nicht kontrolliert werden konnte, wies ein Aesthesioneuroblastom mit Einbruch in die Orbita auf. Zur Schonung des einzig verbliebenen Sehnervs musste ein Kompromiss in der Dosisverteilung geschlossen werden.Schlussfolgerungen: Die endokavitäre Brachytherapie in Moulagetechnik erweist sich als geeignetes Mittel zur Behandlung von Rezidiven von Nasennebenhöhlenmalignomen

Regeneration of Inner Ear Cells from Stem Cell Precursors—A Future Concept of Hearing Rehabilitation?

Dazert S, Aletsee C, Brors D, Sudhoff H, Ryan AF, Müller AM. Regeneration of Inner Ear Cells from Stem Cell Precursors—A Future Concept of Hearing Rehabilitation? DNA and Cell Biology. 2003;22(9):565-570.The use of stem cells offers new and powerful strategies for future tissue development and engineering. Common features of stem cells are both their capacity for self-renewal and the ability to differentiate into mature effector cells. Since the establishment of embryonic stem cells from early human embryos, research on and clinical application of human ES cells belong to the most controversial topics in our society. Great hopes are based upon the remarkable observation that human ES cells can be greatly expanded in vitro, and that they can differentiate into various clinically important cell types. Recent advances in the cloning of mammals by nuclear transplantation provide new concepts for autologous replacement of damaged and degenerated tissues. In contrast, somatic stem cells of the adult organism were considered to be more restricted in their developmental potential. However, recent investigations suggest that somatic stem cells may have a wider differentiation potential than previously thought. In otology, initial experiments have revealed neural stem cell survival in cochlear cell cultures and under neurotrophin influence, neural stem cells seemed to develop into a neuronal phenotype. Further studies have to be carried out to investigate the full potential of stem cells as well as the molecular mechanisms that are involved in regulating cellular identity and plasticity. Clinically, advances in stem cell biology may provide a permanent source of replacement cells for treating human diseases and could open the development of new concepts for cell and tissue regeneration for a causal treatment of chronic degenerative diseases

Molekulargenetische Diagnostik der Connexin-Gene und genetische Beratung

Kunstmann E, Hildmann A, Lautermann J, Aletsee C, Epplen JT, Sudhoff H. Kongenitale Schwerhörigkeit. HNO. 2005;53(9):773-778

Clostridium difficile toxin B, an inhibitor of the small GTPases Rho, Rac and Cdc42, influences spiral ganglion neurite outgrowth

OBJECTIVE: Neurotrophins and extracellular matrix (ECM) molecules are involved in neurite guidance during the development of spiral ganglion (SG) neurons. Several intracellular signaling molecules can be activated by ECMs and neurotrophins via their cognate receptors. In other systems these include the Rho small GTPases, which influence reorganization of the actin cytoskeleton that is required for axon growth. The aim of this study was to determine whether neurotrophin-3 (NT-3)-mediated SG neurite outgrowth on laminin-1 (LN) is dependent on the activation of the small GTPases Rho/Rac/Cdc42. MATERIAL AND METHODS: SG explants from postnatal day 4 rats were cultured on LN with and without NT-3 and increasing concentrations of Clostridium difficile Toxin B, an inhibitor of Rho GTPases. After fixation and immunocytochemical labeling, neurite growth was evaluated. RESULTS: Treatment with C. difficile Toxin B without NT-3 led to a dose-dependent decrease in the length and number of processes on LN. In contrast, C. difficile Toxin B had no significant effect on NT-3-mediated stimulation of neurite growth on LN, in terms of either number or length. CONCLUSION: The results suggest that the Rho GTPases (Rho, Rac and Cdc42) are not involved in the pathways linking NT-3 signals to neurite outgrowth, but appear to be involved in LN signaling in these neurons. However, NT-3 can override or bypass LN signaling to promote neurite extension