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| 2. |
- Koskinen, A. R., et al.
(författare)
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Complement Activation During Liver Transplantation : Special Emphasis on Patients With Atypical Hemolytic Uremic Syndrome
- 2011
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:9, s. 1885-1895
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Tidskriftsartikel (refereegranskat)abstract
- Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy often caused by mutations in complement factor H (CFH), the main regulator of alternative complement pathway. Because CFH is produced mainly by the liver, combined liver-kidney transplantation is a reasonable option in treatment of patients with severe aHUS. We studied complement activation by monitoring activation markers during liver transplantation in two aHUS patients treated extensively with plasma exchange and nine other liver transplantation patients. After the reperfusion, a clear increase in all the activation markers except C4d was observed indicating that the activation occurs mainly through the alternative pathway. Concentration of SC5b-9 was higher in the hepatic than the portal vein indicating complement activation in the graft. Preoperatively and early during the operation, the aHUS patients showed highest C3d concentrations but otherwise their activation markers were similar to the other patients. In the other patients, correlation was found between perioperative SC5b-9 concentration and postoperative alanine aminotransferase and histological changes. This study explains why supply of normal CFH by extensive plasma exchange is beneficial before combined liver-kidney transplantation of aHUS patients. Also the results suggest that perioperative inhibition of the terminal complement cascade might be beneficial if enhanced complement activation is expected.
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| 3. |
- Puustinen, J., et al.
(författare)
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1.22 µm GaInNAs saturable absorber mirrors with tailored recovery time
- 2010
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Ingår i: Emerging trends and novel materials in photonics. - : American Institute of Physics (AIP). - 9780735408432 ; , s. 200-203
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Konferensbidrag (refereegranskat)abstract
- The effect of in-situ N-ion irradiation on the recombination dynamics of GaInNAs/GaAs semiconductor saturable absorber mirrors has been studied. The samples were fabricated by molecular beam epitaxy using a radio frequency plasma source for nitrogen incorporation in the absorber layers as well as for the irradiation. The recombination dynamics of irradiated samples were studied by pump-probe measurements. The recombination time of the absorbers could be reduced by increasing the irradiation time. The effect of the reduced recombination time on the pulse dynamics of a mode-locked laser setup was studied with a Bi-doped fibre laser. The pulse quality was found to improve with increased irradiation time and reduced recombination time, demonstrating the potential of the in-situ irradiation method for device applications.
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| 4. |
- Lim, Elaine T, et al.
(författare)
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Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10-8) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10-117). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10-4), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.
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