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- Jonsson, Ing-Marie, 1949, et al.
(författare)
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Ethanol prevents development of destructive arthritis
- 2007
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Ingår i: Proc Natl Acad Sci U S A. - Washington, DC : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:1, s. 258-63
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collagen-induced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-kappaB activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.
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- Khan, Omar M., 1980, et al.
(författare)
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Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice.
- 2011
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Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39
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Tidskriftsartikel (refereegranskat)abstract
- RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
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- Tingstedt, Bobby, et al.
(författare)
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First results from the Swedish National Pancreatic and Periampullary Cancer Registry
- 2019
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Ingår i: HPB. - : Elsevier BV. - 1365-182X .- 1477-2574. ; 21:1, s. 34-42
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improvements in therapy regimens over the past decades, overall survival rates for pancreatic and periampullary cancer are poor. Specific cancer registries are set up in various nations to regional differences and to enable larger prospective trials. The aim of this study was to describe the Swedish register, including possibilities to improve diagnostic work-ups, treatment, and follow-up by means of the register.Methods: Since 2010, all patients with pancreatic and periampullary cancer (including also patients who have undergone pancreatic surgery due to premalignant or benign lesions) have been registered in the Swedish National Periampullary and Pancreatic Cancer registry.Results: In total 9887 patients are listed in the registry; 8207 of those have malignant periampullary cancer. Approximately one-third (3282 patients) have had resections performed, including benign/premalignant resections. 30-day and 90-day mortality after pancreatoduodenectomy is 1.5% and 3.5%, respectively. The overall 3-year survival for resected pancreatic ductal adenocarcinoma is 35%. Regional variations decreased over the studied period, but still exist.Conclusion: Results from the Swedish National Registry are satisfactory and comparable to international standards. Trends over time show increasing resection rates and some improved results. Better collaboration and openness within pancreatic surgeons is an important side effect.
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