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- Spok, A, et al.
(författare)
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Suggestions for the assessment of the allergenic potential of genetically modified organisms
- 2005
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 137:2, s. 167-180
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of allergic diseases has been increasing continuously and, accordingly, there is a great desire to evaluate the allergenic potential of components in our daily environment (e.g., food). Although there is almost no scientific evidence that genetically modified organisms (GMOs) exhibit increased allergenicity compared with the corresponding wild type significant concerns have been raised regarding this matter. In principle, it is possible that the allergenic potential of GMOs may be increased due to the introduction of potential foreign allergens, to potentially upregulated expression of allergenic components caused by the modification of the wild type organism or to different means of exposure. According to the current practice, the proteins to be introduced into a GMO are evaluated for their physiochemical properties, sequence homology with known allergens and occasionally regarding their allergenic activity. We discuss why these current rules and procedures cannot predict or exclude the allergenicity of a given GMO with certainty. As an alternative we suggest to improve the current evaluation by an experimental comparison of the wild-type organism with the whole GMO regarding their potential to elicit reactions in allergic individuals and to induce de novo sensitizations. We also recommend that the suggested assessment procedures be equally applied to GMOs as well as to natural cultivars in order to establish effective measures for allergy prevention.
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| 2. |
- Gafvelin, G, et al.
(författare)
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Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1
- 2005
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 138:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, recombinant hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of this study was to evaluate the effects of vaccination with aluminium-hydroxide-adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and antibody responses in a subgroup of patients. Methods: Blood was drawn from patients of the Swedish centre (n=27; rBet v 1 fragments: n=10; rBet v 1 trimer: n=8, and placebo-aluminium hydroxide: n=9) before the start and after completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were performed before and 10-11 months after the beginning of the study. Results: Bet v 1-specific IgG levels, consisting of IgG 1, IgG 2 and IgG 4, were significantly increased after treatment with recombinant allergen derivatives. Treatment with rBet v 1 trimer led to a significant (p<0.05) reduction of Bet v 1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In addition, a decreased number of Bet v 1-reactive IL-4 producing (p=0.07) and an increase of IL-12-producing (p=0.06) cells was noted in the trimer-treated patients. In contrast to placebo, active treatment resulted in significantly reduced immediate-type skin reactions to Bet v 1 even 10-11 months after treatment. Conclusion: Vaccination with recombinant hypoallergenic Bet v 1 derivatives induces a Bet v 1-specific IgG response and leads to reduced skin reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses was observed in trimer-treated patients, which may reflect the intrinsic property of this allergen derivative. Copyright (C) 2005 S. Karger AG, Basel.
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| 4. |
- Dullinger, S., et al.
(författare)
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Weak and variable relationships between environmental severity and small-scale co-occurrence in alpine plant communities
- 2007
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 95:6, s. 1284-1295
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Tidskriftsartikel (refereegranskat)abstract
- 1. The stress gradient hypothesis suggests a shift from predominant competition to facilitation along gradients of increasing environmental severity. This shift is proposed to cause parallel changes from prevailing spatial segregation to aggregation among the species within a community. 2. We used 904 1-m(2) plots, each subdivided into 100 10 x 10 cm, or 25 20 x 20 cm cells, respectively, from 67 European mountain summits grouped into 18 regional altitudinal transects, to test this hypothesized correlation between fine-scale spatial patterns and environmental severity. 3. The data were analysed by first calculating standardized differences between observed and simulated random co-occurrence patterns for each plot. These standardized effect sizes were correlated to indicators of environmental severity by means of linear mixed models. In a factorial design, separate analyses were made for four different indicators of environmental severity (the mean temperature of the coldest month, the temperature sum of the growing season, the altitude above tree line, and the percentage cover of vascular plants in the whole plot), four different species groups (all species, graminoids, herbs, and all growth forms considered as pseudospecies) and at the 10 x 10 cm and 20 x 20 cm grain sizes. 4. The hypothesized trends were generally weak and could only be detected by using the mean temperature of the coldest month or the percentage cover of vascular plants as the indicator of environmental severity. The spatial arrangement of the full species set proved more responsive to changes in severity than that of herbs or graminoids. The expected trends were more pronounced at a grain size of 10 x 10 cm than at 20 x 20 cm. 5. Synthesis. In European alpine plant communities the relationships between small-scale co-occurrence patterns of vascular plants and environmental severity are weak and variable. This variation indicates that shifts in net interactions with environmental severity may differ among indicators of severity, growth forms and scales. Recognition of such variation may help to resolve some of the current debate surrounding the stress gradient hypothesis.
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| 5. |
- Frey, Alexander D., et al.
(författare)
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Globin-expression postpones onset of stationary phase specific gene expression in Escherichia coli
- 2007
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 129:3, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- We have analyzed gene expression of Escherichia coli MG1655 expressing native and engineered bacterial globin proteins, in order to identify the molecular mechanisms leading to the improved phenotypical traits relative to control cells under oxygen-limited conditions. Regulated expression of hemoglobin and flavohemoglobin proteins postponed the onset of rpoS expression relative to plasmid bearing control cells. This change in expression pattern coincided with the expression pattern of stationary-phase specific genes including sigma(S)-dependent and sigma(S)-independent genes. Furthermore, several genes known to affect rpoS transcription, rpoS mRNA stability and sigma(S) turnover were regulated in such a manner as to ultimately lower the cellular level of sigma(S) in all globin-expressing strains. In a strain harboring an rpoS-lacZ fusion, lacZ expression correlated with acetate accumulation, a metabolite that is known to activate rpoS transcription, but not with growth. Therefore, we hypothesize that reduced excretion of acetate in globin expressing cells prevents induction of stationary phase specific genes. Additionally, several genes responding to carbon starvation (e.g. csrAB, cstA, sspA) were expressed at lower levels in globin-expressing cells. These findings are in good agreement with previous reports showing a more efficient energy household, i.e. also reduced glucose consumption, in hemoglobin- and flavohemoglobin-expressing cells relative to controls. (c) 2007 Elsevier B.V. All rights reserved.
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| 8. |
- Pauli, Gabrielle, et al.
(författare)
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Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis.
- 2008
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 122:5, s. 951-60
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years. RESULTS: Significant reductions (about 50%) in rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025; birch extract, P = .0063), and skin sensitivities (P < .0001) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons. Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels, which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups. New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract, but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients. No severe systemic adverse events were observed in the rBet v 1-treated group. CONCLUSION: The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.
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| 10. |
- Schubert, H., et al.
(författare)
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Relationship between photosynthesis and non-photochemical quenching of chlorophyll fluorescence in two red algae with different carotenoid compositions
- 2006
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 149:5, s. 1003-1013
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Tidskriftsartikel (refereegranskat)abstract
- Algae are continuously exposed to short-term fluctuations in irradiance. We investigate how two red algae species regulate photosynthetic efficiency to cope with such changes and identify some strategies that differ from higher plants. Two red algae, Gracilaria domingensis and Kappaphycus alvarezii, with antheraxanthin and lutein as major xanthophylls, respectively, reacted to the onset of low light (below E-k) with a substantial decrease of NPQ. This is different from higher plants, but similar to previous observations in, e.g. cyanobacteria where it indicates an increase in the effective absorbance cross-section of Photosystem II (PSII) by state transition. Kinetic studies in continuous light revealed a high susceptibility of PSII to light stress ((1-q(P))/NPQ) in K. alvarezii immediately after the sudden onset of high light, followed by a decrease. This was caused by a slower onset of NPQ in K. alvarezii, followed by acclimation. In G. domingensis, susceptibility of PSII to light stress was stable with time, but absolute values of (1-q(P))/NPQ were higher than in K. alvarezii. These observations suggest that K. alvarezii may be better adapted to high light levels, but is less well prepared for large sudden changes in irradiation. In K. alvarezii, photosynthesis continued to increase with increasing irradiation when NPQ was saturated. As (1-q(P)) and NPQ were still balanced in this situation, most likely, processes other than photosynthetic oxygen release are responsible for the increasing net O-2 production observed.
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