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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of metamorphic geology 8 (1990), S. 0 
    ISSN: 1525-1314
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: In the Proterozoic Mary Kathleen Fold Belt, northern Australia, infiltration of large volumes of externally derived fluid occurred synchronously with regional amphibolite-facies metamorphism and deformation. This paper develops a model of structurally controlled fluid migration by comparing the distribution of fossil fluid pathways with the inferred stress and strain patterns during the deformation. Intense fluid flow was localized within strong, relatively brittle meta-intrusive bodies, and in discrete, veined, brecciated and altered zones around their margins. In metasediments folded in a ductile manner outside these areas, fluid infiltration was negligible. The direct correlation between structural styles and the magnitude of veining and metasomatism suggests control of permeability enhancement, and hence fluid flow, by deformation. Finite difference modelling of a strong body in a weaker matrix has been used to evaluate the variation of stresses during the deformation, from which it is clear that stress and strain heterogeneities have systematically influenced the development and maintenance of metamorphic fluid pathways. Particular regions in which mean stress may be significantly lower than the average lithostatic pressures include the ‘strain shadow’zones adjacent to the strong bodies, other dilatant zones around the bodies, and the bodies themselves. This geometry is favourable not only for localized brittle deformation under amphilobite facies conditions, but also for focused fluid flow in the low mean stress regions, as evidenced by the abundance of veins. Fluid access through these metamorphic aquifers occurred during tensile failure episodes, with particularly large dilations and decimetre-scale veining in areas of strain incompatibility. It appears likely that fluid circulated many times through the Fold Belt, with flow concentrated in the metamorphic aquifers. A model is developed that explains both the structurally focused fluid flow and the postulated multi-pass recirculation by dilatancy pumping, the ‘pump engines’comprising the low mean stress zones.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1525-1314
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: During the Alice Springs Orogeny, deformation at Ormiston Gorge, central Australia, occurred under lower- to middle-greenschist facies conditions. Dolomites of the Bitter Springs Formation and quartzites. metagreywackes, and metapelites of the Heavitree Quartzite contain abundant early-, syn-, and post-tectonic veins. However, though vein densities locally approach 15%, the distribution of veins and the oxygen isotope geochemistry of wallrocks and veins suggest that fluid movement was on a local scale. The Heavitree Quartzite contains quartz veins that, even along the main thrust plane, have similar δ18O values (13.5–16.9%o) to those of their wallrocks (13.6–16.9%o), with Δ18O(vein-wallrock) values of -0.6 to 0.4%o. In contrast, the Bitter Springs Formation contains predominantly dolomite veins that have δ18O values of 23.4 to 27.7%o. These differences are observed even at the boundary between the Heavitree and Bitter Springs rocks, implying that significant fluid exchange between these rocks has not occurred, or that fluid flow was channelled through areas outside those sampled for this study. By contrast with the Heavitree Quartzite, δ18O values of wallrocks in individual samples of the Bitter Springs Formation are significantly higher (23.3–29.1%o) than those of the veins, with δ18O(vein-wallrock) values up to -4%o (average of -2.1%o). These systematic differences in δ18O values most likely result from oxygen isotope fractionation caused by fluid immiscibility or disequilibrium dissolution. Smaller differences in δ13C values between some dolomite veins and wallrocks [δ13C(vein-wallrock) up to -1.9%o, average of -0.5%o] are also explained by these processes. This study indicates that large volumes of veins may be produced by repeated fracturing and fluid migration within particular rock units, without involving large volumes of externally derived fluids.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of metamorphic geology 12 (1994), S. 0 
    ISSN: 1525-1314
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: A breccia vein sampled from a shear zone in greenschist facies metapelites at Mount Isa, Queensland, Australia, shows a systematic variation in vein geometry that is related to the geometry of folding and faulting within the sample. Calcite vein-fill is coarse grained and equigranular, suggesting precipitation in a fluid-filled space. Partially folded veins suggest that veining occurred during folding and faulting. The breccia vein contains a central zone in which dilation has occurred simultaneously in all directions in the plane of section, implying that this was a zone of high fluid pressure and nearly isostatic differential stress during folding and faulting. From these observations, it can be inferred that the breccia vein was a zone of high permeability and a likely fluid channel during deformation. This hypothesis was tested by stable isotope analysis of veins and host rocks. The calcite veins have δ13C values of -11.1 ± 0.1% and δ18O values of 6-10%o, whereas the host metapelite has δ13C values of -10.62 and -10.11% and δ18O values of 14-15%o. These values are consistent with an igneous-derived, H2O-dominated fluid that exchanged little oxygen with the host rocks, but derived much of its carbon from the wall rock. The isotopic disequilibrium between the veins and the wall rock confirms that the fluid was externally derived, and that the breccia vein acted as a channel for large-volume fluid flow within the shear zone.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 53 (1998), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A great variety of recombinant plant, mite, mold, mammal, and insect allergens have been expressed in heterologous hosts (e.g., Escherichia coli), their cDNA being used as a template. The number of biologically active recombinant allergens available for experimental, diagnostic, and therapeutic purposes is increasing tremendously. Recombinant allergens have proven to be valuable tools to investigate T-cell and B-cell recognition of allergens as well as to study mechanisms of specific IgE regulation. The immunologic equivalence of many relevant recombinant allergens with their natural counterparts has been demonstrated, and the three-dimensional structures of several recombinant allergens have been described recently. As a result of extensive cross-reactivities among the relevant allergens, it appears that the number of epitopes needed for diagnosis and specific immunotherapy is less diverse than originally anticipated and might be soon covered by recombinant molecules. Recombinant allergens have been used for successful in vitro, as well as in vivo, allergy diagnosis, and work is in progress to produce recombinant allergen derivatives with reduced anaphylactic potential to improve current forms of immunotherapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The allergens of the house dust mite (Dermatophagoides pteronyssinus, Der p), one of the most important indoor allergen sources, occur as isoallergens that differ in their amino acid sequence. These variations may influence allergenic activity and thus may have impact on diagnostic tests and specific immunotherapy.Objective We investigated whether single purified recombinant mite allergens contain the IgE epitopes of the natural Der p isoallergens.Methods A panel of purified recombinant (rDer p 2, 5, 7, 8, 10 and 14) and two natural (nDer p 1 and 4) mite allergens were used to establish IgE reactivity profiles of Der p allergic patients and to inhibit IgE reactivity to two-dimensionally separated Der p isoallergens. In addition, we determined the percentage of Der p extract-specific IgE which could be preadsorbed with a mixture of purified mite allergens (nDer p 1, rDer p 2, 5, 7, 8 and 10) from sera of mite-allergic patients (n=18) in a non-denaturing RAST-based inhibition.Results We demonstrate that single recombinant mite allergens inhibit IgE reactivity to the corresponding natural isoallergens. A mixture of purified mite allergens (nDer p 1, rDer p 2, 5, 7, 8 and 10) bound on an average 76% of Der p-specific IgE antibodies.Conclusion The studied recombinant and natural mite allergens contain a large portion of Der p-specific IgE and may be used for diagnostic tests and therapy of Der p allergy.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Mites belong to the most frequent and potent allergen sources. Immunotherapy with mite allergen extracts is frequently performed if allergen avoidance is not possible or successful. However, highly controversial results have been reported for mite-specific immunotherapy.Objective The aim of this study was to develop diagnostic concepts that may contribute to an improved selection of patients for immunotherapy with Der p allergen extracts and that may be used for immunological monitoring of patients undergoing this treatment.Methods The IgE reactivity profiles to Der p extract were determined in a Middle European mite-allergic population by IgE immunoblotting and by using a panel of seven purified natural or recombinant Der p allergens (nDer p 1, nDer p 4, rDer p 2, rDer p 5, rDer p 7, rDer p 8, rDer p 10). Furthermore, we investigated the sensitization and cross-reactivity to house-dust- and storage-mite allergen extracts by CAP FEIA measurements and by IgE competition studies.Results More than 95% of the patients could be diagnosed with a combination of nDer p 1 and rDer p 2. With the methods used, we could discriminate mite-allergic patients who were mainly sensitized to the major Der p allergens (Der p 1, Der p 2) from patients with a broad sensitization profile, including highly cross-reactive allergens (e.g. Der p 10: tropomyosin) as well as reactivity to storage mites.Conclusions Diagnostic tests containing the major mite allergens (i.e. Der p 1, Der p 2) and highly cross-reactive mite allergens (e.g. Der p 10) may improve the diagnostic selection of patients for immunotherapy with Der p extracts. These tests may also be used for the immunological monitoring of patients undergoing immunotherapy.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Almost 100 million allergic patients are sensitized to the major birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE epitopes present in pollens of trees belonging to the Fagales order and plant-derived food.Objective Our aim was to develop an approach for the rational design of B cell epitope-derived, non-allergenic peptide allergy vaccines.Methods According to the three-dimensional (3-D) structure of birch pollen allergen, Bet v 1, six peptides comprising 25–32 preferably solvent-exposed amino acids were synthesized.Results Because of lack of secondary structure, the peptides showed no allergenic activity in allergic patients. In a mouse model of birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of peptide-induced blocking antibodies is demonstrated by inhibition of allergic patients IgE binding to the allergen and by blocking of allergen-induced basophil degranulation.Conclusion Our results indicate the mechanistic importance of blocking antibodies for allergy vaccination and present a B cell epitope-based approach for the rational design of safe peptide allergy vaccines whenever the structure of the disease-eliciting allergen is known.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background We have recently engineered recombinant derivatives of the major birch pollen allergen Bet v 1 (rBet v 1 fragments and trimer) with strongly reduced allergenic activity.Objective The aim of this study was the in vivo characterization of potential allergy vaccines based on Al(OH)3-adsorbed genetically modified rBet v 1 derivatives in mice.Methods BALB/c mice were immunized either with courses of nine injections of increasing doses of Al(OH)3-adsorbed rBet v 1 wild-type, rBet v 1 fragments, rBet v 1 trimer or Al(OH)3 alone in weekly intervals or with three high-dose injections applied in intervals of 3 weeks. Humoral immune responses to rBet v 1 wild-type and homologous plant allergens were measured by ELISA and Western blotting, and the ability of mouse antibodies to inhibit the binding of allergic patients IgE to Bet v 1 was studied by ELISA competition experiments.Results In both schemes, hypoallergenic rBet v 1 derivatives induced low IgE but high IgG1 responses against rBet v 1 wild-type. The IgG1 antibodies induced by genetically modified rBet v 1 derivatives cross-reacted with natural Bet v 1 and its homologues from alder (Aln g 1) as well as hazel (Cor a 1) and strongly inhibited the binding of birch pollen allergic patients' IgE to Bet v 1 wild-type.Conclusion Genetically modified hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their safety and efficacy for the treatment of birch pollen and associated plant allergies can now be evaluated in clinical immunotherapy studies.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Interleukin (IL)-4 and IL-13 have been shown to be potent switch factors for IgE synthesis in human B cells.Objective: In this study we investigated the effects of recombinant human IL-4 and IL-13 on total and allergen specific IgE synthesis by peripheral blood inononuclear colls (PBMC) from pollen allergic patients and healthy control individuals.Methods: Peripheral blood mononuclear cells (PBMC) from allergic patients were investigated for their capacity to produce allergen specific IgE in vitro. Total protein extracts from birch pollen and timothy grass pollen as well as purified recombinant birch pollen allergens, Bet v I, birch profiling (Bet v II) and recombinant timothy grass pollen allergens. Phi p I, Phi p II, and Phi p V were used to measure specific IgE-antibody synthesis in cell culture supernatants by IgE-immunoblot and ELISA. Reults PBMC obtained from allergic patients spontaneously secreted allergen specific IgE in the culture supernatants. Addition of Interleukin 4, Interleukin 13 and anti-CD40 antibody to the cultures alone or in combinations significantly induced total IgE production whereas allergen specific IgE production was not affected.Conclusion: Our results indicate that the peripheral blood of allergic individuals contains long lived allergen specific B cells which have already switched to IgE production and which are not sensitive to IL-4 and IL-13 treatment. These results may have implications on attempts to use cytokines or cytokine antagonists in therapy of Type I allergy.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Considering the high occurrence of profilin as an allergen in many plant species, the assumption was made that profilin might be an allergen in Hevea brasiliensis, a member of the latex producing Euphorbiaceae family. Using IgE-binding inhibition by purified profilins we demonstrated that profilin is an IgE-binding component in the cytosolic fraction of natural latex and, to a lower extent, in the rubber fraction. Thirty-five out of 36 sera containing IgE to ragweed-profilin reacted with profilin from latex, indicating structural homologies between profilins from latex and ragweed. A large percentage (59%) of these sera were found to be positive in CAP latex assay. The preincubation of these sera with purified ragweed profilin greatly inhibited the CAP latex. Because profilin is also present in banana extract, it is likely to be involved in cross-sensitivity to banana and latex. In a group of 19 individuals allergic to latex only two had antiprofilin IgE antibodies. Profilin was barely detectable on glove extract immunoblots, whereas some sera from patients allergic to latex reacted with a 15 kDa allergen which was not profilin. Consequently, IgE antibodies to latex-profilin is a questionable factor for sensitization of occupationally-exposed patients; however, sensitization to profilin should be taken into account when interpreting the results of latex IgE antibody assays.
    Type of Medium: Electronic Resource
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