| 1. |
- Koivunen, J., et al.
(författare)
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PET amyloid ligand [C-11]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease
- 2008
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 131:Pt 7, s. 1845-1853
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Tidskriftsartikel (refereegranskat)abstract
- Variant Alzheimers disease (VarAD) with spastic paraparesis and presenile dementia is associated with certain mutations of the presenilin 1 (PS-1) gene, particularly those leading to deletion of exon 9 (PS-1 E9). VarAD is neuropathologically characterized by the presence of unusually large, A42 positive, non-cored cotton wool plaques (CWPs), also devoid of dystrophic neurites. The aim of the present study was to find out whether [C-11]PIB would show increased uptake and serve as an in vivo biomarker of amyloid accumulation in VarAD. A further aim was to assess the correspondence of the [C-11]PIB binding to the amount and type of A deposits in another group of deceased VarAD patients brains. We studied four patients with VarAD and eight healthy controls with PET using [C-11]PIB as tracer. Parametric images were computed by calculating the region-to-cerebellum and region-to-pons ratio in each voxel over 6090 min. Group differences in [C-11]PIB uptake were analysed with automated region-of-interest (ROI) analysis. [C-11]PIB uptake was compared to the immunohistochemically demonstrated deposition of A in the brains of another group of four deceased VarAD patients. Patients with VarAD had significantly higher [C-11] PIB uptake than the control group in the striatum (caudate nucleus and putamen), anterior and posterior cingulate gyrus, occipital cortex and thalamus. In the caudate and putamen [C-11]PIB uptake, expressed as region-to-cerebellum ratio, was on the average 43 greater than the mean of the control group. The increases in the anterior (28) and posterior (27) cingulate gyrus, occipital cortex (21) and thalamus (14) were smaller. All VarAD patients showed this similar topographical pattern of increased [C-11]PIB uptake. The results were essentially similar when the uptake was expressed as region-to-pons ratios. [C-11]PIB imaging shows increased uptake in patients with VarAD especially in the striatum, and it can be used to detect amyloid accumulation in vivo in these patients. The pattern of increased [C-11]PIB uptake is different from that described in sporadic Alzheimers disease and resembles that seen in Alzheimers disease patients with certain presenilin-1 mutations or amyloid precursor protein gene duplication showing predominantly striatal increase in [C-11]PIB uptake.
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| 2. |
- Leinonen, V., et al.
(författare)
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S- F-18 THK-5117-PET and C-11 PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-beta Plaques and Tau in Brain Biopsies
- 2018
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 64:1, s. 171-179
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Tidskriftsartikel (refereegranskat)abstract
- Background: Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[F-18] THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[F-18] THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo. Objective: Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[F-18] THK-5117, and [C-11] PIB PET against tau and amyloid lesions in brain biopsy. Methods: Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF A beta(1-42), total tau, and P-tau(181) measures, underwent brain MRI, [C-11] PIB PET, and S-[F-18] THK-5117 PET imaging. Results: Seven patients had amyloid-beta(A beta, 4G8) plaques, two both A beta and phosphorylated tau (P tau, AT8) and one only P tau in biopsy. As expected, increased brain biopsy A beta was well associated with higher [C-11] PIB uptake in PET. However, S-[F-18] THK-5117 uptake did not show any statistically significant correlation with either brain biopsy P tau or CSF P-tau(181) or total tau. Conclusions: S-[F-18] THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous A beta and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.
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| 5. |
- Rokka, Joonas, et al.
(författare)
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Consumer Identity Work: Identity and Consumption
- 2023. - 2'nd
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Ingår i: Consumer Culture Theory : 2'nd Edition - 2'nd Edition. - 9781529609257 - 9781529609264 - 9781529614435 ; , s. 15-32
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Bokkapitel (refereegranskat)
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| 6. |
- Kallionpaa, R. A., et al.
(författare)
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Mast Cells in Human Cutaneous Neurofibromas: Density, Subtypes, and Association with Clinical Features in Neurofibromatosis 1
- 2022
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Ingår i: Dermatology. - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 238:2, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cutaneous neurofibromas (cNFs) are hallmarks of neurofibromatosis 1 (NF1) and cause the main disease burden in adults with NF1. Mast cells are a known component of cNFs. However, no comprehensive characterization of mast cells in cNFs is available, and their contributions to cNF growth and symptoms such as itch are not known. Methods: We collected 60 cNFs from ten individuals with NF1, studied their mast cell proteinase content, and compared the mast cell numbers to selected clinical features of the tumors and patients. The tumors were immunolabeled for the mast cell markers CD117, tryptase, and chymase, and the percentage of immunopositive cells was determined using computer-assisted methods. Results: The median proportions of positive cells were 5.5% (range 0.1-14.4) for CD117, 4.0% (1.2-7.0) for tryptase, and 5.0% (1.1-15.9) for chymase. The median densities of cells immunopositive for CD117, tryptase, and chymase were 280, 243, and 250 cells/mm(2), respectively. Small tumors, growing tumors, and tumors from patients below the median age of 33 years displayed a high proportion of mast cells. Cells expressing both tryptase and chymase were the predominant mast cell type in cNFs, followed by cells expressing chymase only. Conclusion: The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.
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| 8. |
- Oksa, L, et al.
(författare)
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Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.
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