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| 1 | Large aggregates are the major soluble AI3 species in AD brain fractionated with density gradient ul- tracentrifugatian显示文摘 | Sehlin D Englund H Simu B | 2012 | PLoS One2012，7，32： | 1 |
| 2 | Internet-delivered attention bias modification training in individuals with social anxiety disorder-A double blind randomized controlled trial显示文摘 | Carlbring P Apelstrand M Sehlin H | 2012 | BMC Psychiatry2012，12，1： | 1 |
| 3 | Effects of D-glucose on chemokinesis and resting production of reactive oxygen species in neutrophil granulocytes of lean or obese-hyperglycemic mouse显示文摘 | OLDENBORG P A SEHLIN J | | 0，，05： | 1 |
| 4 | Bile acids and lipoproteinmetabolism:effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression显示文摘 | Nilsson LM Abrahamsson A Sehlin S | 2007 | Biochem Biophys Res Commun2007，357，8： | 1 |
| 5 | Potassium and chloride fluxes are involved in volume regulation in mouse pancreatic islet cells显示文摘 | Norlund L Sehlin J | 1986 | Acta Physiol Scand1986，128，4： | 1 |
| 6 | Reactive changes in the smooth muscle tissue of the rat small intestine during experimental intestinal ob-struction显示文摘 | Zashikhin AL Sehlin J Barmina AO | 2010 | Morfologiia2010，137，2： | 1 |
| 7 | Antibody-based PETimaging of amyloid beta in mouse models of Alzheimer’s disease显示文摘 | SEHLIN D FANG XT CATO L | 2016 | Nat Commun2016，7，10： | 1 |
| 8 | The susceptibility to nephrotoxicity of streptozotocin-induced diabetic rats subchronically exposed to cadmium chloride in drinking water显示文摘 | Jin T Nordberg G Sehlin J | 1999 | Toxicology1999，142，1： | 1 |
| 9 | SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer's disease显示文摘Background:Alzheimer's disease(AD)immunotherapy with antibodies targeting amyloid-B(AB)has been extensively explored in clinical trials.The aim of this study was to study the long-term brain distribution of two radiolabeled monoclonal Aβ antibody variants-RmAb158,the recombinant murine version of BAN2401,which has recently demonstrated amyloid removal and reduced cognitive decline in AD patients,and the bispecific RmAb158-scFv8D3,which has been engineered for enhanced brain uptake via transferrin receptor-mediated transcytosis.Methods:A single intravenous injection of iodine-125(251)-labeled RmAb158-scFv8D3 or RmAb158 was administered to AD transgenic mice(tg-ArcSwe).In vivo single photon emission computed tomography was used to investigate brain retention and intrabrain distribution of the antibodies over a period of 4 weeks.Activity in blood and brain tissue was measured ex vivo and autoradiography was performed in combination with Aβand CD31 immunostaining to investigate the intrabrain distribution of the antibodies and their interactions with AB.Results:Despite faster blood clearance,[125]RmAb158-scFv8D3 displayed higher brain exposure than[25]RmAb158 throughout the study.The brain distribution of[l25]RmAb158-scFv8D3 was more uniform and coincided with parenchymal Aβ pathology,while[2 I]RmAb158 displayed a more scattered distribution pattern and accumulated in central parts of the brain at later times.Ex vivo autoradiography indicated greater vascular escape and parenchymal Aβ interactions for[25]RmAb158-scFv8D3,whereas[25]RmAb158 displayed retention and Aβ interactions in lateral ventricles.Conclusions:The high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging.Moreover,it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy. | Tobias Gustavsson Stina Syvänen Paul O'Callaghan Dag Sehlin | 2020 | Translational Neurodegeneration2020，9，3： | 1 |
| 10 | The susceptibility to nephrotoxicity of streptozotocin-induced diabetic rats subchronically exposed to cadmium chloride in drinking water显示文摘 | Taiyi Jin Gunnar Nordberg Janove Sehlin Helena Wallin Susanne Sandberg | 1999 | Toxicology1999，，1： | 1 |
| 11 | Heavy-chain complementarity-determining regions determine conforma- tion selectivity of anti-abeta antibodies 显示文摘 | SEHLIN D HEDLUND M LORD A | 2011 | Neurodegener Dis2011，8，3： | 1 |
| 12 | The susceptibility to nephrotoxicity of streptozotocin-induced diabetic rats subchronically exposed to cadmium chloride in drinking water显示文摘 | Jin T Nordberg G Sehlin | 1999 | Toxicology1999，142，1： | 1 |
| 13 | Structure and electrical properties of La1-xSrxCo1-yFeyO3 显示文摘 | Tai L W Nasrallah M M Anderson H U Sparlin D M Sehlin S R | 1995 | Solid State Ionics1995，76，34： | 1 |
| 14 | Heavy-chain complementarity-determining regions determine conformation selectivity of anti-αβ antibodies显示文摘 | Sehlin D Hedlund M Lord A | 2011 | Neurodegener Dis2011，8，3： | 1 |
| 15 | Toxicity of arsenic during high temperature bioleaching of gold-bearing arsenical pyrite 显示文摘 | Hallberg K B Sehlin H M Lindstrom E B | 1996 | Appl Microbiol Biotechnol1996，45，12： | 1 |
| 16 | Heavy-chain complementarity-determining regions determine conformation selectivity of anti-otl3 antibodies显示文摘 | Sehlin D Hedlund M Lord A | 2011 | Neurodegener Dis2011，8，3： | 1 |
| 17 | Different effects of glucose on extracellular and intracellular respiratory burst response in normal human neutrophils activated with the soluble agonist fMet - Leu - Phe 显示文摘 | Oldenborg PA Sundqvist IM Sehlin J | 2000 | Diabet Med2000，17，7： | 1 |
| 18 | Physiological responses to positive expiratory pressure breathing: a comparison of the PEP bottle and the PEP mask显示文摘 | Maria Sehlin RPT MSc FredrikO hberg GO ran Johansson MSc | 2007 | Respiratory Care2007，52，8： | 1 |
| 19 | Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta显示文摘Background:Amyloid-β(Aβ)immunotherapy is a promising therapeutic strategy in the fght against Alzheimer’s disease(AD).A number of monoclonal antibodies have entered clinical trials for AD.Some of them have failed due to the lack of efcacy or side-efects,two antibodies are currently in phase 3,and one has been approved by FDA.The soluble intermediate aggregated species of Aβ,termed oligomers and protofbrils,are believed to be key pathogenic forms,responsible for synaptic and neuronal degeneration in AD.Therefore,antibodies that can strongly and selectively bind to these soluble intermediate aggregates are of great diagnostic and therapeutic interest.Methods:We designed and recombinantly produced a hexavalent antibody based on mAb158,an Aβprotofbrilselective antibody.The humanized version of mAb158,lecanemab(BAN2401),is currently in phase 3 clinical trials for the treatment of AD.The new designs involved recombinantly fusing single-chain fragment variables to the N-terminal ends of mAb158 antibody.Real-time interaction analysis with LigandTracer and surface plasmon resonance were used to evaluate the kinetic binding properties of the generated antibodies to Aβprotofbrils.Diferent ELISA setups were applied to demonstrate the binding strength of the hexavalent antibody to Aβaggregates of diferent sizes.Finally,the ability of the antibodies to protect cells from Aβ-induced efects was evaluated by MTT assay.Results:Using real-time interaction analysis with LigandTracer,the hexavalent design promoted a 40-times enhanced binding with avidity to protofbrils,and most of the added binding strength was attributed to the reduced rate of dissociation.Furthermore,ELISA experiments demonstrated that the hexavalent design also had strong binding to small oligomers,while retaining weak and intermediate binding to monomers and insoluble fbrils.The hexavalent antibody also reduced cell death induced by a mixture of soluble Aβaggregates.Conclusion:We provide a new antibody design with increased valency to promote binding avidity to an enhanced range of sizes of Aβaggregates.This approach should be general and work for any aggregated protein or repetitive target. | Fadi Rofo Jos Buijs Ronny Falk Ken Honek Lars Lannfelt Anna M.Lilja Nicole G.Metzendorf Tobias Gustavsson Dag Sehlin Linda Söderberg Greta Hultqvist | 2021 | Translational Neurodegeneration2021，10，3： | 0 |
| 20 | ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific,brain-penetrating fusion protein显示文摘Background:Hijacking the transferrin receptor(TfR)is an effective strategy to transport amyloid-beta(Aβ)immuno-positron emission tomography(immunoPET)ligands across the blood-brain barrier(BBB).Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβpathology in mouse models of Alzheimer’s disease(AD).This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands.Methods:Two affinity variants of the rat TfR antibody,OX26,were chemically conjugated to a F(ab′)2 fragment of the anti-Aβantibody,bapineuzumab(Bapi),to generate two bispecific fusion proteins:OX265-F(ab′)2-Bapi and OX2676-F(ab′)2-Bapi.Pharmacokinetic analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type(WT)rats.[124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET imaging.Ex vivo distribution of injected[124I]I-OX265-F(ab′)2-Bapi and Aβpathology were assessed.Results:More[125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than[124I]I-OX2676-F(ab′)2-Bapi.[124I]I-OX265-F(ab′)2-Bapi PET visualized Aβpathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβpathology.The PET signals significantly correlated with Aβlevels in AD animals.Conclusion:Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB,such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently.Furthermore,bispecific immunoPET imaging of brain Aβpathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats,suggesting that this immunoPET strategy has the potential to be translated to higher species. | Gillian Bonvicini Stina Syvänen Ken G.Andersson Merja Haaparanta-Solin Francisco López-Picón Dag Sehlin | 2022 | Translational Neurodegeneration2022，11，1： | 0 |
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