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- Gotlind, Yu-Yuan C., et al.
(författare)
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CD4(+)FoxP3(+) Regulatory T Cells from G alpha i2(-/-) Mice Are Functionally Active In Vitro, but Do Not Prevent Colitis
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9, s. e25073-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mice deficient in the inhibitory G protein subunit G alpha i2 spontaneously develop a T helper 1 dominated colitis. We examined whether a defect in CD4(+) FoxP3(+) regulatory T cells (Treg) underpins the pathogenesis of colitis in the G alpha i2(-/-) (G alpha i2-deficient) colitis model. Methodology/Principal Findings: Using flow cytometry, we found that thymus and colonic lamina propria, but not spleen and mesenteric lymph nodes, of colitic G alpha i2(-/-) mice contained increased frequencies of Treg, whereas FoxP3 expression intensity was similar in G alpha i2(-/-) compared to G alpha i2(-/-) or G alpha i2(+/+) wild type (WT) mice. The frequency of CD4(+)FoxP3(+) T cells expressing CD103 was significantly increased in G alpha i2(-/-) compared to WT mice. Treg in colons from WT mice clustered in the T cell areas of colonic lymphoid patches (CLP), with relatively few Treg in the lamina propria, as demonstrated by immunohistochemistry. In G alpha i2(-/-) mice, CLP were not observed but lamina propria Treg were increased in number and frequency within the CD4(+) infiltrate, compared to WT mice. Using an in vitro co-culture system and flow cytometric analysis of cell division we could demonstrate that the in vitro suppressive function of WT and G alpha i2(-/-) CD4(+)FoxP3(+) regulatory T cells (WT-Treg and KO-Treg) was indistinguishable, but that T effector cells (CD4(+)25(-) T cells) from G alpha i2(-/-) mice were less readily suppressed than WT effectors (WT-Teff) by Treg from either source. However, neither WT nor G alpha i2(-/-) Treg was able to suppress colitis induced by adoptive transfer of G alpha i2(-/-) effector T cells (KO-Teff) to RAG2(-/-) recipients. The enhanced inflammatory activity of G alpha i2(-/-) effectors was accompanied by increased expression of an effector/memory T cell phenotype and increased cytokine secretion, especially IL-4, IL-6 and IFN-gamma. Conclusions: There is an increased frequency of G alpha i2(-/-) Treg in the colon, and they demonstrate no endogenous functional defect. However, G alpha i2(-/-) T effector cells are dramatically less susceptible to suppression in vitro, and in vivo, despite increased effective numbers of Treg, they cannot prevent disease.
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- Göranzon, C., et al.
(författare)
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Immunohistochemical characterization of lymphocytes in microscopic colitis
- 2013
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Ingår i: Journal of Crohn's and Colitis. - : Elsevier. - 1197-4982 .- 1873-9946. ; 7:10, s. e434-e442
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Microscopic colitis (MC), encompassing the subgroups collagenous colitis (CC) and lymphocytic colitis (LC), is characterized by macroscopically normal or near-normal colonic mucosa, and an increased number of intraepithelial lymphocytes (IELs) and mononuclear cell infiltration in the underlying lamina propria (LP), in addition to an increased collagen layer in CC. This study aimed to characterize the inflammatory cells involved in mucosal inflammation, using immunohistochemistry.Methods Paraffin-embedded biopsies from 23 untreated patients with MC (CC = 13, LC = 10) and 17 controls were stained with antibodies against CD3, CD4, CD8, CD20, CD30, Foxp3, CD45RO and Ki67. Computerized image analysis was used to calculate areas of stained lymphocytes in the surface and crypt epithelia as well as in the LP.Results In CC and LC, an increase of predominantly CD8+ lymphocytes was seen in both the epithelium and the lamina propria, whereas a decreased amount of CD4+ lymphocytes was found in the lamina propria. CD45RO+ and Foxp3+ cells were more abundant in all areas in both patient groups compared to controls, as were CD20+ areas, although more scarce. Ki67+ areas were only more abundant in the epithelium, whereas CD30+ areas were more abundant in the lamina propria of both patient groups compared to controls.Conclusions This study confirms an increased amount of CD8+ lymphocytes in the epithelium. Lymphocytic proliferation and activation markers were more abundant, whereas a decreased amount of CD4+ lymphocytes was seen in the LP. Further studies are needed to reveal the underlying mechanism(s).
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- Hannan, T. J., et al.
(författare)
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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
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- Hultgren, T., et al.
(författare)
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Structural characteristics of the subscapularis muscle in children with medial rotation contracture of the shoulder after obstetric brachial plexus injury
- 2010
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Ingår i: Journal of Hand Surgery (European Volume). - : SAGE Publications. - 1532-2211 .- 1753-1934 .- 2043-6289. ; 35:1, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to obtain a better understanding of the cause of the medial rotation contracture of the shoulder after obstetric brachial plexus lesions by studying the morphology of the shortened subscapularis muscle. Muscle biopsy specimens were harvested from 13 children with obstetric brachial plexus palsy who underwent corrective surgery for the rotation contracture. The majority of the subscapularis muscle biopsy samples had an essentially normal morphology and showed a predominance of type I myosin heavy chain isoform, while one biopsy showed signs of marked fibrosis and a predominance of type II myosin heavy chain isoform. The findings support the assumption that shortening of the subscapularis is caused primarily by the nerve injury, which weakens the antagonistic lateral rotators, but that direct injury to the muscle might be a contributory factor.
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- Leopold, Tobias, et al.
(författare)
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Feasibility of photodetachment isobar suppression of WF5- with respect to HfF5
- 2014
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Ingår i: International Journal of Mass Spectrometry. - : Elsevier BV. - 1387-3806 .- 1873-2798. ; 359, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of using laser photodetachment as a means for isobar suppression in accelerator mass spectrometry has been investigated for the special case of HfF5-/WF5-. A method for absolute photodetachrnent cross section measurements was applied and the cross sections of tungsten pentafluoride and hafnium pentafluoride negative ions were measured. The measurements indicate that the photodetachment cross section for WF5- is at least 100 times larger than for HfF5- at the wavelength of the fourth harmonic of the Nd:YAG laser at 266 nm. The absolute cross section for WF5- at this photon energy was found to be (2.8 +/- 0.3) x 10(-18) cm(2), while an upper limit of 2 x 10(-2) cm(2) was obtained for the HfF5- cross section. The measured cross sections indicate that an optical filtering scheme for isobar suppression in accelerator mass spectrometry for the case of Hf-182 should be feasible. (C) 2013 Elsevier B.V. All rights reserved.
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- Lindahl, Anton, 1982, et al.
(författare)
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Experimental studies of partial photodetachment cross sections in K- below the K(7 2P) threshold
- 2012
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Ingår i: Physical Review A. - : American Physical Society. - 1050-2947. ; 85:3
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Tidskriftsartikel (refereegranskat)abstract
- A collinear beams apparatus has been used to determine photodetachment cross sections for K− in the photon energy range 4.250–4.360 eV. State-selective detection, utilizing a resonance ionization scheme, was applied to measure partial cross sections for those channels which leave the residual K atoms in the excited 7 2S, 5 2F, and 5 2G states. The energy region studied encompassed the openings of the aforementioned channels, as well as the channel that leaves the K atom in the 7 2P state. Two previously unobserved resonances were seen in all three partial cross sections between the K(5 2G) and K(7 2P) thresholds. It is shown that a more reliable determination of resonance parameters can be made if the same resonances are observed in several channels. In the region below the K(5 2F) threshold, three previously observed resonances were investigated [Kiyan et al. Phys. Rev. Lett. 84 5979 (2000)]. A greatly increased modulation of the signal was obtained by detecting in the K(7 2S) channel instead of the K(5 2S) channel used in the previous study. Furthermore, the shapes of the cross sections in the threshold regions are discussed. A detailed description of the apparatus and the experimental procedure employed is presented in the paper.
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- Lindahl, Anton, 1982, et al.
(författare)
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Observation of thresholds and overlapping resonances below the 10(2)P(1/2) and P-2(3/2) thresholds in the photodetachment of Cs
- 2013
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Ingår i: Physical Review A. - 1050-2947. ; 88:5
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Tidskriftsartikel (refereegranskat)abstract
- A collinear beam apparatus has been used to study photodetachment of Cs-. Partial cross sections were measured using state-selective detection based on a resonance ionization scheme. Several resonances were observed in the Cs(10(2)S), Cs(6 2F), Cs(6 2G), and Cs(6 2H) final-state channels below the Cs(10(2)P3/2) channel opening. A model was developed to account for the interference between overlapping resonances. This model is essentially a generalization of the Fano [U. Fano, Phys. Rev. 124, 1866 (1961)] and Shore [B. W. Shore, Phys. Rev. 171, 43 (1968)] parametrizations for single resonances. Resonance parameters were extracted by fitting the model to the data sets. The openings of the Cs(10(2)S) and Cs(6 2F) channels, where the polarizabilities of the atomic states are large and positive, showed rapid onsets. In the case of the Cs(6(2)G) and Cs(6(2)H) channels, on the other hand, the photodetachment cross sections increased slowly with energy. For the Cs(6(2)H) channel this is the expected behavior, since it is the result of a large and negative polarizability of the 6(2)H state. In addition, the excitation of the Cs(6(2)H) state with respect to the Cs ground state was found to be 28 356.3(2) cm(-1), in agreement with a previous experiment.
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