Publications

960 Publications visible to you, out of a total of 960

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BACKGROUND\backslashr\backslashnOne of the most promising options for treatment of stroke using adult stem cells are human umbilical cord blood (HUCB) cells that were already approved for therapeutic efficacy in vivo. However, complexity of animal models has thus far limited the understanding of beneficial cellular mechanisms. To address the influence of HUCB cells on neuronal tissue after stroke we established and employed a human in vitro model of neuronal hypoxia using fully differentiated vulnerable SH-SY5Y cells. These cells were incubated under an oxygen-reduced atmosphere (O2\textless 1%) for 48 hours. Subsequently, HUCB mononuclear cells (MNC) were added to post-hypoxic neuronal cultures. These cultures were characterized regarding to the development of apoptosis and necrosis over three days. Based on this we investigated the therapeutic influence of HUCB MNC on the progression of apoptotic cell death. The impact of HUCB cells and hypoxia on secretion of neuroprotective and inflammatory cytokines, chemokines and expression of adhesion molecules was proved.\backslashr\backslashnRESULTS\backslashr\backslashnHypoxic cultivation of neurons initially induced a rate of 26% +/- 13% of apoptosis. Hypoxia also caused an enhanced expression of Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Necrosis was only detected in low amounts. Within the next three days rate of apoptosis in untreated hypoxic cultures cumulated to 85% +/- 11% (p \textless or = 0.001). Specific cytokine (VEGF) patterns also suggest anti-apoptotic strategies of neuronal cells. Remarkably, the administration of MNC showed a noticeable reduction of apoptosis rates to levels of normoxic control cultures (7% +/- 3%; p \textless or = 0.001). In parallel, clustering of administered MNC next to axons and somata of neuronal cells was observed. Furthermore, MNC caused a pronounced increase of chemokines (CCL5; CCL3 and CXCL10).\backslashr\backslashnCONCLUSION\backslashr\backslashnWe established an in vitro model of neuronal hypoxia that affords the possibility to investigate both, apoptotic neuronal cell death and neuroprotective therapies. Here we employed the therapeutic model to study neuroprotective properties of HUCB cells. We hypothesize that the neuroprotective effect of MNC was due to anti-apoptotic mechanisms related to direct cell-cell contacts with injured neuronal cells and distinct changes in neuroprotective, inflammatory cytokines as well as to the upregulation of chemokines within the co-cultures. BACKGROUND One of the most promising options for treatment of stroke using adult stem cells are human umbilical cord blood (HUCB) cells that were already approved for therapeutic efficacy in vivo. However, complexity of animal models has thus far limited the understanding of beneficial cellular mechanisms. To address the influence of HUCB cells on neuronal tissue after stroke we established and employed a human in vitro model of neuronal hypoxia using fully differentiated vulnerable SH-SY5Y cells. These cells were incubated under an oxygen-reduced atmosphere (O2\textless 1%) for 48 hours. Subsequently, HUCB mononuclear cells (MNC) were added to post-hypoxic neuronal cultures. These cultures were characterized regarding to the development of apoptosis and necrosis over three days. Based on this we investigated the therapeutic influence of HUCB MNC on the progression of apoptotic cell death. The impact of HUCB cells and hypoxia on secretion of neuroprotective and inflammatory cytokines, chemokines and expression of adhesion molecules was proved. RESULTS Hypoxic cultivation of neurons initially induced a rate of 26% +/- 13% of apoptosis. Hypoxia also caused an enhanced expression of Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Necrosis was only detected in low amounts. Within the next three days rate of apoptosis in untreated hypoxic cultures cumulated to 85% +/- 11% (p \textless or = 0.001). Specific cytokine (VEGF) patterns also suggest anti-apoptotic strategies of neuronal cells. Remarkably, the administration of MNC showed a noticeable reduction of apoptosis rates to levels of normoxic control cultures (7% +/- 3%; p \textless or = 0.001). In parallel, clustering of administered MNC next to axons and somata of neuronal cells was observed. Furthermore, MNC caused a pronounced increase of chemokines (CCL5; CCL3 and CXCL10). CONCLUSION We established an in vitro model of neuronal hypoxia that affords the possibility to investigate both, apoptotic neuronal cell death and neuroprotective therapies. Here we employed the therapeutic model to study neuroprotective properties of HUCB cells. We hypothesize that the neuroprotective effect of MNC was due to anti-apoptotic mechanisms related to direct cell-cell contacts with injured neuronal cells and distinct changes in neuroprotective, inflammatory cytokines as well as to the upregulation of chemokines within the co-cultures.

Authors: Susann Hau, Doreen M. Reich, Markus Scholz, Wilfried Naumann, Frank Emmrich, Manja Kamprad, Johannes Boltze

Date Published: 2008

Publication Type: Journal article

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OBJECTIVE The functional variant C77G (rs17612648) of PTPRC (CD45) was described to confer risk for systemic sclerosis (SSc) in German Caucasians. We analyzed this association in an independent, largerr German cohort. METHODS We genotyped 171 cases and 179 controls. Cases were subgrouped according to sex, autoantibody profiles, or clinical subsets. RESULTS No association of SSc with C77G was detected in the whole dataset, in subgroups, or in combined analyses with a previous study. CONCLUSION The results do not confirm PTPRC C77G as a general and independent risk factor for development of SSc.

Authors: Holger Kirsten, Mechthild Blume, Frank Emmrich, Nico Hunzelmann, Rudolf Mierau, Rita Rzepka, Peter Vaith, Torsten Witte, Inga Melchers, Peter Ahnert

Date Published: 2008

Publication Type: Journal article

Abstract

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Authors: Markus Scholz, Harald Niesch, Olaf Steffen, Baerbel Ernst, Markus Loeffler, Evelin Witruk, Hans Schwarz

Date Published: 2008

Publication Type: Journal article

Abstract (Expand)

Zusammenfassung  Die Medizin ist geprägt sowohl durch ihren besonderen unmittelbaren und existenziellen Bezug zu Menschen als auch durch ihre zunehmende Ã\Pkonomische Bedeutung. Ein Medizinisches Informationssystem ist das umfassende System aller Informationsverarbeitung einer medizinischen Einrichtung oder Region. Während die Architekturprinzipien des rechnerbasierten Teils solcher Informationssysteme wenige Besonderheiten aufweist, bÃ\textonequarterndelt das Management dieser Informationssysteme viele Herausforderungen und Probleme, die wegen der besonderen Bedeutung der Medizin besondere Priorität bei der LÃ\Psung haben mÃ\textonequarterssen.

Author: Alfred Winter

Date Published: 2008

Publication Type: Journal article

Abstract

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Authors: Alfred Winter, W. Ahrens, B. Bergh, M. Bohrer-Steck, J. Chang-Claude, H. Christ, Thomas M. Deserno, C. Dujat, J. Haerting, C. O. Köhler, U. Kutscha, O. Mosbach-Schulz, J. Müller, A. Mulder-Rathgeber, W. Niederlag, M. Niehsen-Zehrer, K. Pommerening, A. Scharsky, C. Stark, R. Vollmar

Date Published: 2008

Publication Type: Journal article

Abstract

Not specified

Authors: Alfred Winter, Franziska Jahn, Lutz Ißler, Katsuhiko Takabayashi

Date Published: 2008

Publication Type: Journal article

Abstract

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Authors: Alfred Winter, Alexander Strübing

Date Published: 2008

Publication Type: Journal article

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