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- Kockum, Ingrid, et al.
(författare)
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Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus
- 1996
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 28:7, s. 344-347
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Tidskriftsartikel (refereegranskat)abstract
- Two large population-based case-control studies are reviewed. The aim is to determine the effects of HLA, other genetic factors and immune markers (ICA, IAA and GAD65Ab) on the age at onset of insulin-dependent diabetes mellitus (IDDM) in 0-34 year olds. The primary HLA risk gene sequence for IDDM was difficult to identify because of the low recombination frequency within the HLA region. The frequency of the DR3-DQA1 * 0501-DQB1 * 0201 haplotype and the DR3-DQA1 * 0501 DQB1 * 0201 (DQ2)/DR4-DQA1 * 0301-DQB1 * 0302 (DQ8) genotype were higher among patients diagnosed before the age of 10 compared with those diagnosed after the age of 30. The negatively associated haplotype, DR15-DQA1 * 0102-DQB1 * 0602 was absent before the age of 10, but the frequency increased with increasing age at onset. The IDDM2 gene representing the variable number of tandem repeat (VNTR) sequences and 5' of the insulin gene on chromosome 11 were associated with IDDM since homozygous short VNTR was positive but not homozygous, and heterozygous long VNTR was negatively associated with the disease. The diagnostic sensitivity and specificity of GAD65 (GA65Ab) and insulin (IAA) autoantibodies varied with the age at onset and gender. GAD65Ab had the highest sensitivity (> 80%) in patients older than 20 years of age with no difference in gender. The lowest sensitivity (54%) was in 0-10 year old boys, while age did not affect the sensitivity in girls. In contrast, the sensitivity of IAA was highest (46%) before the age of 15 but decreased thereafter as did the sensitivity for ICA. Classification of patients who develop IDDM above 20-25 years of age was inadequate since many patients classified with NIDDM either had GAD65Ab or ICA or developed these antibodies after 1-2 years of NIDDM. We conclude that not only age but also gender affects the risk for IDDM associated with HLA, other IDDM genes as well as commonly used immunological markers for IDDM.
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- Lernmark, Å, et al.
(författare)
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Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus
- 1995
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Ingår i: Virchows Archiv. - 0945-6317. ; 425:6, s. 631-640
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.
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- Melin, L. Gunnar, et al.
(författare)
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A study of Mode-I delamination cracks by high-magnification moiré interferometry
- 1998
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Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 58:3-4, s. 515-525
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Tidskriftsartikel (refereegranskat)abstract
- Delamination cracks in carbon-fibre/epoxy composites loaded in Mode-I have been studied by high-magnification moiré interferometry. The moiré interferometer has the capability of switching between laser illumination for acquiring the displacement field and white-light illumination for visualisation of the underlying microstructure. Four specimens with different stacking geometries have been investigated. The delamination cracks have been simulated by using Teflon films. The resulting displacement fields have been compared to numerical solutions calculated by the finite-element method. The comparisons indicate that the Teflon films for some of the specimens did not delaminate fully. Otherwise the agreement is good, confirming that the displacement field around such cracks is satisfactorily described by linear-elastic fracture mechanics. The agreement was improved when a matrix-rich region in front of the crack tip was included in the finite-element model.
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- Melin, L. Gunnar, et al.
(författare)
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A study of the displacement field around embedded fibre optic sensors
- 1999
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Ingår i: Composites. Part A, Applied science and manufacturing. - 1359-835X .- 1878-5840. ; 30:11, s. 1267-1275
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Tidskriftsartikel (refereegranskat)abstract
- Deformation fields around optical fibres embedded in carbon fibre/epoxy composite specimens have been measured using moiré interferometry. The inclusion of the optical fibre resulted in large strain gradients. Calculated displacements from finite element analysis were compared to the experimental results. The numerical analysis showed that the displacement field on the specimen surface is smoothed out through the moiré grating thickness, an effect which is most pronounced at the material interfaces. With this influence taken into consideration a reasonable good quantitative agreement between the experiments and the finite element analysis was obtained. The finite element analysis also showed that the grating stiffness did not affect the measured displacements as long as the grating had a lower stiffness than the specimen
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| 7. |
- Huntley, Jonathan M., et al.
(författare)
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Microstructural strain analysis by high magnification moiré interferometry
- 1995
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Ingår i: Interferometry VII. - Bellingham, Wash : SPIE - International Society for Optical Engineering. - 9780819419040
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Konferensbidrag (refereegranskat)abstract
- A high magnification phase-stepping interferometer has been constructed which has a spatial resolution of the order of one micrometers and a sub-mm field of view. Laser illumination is delivered to the microscope head by polarization-preserving single-mode optical fibers. The head itself is a compact unit consisting of collimating optics, objective lens, CCD camera, and a separate white light source. Phase gratings are cast on the polished specimen surface by replication from a master grating, in either silicone rubber or epoxy resin. Subsequent evaporation of a thin layer of gold onto the grating increases the reflectivity and reduces the speckle noise in the images. By switching between the laser illumination and the white light unit, it is possible to view the underlying microstructure in exact registration with the measured displacement fields. The instrument is illustrated with several applications including the visualization of delamination cracks in graphite-epoxy composites and measurement of the strain-to-failure of polymer-bonded-explosives.
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- Sanjeevi, C. B., et al.
(författare)
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Association between autoantibody markers and subtypes of DR4 and DR4-DQ in Swedish children with insulin-dependent diabetes reveals closer association of tyrosine pyrophosphatase autoimmunity with DR4 than DQ8
- 1998
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Ingår i: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 51:3, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- HLA DQA1(*)0301-DQB1(*)0302 (DQ8) and DQA1(*)0501-DQB1(*)0201 (DQ2) are positively and DQA1(*)0102-DQB1(*)0602 (DQ6) negatively associated with IDDM. In DQA1(*)0301-DQB1(*)0302 (DQ8)-positive patients, susceptibility is also mediated by DRB1(*)0401. The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0-15 years. We found that ICA512 autoantibodies were associated primarily with DRB1(*)0401 and not with DQA1(*)0301-DQB1(*)0302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA1(*)0301-DQB1(*)0302 (DQ8) and DRB1(*)0401. GAD65 autoantibodies, known to be closely associated with DQA1(*)0501-DQB1(*)0201 (DQ2)-DRB1(*)0301 haplotype, also showed no preferential association with DQA1(*)0301-DQB1(*)0302 (DQ8) versus DRB1(*)04. These results suggest that the immune response to different β-cell autoantigens may be mediated via HLA class II molecules from different loci. Design of the antigen-specific immuno-intervention trials should take into account these HLA-DR and DQ subtype associations.
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