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15. Absract

Author

Kaszkin, Marietta, Kinzel, Volker, Maly, Karl, Bichler, Irina, Lang, Florian, Grunicke, Hans H., Pepperkok, R., Jakobi, R., Lorenz, P., Ansorge, W., Pyerin, W., Borowski, P., Harbers, M., Ludwig, A., Kischel, T., Hilz, H., Eckert, K., Granetzny, A., Fischer, J., Grosse, R., Manch, V., Wehner, S., Kornhuber, B., Ebener, U., Müller-Decker, K., Fürstenberger, G., Vogt, I., Marks, F., Graschew, G., Küsel, A., Hull, W., Lorenz, W., Thielmann, H. W., Degen, Gisela H., Freyberger, Alexius, Müller, A., Linscheid, M., Hindermeier, Ulrike, Jorritsma, Ute, Golka, K., Föllmann, W., Peter, H., Bolt, H. M., Monnerjahn, S., Phillips, D. N., Never, A., Seidel, A., Glatt, A. R., Wiench, K., Frei, E., Schroth, P., Wiessler, M., Schäfer, T., Hergenhahn, M., Hecker, E., Proft, D., Bartholmes, P., Bagewadikar, R. S., Bertram, B., Frank, N., Leibersperger, Hanno, Gschwendt, Michael, Marks, Friedrich, Fasco, S., Plein, Peter, Schiess, Karin, Seidler, Lothar, Jacobi, T., Besemfelder, E., Stephan, M., Lehmann, W. D., Grell, M., Thoma, B., Scheurich, P., Meyer, Markus, Grunicke, Hans, Jaques G., Wegmann B., Ravemann K., Popanda, Odilia, Thielmann, Heinz Walter, Voss, H., Wirkner, U., Werner, Dieter, Strand, D., Kalmes, A., Walther, H. -P., Mechler, B., Schirrmacher, S. Volker, Kinzel, V., Hess, R., Hanagarth, H. -G., Hässler, C., Brandner, G., Ertel, Christian, Gückel, B., Schirrmacher, V., Kyewski, B. A., Bogdahn U., Jachimczak P., Schneider J., Brysch W., Schlingensiepen W., Drenkard D., Behl C., Winkler J., Apfel R., Meixensberger J., Stulle, K., Marquardt, P., Vollmers, H. P., Müller, J., Müller-Hermelink, H. -K., Schuermann, M., Seemann, G., Ptok, Angelika, Ptok, M., Carey, T. E., Steffen M., Nitz U. C., Everding B., Hölzel F., Kantwerk-Funke, G., Boll, G., Zänker, K. S., Everding, B., Steffen, M., Hölzel, P., Heymanns, J., Hennig, C., Rotsch, M., Havemann, K., Fischer, Jürgen R., Stehr, Sabine, Lahm, Harald, Drings, Peter, Krammer, Peter H., Kirsch M., Strubel A., Kist A., Hinn R., Fischer H., Buttler A., Schackert G., Friedenauer, S., Lindner, D., Marczynski, B., Karcls, H., Goergens, H. W., Epe, B., Müller, E., Schütze, D., Boiteux, S., Eder, E., Deininger, C., Hoffman, C., Scherer, E., Vermeulen, E., van Kranen, H. J., Bax, J., Woutersen, R. A., van Kreijl, C. F., Schurich, B., Hagedorn, H., Kamp, E., Eisenbrand, G., Spiegelhalder B., Bolm-Audorff U., Bienfait H. G., Preussmann R., Wacker, C. -D., Preussmann, R., Kehl, H., Spiegelhalder, B., Akkan, Z., Ries, J., Meger, M., Shephard, S. E., Gunz, D., Lutz, W. K., Tricker, A. R., Kurnar, R., Siddiqi, M., Mende, P., Pfundstein, B., Scholl, A., Janzowski, C., Jacob, D., Goelzer, P., Henn, I., Zankl, H., Zimlich, K. -H., Gansewendt, Barbara, Thier, Ricarda, Schroeder, K. R., Hallier, E., Moeckel, G., Heiden, W., Waldherr-Teschner, M., Brickmann, J., Roeser, H., Krauter, G., Scherer, G., Krätschmer, A., Hauenstein, H., Adlkofer, F., Fernando, R. C., Schmeiser, H. H., Nicklas, W., Pfau, Wolfgang, Phillips, David H., Scheckenbach, S., Cantoreggi, S., Leutbecher, Monika, Ottenwälder, H., Föst, U., Baumgart, P. M., Kliem, H. -C., Data, S., Pfeiffer, C., Fuchs, A., Schmezer, P., Kuchenmeister, F., Pool-Zober, B. L., Liegibel, U. M., Pool-Zobel, B. L., Steeb, L., Friesel, H., Schneider, Th., Scherf, H. R., Buchmann, A., Bauer-Hofmann, R., Mahr, J., Schwarz, M., Schmidt, R., Rippmann, F., Steinbauer, B., Zlfu, P., Bunk, B., Hefter, W., Klinga, K., Berger, M. R., Robertson, L. W., Luebeck, G., Moolgavkar, S., Torsten U., Kowalczyk-Wagner M., Weitzel H., Zechel, Ch., Peters, H., Anders, F., Ambs, S., Kirchner, T., Neumann, H. -G., Einig, C., Eigenbrodt, E., Oesterle, D., Deml, E., Weisse, G., Gerbracht, U., Stumpf, H., Filsingcr, E., Bannasch, P., Muster, W., Cikryt, P., Münzel, P., Röhrdanz, E., Bock, K. W., Lipp, H. -P., Wiesmüller, T., Hagenmaier, H., Schrenk, D., Karger, A., Bauer, G., Höfler, P., Götschl, M., Viesel, E., Jürgensmeier, J., Schaefer, D., Picht, G., Kiefer, J., Krieg, P., Schnapke, R., Feil, S., Wagner, E., Schleenbecker, U., Anders, A., Gross, M. M., Unger, S., Stanbridge, E. J., Boukamp, Petra, Pascheberg, Ulrich, Fusenig, Norbert E., Abken, H., Weidle, U. H., Grummt, F., Willecke, K., Schäfer, R., Hajnal, A., Balmer, I., Klemenz, R., Goretzki, P. E., Reishaus, H., Demeure, M., Haubruck, H., Lyons, J., Röher, H. D., Trouliaris, Sylvia, Hadwiger-Fangmeier, Angelika, Simon, Elke, Niemann, Heiner, Tamura, Teruko, Westphal, G., Turner, Elke, Karels, H., Blaszkewicz, M., Stopper, Helga, Schiffmann, Dietmar, De Boni, Umberto, Schuler, M., Schnitzler, R., Metzler, M., Pfeiffer, E., Aulenbacher, R., Langhof, T., Schröder, K. R., Saal, K., Müller-Hermelink, H. K., Henn W., Seitz G., Lagoda P., Christmann A., Blin N., Welter C., Adam, D., Fömzler, D., Winkler, C., Mäueler, W., Schartl, M., Theisinger B., Schüder G., Rüther U., Nunnensiek C., Müller H. A. G., Rupp W., Lüthgens M., Jipp P., Kinzler, I., Gulich, M., Seidel, H. J., Clark, O. H., McCormick, F., Bourne, H. R., Gieseler, F., Boege, F., Biersack, H., Spohn, B., Clark, M., Wilms, K., Boege, Fritz, Gieseler, Frank, Biersack, Harald, Clark, Michael, Wllms, Klaus, Polack, Axel, Strobl, Lothar, Feederle, Regina, Schweizer, Matthias, Eick, Dirk, Bornkamm, Georg W., Kopun M., Scherthan H., Granzow C., Janiaud, P., Rueß, D., Mechler, B. M., Strauss, P. G., Erfle, V., Fritsche, M., Haessler, C., Christiansen, H., Schestag, J., Christiansen, N. M., Lampert, F., Schulz, Wolfgang A., Hasse, Andreas, Sies, Helmut, Orend, G., Kuhlmann, I., Doerfler, W., Behn-Krappa, A., Hölker, I., Sandaradura de Silva, U., Smola, Ute, Hennig, Dagmar, Hadviger-Fangmeier, Angelika, Schütz, Burkhard, Kerler R., Rabes H. M., Dölken, G., Fauser, A. A., Kerkert, R., Ragoczy, U., Fritzen, R., Lange, W., Finke, J., Nowicki, B., Schalipp, E., Siegert, W., Mertelsmann, R., Schilling, U., Sinn, H. J., Maier-Borst, W., Friedrich, E. A., Löhde E., Lück M., Raude H., Schlicker H., Barzen G., Kraas E., Milleck, J., Keymer, R., Störkel, S., Reichert, T., Steinbach, F., Lippold, R., Thoenes, W., Wagner, W., Reiffen, K. -A., Bardosi, A., Brkovic, D., Gabius, H. -J., Brandt B., Jackisch C., Seitzer D., Hillebrand M., Habermann, F. A., Rabes, H. M., Zeindl-Eberhart, Evelyn, Robl, C., Röttgen, V., Nowak, C., Richter-Reichhelm, H. -B., Waldmann, V., Suchy, B., Zietz, Ch., Sarafoff, M., Ostermayr, Richard, Rabes, Hartmut M., Lorenz, J., Friedberg, T., Paulus, W., Ferlinz, R., Oesch, F., Jähde, E., Glüsenkamp, K. -H., Tietze, L. F., Rajewsky, M. F., Chen, G., Hutter, K. -J., Bullerdiek, J., Zeller, W. J., Schirner, M., Schneider, M. R., Zbu, P., Gebelein, M., Naser-Hijazi, B., Hynes, Nancy E., Reinhardt, M., Heyl, P., Schmähl, D., Presek, P., Liebenhoff, U., Findik, D., Hartmann, G. H., Fischer, H., Kliesch, C., Schackert, G., Albert, F., Kunze, S., Wannnenmacher, M., Boese-Landgraf, J., Lorenz, E., Albrecht, D., Dulce, M., Aigner, K. R., Thiem, N., Müller, H., Leonardi, M., Bogdahn, U., Justh, A., Drenkard, D., Lutz, M., Apfel, R., Behl, C., Lang, E., Lieth, C. W. v. d., Sinn, H., Betsch, B. R., Hengstler, Jan Georg, Fuchs, Jürgen, Oesch, Franz, Busch, F. J., Cato, A. B. C., Schied, G., Tang, W., Bogdahn U., Richter B., Schaefer, C., Kelleher, D. K., Vaupel, P., Mundt, D., Bartsch, H. H., Meden, H., Meyer, M., Vehmeyer, K., Mull, R., Kuhn, W., Hoffmann, S., Berger, D., Fiebig, H., Moog, Ch., Luu, B., Frühauf, S., Keppler, B. K., Galeano, A., Valenzuela-Paz, P., Klenner, T., Stadler, H., Golomb, G., Breuer, E., Voegeli, R., Hilgard, P., Nowrousian, H. R., Aulenbacher, P., Winterhalter, B., Granson, C., Stöhr, M., Ponstingl, H., Granzow, C., Drings, P., Osswald, H., Sobottka, S. B., Amtmann, E., Sauer, G., Hornung, B., Volland, S., Kahl, S., Gerspach, R., Matz, B., Schmidt, J., Lipp, M., Brehm, G., Luz, A., Rüther, U., Wendel, S., Strauß, P. G., Erflte, V., Greehmann, S., Zobel, A., Kalkbrenner, F., Vorbrüggen, G., Moelling, K., Iftner, T., Müller, A. H., Fuchs, P. G., Pfister, H., Cichutek, Klaus, Treinies, Iris, Lang, Matthias, Braun, C., Denner J., Norley S., Kurth R., Music, L., Wiestler, O. D., Aguzzi, A., von Deimling, A., Schneemann, M., Elbl, R., Kleihues, P., Land, H., Hohn, H. -P., Höök, M., Denker, H. -W., Kemmner, W., Zaar, K., Jones, Peter A., Kath, R., Herlyn, M., Maier, P., Schawalder, H. P., Elsner, J., Parzefall, W., Erber, E., Sedivy, R., Schulte-Hermann, R., Hemmer, J., Tomakidi, P., Boukamp, P., Breitkreutz, D., Fusenig, N. E., Kallinowski, F., Strauss, W., Brownell, A. L., Bassukas, I. D., Vester, G., Maurer-Schultze, B., Langbein, L., Kosmehl, H., Katenkamp, D., Spiess, Eberhard, Trefz, Günther, Ebert, Werner, Jordan, Peter, Kübler, Dieter, Lichtner, Rosemarie B., Wiedemuth, Marion, Kittmann, Annette, Ullrich, Axel, Khazaie, Khashayarsha, Kowitz, Aiga, Kadmon, Guni, Altevogt, Peter, Frixen, U. H., Behrens, J., Schipper, J., Sachs, M., Birchmeier, H., Hackenberg, R., Hawighorst, Th., Hofmann, J., Beato, H., Schulz, K. -D., Erbil, C., Maasberg, M., Kunz, L. A., Simm, A., Adam, G., Mueller-Klieser, W., Kaufmann, Andreas M., Stoeck, Michael, Hülsen A., Boukamp P., Game S., Donnelly M., Fusenig N. E., Stark, H. -J., Schlingensiepen K. -H., Kurzik-Dumke U., Phannavong B., Gundacker D., Gateff E., Gabius, S., Joshi, S. S., Franz, H., John, N. J., Grümmer, R., Denker, H. W., Gross, M. W., and Karbach, U.

Published
1991
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19. Destabilizing the interplay between miR-1275 and IGF2BPs by Tamarix articulata and quercetin in hepatocellular carcinoma.

Author

Shaalan, Yasmin M., Handoussa, H., Youness, R. A., Assal, R. A., El-Khatib, A. H., Linscheid, M. W., El Tayebi, H. M., and Abdelaziz, A. I.

Abstract

Insulin-like growth factor-2 binding proteins (IGF2BPs) are oncogenic RNA-binding proteins, highly up-regulated in HCC, and were recently validated as direct targets of the tumour suppressor miR-1275. It is worth noting that around 47% of FDA approved anticancer drugs are derived from plants. Modulation by miRNAs and their cellular signalling cascades could constitute new pathways by which these phytochemicals exert their effects. This study aimed to investigate the potential use of Tamarix articulata, quercetin and epigallocatechin gallate (EGCG) in HCC and how these phytochemicals could epigenetically modulate the IGF axis using their impact on miR-1275. T. articulata ethyl acetate fraction significantly reduced the viability of Huh-7 cells compared to control cells. Treatment with T. articulata ethyl acetate fraction, quercetin and EGCG significantly enhanced miR-1275, while suppressed IGF2BP1 and IGF2BP3 mRNA expression levels. In summary, T. articulata, quercetin and EGCG have important implications for HCC molecular-targeted therapy through destabilizing the interplay between miR-1275 and the IGF axis. [ABSTRACT FROM AUTHOR]

Published
2018
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21. Hexabromcyclododecan in Biota

Author

Linscheid, M., Nehls, I., Köppen, Robert, Linscheid, M., Nehls, I., and Köppen, Robert

Abstract

Ziel dieser Arbeit war es, ein enantiomerenspezifisches Analysenverfahren für die Bestimmung von Hexabromcyclododecan (HBCD) in Biota-Proben zu entwickeln und die bei erhöhten Temperaturen auftretende Isomerisierung der HBCD-Stereoisomere zu untersuchen. Als erstes wurden die sechs HBCD-Enantiomere isoliert, mittels Einkristallstrukturanalyse, NMR- und IR-Spektroskopie charakterisiert und erstmals die spezifischen Drehwinkel der reinen Enantiomere mit den absoluten Konfigurationen und der Elutionsreihenfolge auf einer chiralen beta-PM-Cyclodextrin-Phase korreliert. Die Untersuchungen der HBCD-Enantiomere in Biota-Proben wurden mit einem HPLC-Tandem-MS-System unter Verwendung einer Kombination aus einer C18- und einer chiralen beta-PM-Cyclodextrin-Phase durchgeführt. Das entwickelte Analysenverfahren wurde validiert und ein Messunsicherheitsbudget erstellt. Die mittlere Wiederfindung für die internen Standards lag im Bereich von 96 - 104 % und die Nachweisgrenzen lagen zwischen 6 und 21 pg/g. Mit Hilfe dieses Analysenverfahrens wurden sowohl maritime als auch Süßwasser Biota-Proben von verschiedenen Probenahmepunkten in Europa untersucht. Die ermittelten Enantiomeren-Verhältnisse, die in allen Fällen vom (±)-alpha-HBCD dominiert wurden, zeigten signifikante Abweichungen von den razemischen Zusammensetzungen. Auffällig hierbei war, dass eine bevorzugte Anreicherung der zuerst eluierenden HBCD-Enantiomere ((-)-alpha-, (-)-beta- und (+)-gamma-HBCD) stattfand. Im Ergebnis der Untersuchungen zur thermisch induzierten intramolekularen Isomerisierung der HBCD-Stereoisomere konnten die verschiedenen Isomerisierungsreaktionen eindeutig aufgeklärt und die jeweiligen Geschwindigkeitskonstanten bei einer Temperatur von 160 °C ermittelt werden. Ergänzend wurde die Isomerisierung mit Hilfe der statistischen Thermodynamik unter Verwendung eines neuen Ansatzes für die klassische Hybrid Monte-Carlo-Simulation untersucht., The major objectives of this thesis were the development of an analytical procedure for the enantio-specific determination of hexabromocyclododecane (HBCD) in biota samples and the investigation of the interconversion of the individual HBCD isomers at elevated temperatures. The six HBCD enantiomers were isolated, characterised by X-ray diffractometry, NMR- and IR-spectroscopy and the sense of rotation was correlated for the first time with the absolute configurations of the HBCD enantiomers as well as their order of elution on a chiral beta-PM-cyclodextrine-phase. Trace quantification of the individual HBCD enantiomers was achieved by means of high performance liquid chromatography coupled to tandem mass spectrometry equipped with a combination of a C18- and a chiral analytical column. Validation data and an uncertainty budget were determined. The mean recoveries of the different enantiomeric internal standards ranged from 96 to 104 % and the limits of detection are in the range of 6 to 21 pg/g. The analytical procedure was successfully applied to marine and freshwater biota samples from different European sites. The enantiomeric pattern of the six HBCD enantiomers, with (±)-alpha-HBCD as the dominant diastereomer, was determined for all biota samples and showed in most cases a significant deviation from the technical racemate. In these cases a preferential enrichment of the first eluted enantiomers ((-)-alpha-, (-)-beta- and (+)-gamma-HBCD) could be observed. The unambiguous elucidation of the individual isomerisation reactions as well as the quantification of all respective rate constants for the interconversion of the HBCD stereoisomers at 160 °C was done. A mechanistic explanation for the differences of the rate constants which govern the composition of HBCD diastereomers at equilibrium was given. Additionally, the interconversion was investigated by means of statistical thermodynamics using a new approach to classical hybrid Monte-Carlo simulations.

Published
2008

43. Assessment of the vasodilator response in primary pulmonary hypertension.

Author

Opitz, C.F, Wensel, R, Bettmann, M, Schaffarczyk, R, Linscheid, M, Hetzer, R, and Ewert, R

Abstract

Aims To directly compare the differential effects of oxygen, prostacyclin and iloprost (aerosolized and intravenous) in primary pulmonary hypertension.Methods and results Twenty-one patients with severe primary pulmonary hypertension underwent right heart catheterization following oxygen inhalation, inhalation of aerosolized iloprost, intravenous prostacyclin or intravenous iloprost. The stability of the iloprost solution was tested for up to 4 weeks. Oxygen slightly decreased pulmonary vascular resistance. Intravenous prostacyclin (7.2±3.4ngkg−1min−1) reduced pulmonary (1772±844 vs 1325±615dynscm−5, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.001\) \end{document}) and systemic vascular resistance, and arterial and right atrial pressure, while cardiac output increased. Iloprost inhalation diminished pulmonary (1813±827 vs 1323±614dynscm−5, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.001\) \end{document}) and systemic vascular resistance, and pulmonary artery (58±12 vs 50±12mmHg,\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.001\) \end{document}) and right atrial pressure, while cardiac output increased. With intravenous iloprost (1.2±0.5ngkg−1min−1, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=8\) \end{document}) a decrease in pulmonary (2202±529 vs 1515±356dynscm−5, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(P{<}0.05\) \end{document}) and systemic vascular resistance and right atrialpressure occurred while cardiac output increased. Iloprost solution remained stable for 33 days while losing <10% (4°C) of its active drug concentration.Conclusions Intravenous iloprost and prostacyclin have very similar haemodynamic profiles. In contrast, only inhaled iloprost exerted selective pulmonary vasodilation, reducing pulmonary vascular resistance and pulmonary artery pressure withoutsystemic vasodilation. The longer half-life and extended stability despite lower costs render iloprost an attractive alternative to chronic prostacyclin treatment in primary pulmonary hypertension. [ABSTRACT FROM PUBLISHER]

Published
2003
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45. High-performance Liquid Chromatographic/Electrospray Ionization Mass Spectrometric Screening for Polyphenolic Compounds of Epilobium hirsutum—The Structure of the Unique Ellagitannin Epilobamide-A

Author

Nawwar, M. A. M., Marzouk, M. S., Nigge, W., and Linscheid, M.

Abstract

A screening method based on high-performance liquid chromatography (HPLC) interfaced to electrospray ionization mass spectrometry (ESI-MS) with detection of negative ions was devised and the conditions for assaying the complex mixture of gallotannins, ellagitannins and flavonoids of aqueous ethanolic Epilobium hirsutum L. whole plant extract were established. Twenty-eight polyphenolic compounds were tentatively identified and one unique ellagitannin with an odd molecular mass was detected in the extract. This compound was taken as the target and isolated by means of consecutive polyamide and Sephadex LH-20 column fractionation; repeatedly, the isolation and purification were monitored by HPLC/ESI-MS. The compound was isolated and subsequently identified as valoneic acid amide bilactone (epilobamide-A). The parent acid, known as valoneic acid bilactone, was also isolated and mass and 1H and 13C NMR spectra were recorded and completely interpreted. Eventually, all relevant structures were elucidated by established methods of structure analysis and confirmed by 1D and 2D NMR spectroscopy. Further, ESI-MS with in-source collision-induced dissociation of the two valoneic acid derivatives and the formation of distonic radical anions is discussed, together with oxidation processes during fragmentation. © 1997 John Wiley & Sons, Ltd.

Published
1997
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46. Field Ionization Mass Spectrometry. II. FD Spectra of Nucleotides — Analysis of Methylation Products of Dinucleoside Phosphates

Author

Linscheid, M., Feistner, G., and Budzikiewicz, H.

Abstract

The analysis of reaction products in methylation of four dinucleoside monophosphates (ApA, UpU, ApU, UpA) by FDMS is reported. Both the relative amounts of the various methylation products and the sites of methylation could be determined, the latter from the fragmentation patterns. The results are explained by the different reaction rates of the nucleoside moieties.

Published
1978
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48. Collisionally activated dissociation of field desorbed protonated dinucleoside phosphates.

Author

Linscheid, M. and Burlingame, A. L.

Abstract

The collisionally activated dissociation (CAD) of six protonated dinucleoside monophosphates produced by field desorption has been studied by linked scanning ( B/E=constant). Complete spectra with detailed structure information have been obtained despite the small ion currents and other technical problems. It is possible to distinguish isomeric sequences in both ribo- and deoxyribo-nucleotides series. [ABSTRACT FROM AUTHOR]

Published
1983
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