| 1. |
- Bredberg, Anders, et al.
(författare)
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A role of the macrophage in Sjogen's syndrome?
- 2003
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 32:4, s. 255-255
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Bredberg, Anders, et al.
(författare)
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Sjogren's syndrome and the danger model.
- 2005
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 44:8, s. 965-970
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Forskningsöversikt (refereegranskat)
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| 3. |
- Du, Liping, et al.
(författare)
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Exposure of HEp-2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity.
- 2002
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Ingår i: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 9:2, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- This study of stress-related antinuclear antibody (ANA) reactivity was undertaken with the objective of improving clinical ANA testing. ANA was determined by parallel enzyme-linked immunosorbent assays of crude nuclear protein antigen extracted from HEp-2 cells either grown under optimal conditions (providing nonstress ANA antigen) or exposed to stress (providing stress ANA antigen). The stress stimuli used were gamma radiation (causing DNA damage) and a hypertonic environment (causing apoptosis). Signs of stress-related ANA reactivity were seen among connective tissue disease (CTD) patients (including patients with systemic lupus erythematosus; mixed CTD; calcinosis, Reynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia; scleroderma; and Sjögren's syndrome): 11% showed stress-positive ANA (i.e., a significantly stronger ANA reactivity with the extract from stressed cells), whereas 21% showed a markedly weaker reaction with the stress antigen. In contrast, among ANA screening patient sera, with no diagnosis of CTD, the fraction showing stress-positive ANA was higher (7 to 8%, depending on the type of stress) than among those showing a lower reactivity with stress antigen (1.5 to 2.5%). Only one serum among 89 (1%) tested sera from healthy individuals showed a stress-related ANA reaction. This demonstration of stress-related ANA suggests a means to improve the performance of clinical ANA testing.
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| 4. |
- Henriksson, Gunnel, et al.
(författare)
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Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjögren's syndrome cells.
- 2002
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 32:6, s. 458-465
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCells from primary Sjögren's syndrome (SS) patients have been reported to show alterations in DNA repair and p53 expression. The DNA-dependent protein kinase (DNA-PK) autoantigen may be involved in both of these alterations in relation to cellular DNA damage responses. We conducted this study of cell-cycle kinetics and p53 to find additional evidence for an abnormal stress response role in the pathogenesis of SS. DesignDNA-dependent protein kinase activity, p53 peptide phosphorylation and p53 protein levels were determined in gamma-irradiated long-term T lymphocyte cultures. Cell-cycle progression of peripheral blood mononuclear cells was analysed with flow cytometry. ResultsNo significant differences in the DNA-PK activities or p53 protein levels appeared between the SS patients and the healthy individuals. However, patients with the SS hallmark Ro/SS-A and La/SS-B autoantibodies showed enhancement of both p53 peptide phosphorylation (P = 0·036) and G1 cell-cycle arrest (P = 0·015) in response to gamma radiation. ConclusionsSjögren's syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.
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| 5. |
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| 6. |
- Larsson, Åke, et al.
(författare)
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Immunohistochemistry of the B-cell Component in Lower Lip Salivary Glands of Sjögren's Syndrome and Healthy Subjects
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:1, s. 98-107
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Serial sections of lower lip salivary gland (LSG) biopsies were examined by immunohistochemistry, using a battery of B- and partly T-related antibodies (CD5, CD20, CD21, CD27, CD38, CD45RO, CD79a, Bcl-2 and Bcl-6) in different groups of subjects: healthy controls and clinically verified smoking or nonsmoking cases of primary Sjögren's syndrome (SS). The purpose was to characterize the B-cell pattern of the lymphocytic foci and of the tiny perivascular infiltrates preceding the development of foci. Hyperplastic tonsil was used as stain control. In normal LSG, widely dispersed CD38+ and CD79a+ as well as some CD5+ cells are a normal constituent, with lack of staining with the other antibodies. In SS/LSG, the lymphocytic foci showed staining with all the antibodies, with variable degrees of overlapping or nonoverlapping. In SS/LSG of nonsmokers, CD20+ B cells make up a prominent part of the fully developed periductal lymphocytic foci, not overlapping with CD45RO. Also, CD20+ B cells did not overlap in the infiltrates with colocalized CD27+/CD38+ cells. CD20+ B cells and CD45RO+ T cells also occur as minute infiltrates perivascularly in areas of no foci in SS/LSG as well as in SS smokers lacking the typical foci. Smokers lack foci, but tiny infiltrates express CD20 as well CD45R0. Our findings suggest that CD20+ B cells and CD45RO+ T cells are early immigrants in the LSG of SS of smokers as well as nonsmokers and that another subgroup of CD27+/CD38+ B cells gradually mix with the first two to form the characteristic foci in SS/LSG. The simultaneous demonstration of CD20+ and CD27+ B cells in SS/LSG may constitute a significant diagnostic tool. Further, the findings suggest that the early immigrating lymphocytes may have been primed at a site remote from the glands before arriving via the blood to the gland tissue.
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| 7. |
- Larsson, Å., et al.
(författare)
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Ku protein and DNA strand breaks in lip glands of normal and primary Sjogren's syndrome subjects: Lack of correlation with apoptosis
- 2001
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 54:3, s. 328-334
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to examine tissue expression of Ku protein in lower lip salivary gland (LSG) biopsies from cases of primary Sjogren's syndrome (SS) and from normal subjects. Methods: immunohistochemistry was used with antibodies to Ku70/86 and also Ki67, PCNA and p53. In addition, the Klenow method was applied in order to detect evidence of apoptosis. Sections of hyperplastic tonsil served as additional controls. Results: in normal controls, LSG acinar cells stained negatively whereas LSG excretory duct cell nuclei stained positively with Ku and Klenow and occasionally with PCNA but negatively with Ki67 and p53. In LSG focal sialadenitis of SS cases, some lymphocytic cells showed staining with Ku, Ki67, PCNA, Klenow and p53. In addition to duct cell Ku and Klenow as well as PCNA staining which was not much different from normals, a few ductal epithelial and also mononuclear cells stained with p53. In focal sialadenitis, some acinar cells showed staining with PCNA as well as with Klenow. Conclusions: our findings in LSG biopsies of SS cases added little to an increased understanding about the pathogenetic mechanisms in the development of focal sialadenitis in SS. However. in normal LSG. ductal epithelial but not acinar cells seem to express a constitutively specific Ku protein and Klenow profile, suggestive of DNA strand breaks but not clearly associated with ongoing apoptotic events. It may reflect an enhanced stress response, which may be pathogenetically important in the early events of focal sialadenitis development in primary Sjogren's syndrome.
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| 8. |
- Sallmyr, Annahita, et al.
(författare)
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An inducible Ku86-degrading serine protease in human cells.
- 2002
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002. ; 1593:1, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- The Ku autoantigen has been implicated in a number of cellular functions including growth control, immunoglobulin gene rearrangement and DNA repair. A variant truncated form of Ku86, with an apparent molecular weight of 70 kDa, has been reported to be present in many human cell types. We have previously shown that the amount of variant Ku86 is strongly increased in human peripheral blood mononuclear cells (PBMC) by storage of blood prior to isolation of the PBMC. In this study we report that formation of variant Ku86 in protein extracts is mediated by an inducible trypsin-like serine protease with a higher concentration in the nuclear compartment, as compared with the cytoplasm. However, experiments with SDS-PAGE assay of whole cells yielded no evidence of truncated Ku86, suggesting that the protease is not active in intact cells, but is exerting a marked activity during the protein extraction procedure. Interestingly, the protease level became markedly reduced upon transfer of the cells to growth medium. Protease induction did not correlate with apoptosis, necrotic cell death or with signs of general proteolysis or cytotoxicity. Our findings have methodological implications for the interpretation of experimental Ku86 data, and suggest that this protease may play a role for cellular regulation of Ku function. (C) 2002 Elsevier Science B.V All rights reserved.
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| 9. |
- Sallmyr, Annahita
(författare)
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DNA-dependent protein kinase in human cells
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DNA-dependent protein kinase (DNA-PK) is a holoenzyme consisting of a regulatory subunit, the heterodimeric Ku70/86, and a catalytic subunit known as DNA-dependent protein kinase catalytic subunit (DNA-PKcs). DNA-PK takes part in a number of cellular functions including growth control, immunoglobulin gene rearrangement and DNA repair. The Ku86 subunit of DNA-PK has been reported to exist in human B lymphocytes in a truncated form capable of binding to broken DNA but lacking the ability to activate the kinase function of DNA-PK, causing a dominant-negative inhibition of DNA repair. In the present work we demonstrate that B lymphocytes show apparently full length Ku86 and display DNA-dependent kinase activity. However, a minor fraction of Ku86 in lymphocytes was observed to be truncated. The amount of variant Ku86 is strongly increased in human peripheral blood mononuclear cells (PBMC) by storage of blood prior to the isolation of PBMC. We report that formation of variant Ku86 in protein extracts is mediated by an inducible trypsin-like serine protease with a higher concentration in the nuclear compartment, as compared with the cytoplasm. However, whole cell analysis yielded no evidence of truncated Ku86, suggesting that the protease is not active in intact cells, but is exerting a marked activity during the protein extraction procedure. Interestingly, the protease level became markedly reduced upon transfer of the cells to growth medium. Protease induction did not correlate with apoptosis, necrotic cell death or with signs of general proteolysis or cytotoxicity. Human polymorphonuclear leucocytes (PMN) have been reported to completely lack DNA-PK, and promyelocytic HL-60 cells to express a variant form of Ku resulting in enhanced radiation sensitivity. Here we confirmed the complete lack of DNA-PK in PMN protein extracts, and the expression of the truncated Ku86 variant form in HL-60 extracts. However, by using a protease-resistant whole cell assay, both Ku86 and DNA-PKcs could be demonstrated in PMN, although at a much reduced level, as compared with HL-60. Our findings have methodological implications for the interpretation of experimental Ku86 data, and suggest that this protease may play a role for cellular regulation of Ku function. To examine the stress response, including the role of DNA-PK in patients with autoimmune disease, B-cell lines were exposed to gamma-radiation and then post-incubated to allow for inducible stress functions to develop. An enhanced DNA damage response could be demonstrated, with respect to DNA-PK phosphorylation of a p53 peptide, flow cytometry analysis of cell cycle phases and apoptosis. These data are in agreement with previous results from studies on Sjögren’s syndrome, suggesting an elevated stress response in these patients.
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| 10. |
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