Institution
Karolinska Institutet
Education•Stockholm, Sweden•
About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Poison control. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.
Topics: Population, Poison control, Cancer, Cohort study, Breast cancer
Papers published on a yearly basis
Papers
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TL;DR: Functional analysis revealed that the vesicle preparation inhibited anti-CD3-induced IL-2 and IFN-γ production from allogeneic and autologous PBMC incubated with milk vesicles, concluding that human breast milk contains exosomes with the capacity to influence immune responses.
Abstract: Breast milk is a complex liquid with immune-competent cells and soluble proteins that provide immunity to the infant and affect the maturation of the infant's immune system. Exosomes are nanovesicles (30-100 nm) with an endosome-derived limiting membrane secreted by a diverse range of cell types. Because exosomes carry immunorelevant structures, they are suggested to participate in directing the immune response. We hypothesized that human breast milk contain exosomes, which may be important for the development of the infant's immune system. We isolated vesicles from the human colostrum and mature breast milk by ultracentrifugations and/or immuno-isolation on paramagnetic beads. We found that the vesicles displayed a typical exosome-like size and morphology as analyzed by electron microscopy. Furthermore, they floated at a density between 1.10 and 1.18 g/ml in a sucrose gradient, corresponding to the known density of exosomes. In addition, MHC classes I and II, CD63, CD81, and CD86 were detected on the vesicles by flow cytometry. Western blot and mass spectrometry further confirmed the presence of several exosome-associated molecules. Functional analysis revealed that the vesicle preparation inhibited anti-CD3-induced IL-2 and IFN-gamma production from allogeneic and autologous PBMC. In addition, an increased number of Foxp3(+)CD4(+)CD25(+) T regulatory cells were observed in PBMC incubated with milk vesicle preparations. We conclude that human breast milk contains exosomes with the capacity to influence immune responses.
999 citations
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TL;DR: It is shown that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes, which suggest that CypA is a key target for treating APoe4-mediated neurovascular injury and the resulting neuronal Dysfunction and degeneration.
Abstract: Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.
997 citations
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TL;DR: This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.
Abstract: Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in a diverse range of biological processes. For future therapeutic applications and for EV biology research in general, understanding the in vivo fate of EVs is of utmost importance. Here we studied biodistribution of EVs in mice after systemic delivery. EVs were isolated from 3 different mouse cell sources, including dendritic cells (DCs) derived from bone marrow, and labelled with a near-infrared lipophilic dye. Xenotransplantation of EVs was further carried out for cross-species comparison. The reliability of the labelling technique was confirmed by sucrose gradient fractionation, organ perfusion and further supported by immunohistochemical staining using CD63-EGFP probed vesicles. While vesicles accumulated mainly in liver, spleen, gastrointestinal tract and lungs, differences related to EV cell origin were detected. EVs accumulated in the tumour tissue of tumour-bearing mice and, after introduction of the rabies virus glycoprotein-targeting moiety, they were found more readily in acetylcholine-receptor-rich organs. In addition, the route of administration and the dose of injected EVs influenced the biodistribution pattern. This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.
997 citations
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TL;DR: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year, but it cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.
996 citations
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Columbia University1, University of Zulia2, University of Buenos Aires3, Case Western Reserve University4, University of California, San Diego5, Indiana University6, University College Hospital, Ibadan7, Stellenbosch University8, King's College London9, Karolinska Institutet10, Peking Union Medical College Hospital11, Medical College of Wisconsin12
TL;DR: Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions, and use of traditional diets and medicinal plant extracts might aid prevention and treatment.
Abstract: Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa Illiteracy remains a risk factor for dementia The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia Use of traditional diets and medicinal plant extracts might aid prevention and treatment Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions
995 citations
Authors
Showing all 46522 results
Name | H-index | Papers | Citations |
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Meir J. Stampfer | 277 | 1414 | 283776 |
Albert Hofman | 267 | 2530 | 321405 |
Guido Kroemer | 236 | 1404 | 246571 |
Eric B. Rimm | 196 | 988 | 147119 |
Scott M. Grundy | 187 | 841 | 231821 |
Jing Wang | 184 | 4046 | 202769 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
John Hardy | 177 | 1178 | 171694 |
Marc G. Caron | 173 | 674 | 99802 |
Ramachandran S. Vasan | 172 | 1100 | 138108 |
Adrian L. Harris | 170 | 1084 | 120365 |
Douglas F. Easton | 165 | 844 | 113809 |
Zulfiqar A Bhutta | 165 | 1231 | 169329 |
Judah Folkman | 165 | 499 | 148611 |
Ralph A. DeFronzo | 160 | 759 | 132993 |