Institution
University of Cologne
Education•Cologne, Germany•
About: University of Cologne is a education organization based out in Cologne, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 32050 authors who have published 66350 publications receiving 2210092 citations. The organization is also known as: Universität zu Köln & Universitatis Coloniensis.
Topics: Population, Gene, Transplantation, Medicine, Cancer
Papers published on a yearly basis
Papers
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University of Ulm1, University of Cologne2, Dresden University of Technology3, Stanford University4, Peter MacCallum Cancer Centre5, St James's University Hospital6, University of Arizona7, Royal Melbourne Hospital8, Jagiellonian University9, Royal North Shore Hospital10, Genentech11, University of Texas MD Anderson Cancer Center12
TL;DR: Results of this trial show that venetoclax monotherapy is active and well tolerated in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia, providing a new therapeutic option for this very poor prognosis population.
Abstract: Summary Background Deletion of chromosome 17p (del[17p]) in patients with chronic lymphocytic leukaemia confers very poor prognosis when treated with standard chemo-immunotherapy. Venetoclax is an oral small-molecule BCL2 inhibitor that induces chronic lymphocytic leukaemia cell apoptosis. In a previous first-in-human study of venetoclax, 77% of patients with relapsed or refractory chronic lymphocytic leukaemia achieved an overall response. Here we aimed to assess the activity and safety of venetoclax monotherapy in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia. Methods In this phase 2, single-arm, multicentre study, we recruited patients aged 18 years and older with del(17p) relapsed or refractory chronic lymphocytic leukaemia (as defined by 2008 Modified International Workshop on Chronic Lymphocytic Leukemia guidelines) from 31 centres in the USA, Canada, UK, Germany, Poland, and Australia. Patients started once daily venetoclax with a weekly dose ramp-up schedule (20, 50, 100, 200, 400 mg) over 4–5 weeks. Patients were then given daily 400 mg continuous dosing until disease progression or discontinuation for another reason. The primary endpoint was the proportion of patients achieving an overall response, assessed by an independent review committee. Activity and safety analyses included all patients who received at least one dose of study drug (per protocol). This study is registered with ClinicalTrials.gov, number NCT01889186. Follow-up is ongoing, and patients are still receiving treatment. Findings Between May 27, 2013, and June 27, 2014, 107 patients were enrolled into the study. At a median follow-up of 12·1 months (IQR 10·1–14·2), an overall response by independent review was achieved in 85 (79·4%; 95% CI 70·5–86·6) of 107 patients. The most common grade 3–4 adverse events were neutropenia (43 [40%]), infection (21 [20%]), anaemia (19 [18%]), and thrombocytopenia (16 [15%]). Serious adverse events occurred in 59 (55%) patients, irrespective of their relationship to treatment, with the most common (≥5% of patients) being pyrexia and autoimmune haemolytic anaemia (seven [7%] each), pneumonia (six [6%]), and febrile neutropenia (five [5%]). 11 patients died in the study within 30 days of the last dose of venetoclax; seven due to disease progression and four from an adverse event (none assessed as treatment related). Interpretation Results of this trial show that venetoclax monotherapy is active and well tolerated in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia, providing a new therapeutic option for this very poor prognosis population. Additionally, in view of the distinct mechanism-of-action of venetoclax, combinations or sequencing with other novel targeted agents should be investigated to further advance treatment of del(17p) chronic lymphocytic leukaemia. Funding AbbVie and Genentech.
644 citations
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TL;DR: Recent findings that highlight the complex regulatory networks that control skin immunity are discussed, and new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation are provided.
Abstract: Immune responses in the skin are important for host defence against pathogenic microorganisms However, dysregulated immune reactions can cause chronic inflammatory skin diseases Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation
644 citations
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Janssen Pharmaceutica1, University of Padua2, Open University3, Tel Aviv University4, Ames Research Center5, European Space Agency6, Agenzia Spaziale Italiana7, Centre national de la recherche scientifique8, Finnish Meteorological Institute9, Austrian Academy of Sciences10, Spanish National Research Council11, University of Murcia12, University of Cologne13, University of Catania14, Polytechnic University of Milan15, Boston University16
TL;DR: The temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface were higher than expected and the extent of atmospheric electricity was also hitherto unknown.
Abstract: On the basis of previous ground-based and fly-by information, we knew that Titan's atmosphere was mainly nitrogen, with some methane, but its temperature and pressure profiles were poorly constrained because of uncertainties in the detailed composition. The extent of atmospheric electricity (‘lightning’) was also hitherto unknown. Here we report the temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface. In the upper part of the atmosphere, the temperature and density were both higher than expected. There is a lower ionospheric layer between 140 km and 40 km, with electrical conductivity peaking near 60 km. We may also have seen the signature of lightning. At the surface, the temperature was 93.65 ± 0.25 K, and the pressure was 1,467 ± 1 hPa.
643 citations
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TL;DR: In this paper, it was shown that any interaction of pressureless dark matter with holographic dark energy, whose infrared cutoff is set by the Hubble scale, implies a constant ratio of the energy densities of both components thus solving the coincidence problem.
641 citations
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TL;DR: A model in which the helper serves as a pore for excretion of the protease domain through the outer membrane of IgA protease acquires an active conformation as its extracellular transport proceeds and is released as a proform from the membrane-bound helper by autoproteolysis.
Abstract: Several human bacterial pathogens, including the Gram-negative diplococcus Neisseria gonorrhoeae, produce extracellular proteases that are specific for human immunoglobulin IgA1, (refs 1, 2). Immunoglobulin A (IgA) proteases have been studied extensively and the genes of some species cloned in Escherichia coli3–7, but their role in pathogenesis remains unclear8. Recently we derived a DNA fragment of 5 kilobases (kb) from N. gonorrhoeae MS 11 directing extracellular active enzyme in E. coli4. Although the mature enzyme of strain MS 11 was shown to have a relative molecular mass of 106,000 (Mr 106K) in gels4, the DNA sequence of this cloned fragment reveals a single gene coding for a 169K precursor of IgA protease. The precursor contains three functional domains, the amino-terminal leader which is assumed to initiate the inner membrane transport of the precursor, the protease, and a carboxyl-terminal 'helper' domain apparently required for extracellular secretion (excretion). Based on the structural features of the precursor, we propose a model in which the helper serves as a pore for excretion of the protease domain through the outer membrane. IgA protease acquires an active conformation as its extracellular transport proceeds and is released as a proform from the membrane-bound helper by autoproteolysis. The soluble proform further matures into the 106 K IgA protease and a small stable α-protein.
640 citations
Authors
Showing all 32558 results
Name | H-index | Papers | Citations |
---|---|---|---|
Julie E. Buring | 186 | 950 | 132967 |
Stuart H. Orkin | 186 | 715 | 112182 |
Cornelia M. van Duijn | 183 | 1030 | 146009 |
Dorret I. Boomsma | 176 | 1507 | 136353 |
Frederick W. Alt | 171 | 577 | 95573 |
Donald E. Ingber | 164 | 610 | 100682 |
Klaus Müllen | 164 | 2125 | 140748 |
Klaus Rajewsky | 154 | 504 | 88793 |
Frederik Barkhof | 154 | 1449 | 104982 |
Stefanie Dimmeler | 147 | 574 | 81658 |
Detlef Weigel | 142 | 516 | 84670 |
Hidde L. Ploegh | 135 | 674 | 67437 |
Luca Valenziano | 130 | 437 | 94728 |
Peter Walter | 126 | 841 | 71580 |
Peter G. Martin | 125 | 553 | 97257 |