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Institution

Charité

HealthcareBerlin, Germany
About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.


Papers
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Journal ArticleDOI
TL;DR: There is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes.
Abstract: Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.

414 citations

Journal ArticleDOI
TL;DR: Continuous RCB index was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer and stratified prognostic risk overall, within each phenotypesic subset, and within yp-stage categories.
Abstract: PurposeTo determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment.MethodsWe conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subse...

414 citations

Journal ArticleDOI
TL;DR: The O4-mediated acceleration of Aβ fibrillogenesis through the action of the orcein-related small molecule O4 efficiently decreases the concentration of small, toxic Aβ oligomers in complex, heterogeneous aggregation reactions, and support the hypothesis that small, diffusible prefibrillar amyloid species rather than mature fibrillsar aggregates are toxic for mammalian cells.
Abstract: Several lines of evidence indicate that prefibrillar assemblies of amyloid-β (Aβ) polypeptides, such as soluble oligomers or protofibrils, rather than mature, end-stage amyloid fibrils cause neuronal dysfunction and memory impairment in Alzheimer's disease. These findings suggest that reducing the prevalence of transient intermediates by small molecule-mediated stimulation of amyloid polymerization might decrease toxicity. Here we demonstrate the acceleration of Aβ fibrillogenesis through the action of the orcein-related small molecule O4, which directly binds to hydrophobic amino acid residues in Aβ peptides and stabilizes the self-assembly of seeding-competent, β-sheet-rich protofibrils and fibrils. Notably, the O4-mediated acceleration of amyloid fibril formation efficiently decreases the concentration of small, toxic Aβ oligomers in complex, heterogeneous aggregation reactions. In addition, O4 treatment suppresses inhibition of long-term potentiation by Aβ oligomers in hippocampal brain slices. These results support the hypothesis that small, diffusible prefibrillar amyloid species rather than mature fibrillar aggregates are toxic for mammalian cells.

414 citations

Journal ArticleDOI
TL;DR: The dynamic yet discrete self-organization of mature microglia in the healthy and diseased CNS is unravels and a new multicolor fluorescence fate mapping system is established to monitor microglial dynamics during steady state and disease.
Abstract: Microglia constitute a highly specialized network of tissue-resident immune cells that is important for the control of tissue homeostasis and the resolution of diseases of the CNS. Little is known about how their spatial distribution is established and maintained in vivo. Here we establish a new multicolor fluorescence fate mapping system to monitor microglial dynamics during steady state and disease. Our findings suggest that microglia establish a dense network with regional differences, and the high regional turnover rates found challenge the universal concept of microglial longevity. Microglial self-renewal under steady state conditions constitutes a stochastic process. During pathology this randomness shifts to selected clonal microglial expansion. In the resolution phase, excess disease-associated microglia are removed by a dual mechanism of cell egress and apoptosis to re-establish the stable microglial network. This study unravels the dynamic yet discrete self-organization of mature microglia in the healthy and diseased CNS.

414 citations

Journal ArticleDOI
Claus Meyer1, Julia Hofmann1, Thomas Burmeister2, Daniela Gröger2, T S Park3, Mariana Emerenciano, M. Pombo De Oliveira, Aline Renneville4, Patrick Villarese5, Elizabeth Macintyre5, Hélène Cavé5, Emmanuelle Clappier5, K. Mass-Malo5, Jan Zuna6, Jan Trka6, E De Braekeleer7, M. De Braekeleer7, S H Oh8, Grigory Tsaur, L Fechina, V H J van der Velden9, J J M van Dongen9, Eric Delabesse, Renata Binato, Mara Silva, AM Kustanovich, Olga V. Aleinikova, Marian H. Harris10, T Lund-Aho, Vesa Juvonen11, Olaf Heidenreich12, Josef Vormoor12, William W.L. Choi13, Marie Jarošová, A. Kolenova14, Clara Bueno15, Pablo Menendez15, S. Wehner1, Cornelia Eckert2, Pascaline Talmant16, Sylvie Tondeur, Eric Lippert, E. Launay17, Catherine Henry17, Paola Ballerini18, H. Lapillone18, Mary Callanan19, Jean Michel Cayuela5, Charles Herbaux, Giovanni Cazzaniga20, P. M. Kakadiya21, Stefan K. Bohlander21, Martina Ahlmann, Jong Rak Choi22, Paula Gameiro23, Dongsoon Lee24, Juergen Krauter25, Pascale Cornillet-Lefebvre, G te Kronnie26, Beat W. Schäfer27, S. Kubetzko27, Cristina N. Alonso, U. Zur Stadt28, Rosemary Sutton29, N. C. Venn29, Shai Izraeli30, Luba Trakhtenbrot31, H. O. Madsen32, P. Archer33, Jeremy Hancock33, Nuno Cerveira34, Manuel R. Teixeira34, L Lo Nigro35, Anja Möricke36, Martin Stanulla36, Martin Schrappe36, Lukasz Sedek37, Tomasz Szczepański37, Christian M. Zwaan9, Eva A. Coenen9, M.M. van den Heuvel-Eibrink9, Sabine Strehl38, Michael Dworzak38, Renate Panzer-Grümayer38, Theodor Dingermann1, Thomas Klingebiel1, Rolf Marschalek1 
30 Apr 2013-Leukemia
TL;DR: Long-distance inverse-polymerase chain reaction was used to characterize the chromosomal rearrangement of individual acute leukemia patients and revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level.
Abstract: Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.

414 citations


Authors

Showing all 30787 results

NameH-indexPapersCitations
JoAnn E. Manson2701819258509
Yi Chen2174342293080
David J. Hunter2131836207050
Raymond J. Dolan196919138540
John P. A. Ioannidis1851311193612
Stefan Schreiber1781233138528
Kenneth C. Anderson1781138126072
Eric J. Nestler178748116947
Klaus Rajewsky15450488793
Charles B. Nemeroff14997990426
Andreas Pfeiffer1491756131080
Rinaldo Bellomo1471714120052
Jean Bousquet145128896769
Christopher Hill1441562128098
Holger J. Schünemann141810113169
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202339
2022317
20214,865
20204,577
20194,042
20183,718