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- Bausch, Birke, et al.
(författare)
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Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1.
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:7, s. 2784-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma.MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed.RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype.CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.
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- Huberle, Alexander, et al.
(författare)
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Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barre Syndrome
- 2009
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 182:7, s. 4432-4438
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Tidskriftsartikel (refereegranskat)abstract
- We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barre syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-gamma secretion and disease severity. All quantitative trait loci were shared with other models of complex inflammatory diseases. The quantitative trait locus showing strongest linkage to clinical disease was Ean6 and spans 4.3 Mb on RNO12, harboring the neutrophil cytosolic factor 1 (Ncf1) among other genes. Polymorphisms in Ncf1, a member of the NADPH oxidase complex, have been associated with disease regulation in experimental arthritis and encephalomyelitis. We therefore tested the Ncf1 pathway by treating rats with a NADPH oxidase complex activator and ameliorated EAN compared the oil-treated control group. By proving the therapeutic effect of stimulating the NADPH oxidase complex, our data strongly suggest the first identification of a gene regulating peripheral nervous system inflammation. Taken together with previous reports, our findings suggest a general role of Ncf1 and oxidative burst in pathogenesis of experimental autoimmune animal models. The Journal of Immunology, 2009, 182: 4432-4438.
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- Schönbäck, Hedvig, 1961-
(författare)
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De svenska städernas begravningsplatser 1770-1830 : Arkitektur, sanitet och det sociala rummet
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The second half of the eighteenth and beginning of the nineteenth centuries meant a reform of burial practice across Europe. Urban graveyards were criticised as unsanitary and socially deficient and the authorities therefore urged towns to establish cemeteries on the urban periphery. Sweden was influenced by these changes and between 1770 and 1830 many towns replaced the ancient graveyard with a new cemetery on the urban periphery. A letters patent of 1805 brought the cemeteries under the control of the Board of Public Works and Buildings (Överintendentsämbetet). Architects were thus assigned a new type of task.The purpose of this thesis is to describe, analyse and discuss the new funerary architecture in relation to contemporaneous architectural theory and practice. The study comprises numerous cemeteries dating from a limited time period, including those of a seemingly anonymous and simple nature. The study is based on architecture, architectural drawings and the cemeteries themselves, but it has also been essential to widen the focus of attention to include the histories of science, religion, ideas and society in order to interpret the material more fully. The study of building types in relation to their socio-historical context has been my primary concern. The thesis divides into three main themes, of which the first two parts deal with prototype and how ideas were put into practice. They also look at how central authority fulfilled its architectural responsibilities. Part three takes up the theme of how the dead, following the wide-ranging plague epidemic 1710-1713, came to be seen as a problem for society. Part four looks at social aspects including opposition to the cemeteries. It also analyses how the emerging middle classes used cemeteries to mark their increasingly prominent position in society. The thesis demonstrates that cemetery origin and form stemmed not only from architectural theory but also from social ambition and the demands of sanitation. Above all, the cemeteries belong to an urban-planning tradition that aimed to create the ideal, well-ordered and healthy town.
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