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{userid:"friedrich.metzger", "refid":41,"repocollections":"","attachment":"","_thumb":"","articletype":"article","sectionheading":"","title":"PEGylation of lysine residues reduces the pro-migratory activity of IGF-I","year":"2013","author":"Sivaramakrishnan M, Kashyap AS, Amrein B, Saenger S, Meier S, Staudenmaier C, Upton Z, Metzger F","journal":"Biochim Biophys Acta","volume":"1830","number":"10","pages":"4734-4742","month":"Jun ","doi":"http:\/\/dx.doi.org\/10.1016\/j.bbagen.2013.06.012","pubmed":"23800578","pdflink":"","urllink":"","abstract":"","note":"","tags":""}
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{userid:"friedrich.metzger", "refid":"26","repocollections":"","attachment":"","_thumb":"","articletype":"article","sectionheading":"","title":"Separation of Fast from Slow Anabolism by Site-specific PEGylation of Insulin-like Growth Factor I (IGF-I).\r\n","year":"2011","author":"Metzger F, Sajid W, Saenger S, Staudenmaier C, van der Poel C, Sobottka B, Schuler A, Sawitzky M, Poirier R, Tuerck D, Schick E, Schaubmar A, Hesse F, Amrein K, Loetscher H, Lynch GS, Hoeflich A, De Meyts P, Schoenfeld HJ.","journal":"Journal of Biological Chemistry","volume":"286","number":"22","pages":"19501-19511","month":"Jul","doi":"10.1074\/jbc.M110.172189","pubmed":"21460230","pdflink":"","urllink":"","abstract":"Insulin-like growth factor I (IGF-I) has important anabolic and homeostatic functions in tissues like skeletal muscle, and a decline in circulating levels is linked with catabolic conditions. Whereas IGF-I therapies for musculoskeletal disorders have been postulated, dosing issues and disruptions of the homeostasis have so far precluded clinical application. We have developed a novel IGF-I variant by site-specific addition of polyethylene glycol (PEG) to lysine 68 (PEG-IGF-I). In vitro, this modification decreased the affinity for the IGF-I and insulin receptors, presumably through decreased association rates, and slowed down the association to IGF-I-binding proteins, selectively limiting fast but maintaining sustained anabolic activity. Desirable in vivo effects of PEG-IGF-I included increased half-life and recruitment of IGF-binding proteins, thereby reducing risk of hypoglycemia. PEG-IGF-I was equipotent to IGF-I in ameliorating contraction-induced muscle injury in vivo without affecting muscle metabolism as IGF-I did. The data provide an important step in understanding the differences of IGF-I and insulin receptor contribution to the in vivo activity of IGF-I. In addition, PEG-IGF-I presents an innovative concept for IGF-I therapy in diseases with indicated muscle dysfunction.","note":"","tags":""}
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{userid:"suzanne.dahlberg", "articletype":"article","pages":"526-534","author":"D J DeAngelo, K E Stevenson, S E Dahlberg, L B Silverman, S Couban, J G Supko, P C Amrein, K K Ballen, M D Seftel, A R Turner, B Leber, K Howson-Jan, K Kelly, S Cohen, J H Matthews, L Savoie, M Wadleigh, L A Sirulnik, I Galinsky, D S Neuberg, S E Sallan, R M Stone","year":"2015","title":"Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia.","month":"Mar","journal":"Leukemia","publisher":"","volume":"29","number":"3","note":"","tags":"Adolescent,Adult,Antineoplastic Combined Chemotherapy Protocols,Asparaginase,Cytarabine,Doxorubicin,Drug Administration Schedule,Female,Humans,Karyotyping,Male,Methotrexate,Middle Aged,Precision Medicine,Precursor Cell Lymphoblastic Leukemia-Lymphoma,Prednisone,Remission Induction,Survival Analysis,Treatment Outcome,Vincristine","booktitle":"","editor":"","abstract":"On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18-50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56-78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56-76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph-) was 71% (95% CI 58-81%), and for all 74 Ph- patients the 4-year OS was 70% (95% CI 58-79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.","address":"","school":"","issn":"1476-5551","doi":"10.1038\/leu.2014.229","isi":"","pubmed":"25079173","key":"DeAngelo2015","howpublished":"","urllink":"","refid":18,"weight":18}
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{userid:"pal.klepstad", "articletype":"article","pages":"","author":"Philippe R Bauer, Sylvie Chevret, Hemang Yadav, Sangeeta Mehta, Peter Pickkers, Ramin B Bukan, Jordi Rello, Andry van de Louw, Kada Klouche, Anne-Pascale Meert, Ignacio Martin-Loeches, Brian Marsh, Lorenzo Socias Crespi, Gabriel Moreno-Gonzalez, Nina Buchtele, Karin Amrein, Martin Balik, Massimo Antonelli, Martine Nyunga, Andreas Barratt-Due, Dennis C J J Bergmans, Ang\u00e9lique M E Spoelstra-de Man, Anne Kuitunen, Florent Wallet, Amelie Seguin, Victoria Metaxa, Virginie Lemiale, Gaston Burghi, Alexandre Demoule, Thomas Karvunidis, Antonella Cotoia, P\u00e5l Klepstad, Ann M M\u00f8ller, Djamel Mokart, Elie Azoulay,  ","year":"2019","title":"Diagnosis and outcome of acute\u00a0respiratory failure in immunocompromised patients after\u00a0bronchoscopy.","month":"07","journal":"The European respiratory journal","publisher":"","volume":"54","number":"1","note":"","tags":"Aged,Bronchoscopy,Female,Hematologic Neoplasms,Hospital Mortality,Humans,Immunocompromised Host,Intensive Care Units,Logistic Models,Male,Middle Aged,Noninvasive Ventilation,Prospective Studies,Respiratory Insufficiency","booktitle":"","editor":"","abstract":"We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain.","address":"","school":"","issn":"1399-3003","doi":"10.1183\/13993003.02442-2018","isi":"","pubmed":"31109985","key":"Bauer2019","howpublished":"","urllink":"","refid":269,"weight":269}
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