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| 10. |
- Asarnoj, A., et al.
(author)
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IgE to peanut allergen components : relation to peanut symptoms and pollen sensitization in 8-year-olds
- 2010
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:9, s. 1189-1195
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Journal article (peer-reviewed)abstract
- Background: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. Methods: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. Results: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97% vs 70%, P = 0.016), particularly respiratory symptoms (50% vs 9%, P = 0.002). Conclusions: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.
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| 11. |
- Brommage, Robert, et al.
(author)
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NOTUM inhibition increases endocortical bone formation and bone strength
- 2019
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In: Bone Research. - : Springer Science and Business Media LLC. - 2095-4700 .- 2095-6231. ; 7:2
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Journal article (peer-reviewed)abstract
- The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum(-/-) mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.
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| 12. |
- Chagin, A S, et al.
(author)
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Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice.
- 2004
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In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 19:1, s. 72-7
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Journal article (peer-reviewed)abstract
- To determine the long-term role of ER beta in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. Our results show that ER beta inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. INTRODUCTION: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER) alpha-/- and the ER alpha-/- beta-/-, but not the ER beta-/-, mouse models have clearly increased serum levels of estradiol. MATERIALS AND METHODS: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. RESULTS: Young adult (4-month-old) ER beta-/- mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER beta inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER alpha-/- mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER alpha-/- mice, must be mediated through ER beta because old ER alpah-/- beta-/- mice displayed unchanged, unfused growth plates. CONCLUSIONS: Our results confirm that ER beta is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER beta, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice.
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| 13. |
- Ebisawa, M., et al.
(author)
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Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children
- 2012
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 23:6, s. 573-581
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Journal article (peer-reviewed)abstract
- To cite this article: Ebisawa M, Moverare R, Sato S, Maruyama N, Borres MP, Komata T. Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children. Pediatr Allergy Immunol 2012: 23: 573581. Abstract Background: Food challenges are time-consuming, expensive, and not always possible to perform. Therefore, new tools to diagnose food allergy are desired. The aim was to evaluate IgE antibodies to peanut allergens in the diagnosis of peanut allergy in Japanese children using ImmunoCAP (R) and IgE immunoblotting. Methods: The study included 213-yr-old consecutive patients (n = 57) referred to our specialist clinic for investigation of current peanut allergy using food challenge. All children had a previous doctors diagnosis of peanut allergy and were on elimination diet. Serum samples were analyzed for IgE reactivity to peanut, recombinant (r) Ara h 1, 2, 3, 5, 8, and 9. IgE immunoblotting (n = 23) was performed using extracts from raw and roasted peanut. Results: Twenty-six of the children failed (allergic group), and 31 passed the peanut challenge (tolerant group). The rAra h 2 ImmunoCAP test was superior in its ability to differentiate between children in the allergic and tolerant groups with a sensitivity and specificity of 88% and 84%, respectively (cutoff, 0.35 kUA/l). The combination of rAra h 1, 2, and 3 resulted in a higher specificity (94%) when IgE to all of them was the criteria for positivity. ImmunoCAP generally showed a good agreement with immunoblotting using both raw and roasted peanut for IgE reactivity to Ara h 1, 2, and 3. Conclusions: Measurement of IgE antibodies to rAra h 1, 2, and 3 is useful in the diagnosis of peanut allergy and in the investigation of reactions to raw and roasted peanut.
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- Islander, Ulrika, 1975, et al.
(author)
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Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent
- 2005
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In: Clin Exp Immunol. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 139:2, s. 210-5
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Journal article (peer-reviewed)abstract
- Estrogen has extensive effects on the immune system. The aim of the present experiments was to compare the effects of 17beta-estradiol (E2) and 4-estren-3alpha,17beta-diol (estren) on T lymphopoiesis and T cell-dependent inflammation. In order to investigate the role of estrogen receptors (ER) in the effects of E2 and estren on the immune system, ER knock-out mice lacking both ERalpha and ERbeta (DERKO) were used. T lymphopoiesis and T cell-dependent inflammation were studied by investigating thymus cellularity, the delayed-type hypersensitivity (DTH) reaction, CD4(+) T cells in spleen and serum levels of interleukin (IL)-6. As expected, the presence of ERs was mandatory for all the effects of E2. In contrast, treatment with estren reduced thymus cellularity in ER knock-out mice, indicating an effect through ER-independent pathways. Interestingly, estren suppressed only DTH, the frequency of CD4(+) T cells in spleen and serum levels of IL-6 in wild-type (WT) mice, but not in mice lacking ERs. Thus, our study is the first to show that estren inhibits T lymphopoiesis via ER-independent pathways, whereas its suppressive effects on inflammation are ER-dependent.
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| 17. |
- Jiang, S., et al.
(author)
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Micromechanical behavior of multilayered Ti/Nb composites processed by accumulative roll bonding : An in-situ synchrotron X-ray diffraction investigation
- 2021
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In: Acta Materialia. - Oxford, United Kingdom : Elsevier. - 1359-6454 .- 1873-2453. ; 205
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Journal article (peer-reviewed)abstract
- Heterophase interfaces play a crucial role in deformation microstructures and thus govern mechanical properties of multilayered composites. Here, we fabricated Ti/Nb multilayers by accumulative roll bonding (ARB) where shear bands became predominant with increasing rolling cycles. To explore correlation between micromechanical behavior and mechanical properties of the composites with various lamellar morphologies, in-situ high-energy X-ray diffraction tensile tests were performed. The results quantitatively reveal that the rapid strengthening of the composites with increasing ARB cycles mainly originates from the Nb layers strengthened by dislocations, grain boundaries and heterophase interfaces, and the {211} grains mostly contribute to the global strain hardening. The softer Ti grains also extend global strain hardening to a wide range and postpone necking. Furthermore, complete stress state analysis show that in the presence of extensive shear bands, significant load partitioning between the neighboring metals leads to triaxial stresses in each constituent and dislocations tend to slip along the shear direction. This promotes dislocation multiplication and motion, which is conducive to overall strength enhancement while maintaining a satisfactory ductility. These findings elucidate the effect of strong constraints of the interfaces on mechanical properties, which provides a fundamental understanding of load partitioning and strengthening mechanisms of the multilayers processed by multiple ARB cycles.
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| 18. |
- Johansson, S., et al.
(author)
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Fracture mechanisms during intergranular hold time fatigue crack growth in Inconel 718 superalloy
- 2013
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In: 13th International Conference on Fracture 2013, ICF 2013; Beijing; China; 16 June 2013 through 21 June 2013. ; 3, s. 1833-1841
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Conference paper (peer-reviewed)abstract
- Ni-base superalloy IN718 is known to display time-dependent intergranular crack growth under dwell time mechanical loading at high temperature under atmospheric conditions. Oxygen has been pointed out as a cause of the intergranular damage causing embrittled crack growth during both cyclic and hold time loading. Investigation of the mechanisms responsible for the embrittlement should not only focus on the effect of environment but also on the combined action of fatigue, creep, temperature and time. In this work material from experiments with fatigue crack growth in combination with hold times of different length at different temperatures has been investigated. Fractographic studies and metallographic cross sections of fatigued specimens has been subjected to careful analysis using ECCI-imaging in order to shed light on the fracture mechanisms. The results show that the damage is caused by the influence of a combination of environment and severe local damage manifested as a transformation of the microstructure into sub cells, micro twins and recrystallised areas close to the crack tip. The damage mechanism is thus influenced by a combination of oxidation and severe local plastic deformation.
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| 19. |
- Kuitunen, M., et al.
(author)
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High IgE levels to -lactalbumin, -lactoglobulin and casein predict less successful cow's milk oral immunotherapy
- 2015
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 70:8, s. 955-962
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Journal article (peer-reviewed)abstract
- BackgroundA new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG(4) antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome. MethodsSeventy-six children (5-17years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200ml CM (high dose=HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG(4) to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT. ResultsFifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens -lactalbumin (P=0.048), -lactoglobulin (P=0.006) and casein (P=0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG(4) levels to -lactalbumin (P=0.034), -lactoglobulin (P=0.010), casein (P=0.047) and lactoferrin (P=0.030) during treatment than those who failed. ConclusionsComponent-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to -lactalbumin, -lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG(4) concentration to milk components during treatment indicated effective desensitization.
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| 21. |
- Maruyama, N., et al.
(author)
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Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of sesame allergy
- 2016
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:1, s. 163-171
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Journal article (peer-reviewed)abstract
- Background The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. Objective The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. Methods Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Results Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA/L) were 86.1% and 85.7%, respectively. Conclusion and Clinical Relevance Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.
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