| 41. |
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| 42. |
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| 43. |
- Olofsson, A., et al.
(författare)
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Amyloid : Morphology and Toxicity
- 2002
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 40:12, s. 1266-1270
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Tidskriftsartikel (refereegranskat)abstract
- We have expressed transthyretin (TTR) mutants which have significantly destabilised tetramers that aggregate into amyloid fibrils via a series of intermediates. We used atomic force microscopy to follow the morphology of aggregates during fibril formation. Initially, amorphous aggregates are formed that subsequently mature into fibrillar structures. This observation is interpreted as an optimisation of beta-strand registers. The rate of aggregation and maturation is highly temperature-dependent suggesting that entropic forces significantly contribute to stability. In addition, we identified a correlation between the presence of early formed aggregates of TTR and cytotoxicity. The toxic response was mediated via an apoptotic mechanism. The fact that early formed amorphous aggregates, but not more mature fibrils, exert a toxic response suggests that the rate of fibril formation may be a critical parameter. We propose that a slow rate of aggregation facilitates an increased concentration of a toxic intermediate.
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| 44. |
- Stoltzfus, Patricia, et al.
(författare)
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Laminin-5 gamma2 chain expression facilitates detection of invasive squamous cell carcinoma of the uterine cervix.
- 2004
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Ingår i: International Journal of Gynecological Pathology. - : Lippincott Williams & Wilkins. - 0277-1691 .- 1538-7151. ; 23:3, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- Because it has been suggested that laminin-5 can be used as a sensitive marker for epithelial cell invasion, specimens from patients with invasive squamous cell carcinoma of the uterine cervix with a previous history of preinvasive lesions were evaluated by a newly developed monoclonal antibody directed against the gamma2 chain of laminin-5. Thirty-two archival paraffin specimens consisting of the matched preinvasive and invasive lesions from 15 women were evaluated to determine whether gamma2 chain laminin-5 staining was present in lesions that progressed to invasive cancer. With the exception of one tumor (a small cell nonkeratinizing squamous carcinoma), all squamous cell carcinomas exhibited positive staining. Five of 17 preinvasive lesions also were immunoreactive for the laminin-5 protein. A blinded histologic reevaluation revealed invasion or lesions suspicious for invasion in four of five preinvasive lesions. Our findings suggest that laminin-5 determined by a monoclonal antibody facilitates the identification of invasive lesions that are difficult or impossible to identify on routinely stained histologic sections.
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| 45. |
- Tencer, Jan, et al.
(författare)
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Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases
- 2000
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Ingår i: Clinica Chimica Acta. - 0009-8981. ; 297:1-2, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- The proteinuria selectivity index (SI) describes changes of the glomerular permeability for macromolecules. In the present study, we examine the implications of SI as a diagnostic (199 patients) and a prognostic (49 patients) marker in glomerular diseases. Using SI based on alpha(2)-macroglobulin (alpha(2)-M-SI) or on IgM (IgM-SI) we found that minimal change nephropathy could be discriminated by low SI values and crescentic necrotizing glomerulonephritis by high SI values compared to other diseases. SI based on IgG (IgG-SI) was less useful in determining specific diagnoses. During a follow-up of 46 months creatinine clearance (Cr cl) decreased 36% in a group of patients with high IgG-SI (>0.2) and 38% in a group of patients with high IgM-SI (>1.5(-3)) compared to only 8% in patients with low IgG-SI (
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| 46. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos.
- 2002
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 10:2, s. 113-8
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of spontaneous abortion is complex, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms are commonly associated with defects in folate dependent homocysteine metabolism and have been implicated as risk factors for recurrent embryo loss in early pregnancy. In the present study we have determined the prevalence of combined MTHFR C677T and A1298C polymorphisms in DNA samples from spontaneously aborted embryos (foetal death between sixth and twentieth week after conception) and adult controls using solid-phase minisequencing technique. There was a significant odds ratio of 14.2 (95% CI 1.78-113) in spontaneously aborted embryos comparing the prevalence of one or more 677T and 1298C alleles vs the wild type combined genotype (677CC/1298AA), indicating that the MTHFR polymorphisms may have a major impact on foetal survival. Combined 677CT/1298CC, 677TT/1298AC or 677TT/1298CC genotypes, which contain three or four mutant alleles, were not detected in any of the groups, suggesting complete linkage disequilibrium between the two polymorphisms. The present finding of high prevalence of mutated MTHFR genotypes in spontaneously aborted embryos emphasises the potential protective role of periconceptional folic acid supplementation.
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| 47. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Influence of the apolipoprotein E epsilon4 allele on human embryonic development.
- 2002
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Ingår i: Neuroscience letters. - 0304-3940. ; 324:3, s. 189-92
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Tidskriftsartikel (refereegranskat)abstract
- Human apolipoprotein E (apoE) exists in three major isoforms encoded by distinct alleles (APOE epsilon2, epsilon3 and epsilon4) and has important functions in nerve development and repair. Inheritance of the 4 allele is a major risk factor for the development of Alzheimer's disease. To investigate the role of APOE polymorphisms in embryonic development, we analyzed the APOE genotypes of 81 spontaneously aborted embryos and 110 adult controls using a solid-phase minisequencing technique. The epsilon4 allele was significantly less frequent in the spontaneous abortion group than in the control group (P=0.009), while the frequency of epsilon3 was significantly increased (P=0.005), suggesting that epsilon4 may have protective effects during embryogenesis. These protective effects might counterbalance the deleterious age-related effects of the epsilon4 allele in natural selection.
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