| 1. |
- Stanton, Biba R, et al.
(författare)
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Diffusion tensor imaging in sporadic and familial (D90A SOD1) forms of amyotrophic lateral sclerosis
- 2009
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Ingår i: Archives of Neurology. - : American Medical Association. - 0003-9942 .- 1538-3687. ; 66:1, s. 109-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The basis of heterogeneity in the clinical presentation and rate of progression of amyotrophic lateral sclerosis (ALS) is poorly understood. OBJECTIVES: To use diffusion tensor imaging as a measure of axonal pathologic features in vivo in ALS and to compare a homogeneous form of familial ALS (homozygous D90A SOD1 [superoxide dismutase 1]) with sporadic ALS. DESIGN: Cross-sectional diffusion tensor imaging study. SETTING: Tertiary referral neurology clinic. PATIENTS: Twenty patients with sporadic ALS, 6 patients with homozygous D90A SOD1 ALS, and 21 healthy control subjects. MAIN OUTCOME MEASURE: Fractional anisotropy in cerebral white matter. RESULTS: Patients with homozygous D90A SOD1 ALS showed less extensive pathologic white matter in motor and extramotor pathways compared with patients with sporadic ALS, despite similar disease severity assessed clinically using a standard functional rating scale. Fractional anisotropy correlated with clinical measures of severity and upper motor neuron involvement. CONCLUSION: In vivo diffusion tensor imaging measures demonstrate differences in white matter degeneration between sporadic ALS and a unique familial form of the disease, indicating that genotype influences the distribution of cerebral pathologic features in ALS.
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| 2. |
- Aksentijevich, Ivona, et al.
(författare)
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An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 360:23, s. 2426-2437
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
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| 3. |
- Breitbarth, Eike, et al.
(författare)
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Dissolved iron (II) in the Baltic Sea surface water and implications for cyanobacterial bloom development
- 2009
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Ingår i: Biogeosciences. ; 6, s. 2397-2420
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Tidskriftsartikel (refereegranskat)abstract
- Iron chemistry measurements were conducted during summer 2007 at two distinct locations in the Baltic Sea (Gotland Deep and Landsort Deep) to evaluate the role of iron for cyanobacterial bloom development in these estuarine waters. Depth profiles of Fe(II) were measured by chemiluminescent flow injection analysis (CL-FIA) and reveal several origins of Fe(II) to the water column. Photoreduction of Fe(III)-complexes and deposition by rain are main sources of Fe(II) (up to 0.9 nmol L−1) in light penetrated surface waters. Indication for organic Fe(II) complexation resulting in prolonged residence times in oxygenated water was observed. Surface dwelling heterocystous cyanobacteria where mainly responsible for Fe(II) consumption in comparison to other phytoplankton. The significant Fe(II) concentrations in surface waters apparently play a major role in cyanobacterial bloom development in the Baltic Sea and are a major contributor to the Fe requirements of diazotrophs. Second, Fe(II) concentrations up to 1.44 nmol L−1 were observed at water depths below the euphotic zone, but above the oxic anoxic interface. Finally, all Fe(III) is reduced to Fe(II) in anoxic deep water. However, only a fraction thereof is present as ferrous ions (up to 28 nmol L−1) and was detected by the CL-FIA method applied. Despite their high concentrations, it is unlikely that ferrous ions originating from sub-oxic waters could be a temporary source of bioavailable iron to the euphotic zone since mixed layer depths after strong wind events are not deep enough in summer time.
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| 4. |
- Breitbarth, Eike, et al.
(författare)
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Dissolved iron (II) in the Baltic Sea surface water and implications for cyanobacterial bloom development
- 2009
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 6:Special issue, s. 2397-2420
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Tidskriftsartikel (refereegranskat)abstract
- Iron chemistry measurements were conducted during summer 2007 at two distinct locations in the Baltic Sea (Gotland Deep and Landsort Deep) to evaluate the role of iron for cyanobacterial bloom development in these estuarine waters. Depth profiles of Fe(II) were measured by chemiluminescent flow injection analysis (CL-FIA). Up to 0.9 nmol Fe(II) L−1 were detected in light penetrated surface waters, which constitutes up to 20% to the dissolved Fe pool. This bioavailable iron source is a major contributor to the Fe requirements of Baltic Sea phytoplankton and apparently plays a major role for cyanobacterial bloom development during our study. Measured Fe(II) half life times in oxygenated water exceed predicted values and indicate organic Fe(II) complexation. Potential sources for Fe(II) ligands, including rainwater, are discussed. Fe(II) concentrations of up to 1.44 nmol L−1 were detected at water depths below the euphotic zone, but above the oxic anoxic interface. Mixed layer depths after strong wind events are not deep enough in summer time to penetrate the oxic-anoxic boundary layer. However, Fe(II) from anoxic bottom water may enter the sub-oxic zone via diapycnal mixing and diffusion.
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