1. |
- Sanjeevi, Carani B., et al.
(author)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Journal article (peer-reviewed)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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2. |
- Törn, Carina, et al.
(author)
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Increased autoantibodies to SOX13 in Swedish patients with type 1 diabetes.
- 2002
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 218-223
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Journal article (peer-reviewed)abstract
- This article aims to estimate the prevalence of SOX13 antibodies in Swedish patients with type 1 diabetes and healthy controls. The patients (n = 102; median age 35 years [range, 9-89]) were newly diagnosed with type 1 diabetes in a defined area in southern Sweden during 1995-1998. Islet cell antibodies (ICA) were analyzed with immunofluorescence, while glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase antibodies (IA-2A), and antibodies against the transcription factor SOX13 (SOX13Ab) were analyzed with radioimmunoprecipitating assays. SOX13Ab were found in 9.8% (10/102) of type 1 patients compared to 2.0% (2/99) in healthy controls (P = 0.033). At least one of the four autoantibodies (ICA, GADA, IA-2A or SOX13Ab) were identified in 67% (68/102) of the patients. Samples positive for IA-2A were only in one case positive also for SOX13Ab. IA-2A-positive patients were often positive also for ICA and GADA (19/27), and the same combination was also common for SOX13Ab-positive patients (6/10). Only 2.0% (2/102) were positive for SOX13Ab alone. ICA, GADA and IA-2A were more frequent in younger patients (
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3. |
- Agmon-Levin, Nancy, et al.
(author)
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Antitreponemal Antibodies Leading to Autoantibody Production and Protection from Atherosclerosis in Kitavans from Papua New Guinea
- 2009
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In: Contemporary Challenges in Autoimmunity. - : Wiley. - 0077-8923 .- 1749-6632. ; 1173, s. 675-682
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Conference paper (peer-reviewed)abstract
- The objective of our study was to determine the prevalence of anti-infectious agent antibodies and autoantibodies in a unique non-Westernized population from Kitava, Papua New Guinea (PNG), compared to Western populations. We matched 120 serum samples from Kitavans with 437 samples from four healthy control groups. Sera were tested for the presence of anti-infectious agent antibodies (treponema, toxoplsmosis, Epstein-Barr virus, cytomegalovirus, rubella) and autoantiobodies [anti-double-stranded (ds)DNA, anti-chromatin, anti-ribonucleoprotein (RNP), anti-SSB, anti-SSA, anti-Scl-70, anti-Smith, anti-centromer, anti-SmRNP, anti-Jo-1, and anti-ribosomal-P] using the Bio-Rad BioPlex 2200. Antitreponemal antibodies were detected in 87% of PNG sera versus 0-6% of controls (P < 0.0001). Anti-dsDNA antibodies were detected in 31% of PNG samples, which was significantly higher than in three of the control groups (<10%). The outstanding high rate of antitreponemal antibodies detected in Kitavans possibly represents prior yaws disease. A low prevalence of cardiovascular disease was previously documented in Kitavans and has been attributed, in addition to their diet, to the high prevalence of natural cardioprotective autoantibodies (the IgM-antiphosphorylcholine antibodies) in this population. Treponemal infection has been shown to induce the appearance of antiphosphorylcholine antibodies. These protective autoantibodies may cross-react with the pathogenic anti-dsDNA antibodies. Thus, it is suggested that infection with treponema is associated with the presence of protective as well as pathogenic autoantibodies.
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5. |
- Horak, Fay B, et al.
(author)
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Vibrotactile biofeedback improves tandem gait in patients with unilateral vestibular loss.
- 2009
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In: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1164, s. 279-81
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Journal article (peer-reviewed)abstract
- In a crossover design, subjects with unilateral vestibular loss (UVL) practiced tandem gait with eyes closed on two days, two weeks apart, with and without vibrotactile biofeedback (BF) applied to the lateral trunk. Results showed an immediate improvement in postural stability (reduction of lateral center-of-mass displacement, trunk tilt, and medial-lateral step width) that was significantly larger than effects of practice alone. However, BF did not increase the rate of improvement or retention of improved stability during gait.
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6. |
- Landin-Olsson, Mona
(author)
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Latent autoimmune diabetes in adults.
- 2002
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 112-116
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Journal article (peer-reviewed)abstract
- Latent autoimmune diabetes in adults (LADA) is a special form of diabetes that is clinically similar to type 2 diabetes but with positivity for pancreatic autoantibodies. The frequency of LADA patients among all patients diagnosed as type 2 varies between 6-50% in various populations. The frequency is higher in younger age groups. It is clear, however, that the frequency of autoimmune diabetes among adults is underestimated. Clinical features such as age and severity of symptoms are of no help in identifying these patients. Body mass index and C peptide levels in the general population increase with age, and these parameters are of limited use in identifying LADA patients. Determination of autoantibodies is necessary in order to correctly classify the type of diabetes. Among antibodies, GADA is the most frequently occurring autoantibody, followed by ICA. The natural course of these patients shows that C peptide will decrease with time in parallel with the curve for C peptide in classical type 1 diabetic patients. Most of the LADA patients will require insulin within three years. Our recommendation is that all patients be tested for pancreatic islet autoantibodies at diagnosis of diabetes to enable correct diagnosis and to avoid future failure of hypoglycemic agents and risk of complications due to hyperglycemia. It is still unclear whether early treatment with insulin is beneficial for the remaining beta cells.
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7. |
- Sanjeevi, CB, et al.
(author)
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The combination of several polymorphic amino acid residues in the DQ alpha and DQ beta chains forms a domain structure pattern and is associated with insulin-dependent diabetes mellitus
- 2002
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 362-375
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Journal article (peer-reviewed)abstract
- IDDM is positively associated with HLA-DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) and negatively associated with DQA1*0102-DQB1*0602 (DQ6). The aim of the present study was to analyze the importance of several polymorphic residues and domains of DQalpha and DQbeta, in addition to residue 52 DQalpha and residue 57 DQbeta, with regard to susceptibility or resistance in new-onset 0- to 15-year-old Swedish children with IDDM (n = 425) and matched controls (n = 367). HLA genotyping identified several polymorphic residues of the DQalpha and DQbeta to be either positively or negatively associated with IDDM, including Arg 52 DQalpha and Asp 57 DQbeta. Leu 69 DQalpha was positively (OR 7.02, P < 0.0001), Ala 69 DQalpha was negatively (OR 0.22, P < 0.0001), Gin 47 DQalpha was positively (OR 5.8, P < 0.0001), Cys 47 DQalpha was positively (OR 2.2, P < 0.0001), Lys 47 DQalpha was negatively (OR 0.47, P < 0.005), and Arg 47 DQalpha was negatively (OR 0.22, P < 0.005) associated with IDDM. Similarly, residues at 11, 18, 45, 48,50,53,55, 61, 64,66,76, and 80 were either positively or negatively associated with IDDM. Likewise, for DQbeta, Leu 53 DQbeta was positively (OR 11.01, P < 0.0001), Gin 53 DQbeta was negatively (OR 0.22, P < 0.0005), Arg 70 DQbeta was positively (OR 11.019 P < 0.0001), and Gly 70 DQbeta was negatively (OR 0.19, P < 0.0001) associated like other residues at 71, 74, 84, 85, 86, 89, and 90 DQbeta with IDDM. Certain domains in the DQalpha RFTIL (at DQalpha positions 52, 61, 64, 66, and 69), were present in 95% of patients compared to 69% of controls (OR 9.01, P, < 0.0001), and DQbeta domain GR (at DQbeta positions 45 and 70) was present in 95% of patients and 68% of controls (OR 8.68, P < 0.0001), which correlated better than the individual amino acid residues with IDDM. A combination of the DQalpha, and DQbeta chain domains was present in 94% of patients compared to 60% of controls (OR 10.6, P < 0.001). In conclusion, domains in the DQalpha, DQbeta, or both in the DQ molecule explain susceptibility or resistance to IDDM better than individual amino acid residues of DQA1 and DQB1.
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9. |
- Koch, Stefan, et al.
(author)
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Dynamic regulation of epithelial cell fate and barrier function by intercellular junctions
- 2009
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In: Annals of the New York Academy of Sciences. - : Wiley-Blackwell Publishing Inc.. - 0077-8923 .- 1749-6632. ; 1165, s. 220-227
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Journal article (peer-reviewed)abstract
- In the intestine, a single layer of epithelial cells effectively separates potentially harmful luminal content from the underlying tissue. The importance of an intact mucosal layer is highlighted by pathological disorders of the gut such as inflammatory bowel disease, in which disruption of the epithelial barrier leads to severe inflammation of the submucosal tissue compartments. Epithelial barrier function is provided by tightly regulated intercellular junctions, which consist of a plethora of membrane-associated and transmembrane proteins organized in discreet, spatially restricted complexes. Classically, these complexes are known to be dynamic seals for fluids and small molecules, as well as to provide mechanical strength by anchoring cell-cell contacts to the cytoskeleton. Rather than just acting as simple gates and adapters, however, junctional complexes themselves can relay extracellular stimuli to the epithelium and initiate cellular responses such as differentiation and apoptosis. In this review, we will highlight recent studies by our group and others which discuss how junctional proteins can promote outside-to-inside signaling and modulate epithelial cell fate. Unraveling the complex crosstalk between epithelial cells and their intercellular junctions is essential to understanding how epithelial barrier function is maintained in vivo and might provide new strategies for the treatment of inflammatory disorders of the intestine.
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10. |
- Gustafsson, Mika, et al.
(author)
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Reverse Engineering of Gene Networks with LASSO and Nonlinear Basis Functions
- 2009
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In: CHALLENGES OF SYSTEMS BIOLOGY: COMMUNITY EFFORTS TO HARNESS BIOLOGICAL COMPLEXITY. - : Wiley. - 0077-8923 .- 1749-6632. ; 1158, s. 265-275
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Journal article (peer-reviewed)abstract
- The quest to determine cause from effect is often referred to as reverse engineering in the context of cellular networks. Here we propose and evaluate an algorithm for reverse engineering a gene regulatory network from time-series kind steady-state data. Our algorithmic pipeline, which is rather standard in its parts but not in its integrative composition, combines ordinary differential equations, parameter estimations by least angle regression, and cross-validation procedures for determining the in-degrees and selection of nonlinear transfer functions. The result of the algorithm is a complete directed net-work, in which each edge has been assigned a score front it bootstrap procedure. To evaluate the performance, we submitted the outcome of the algorithm to the reverse engineering assessment competition DREAM2, where we used the data corresponding to the InSillico1 and InSilico2 networks as input. Our algorithm outperformed all other algorithms when inferring one of the directed gene-to-gene networks.
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