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51.
Sara Rosati Ewald TJ van den Bremer Janine Schuurman Paul WHI Parren Johannis P Kamerling Albert JR Heck 《MABS-AUSTIN》2013,5(6):917-924
Here, we describe a fast, easy-to-use, and sensitive method to profile in-depth structural micro-heterogeneity, including intricate N-glycosylation profiles, of monoclonal antibodies at the native intact protein level by means of mass spectrometry using a recently introduced modified Orbitrap Exactive Plus mass spectrometer. We demonstrate the versatility of our method to probe structural micro-heterogeneity by describing the analysis of three types of molecules: (1) a non-covalently bound IgG4 hinge deleted full-antibody in equilibrium with its half-antibody, (2) IgG4 mutants exhibiting highly complex glycosylation profiles, and (3) antibody-drug conjugates. Using the modified instrument, we obtain baseline separation and accurate mass determination of all different proteoforms that may be induced, for example, by glycosylation, drug loading and partial peptide backbone-truncation. We show that our method can handle highly complex glycosylation profiles, identifying more than 20 different glycoforms per monoclonal antibody preparation and more than 30 proteoforms on a single highly purified antibody. In analyzing antibody-drug conjugates, our method also easily identifies and quantifies more than 15 structurally different proteoforms that may result from the collective differences in drug loading and glycosylation. The method presented here will aid in the comprehensive analytical and functional characterization of protein micro-heterogeneity, which is crucial for successful development and manufacturing of therapeutic antibodies 相似文献
52.
Erhard Schulz 《Historical Biology》2013,25(1-2):137-156
Holocene records from the southern Sahara in Niger allow a reconstruction of the vegetation history and inform us about the former extension of the Mediterranean. Both pollen and charcoal analyses evidenced the direct contact of Sudanian and Saharan savannas during the middle Holocene at about 19°N, whereas at 20°N the transition from the Saharan savanna to the desert was found. In southwestern Libya (26°N) a combination of a Saharan desert vegetation and a semi‐desert Artemisia shrub on the plateaus demonstrated the contact with Mediterranean influenced formations. Regular ash and charcoal layers in middle‐Holocene sediments of the northern Niger prove an early interference of man with the vegetation development. One has to imagine that, in combination with the cattle‐keeping and the later metal production, man could have changed the former northern Sudanian vegetation into the present Sahelian savanna system from the middle Holocene on. 相似文献
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54.
Sebastian Ullrich Phillip Bremer Christine Neumann-Grutzeck Helge Otto Christoph Rüther Cay Uwe von Seydewitz Gerd Peter Meyer Keihan Ahmadi-Simab Joachim R?ther Barbara Hogan Wolfgang Schwenk Roman Fischbach J?rg Caselitz Jochen Puttfarcken Susanne Huggett Petra Tiedeken Jordan Pober Nancy C. Kirkiles-Smith Friedrich Hagenmüller 《PloS one》2013,8(2)
Objectives
Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum β lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany.Methods
The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients’ histories, clinical findings, and complications.Results
EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated.Conclusions
EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as “EAHEC disease”. 相似文献55.
56.
Simon P. Fletcher Daniel J. Chin Lore Gruenbaum Hans Bitter Erik Rasmussen Palanikumar Ravindran David C. Swinney Fabian Birzele Roland Schmucki Stefan H. Lorenz Erhard Kopetzki Jade Carter Miriam Triyatni Linta M. Thampi Junming Yang Dalal AlDeghaither Marta G. Murreddu Paul Cote Stephan Menne 《PLoS pathogens》2016,12(3)
57.
Păunescu V Deak E Herman D Siska IR Tănasie G Bunu C Anghel S Tatu CA Oprea TI Henschler R Rüster B Bistrian R Seifried E 《Journal of cellular and molecular medicine》2007,11(3):502-508
Our study examined whether human bone marrow-derived MSCs are able to differentiate, in vitro, into functional epithelial-like cells. MSCs were isolated from the sternum of 8 patients with different hematological disorders. The surface phenotype of these cells was characterized.To induce epithelial differentiation, MSCs were cultured using Epidermal Growth Factor, Keratinocyte Growth Factor, Hepatocyte Growth Factor and Insulin-like growth Factor-II. Differentiated cells were further characterized both morphologically and functionally by their capacity to express markers with specificity for epithelial lineage. The expression of cytokeratin 19 was assessed by immunocytochemistry, and cytokeratin 18 was evaluated by quantitative RT-PCR (Taq-man). The data demonstrate that human MSCs isolated from human bone marrow can differentiate into epithelial-like cells and may thus serve as a cell source for tissue engineering and cell therapy of epithelial tissue. 相似文献
58.
59.
Tobias Ruck Stefanie Bock Steffen Pfeuffer Christina B.Schroeter Derya Cengiz Paul Marciniak Maren Lindner Alexander Herrmann Marie Liebmann Stjepana Kovac Lukas Gola Leoni Rolfes Marc Pawlitzki Nils Opel Tim Hahn Udo Dannlowski Thomas Pap Felix Luessi Julian A.Schreiber Bernhard Wünsch Tanja Kuhlmann Guiscard Seebohm Bjrn Tackenberg Patricia Seja Frank Dring Erhard Wischmeyer Achmet Imam Chasan Johannes Roth Luisa Klotz Gerd Meyer zu Hrste Heinz Wiendl Tobias Marschall Stefan Floess Jochen Huehn Thomas Budde Tobias Bopp Stefan Bittner Sven G.Meuth 《Cell research》2022,32(1):72-88
It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that driv... 相似文献
60.
Ames RS Lee D Foley JJ Jurewicz AJ Tornetta MA Bautsch W Settmacher B Klos A Erhard KF Cousins RD Sulpizio AC Hieble JP McCafferty G Ward KW Adams JL Bondinell WE Underwood DC Osborn RR Badger AM Sarau HM 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(10):6341-6348
The anaphylatoxin C3a is a potent chemotactic peptide and inflammatory mediator released during complement activation which binds to and activates a G-protein-coupled receptor. Molecular cloning of the C3aR has facilitated studies to identify nonpeptide antagonists of the C3aR. A chemical lead that selectively inhibited the C3aR in a high throughput screen was identified and chemically optimized. The resulting antagonist, N(2)-[(2,2-diphenylethoxy)acetyl]-L-arginine (SB 290157), functioned as a competitive antagonist of (125)I-C3a radioligand binding to rat basophilic leukemia (RBL)-2H3 cells expressing the human C3aR (RBL-C3aR), with an IC(50) of 200 nM. SB 290157 was a functional antagonist, blocking C3a-induced C3aR internalization in a concentration-dependent manner and C3a-induced Ca(2+) mobilization in RBL-C3aR cells and human neutrophils with IC(50)s of 27.7 and 28 nM, respectively. SB 290157 was selective for the C3aR in that it did not antagonize the C5aR or six other chemotactic G protein-coupled receptors. Functional antagonism was not solely limited to the human C3aR; SB 290157 also inhibited C3a-induced Ca(2+) mobilization of RBL-2H3 cells expressing the mouse and guinea pig C3aRS: It potently inhibited C3a-mediated ATP release from guinea pig platelets and inhibited C3a-induced potentiation of the contractile response to field stimulation of perfused rat caudal artery. Furthermore, in animal models, SB 290157, inhibited neutrophil recruitment in a guinea pig LPS-induced airway neutrophilia model and decreased paw edema in a rat adjuvant-induced arthritis model. This selective antagonist may be useful to define the physiological and pathophysiological roles of the C3aR. 相似文献