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- Autti, Taina, et al.
(författare)
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Bone marrow transplantation in aspartylglucosaminuria : histopathological and MRI study
- 1999
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Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 30:6, s. 283-8
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Tidskriftsartikel (refereegranskat)abstract
- This study comprised two patients with aspartylglucosaminuria (AGU), who were followed up for 4 and 7 years. The patients underwent allogeneic bone marrow transplantation (BMT) at the ages of 2 and 2.6 years. Both patients had abnormal speech development and gross motor clumsiness. At the time of the BMT, they were mentally retarded. We report on follow-up data of these patients obtained by MRI, in addition to the histopathological, biochemical and clinical investigations. MR images of six non-transplanted patients and seven healthy children served as controls. In the non-transplanted patients, MRI revealed evident delay of myelination in contrast to the two transplanted patients showing fair or evident grey- vs. white matter differentiation on T2-weighted images. The aspartylglucosaminidase (AGA) activity in blood leukocytes reached a heterozygous level. Urinary excretion of aspartylglucosamine and glycoasparagines slowly decreased but remained about a third of the pre-BMT level 5 years after BMT. Storage lysosomes in electron microscopic investigations were not decreased 6 months after BMT, but after 1.5-2 years, rectal mucosa samples showed a decrease in the storage vacuoles of different cells. Three years after BMT, no cells with storage vacuoles were present. Allogeneic BMT slowly normalises the pathological, biochemical and MRI findings in patients with AGU.
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| 3. |
- Berglund, Erik, et al.
(författare)
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Effects of apixaban compared with warfarin as gain in event-free time : a novel assessment of the results of the ARISTOTLE trial
- 2020
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:12, s. 1311-1319
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A novel approach to determine the effect of a treatment is to calculate the delay of event, which estimates the gain of event-free time. The aim of this study was to estimate gains in event-free time for stroke or systemic embolism, death, bleeding events, and the composite of these events, in patients with atrial fibrillation randomized to either warfarin or apixaban in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE).DESIGN: The ARISTOTLE study was a randomized double-blind trial comparing apixaban with warfarin.METHODS: Laplace regression was used to estimate the delay in time to the outcomes between the apixaban and the warfarin group in 6, 12, 18 and 22 months of follow-up.RESULTS: The gain in event-free time for apixaban versus warfarin was 181 (95% confidence interval 76 to 287) days for stroke or systemic embolism and 55 (-4 to 114) days for death after 22 months of follow-up. The corresponding gains in event-free times for major and intracranial bleeding were 206 (130 to 281) and 392 (249 to 535) days, respectively. The overall gain for the composite of all these events was a gain of 116 (60 to 171) days.CONCLUSIONS: In patients with atrial fibrillation, 22 months of treatment with apixaban, as compared with warfarin, provided gains of approximately 6 months in event-free time for stroke or systemic embolism, 7 months for major bleeding and 13 months for intracranial bleeding.
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| 7. |
- Renlund, N, et al.
(författare)
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Induction of steroidogenesis in immature rat Leydig cells by interleukin-1alpha is dependent on extracellular signal-regulated kinases
- 2006
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Ingår i: Journal of molecular endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 36:2, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1α (IL-1α) plays an important role in the regulation of immune responses as well as in non-inflammatory events in different types of cells. Here we have investigated the involvement of the extracellular signal-regulated kinase (ERK) cascade in IL-1α-induced steroidogenesis by primary cultures of immature rat Leydig cells. Our findings indicate that protein kinase C functions as an upstream component of signal transduction from the IL-1 receptor type I (IL-1RI) to the ERK cascade. It was observed that IL-1α upregulated both steroidogenic acute regulatory (StAR) protein expression and its phosphorylation when compared with controls. Selective inhibition of these mitogen-activated protein kinases (MAPKs) by UO126 enhanced both the expression and phosphorylation of the StAR protein, but suppressed androgen production by the immature Leydig cells as well as dissipating the mitochondrial electrochemical potential (Ψm) in these cells. The evidence that water-soluble cholesterol but not 22R-hydroxycholesterol-stimulated steroidogenesis was inhibited by UO126 suggested that an intact Ψm across the inner mitochondrial membrane is required for cholesterol translocation and is positively regulated by the ERK cascade. We propose that activation of ERKs by IL-1α plays a dual role in the regulation of steroidogenesis in immature Leydig cells: these MAPKs downregulate StAR expression and phosphorylation, while at the same time they support an intact Ψm across the inner mitochondrial membrane, thereby promoting translocation of cholesterol into the mitochondria of the Leydig cell.
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