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| 2. |
- Ihalainen, Saara, et al.
(författare)
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Proteome analysis of cultivated vascular smooth muscle cells from a CADASIL patient
- 2007
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Ingår i: Molecular Medicine. - 1076-1551 .- 1528-3658. ; 13:5-6, s. 305-314
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a vascular dementing disease caused by mutations in NOTCH3 gene, a majority of which are missense mutations leading to an uneven number of cysteine residues in epidermal growth factor like repeats in the extracellular domain of Notch3 receptor (N3ECD). Disease is characterized by degeneration of vascular smooth muscle cells (VSMC) and accumulation of N3ECD on the VSMCs of small and middle-sized arteries. Recent studies have demonstrated that impairment of Notch3 signaling is not the primary cause of the disease. In the present study we have characterized the protein expression pattern of a unique material of genetically genuine cultured human CADASIL VSMCs by proteomic analysis. We identified 11 differentially expressed proteins, which are involved in protein degradation and folding, contraction of VSMCs and cellular stress. Based on the results the misfolding of Notch3 seems to cause endoplasmic reticulum stress and activation of unfolded protein response leading to increased reactive oxygen species and inhibition of cell proliferation. In addition, upregulation of contractile proteins suggests an alteration in the signalling system of VSMC contraction. The accumulation of the N3ECD on the cell surface possibly upregulates the angiotensin II regulatory feedback loop and thereby enhances the readiness of the cells to respond to angiotensin II stimulation.
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| 3. |
- Järvelä, Sally, et al.
(författare)
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Antioxidant enzymes in oligodendroglial brain tumors : association with proliferation, apoptotic activity and survival
- 2006
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:2, s. 131-40
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of the study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in oligodendroglial tumors. The expression of antioxidant enzymes and related proteins (AOEs), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71 primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001 and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann-Whitney test). In the total series Trx was associated with poor prognosis in univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox multivariate analysis (P=0.009) along with age (P=0.002). The results suggest that the expression of Trx has a correlation to patient outcome and that there may be some association between AOEs, like MnSOD and Trx, and clinicopathological features of oligodendrogliomas.
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| 4. |
- Järvelä, Sally, et al.
(författare)
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Decreased expression of antioxidant enzymes is associated with aggressive features in ependymomas
- 2008
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 90:3, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in 67 ependymal tumors. We included into the analysis antioxidant enzymes (AOEs) and related proteins, such as, manganese superoxide dismutase (MnSOD), gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), thioredoxin (Trx) and thioredoxin reductase (TrxR). Their expression was studied in 46 primary (10 grade I, 30 grade II and 6 grade III) and 21 recurrent (3 grade I, 12 grade II and 6 grade III) tumors. Immunoreactivity for MnSOD was found in 87%, GLCL-C in 74%, GLCL-R in 89%, Trx in 72%, TrxR in 54%, of primary tumors. Lower GLCL-C and GLCL-R expression was associated with higher tumor grade (P = 0.047 and 0.049, respectively). MnSOD, GLCL-C and TrxR expressions were significantly higher in tumors located in the spinal cord compared to those in the brain (P = 0.044, 0.046 and 0.004, respectively). In the primary tumors Trx-positivity was found to correlate significantly with patient survival. In univariate survival analysis patients whose tumors did not express Trx had shorter survival (P = 0.045) and there was even more significant association (P = 0.011) when only adults were included in the analysis (in the total material median follow-up time of Trx-positive tumors was 9.7 years and of Trx-negative 5.4 years). The results indicate that AOEs have several biological functions in ependymal tumors. Trx had important prognostic value: all adults with Trx-positive tumors were alive at follow-up (median 7.8 years).
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| 6. |
- Raheem, Olayinka, et al.
(författare)
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Hartia-lantiodystrofioiden molekyyligenetiikka Suomessa
- 2006
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Ingår i: Duodecim; lääketieteellinen aikakauskirja. - 0012-7183. ; 122:17, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Hartia-lantiolihasdystrofia (limb girdle muscular dystrophy, LGMD) oli ennen kyseisen taudin geenien löytämistä käytetty diagnoosi potilasryhmälle, jolla ei ole todettu muuta tunnistettua dystrofiaa, kuten X-kromosomaalista Duchennen tai Beckerin lihasdystrofiaa, vallitsevasti periytyvää fasioskapulohumeraalista lihasdystrofiaa, distaalista myopatiaa tai synnynnäistä lihasdystrofiaa. Suomessa tämän ryhmän potilailla on usein ollut diagnoosina dystrophia musculorum progressiva NUD. Vuonna 1991 löydettiin ensimmäinen LGMD:tä aiheuttava geenivirhe, ja nykyään voidaan molekyyligeneettisesti eritellä 17 eri alalajia, eivätkä nämäkään kata kaikkia tapauksia. Joidenkin alalajien diagnoosi on ollut mahdollista tehdä proteiinipuutoksen osoittavalla immunohistokemiallisella biopsialeikkeen värjäyksellä, ja menetelmä on tarjolla maamme neuropatologian laboratorioissa. TAYS:aan perustetussa lihastautien erityisdiagnostiikan keskuksessa on mahdollista etsiä tämän ryhmän geeni- ja proteiinivirheitä DNA- ja Western blotting -menetelmin. Mutaatiot kalpaiini 3-, FKRP- (fukutin-related protein) ja alfasarkoglykaanigeeneissä näyttävät olevan tärkeimmät suomalaisessa väestössä.
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| 8. |
- Aaltonen, Minna, et al.
(författare)
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Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets
- 2007
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Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 83:2, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Background: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. Aims: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. Study design: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. Results: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. Conclusions: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.
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