| 1. |
- Moll, Guido, et al.
(author)
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Are Therapeutic Human Mesenchymal Stromal Cells Compatible with Human Blood?
- 2012
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In: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 30:7, s. 1565-1574
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Sjöberg, Veronika, et al.
(author)
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Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease
- 2014
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In: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 5
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Journal article (peer-reviewed)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.
(author)
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Field response of the pine sawfly Neodiprion sertifer to the pheromone (2S, 3S, 7S)‐diprionyl acetate and its stereoisomers
- 1992
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In: Entomologia Experimentalis et Applicata. - : Wiley. - 0013-8703. ; 62:2, s. 169-181
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Journal article (peer-reviewed)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.
(author)
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Yersinia pseudotuberculosis-induced calcium signaling in neutrophils is blocked by the virulence effector YopH
- 1999
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 67:5, s. 2567-2574
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Journal article (peer-reviewed)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.
(author)
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Oxygen-charged HTK-F6H8 emulsion reduces ischemia : reperfusion injury in kidneys from brain-dead pigs
- 2012
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In: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 178:2, s. 959-967
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Journal article (peer-reviewed)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.
(author)
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Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium
- 1993
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In: European Journal of Cell Biology. - Jena, Germany : Urban und Fischer Verlag. - 0171-9335 .- 1618-1298. ; 62:1, s. 19-58
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Journal article (peer-reviewed)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.
(author)
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Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer
- 2021
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Journal article (peer-reviewed)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.
(author)
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Influence of solvents and substrates on the morphology and the performance of low-bandgap polyfluorene: PCBM photovoltaic devices
- 2006
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In: Proceedings of SPIE-The International Society for Optical Engineering. ; 6192, s. 61921X/1-
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Conference paper (peer-reviewed)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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