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Sökning: WFRF:(Magnusson Olle)

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1.
  • Moll, Guido, et al. (författare)
  • Are Therapeutic Human Mesenchymal Stromal Cells Compatible with Human Blood?
  • 2012
  • Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 30:7, s. 1565-1574
  • Tidskriftsartikel (refereegranskat)abstract
    • Multipotent mesenchymal stromal cells (MSCs) are tested in numerous clinical trials. Questions have been raised concerning fate and function of these therapeutic cells after systemic infusion. We therefore asked whether culture-expanded human MSCs elicit an innate immune attack, termed instant blood-mediated inflammatory reaction (IBMIR), which has previously been shown to compromise the survival and function of systemically infused islet cells and hepatocytes. We found that MSCs expressed hemostatic regulators similar to those produced by endothelial cells but displayed higher amounts of prothrombotic tissue/stromal factors on their surface, which triggered the IBMIR after blood exposure, as characterized by formation of blood activation markers. This process was dependent on the cell dose, the choice of MSC donor, and particularly the cell-passage number. Short-term expanded MSCs triggered only weak blood responses in vitro, whereas extended culture and coculture with activated lymphocytes increased their prothrombotic properties. After systemic infusion to patients, we found increased formation of blood activation markers, but no formation of hyperfibrinolysis marker D-dimer or acute-phase reactants with the currently applied dose of 1.0-3.0 x 10(6) cells per kilogram. Culture-expanded MSCs trigger the IBMIR in vitro and in vivo. Induction of IBMIR is dose-dependent and increases after prolonged ex vivo expansion. Currently applied doses of low-passage clinical-grade MSCs elicit only minor systemic effects, but higher cell doses and particularly higher passage cells should be handled with care. This deleterious reaction can compromise the survival, engraftment, and function of these therapeutic cells. 
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3.
  • Sjöberg, Veronika, et al. (författare)
  • Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease
  • 2014
  • Ingår i: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.
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4.
  • Anderbrant, Olle, et al. (författare)
  • Field response of the pine sawfly Neodiprion sertifer to the pheromone (2S, 3S, 7S)‐diprionyl acetate and its stereoisomers
  • 1992
  • Ingår i: Entomologia Experimentalis et Applicata. - : Wiley. - 0013-8703. ; 62:2, s. 169-181
  • Tidskriftsartikel (refereegranskat)abstract
    • All eight optical isomers of 3,7‐dimethyl‐2‐pentadecanyl acetate (diprionyl acetate), of high optical purity (>97.4%), were tested for a behavioural activity on male pine sawflies, Neodiprion sertifer (Geoffr.) (Hymenoptera: Diprionidae), in northern Europe. Males were strongly attracted to (2S, 3S, 7S)‐diprionyl acetate. Addition of more than 0.1% of the (2S, 3R, 7R)‐isomer reduced the catch and above 2% the attraction was completely inhibited. Contrary to what has been reported for North American and Japanese populations, so significant synergistic effect of small amounts of the (2S, 3R, 7R)‐isomer could be demonstrated. The effects of addition of the other six optical isomers alone or in combinations, were also studied, but none was found to be a synergist. The (2S, 3R, 7S)‐isomer had a weak inhibitory effect, and completely inhibited the attraction to the (2S, 3S, 7S)‐isomer when applied in about equal amounts as the attractant. In some cases a reduction in catch was noted when other isomers were tested, but this could be attributed to the very small amounts of the inhibitory (2S, 3R, 7R)‐isomer present in these isomers. 1992 The Netherlands Entomological Society
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5.
  • Andersson, Kerstin, et al. (författare)
  • Yersinia pseudotuberculosis-induced calcium signaling in neutrophils is blocked by the virulence effector YopH
  • 1999
  • Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 67:5, s. 2567-2574
  • Tidskriftsartikel (refereegranskat)abstract
    • Pathogenic species of the genus Yersinia evade the bactericidal functions of phagocytes. This evasion is mediated through their virulence effectors, Yops, which act within target cells. In this study we investigated the effect of Yersinia pseudotuberculosis on Ca 2+ signaling in polymorphonuclear neutrophils. The intracellular free calcium concentration in single adherent human neutrophils was monitored during bacterial infection and, in parallel, the encounter between the bacteria and cells was observed. When a plasmid-cured strain was used for infection, adherence of a single bacterium to the cellular surface induced a β 1 integrin-dependent transient increase in the intracellular concentration of free calcium. This was, however, not seen with Yop-expressing wild-type bacteria, which adhered to the cell surface without generating any Ca 2+ signal. Importantly, the overall Ca 2+ homeostasis was not affected by the wild-type strain; the Ca 2+ signal mediated by the G-protein-coupled formyl-methionyl-leucyl- phenylalanine receptor was still functioning. Hence, the blocking effect was restricted to certain receptors and their signaling pathways. The use of different Yop mutant strains revealed that the protein tyrosine phosphatase YopH was responsible for the inhibition. This virulence determinant has previously been implicated in very rapid Yersinia-mediated effects on target cells as the key effector in the blockage of phagocytic uptake. The present finding, that Y. pseudotuberculosis, via YopH, specifically inhibits a self- induced immediate-early Ca 2+ signal in neutrophils, offers more-detailed information concerning the effectiveness of this virulence effector and implies an effect on Ca 2+-dependent, downstream signals.
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6.
  • Asif, Sana, et al. (författare)
  • Oxygen-charged HTK-F6H8 emulsion reduces ischemia : reperfusion injury in kidneys from brain-dead pigs
  • 2012
  • Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 178:2, s. 959-967
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Prolonged cold ischemia is frequently associated with a greater risk of delayed graft function and enhanced graft failure. We hypothesized that media, combining a high oxygen-dissolving capacity with specific qualities of organ preservation solutions, would be more efficient in reducing immediate ischemia-reperfusion injury from organs stored long term compared with standard preservation media.Methods:Kidneys retrieved from brain-dead pigs were flushed using either cold histidine-tryptophan-ketoglutarate (HTK) or oxygen-precharged emulsion composed of 75% HTK and 25% perfluorohexyloctane. After 18 h of cold ischemia the kidneys were transplanted into allogeneic recipients and assessed for adenosine triphosphate content, morphology, and expression of genes related to hypoxia, environmental stress, inflammation, and apoptosis.Results:Compared with HTK-flushed kidneys, organs preserved using oxygen-precharged HTK-perfluorohexyloctane emulsion had increased elevated adenosine triphosphate content and a significantly lower gene expression of hypoxia inducible factor-1 alpha, vascular endothelial growth factor, interleukin-1 alpha, tumor necrosis factor-alpha, interferon-alpha, JNK-1, p38, cytochrome-c, Bax, caspase-8, and caspase-3 at all time points assessed. In contrast, the mRNA expression of Bcl-2 was significantly increased.Conclusions:The present study has demonstrated that in brain-dead pigs the perfusion of kidneys with oxygen-precharged HTK-perfluorohexyloctane emulsion results in significantly reduced inflammation, hypoxic injury, and apoptosis and cellular integrity and energy content are well maintained. Histologic examination revealed less tubular, vascular, and glomerular changes in the emulsion-perfused tissue compared with the HTK-perfused counterparts. The concept of perfusing organs with oxygen-precharged emulsion based on organ preservation media represents an efficient alternative for improved organ preservation.
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7.
  • Bengtsson, T., et al. (författare)
  • Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium
  • 1993
  • Ingår i: European Journal of Cell Biology. - Jena, Germany : Urban und Fischer Verlag. - 0171-9335 .- 1618-1298. ; 62:1, s. 19-58
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of changes in cytosolic free calcium concentration ([Ca2+]i) in the assembly and disassembly of actin during adhesion and phagocytosis was evaluated. Rhodamine-phalloidin staining combined with quantitative fluorescence and confocal laser scanning microscopy was used to measure local F-actin changes in single adherent human neutrophils phagocytosing yeast particles on different surfaces and under different calcium conditions. Cells were suspended in a) calcium-containing medium (CCM) or b) calcium-free medium (CFM) or c) were first depleted of calcium (i.e., MAPT/AM-loaded in CFM) and then suspended in CFM (MAPT). In parallel, local [Ca2+]i changes were monitored using a fura-2 ratio imaging system. In CCM or CFM, attachment to the substrate and formation of pseudopods around a yeast particle generated, within a few seconds, rises in [Ca2+]i, both around the phagosome and in the cell body. During continued phagocytosis, [Ca2+]i was more elevated around the phagosome compared to the rest of the cell. No [Ca2+]i fluctuations were observed in MAPT cells. Adhesion and phagocytosis led to a several-fold increase in F-actin. The increase was transient in cells in CCM and CFM, but remained high in Ca-depleted neutrophils. A distinct ring of F-actin was formed around a phagosome with a yeast particle. Twenty min after ingestion the amount of this actin decreased more than 50% in CCM and CFM cells but increased by 40 to 100% in MAPT cells. The accumulation of F-actin in MAPT cells was reduced to resting levels by adding Ca2+ and ionomycin after ingestion. This treatment reestablished the periphagosomal [Ca2+]i rises, as observed in CCM cells. In conclusion, the present study shows that the actin polymerization, occurring in human neutrophils during adhesion and phagocytosis, is not influenced by changes in [Ca2+]i, whereas the subsequent depolymerization is. The accumulation of actin filaments around the phagosome in calcium-depleted cells could be involved in the inhibition of phagolysosome fusion seen in the absence of [Ca2+]i changes (Jaconi et al., J. Cell Biol. 110, 1555-1564 (1990)). This suggests that the actin network, controlled by [Ca2+]i, regulates the movement of granules during phagocytosis.
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8.
  • Berger, Karoline, 1991, et al. (författare)
  • Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer
  • 2021
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients. Methods We explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers. Results Co-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317-3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ER alpha positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance. Conclusion Data suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.
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10.
  • Bjoerstroem, Cecilia M., et al. (författare)
  • Influence of solvents and substrates on the morphology and the performance of low-bandgap polyfluorene: PCBM photovoltaic devices
  • 2006
  • Ingår i: Proceedings of SPIE-The International Society for Optical Engineering. ; 6192, s. 61921X/1-
  • Konferensbidrag (refereegranskat)abstract
    • Spin-coated thin films of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (APFO-3) blended with [6,6]-phenyl-C61-butyric acid Me ester (PCBM) are used as the active material in polymer photovoltaic cells. Such blends are known for their tendency to phase sep. during film formation. Tuning the morphol. of the blend in a controlled way is one possible road towards higher efficiency. We studied the effect of adding chlorobenzene to chloroform-based blend solns. before spin-coating on the conversion efficiency of APFO-3:PCBM photodiodes, and related that to the lateral and vertical morphol. of thin films of the blend. The lateral morphol. is imaged by at. force microscopy (AFM) and the vertical compositional profile is obtained by dynamic secondary ion mass spectrometry (SIMS). The profiles reveal compositional variations consisting of multilayers of alternating polymer-rich and PCBM-rich domains in the blend film spin-coated from chloroform. The vertical compositional variations are caused by surface-directed spinodal waves and are frozen in during the rapid evapn. of a highly volatile solvent. With addn. of the low-vapor pressure solvent chlorobenzene, a more homogeneous vertical compn. is found. The conversion efficiency for solar cells of this blend was found to be optimal for chloroform:chlorobenzene mixts. with a vol.-ratio of 80:1. We have also investigated the role of the substrate on the morphol. We found that blend films spin-coated from chloroform solns. on PEDOT:PSS-coated ITO show a similar compositional structure as the films on silicon, and that changing the substrate from silicon to gold only affects the vertical phase sepn. in a region close to the substrate interface. [on SciFinder (R)]
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11.
  • Bjorstrom, Cecilia M., et al. (författare)
  • Influence of solvents and substrates on the morphology and the performance of low-bandgap polyfluorene: PCBM photovoltaic devices - art. no. 61921X
  • 2006
  • Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : International Society for Optical Engineering; 1999. - 0277-786X .- 1996-756X. ; 6192, s. X1921-X1921
  • Tidskriftsartikel (refereegranskat)abstract
    • Spin-coated thin films of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-5,5-(4,7-di-2-thienyl-2,1,3-benzothiadiazole)] (APFO-3) blended with [6,6]-phenyl-C-61-butyric acid methyl ester (PCBM) are used as the active material in polymer photovoltaic cells. Such blends are known for their tendency to phase separate during film formation. Tuning the morphology of the blend in a controlled way is one possible road towards higher efficiency. We studied the effect of adding chlorobenzene to chloroform-based blend solutions before spin-coating on the conversion efficiency of APFO-3:PCBM photodiodes, and related that to the lateral and vertical morphology of thin films of the blend. The lateral morphology is imaged by atomic force microscopy (AFM) and the vertical compositional profile is obtained by dynamic secondary ion mass spectrometry (SIMS). The profiles reveal compositional variations consisting of multilayers of alternating polymer-rich and PCBM-rich domains in the blend film spin-coated from chloroform. The vertical compositional variations are caused by surface-directed spinodal waves and are frozen in during the rapid evaporation of a highly volatile solvent. With addition of the low-vapour pressure solvent chlorobenzene, a more homogeneous vertical composition is found. The conversion efficiency for solar cells of this blend was found to be optimal for chloroform: chlorobenzene mixtures with a volume-ratio of 80:1. We have also investigated the role of the substrate on the morphology. We found that blend films spin-coated from chloroform solutions on PEDOT:PSS-coated ITO show a similar compositional structure as the films on silicon, and that changing the substrate from silicon to gold only affects the vertical phase separation in a region close to the substrate interface.
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12.
  • Björkqvist, Olle, 1993-, et al. (författare)
  • Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection
  • 2021
  • Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 16:4
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.
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14.
  • Björström, Cecilia M., et al. (författare)
  • Influence of solvents and substrates on the morphology and the performance of low-bandgap polyfluorene:PCBM photovoltaic devices
  • 2006
  • Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - Cardiff : SPIE - International Society for Optical Engineering. - 0277-786X .- 1996-756X. ; 6192, s. 61921X-
  • Tidskriftsartikel (refereegranskat)abstract
    • Spin-coated thin films of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (APFO-3) blended with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) are used as the active material in polymer photovoltaic cells. Such blends are known for their tendency to phase separate during film formation. Tuning the morphology of the blend in a controlled way is one possible road towards higher efficiency. We studied the effect of adding chlorobenzene to chloroform-based blend solutions before spin-coating on the conversion efficiency of APFO-3:PCBM photodiodes, and related that to the lateral and vertical morphology of thin films of the blend. The lateral morphology is imaged by atomic force microscopy (AFM) and the vertical compositional profile is obtained by dynamic secondary ion mass spectrometry (SIMS). The profiles reveal compositional variations consisting of multilayers of alternating polymer-rich and PCBM-rich domains in the blend film spin-coated from chloroform. The vertical compositional variations are caused by surface-directed spinodal waves and are frozen in during the rapid evaporation of a highly volatile solvent. With addition of the low-vapour pressure solvent chlorobenzene, a more homogeneous vertical composition is found. The conversion efficiency for solar cells of this blend was found to be optimal for chloroform:chlorobenzene mixtures with a volume-ratio of 80:1. We have also investigated the role of the substrate on the morphology. We found that blend films spin-coated from chloroform solutions on PEDOT:PSS-coated ITO show a similar compositional structure as the films on silicon, and that changing the substrate from silicon to gold only affects the vertical phase separation in a region close to the substrate interface
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15.
  • Cabric, Sanja, et al. (författare)
  • Anchoring of vascular endothelial growth factor to surface-immobilized heparin on pancreatic islets : implications for stimulating islet angiogenesis
  • 2010
  • Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 16:3, s. 961-970
  • Tidskriftsartikel (refereegranskat)abstract
    • In pancreatic islet transplantation, early revascularization is necessary for long-term graft function. We have shown in in vitro and in vivo models that modification with surface-attached heparin protects the islets from acute attack by the innate immune system of the blood following intraportal islet transplantation. In this study, we have investigated the ability of an immobilized conjugate composed of heparin to bind the angiogenic growth factor vascular endothelial growth factor-A (VEGF-A) as a means of attracting endothelial cells (ECs) to induce angiogenesis and revascularization. We analyzed the capacity of VEGF-A to bind to immobilized heparin and how this affected the proliferation and adherence of ECs to both artificial glass surfaces and islets. Quartz crystal microbalance with dissipation monitoring and slot-blot demonstrated the binding of VEGF-A to heparin-coated surfaces upon which ECs showed protein-dependent proliferation. Also, ECs cultured on heparin-coated glass surfaces exhibited effects upon focal contacts. Heparinized islets combined with VEGF-A demonstrated unaffected insulin release. Further, covering islets with heparin also increased the adhesion of ECs to the islet surface. Immobilized heparin on the islet surface may be a useful anchor molecule for achieving complete coverage of islets with angiogenic growth factors, ultimately improving islet revascularization and engraftment in pancreatic islet transplantation.
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16.
  • Cabric, Sanja, 1977- (författare)
  • Pancreatic Islet Transplantation : Modifications of Islet Properties to Improve Graft Survival
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • During the past decade clinical islet transplantation has become a viable strategy for curing type 1 diabetes. The limited supply of organs, together with the requirement for islets from multiple donors to achieve insulin independence, has greatly limited the application of this approach. The islets are infused into the liver via the portal vein, and once exposed to the blood, the grafted tissue has been shown to be damaged by the instant blood-mediated inflammatory reaction (IBMIR), which is characterized by coagulation and complement activation as well as leukocyte infiltration into the islets. Islet revascularization is a subsequent critical step for the long-term function of the transplanted graft, which may partially be impeded by the IBMIR. In this thesis, we have explored novel strategies for circumventing the effects of the IBMIR and facilitating islet revascularization. Systemic inhibitors of the IBMIR are typically associated with an increased risk of bleeding. We therefore evaluated alternative strategies for modulating the islets prior to transplantation. We demonstrated, using an adenoviral vector, that a high level of expression and secretion of the anticoagulant hirudin could be induced in human islets. An alternative approach to limiting the IBMIR was developed in which anticoagulant macromolecular heparin complexes were conjugated to the islet surface. This technique proved effective in limiting the IBMIR in both an in vitro blood loop model and an allogeneic porcine model of islet transplantation. An increased adhesion of endothelial cells to the heparin-coated islet surface was demonstrated, as was the capacity of the heparin conjugate to bind the angiogenic factors VEGF and FGF; these results have important implications for the revascularization process. The outcome of the work in this thesis suggests that modulation of the islet surface is an attractive alternative to systemic therapy as a strategy for preventing the IBMIR. Moreover, the same techniques can be employed to induce revascularization and improve the engraftment of the transplanted islets. Ultimately, improved islet viability and engraftment will make islet transplantation a more effective procedure and increase the number of patients whose diabetes can be cured.
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18.
  • Chen, X., et al. (författare)
  • A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
  • 2018
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
  • Tidskriftsartikel (refereegranskat)abstract
    • Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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19.
  • Cheng, Susan, et al. (författare)
  • Distinct metabolomic signatures are associated with longevity in humans.
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.
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20.
  • Cheng, Susan, et al. (författare)
  • Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans
  • 2012
  • Ingår i: Circulation. - 1524-4539. ; 125:18, s. 132-2222
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. Methods and Results-To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmo Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, -0.04 to -0.22 per 1-SD change in log-glutamine; P<0.001), glutamate (0.05 to 0.14; P<0.001), and the glutamine-toglutamate ratio (-0.05 to -0.20; P<0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P=0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and decreased blood pressure (P=0.05). Conclusions-Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice. (Circulation. 2012;125:2222-2231.)
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21.
  • da Silva, Marisa, et al. (författare)
  • Cohort profile : The Obesity and Disease Development Sweden (ODDS) study, a pooled cohort
  • 2024
  • Ingår i: BMJ Open. - 2044-6055. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The Obesity and Disease Development Sweden (ODDS) study was designed to create a large cohort to study body mass index (BMI), waist circumference (WC) and changes in weight and WC, in relation to morbidity and mortality.PARTICIPANTS: ODDS includes 4 295 859 individuals, 2 165 048 men and 2 130 811 women, in Swedish cohorts and national registers with information on weight assessed once (2 555 098 individuals) or more (1 740 761 individuals), in total constituting 7 733 901 weight assessments at the age of 17-103 years in 1963-2020 (recalled weight as of 1911). Information on WC is available in 152 089 men and 212 658 women, out of whom 108 795 have repeated information on WC (in total 512 273 assessments). Information on morbidity and mortality was retrieved from national registers, with follow-up until the end of 2019-2021, varying between the registers.FINDINGS TO DATE: Among all weight assessments (of which 85% are objectively measured), the median year, age and BMI (IQR) is 1985 (1977-1994) in men and 2001 (1991-2010) in women, age 19 (18-40) years in men and 30 (26-36) years in women and BMI 22.9 (20.9-25.4) kg/m 2 in men and 23.2 (21.2-26.1) kg/m 2 in women. Normal weight (BMI 18.5-24.9 kg/m 2) is present in 67% of assessments in men and 64% in women and obesity (BMI≥30 kg/m 2) in 5% of assessments in men and 10% in women. The median (IQR) follow-up time from the first objectively measured or self-reported current weight assessment until emigration, death or end of follow-up is 31.4 (21.8-40.8) years in men and 19.6 (9.3-29.0) years in women. During follow-up, 283 244 men and 123 457 women died. FUTURE PLANS: The large sample size and long follow-up of the ODDS Study will provide robust results on anthropometric measures in relation to risk of common diseases and causes of deaths, and novel findings in subgroups and rarer outcomes.
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22.
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23.
  • Deppert, Knut, et al. (författare)
  • Aerosol fabrication of nanocrystals of InP
  • 1999
  • Ingår i: Japanese Journal of Applied Physics, Part 1: Regular Papers and Short Notes and Review Papers. - 0021-4922. ; 38:2 B, s. 1056-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanocrystals of indium phosphide, with diameters of around 10nm, have been produced via an aerosol route. The method is based on the formation of monodisperse indium droplets and the subsequent reaction with phosphine at elevated temperature. The size of the final InP nanocrystal is self-limited by the size of the introduced size-selected In droplet. This size can be tuned carefully, thus this method allows a narrow size distribution of the nanocrystals. The kinetics of the reaction of In to produce InP depends on the temperature and the phosphine flow. Extensive high resolution transmission electron microscopy studies lead to a consistent picture of the process. Our approach opens the possibility for efficient production of size-selected semiconductor nanocrystals and it will allow new types of self-assembly and control of quantum dots.
  •  
24.
  • Deppert, Knut, et al. (författare)
  • Size-selected nanocrystals of III-V semiconductor materials by the aerotaxy method
  • 1998
  • Ingår i: Journal of Aerosol Science. - 0021-8502. ; 29:5-6, s. 737-748
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we present a fabrication route to produce size-selected III-V semiconductor nanocrystals via a simple, reliable, and efficient aerosol route. Since this approach includes the reaction of aerosol particles and a self-organized growth of a new compound, all in the aerosol phase, we call this process aerotaxy. Size-selected nanocrystals of different III-V compounds in a diameter range below 20 nm were fabricated using this method. Through the reaction of arsine with gallium droplets or of phosphine with indium droplets, GaAs and InP clusters were formed. Our approach opens the possibility to produce contamination-free and size-selected nanocrystals of compound semiconductor materials with considerable freedom in composition and size.
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25.
  • Diaz, Sandra, et al. (författare)
  • Hyperpolarized (3)He apparent diffusion coefficient MRI of the lung: Reproducibility and volume dependency in healthy volunteers and patients with emphysema.
  • 2008
  • Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1522-2586 .- 1053-1807. ; 27, s. 763-770
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To measure the apparent diffusion coefficient (ADC) of hyperpolarized (HP) (3)He gas using diffusion weighted MRI in healthy volunteers and patients with emphysema and examine the reproducibility and volume dependency. MATERIALS AND METHODS: A total of eight healthy volunteers and 16 patients with emphysema were examined after inhalation of HP (3)He gas mixed with nitrogen (N(2)) during breathhold starting from functional residual capacity (FRC) in supine position. Coronal diffusion-sensitized MR images were acquired. Each subject was imaged on three separate days over a seven-day period and received two different volumes (6% and 15% of total lung capacity [TLC]) of HP (3)He each day. ADC maps and histograms were calculated. The mean and standard deviation (SD) of the ADC at different days and volumes were compared. RESULTS: The reproducibility of the mean ADC and SD over several days was good in both healthy volunteers and patients (SD range of 0.003-0.013 cm(2)/second and 0.001-0.009 cm(2)/second at 6% and 15% of TLC for healthy volunteers, and a SD range of 0.001-0.041 cm(2)/second and 0.001-0.011 cm(2)/second, respectively, for patients). A minor but significant increase in mean ADC with increased inhaled gas volume was observed in both groups. CONCLUSION: Mean ADC and SD of HP (3)He MRI is reproducible and discriminates well between healthy controls and patients with emphysema at the higher gas volume. This method is robust and may be useful to gain new insights into the pathophysiology and course of emphysema. J. Magn. Reson. Imaging 2008. (c) 2008 Wiley-Liss, Inc.
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