| 1. |
- Bocchi, Leonardo, et al.
(författare)
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A new evolutionary algorithm for image segmentation
- 2005
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Ingår i: Applications of evolutionary computing. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 3540253963 ; , s. 264-273
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Konferensbidrag (refereegranskat)abstract
- This paper describes a new evolutionary algorithm for image segmentation. The evolution involves the colonization of a bidimensional world by a number of populations. The individuals, belonging to different populations, compete to occupy all the available space and adapt to the local environmental characteristics of the world. We present experiments with synthetic images, where we show the efficiency of the proposed method and compare it to other segmentation algorithm, and an application to medical images. Reported results indicate that the segmentation of noise images is effectively improved. Moreover, the proposed method can be applied to a wide variety of images.
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| 2. |
- Brännström, Johan, et al.
(författare)
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Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens
- 2006
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 121:3, s. 265-273
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.
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| 3. |
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| 4. |
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| 5. |
- Hässler, Signe, et al.
(författare)
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Aire deficiency causes increased susceptibility to streptozotocin-induced murine type 1 diabetes
- 2008
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 67:6, s. 569-580
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Tidskriftsartikel (refereegranskat)abstract
- Aire-deficient mice are a model of the human monogenic disorder autoimmune polyendocrine syndrome type I (APS I) characterized by a progressive autoimmune destruction of multiple endocrine glands such as the adrenal cortex, the parathyroids and the beta-cells of the pancreas. The disease is caused by mutations in the autoimmune regulator (AIRE) gene, a putative transcription factor expressed in thymic medullary epithelial cells and in antigen-presenting cells of the myeloid lineage in peripheral lymphoid organs. As Aire(-/-) mice do not spontaneously develop endocrinopathies, we wanted to evaluate the autoimmune multiple low-dose streptozotocin (MLDSTZ) diabetes model in Aire(-/-) mice. Surprisingly, Aire heterozygote mice were most susceptible to MLDSTZ-induced diabetes, whereas Aire(-/-) mice displayed an intermediate sensitivity to diabetes. Furthermore, Aire(-/-) macrophages produced higher levels of TNF-alpha and lower levels of IL-10 following streptozotocin stimulation, and Aire(-/-) mice developed a higher frequency of islet cells autoantibodies as a sign of increased activation. However, the number of islet infiltrating F4/80(+) Aire(-/-) macrophages was significantly decreased which was attributed to an increased susceptibility to streptozotocin cytotoxicity of Aire(-/-) macrophages. In conclusion, Aire(-/-) macrophages display an increased activation after STZ stimuli, but suffer from increased susceptibility to STZ cytotoxicity. These results support an important function of Aire in the control of peripheral tolerance through myeloid antigen-presenting cells.
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| 6. |
- Hässler, Signe, et al.
(författare)
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Aire deficient mice develop hematopoetic irregularities and marginal zone B cell lymphoma
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 108:6, s. 1941-1948
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads. APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance. Aire(-/-) mice replicate the autoimmune features of APS I patients with the presence of multiple autoantibodies and lymphocytic infiltrates in various tissues, but young mice appear clinically healthy. We here report the investigation of 15- to 24-month-old Aire(-/-) mice. We did not observe any endocrinological abnormalities, nor did sera from these mice recognize known APS I autoantigens. Interestingly, however, there was a high frequency of marginal zone B-cell lymphoma in Aire(-/-) mice and liver infiltrates of B cells, suggesting chronic antigen exposure and exaggerated activation. Furthermore, increased numbers of monocytes in blood were identified as well as augmented numbers of metallophilic macrophages in the spleen. We propose that Aire, in addition to its function in the thymus, also has a peripheral regulatory role by controlling the development of antigen-presenting cells (APCs) and marginal zone B-cell activation.
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| 7. |
- Hässler, Signe, 1976-
(författare)
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Autoimmune Regulator Deficient Mice, an Animal Model of Autoimmune Polyendocrine Syndrome Type I
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autoimmune diseases develop when the immune system fails to distinguish self from non-self or when the immune system is hypersensitive to endogenous or exogenous danger signals, or when a tissue erroneously sends a danger signal to the immune system. The education of the immune system to distinguish self from non-self is mainly carried out in the thymus and gives rise to central tolerance, whereas the ability to sense a danger or a healthy tissue constitutes peripheral tolerance. In these studies we have investigated the peripheral tolerance mechanisms controlled by the autoimmune regulator (Aire) gene in Aire deficient mice, an animal model of the monogenic disease autoimmune polyendocrine syndrome type I (APS I).Aire-/- mice displayed increased numbers of myeloid-derived antigen-presenting cells (APCs) in the spleen, lymph nodes and peritoneum as well as more blood monocytes and metallophilic macrophages in the spleen. Monocytes were also increased in the blood of APS I patients. Monocyte precursors displayed an accelerated development in the bone marrow of Aire-/- mice, and Aire-/- APCs had an altered phenotype that caused an increased immune response in several different contexts. Aire-/- splenic and lymph node dendritic cells had an increased ability to activate naive T cells, partly as a result of an upregulated expression of the costimulatory molecule VCAM-1. In Aire-/- mice increased activity of the metallophilic macrophages in the splenic marginal zone seems to be responsible both for the activated phenotype of marginal zone B cells and for the frequent development of marginal zone lymphoma with aging. In a TCR transgenic model Aire deficiency caused an increased superantigen-mediated TCR revision in the spleen, perhaps as a result of the altered phenotype of APCs in the spleen. Finally, Aire was shown to influence autoimmune disease development by a macrophage-dependent mechanism in diabetes induced with multiple low dose streptozotocin injections.These results indicate that Aire has an important function in peripheral tolerance by controlling the phenotype of myeloid-derived APCs and thereby regulating the activation of T and B lymphocytes.
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| 8. |
- Hässler, Signe, et al.
(författare)
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Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator
- 2006
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 36:2, s. 305-317
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyendocrine syndrome type I (APS I)suffer from endocrine and non-endocrine disorders due to mutations in the autoimmune regulator gene (AIRE). Mouse Aire is expressed both in thymic medullary epithelial cells and in peripheral antigen-presenting cells, suggesting a role in both central and peripheral tolerance. We here report that Aire(-/-) dendritic cells (DC) activate naive T cells more efficiently than do Aire(+/+) DC. Expression array analyses of Aire(-/-) DC revealed differential regulation of 68 transcripts, among which, the vascular cell adhesion molecule-1 (VCAM-1) transcript was up-regulated in Aire(-/-) DC. Concurrently, the expression of the VCAM-1 protein was up-regulated on both Aire(-/-) DC and monocytes from APS I patients. Blocking the interaction of VCAM-1 prevented enhanced Aire(-/-) DC stimulation of T cell hybridomas. We determined an increased number of DC in spleen and lymph nodes and of monocytes in the blood from Aire(-/-) mice, and an increased number of blood monocytes in APS I patients. Our findings imply a role for Aire in peripheral DC regulation of T cell activation, and suggest that Aire participates in peripheral tolerance.
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| 9. |
- Jensen, Poul Erik H., et al.
(författare)
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Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis : Results from the ABIRISK prospective cohort study
- 2019
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 326, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.
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| 10. |
- Lindh, Emma, et al.
(författare)
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Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 1
- 2013
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 42, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy.
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