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Fan Wang, Salih Demir, Franziska Gehringer, Clarissa D Osswald, Felix Seyfried, Stefanie Enzenmüller, Sarah M Eckhoff, Thomas Maier, Karlheinz Holzmann, Klaus-Michael Debatin, Thomas Wirth, Lüder H Meyer, Alexey Ushmorov
The FOXO1 transcription factor plays an essential role in the regulation of proliferation and survival programs at early stages of B-cell differentiation. Here, we show that tightly-regulated FOXO1 activity is essential for maintenance of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Genetic and pharmacological inactivation of FOXO1 in BCP-ALL cell lines produced a strong anti-leukemic effect associated with CCND3 downregulation. Moreover, we demonstrated that CCND3 expression is critical for BCP-ALL survival and overexpression of CCND3 protected BCP-ALL cell lines from growth arrest and apoptosis induced by FOXO1 inactivation...
April 5, 2018: Blood
Z Malik, M Alexiou, B Hallgrimsson, A N Economides, H U Luder, D Graf
Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice...
February 1, 2018: Journal of Dental Research
Luca Pirracchio, Aline Joos, Nina Luder, Anton Sculean, Sigrun Eick
OBJECTIVES: The purpose of this study is to evaluate the activity of two different taurolidine (TAU) gels in comparison with a 0.2% chlorhexidine (CHX) gel on an ex vivo subgingival biofilm. MATERIAL AND METHODS: Subgingival including supragingival biofilm samples from periodontitis patients were cultured for 10 days, before TAU 1% and TAU 3% gels and CHX gel were applied for 10 min and thereafter diluted with nutrient media to 10% for 50 min. One third of the samples were analyzed for bacterial counts, biofilm quantity, and biofilm metabolic activity...
December 14, 2017: Clinical Oral Investigations
David A Quigley, Andliena Tahiri, Torben Lüders, Margit H Riis, Allan Balmain, Anne-Lise Børresen-Dale, Ida Bukholm, Vessela Kristensen
Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. There is a complex relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors. While low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue...
2017: Oncoimmunology
M Koziolek, J Beige, M Wallbach, D Zenker, G Henning, M Halbach, N Mader, F Mahfoud, G Schlieper, V Schwenger, M Hausberg, J Börgel, M Lodde, M van der Giet, J Müller-Ehmsen, J Passauer, S Parmentier, S Lüders, B K Krämer, S Büttner, F Limbourg, J Jordan, O Vonend, H-G Predel, H Reuter
Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients...
October 2017: Der Internist
Vera Münch, Luca Trentin, Julia Herzig, Salih Demir, Felix Seyfried, Johann M Kraus, Hans A Kestler, Rolf Köhler, Thomas F E Barth, Geertruy Te Kronnie, Klaus-Michael Debatin, Lüder H Meyer
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite nondetectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse-free survival, indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae, including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia-cell entry into the CNS need to be understood to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies...
August 3, 2017: Blood
Tim Ripperger, Stefan S Bielack, Arndt Borkhardt, Ines B Brecht, Birgit Burkhardt, Gabriele Calaminus, Klaus-Michael Debatin, Hedwig Deubzer, Uta Dirksen, Cornelia Eckert, Angelika Eggert, Miriam Erlacher, Gudrun Fleischhack, Michael C Frühwald, Astrid Gnekow, Gudrun Goehring, Norbert Graf, Helmut Hanenberg, Julia Hauer, Barbara Hero, Simone Hettmer, Katja von Hoff, Martin Horstmann, Juliane Hoyer, Thomas Illig, Peter Kaatsch, Roland Kappler, Kornelius Kerl, Thomas Klingebiel, Udo Kontny, Uwe Kordes, Dieter Körholz, Ewa Koscielniak, Christof M Kramm, Michaela Kuhlen, Andreas E Kulozik, Britta Lamottke, Ivo Leuschner, Dietmar R Lohmann, Andrea Meinhardt, Markus Metzler, Lüder H Meyer, Olga Moser, Michaela Nathrath, Charlotte M Niemeyer, Rainer Nustede, Kristian W Pajtler, Claudia Paret, Mareike Rasche, Dirk Reinhardt, Olaf Rieß, Alexandra Russo, Stefan Rutkowski, Brigitte Schlegelberger, Dominik Schneider, Reinhard Schneppenheim, Martin Schrappe, Christopher Schroeder, Dietrich von Schweinitz, Thorsten Simon, Monika Sparber-Sauer, Claudia Spix, Martin Stanulla, Doris Steinemann, Brigitte Strahm, Petra Temming, Kathrin Thomay, Andre O von Bueren, Peter Vorwerk, Olaf Witt, Marcin Wlodarski, Willy Wössmann, Martin Zenker, Stefanie Zimmermann, Stefan M Pfister, Christian P Kratz
Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient...
April 2017: American Journal of Medical Genetics. Part A
W Dörffel, M Riepenhausen, H Lüders, J Brämswig
Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed...
November 2016: Klinische Pädiatrie
Luca Caldironi
More and more often analysts work with patients who must develop the capacity to participate in analysis. One such patient, H., conveyed the impression of being "bogged down." He did not work or study, and at home with his family was prone to violent outbursts; his social relationships were centered around drug use. Concepts from Bion and Winnicott helped H.'s analyst take the risks necessary to create a therapeutic relationship with him. The patient has come to realize the worth of analytic thinking, and its potential to transform his life...
August 2016: Journal of the American Psychoanalytic Association
Sabrina Eggmann, Martin L Verra, Gere Luder, Jukka Takala, Stephan M Jakob
BACKGROUND: Prolonged need for intensive care is associated with neuromuscular weakness, termed Intensive Care Unit Acquired Weakness. Those affected suffer from severe functional impairment that can persist for years. First studies suggest a positive effect of physiotherapy and early mobilisation. However, the ideal intervention for a preferential functional outcome is not known. So far no randomised controlled trial has been conducted to specifically evaluate an early endurance and resistance training in the mechanically ventilated, critically ill patient...
August 15, 2016: Trials
Micah John Luderer, Barbara Muz, Pilar de la Puente, Sanmathi Chavalmane, Vaishali Kapoor, Raymundo Marcelo, Pratim Biswas, Dinesh Thotala, Buck Rogers, Abdel Kareem Azab
PURPOSE: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. METHODS: B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA)...
October 2016: Pharmaceutical Research
Hans H Kornhuber, Lüder Deecke
A method of chronological data storage and reverse computation is described by which bio-electrical phenomena preceding 'spontaneous' events within the nervous system can be analysed if these events appear repeatedly and are capable of triggering a computer.Slow brain potentials accompanying voluntary and passive movements of the limbs were analysed by this method. These potentials were recorded from different points of the scalp from 12 healthy subjects in 94 experiments with more than 100 movements in each record...
July 2016: Pflügers Archiv: European Journal of Physiology
Birendra Mishra, Laura Ortiz, Ulrike Luderer
STUDY QUESTION: Do charged iron particles, components of space radiation, cause premature ovarian failure? SUMMARY ANSWER: Exposure to charged iron particles causes ovarian DNA damage, oxidative damage and apoptosis, resulting in premature ovarian failure. WHAT IS KNOWN ALREADY: The ovary is very sensitive to follicle destruction by low linear energy transfer (LET) radiation, such as X-rays and γ-rays. However, it is completely unknown whether high-LET radiation, such as charged iron particles, also destroys ovarian follicles...
August 2016: Human Reproduction
Manuel Wallbach, Marcel Halbach, Hannes Reuter, Jens Passauer, Stephan Lüders, Enrico Böhning, Dieter Zenker, Gerhard A Müller, Rolf Wachter, Michael J Koziolek
BACKGROUND: Both baroreflex activation therapy (BAT) and renal denervation modulate sympathetic activity. The aim of this study was to systematically investigate whether additive modulation of autonomic nervous system by BAT lowers blood pressure (BP) in patients who still suffer from uncontrolled resistant hypertension despite prior renal denervation. METHODS: From 2012 to January 2015, patients treated with BAT for uncontrolled resistant hypertension, who prior received renal denervation were consecutively analyzed in four German centers for hypertension...
August 2016: Journal of Hypertension
Hiroko K Solvang, Arnoldo Frigessi, Fateme Kaveh, Margit L H Riis, Torben Lüders, Ida R K Bukholm, Vessela N Kristensen, Bettina K Andreassen
Tumor size, as indicated by the T-category, is known as a strong prognostic indicator for breast cancer. It is common practice to distinguish the T1 and T2 groups at a tumor size of 2.0 cm. We investigated the 2.0-cm rule from a new point of view. Here, we try to find the optimal threshold based on the differences between the gene expression profiles of the T1 and T2 groups (as defined by the threshold). We developed a numerical algorithm to measure the overall differential gene expression between patients with smaller tumors and those with larger tumors among multiple expression datasets from different studies...
December 2016: EURASIP Journal on Bioinformatics & Systems Biology
Erik S Mittra, Norman Koglin, Camila Mosci, Meena Kumar, Aileen Hoehne, Khun Visith Keu, Andrei H Iagaru, Andre Mueller, Mathias Berndt, Santiago Bullich, Matthias Friebe, Heribert Schmitt-Willich, Volker Gekeler, Lüder M Fels, Claudia Bacher-Stier, Dae Hyuk Moon, Frederick T Chin, Andrew W Stephens, Ludger M Dinkelborg, Sanjiv S Gambhir
PURPOSE: (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies. EXPERIMENTAL DESIGN: For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET...
2016: PloS One
I Lüders, B Tindall, D Young, G van der Horst, S Botha, I Luther, L Maree, H J Bertschinger
Doses for standing sedation allowing for various procedures in otherwise inaccessible, untrained captive African elephant bulls are presented. Thirty-three standing sedations were performed in 12 males aged 8-30 years (one to four sedations per animal). Each bull received a combination of 0.009 ± 0.002 mg/kg medetomidine and 0.03 ± 0.007 mg/kg butorphanol. Full sedation was reached on average 25.5 min after injection. The addition of hyaluronidase (1000-2000 IU) significantly reduced time to full sedation to 16...
March 2016: Veterinary Journal
P D Watson, E J Paul, G E Cooke, N Ward, J M Monti, K M Horecka, C M Allen, C H Hillman, N J Cohen, A F Kramer, A K Barbey
Healthy adults have robust individual differences in neuroanatomy and cognitive ability not captured by demographics or gross morphology (Luders, Narr, Thompson, & Toga, 2009). We used a hierarchical independent component analysis (hICA) to create novel characterizations of individual differences in our participants (N=190). These components fused data across multiple cognitive tests and neuroanatomical variables. The first level contained four independent, underlying sources of phenotypic variance that predominately modeled broad relationships within types of data (e...
April 1, 2016: NeuroImage
Sebastian Damerow, Carolin Hoppe, Giulia Bandini, Patricia Zarnovican, Falk F R Buettner, Carsten G K Lüder, Michael A J Ferguson, Françoise H Routier
[This corrects the article DOI: 10.1371/journal.pntd.0004205.].
January 2016: PLoS Neglected Tropical Diseases
Sebastian Damerow, Carolin Hoppe, Giulia Bandini, Patricia Zarnovican, Falk F R Buettner, Falk R Buettner, Carsten G K Lüder, Michael A J Ferguson, Françoise H Routier
Interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal) by the UDP-Glc 4´-epimerase intimately connects the biosynthesis of these two nucleotide sugars. Their de novo biosynthesis involves transformation of glucose-6-phosphate into glucose-1-phosphate by the phosphoglucomutase and subsequent activation into UDP-Glc by the specific UDP-Glc pyrophosphorylase (UGP). Besides UGP, Leishmania parasites express an uncommon UDP-sugar pyrophosphorylase (USP) able to activate both galactose-1-phosphate and glucose-1-phosphate in vitro...
November 2015: PLoS Neglected Tropical Diseases
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