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- Andersson, Emil, et al.
(författare)
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Low pericyte coverage of endometrial microvessels in heavy menstrual bleeding correlates with the microvessel expression of VEGF-A.
- 2015
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1791-244X .- 1107-3756. ; 35:2, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- A prospective clinical study was carried out to investigate whether endometrial microvessels in patients with idiopathic heavy menstrual bleeding (HMB) of endometrial origin (HMB-E) are fragile due to low pericyte coverage. Idiopathic HMB-E is characterized by large endothelial cell gaps related to the microvascular overexpression of vascular endothelial growth factor (VEGF)-A and VEGF receptors 1-3. A total of 10 women with a normal menstrual cycle and a history of HMB of <5 years, and 17 healthy women with a normal menstrual cycle were recruited from the Karolinska University Hospital. Blood samples were obtained for hormone analysis and coagulation tests. Endometrial biopsies were collected in the proliferative or in the secretory phase. Pericyte coverage was assessed using immunohistochemical staining for smooth muscle actin-α (SMAα) and by image analysis (microvascular density) of endometrial biopsies from 10 patients with HMB-E and 17 healthy ovulating women (control subjects). Previously published data on endothelial cell gap size and the expression of VEGF receptors were used. Although microvascular density did not differ between the patients with HMB-E and the control subjects, the number of SMAα-positive microvessels in the proliferative phase was significantly (P=0.005) lower in the patients with HMB-E than in the control subjects. Moreover, the number of SMAα-positive microvessels in the control subjects was significantly fewer in the secretory (P=0.04) than in the proliferative phase, whereas this number did not differ among the patients with HMB-E regardless of phase. A significant negative correlation was observed between the number of VEGF-A-positive microvessels and microvessels with pericyte coverage (r=0.8; P=0.04). Finally, the endothelial cell layer was significantly thicker in the patients with HMB-E than in the control subjects. Thus, the upregulation of VEGF-A in idiopathic HMB-E is associated with a low pericyte coverage during the proliferative phase of intense angiogenesis, which may confer vessel fragility, possibly leading to excessive blood loss.
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- Andersson, Malin E, 1978, et al.
(författare)
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Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease.
- 2007
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Ingår i: International journal of molecular medicine. - 1107-3756 .- 1791-244X. ; 20:2, s. 233-9
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Tidskriftsartikel (refereegranskat)abstract
- Kinesin is a microtubule-associated motor protein that transports Alzheimer-associated amyloid precursor protein (APP) in neurons. In animal models, impaired kinesin-mediated APP transport seems to enhance formation of the neurotoxic 42 amino acid fragment of beta-amyloid (A beta 42). In man, one study suggests that a polymorphism (rs8702, 56,836G>C) in the kinesin light chain 1 gene (KNS2) may affect the risk of Alzheimer's disease (AD). To further assess KNS2 as a susceptibility gene for AD we analyzed 802 patients with sporadic AD and 286 controls, 134 longitudinally followed patients with mild cognitive impairment (MCI) and 39 cognitively stable controls for the rs8702 polymorphism. The rs8702 polymorphism did not influence risk of AD (p=0.46). However, rs8702 interacted with APOE epsilon 4 carrier status in AD (p=0.006) and influenced cerebrospinal fluid levels of hyperphosphorylated tau in MCI patients who converted to AD during follow-up (p=0.018). These findings support earlier indications that genetic variability in the KNS2 gene may play a role during early stages of AD pathogenesis.
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- Böttiger, Anna K., 1977-, et al.
(författare)
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Association of total plasma homocysteine with methylenetetrahydrofolate reductase genotypes 677C > T, 1298A > C, and 1793G > A and the corresponding haplotypes in Swedish children and adolescents
- 2007
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Ingår i: International Journal of Molecular Medicine. - Athens, Greece : D.A. Spandidos. - 1107-3756 .- 1791-244X. ; 19:4, s. 659-665
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Tidskriftsartikel (refereegranskat)abstract
- We studied 692 Swedish children and adolescents (aged 9-10 or 15-16 years, respectively), in order to evaluate the effect of the methylenetetrahydrofolate reductase (MTHFR) 677C > T, 1298A > C, and 1793G > A polymorphisms on total plasma homocysteine concentrations (tHcy). Genotyping was performed with Pyrosequencing (TM) technology. The MTHFR 677C > T polymorphism was associated with increased tHcy concentrations in both the children and the adolescents (P < 0.001 for both age groups) in both genders. The effect of MTHFR 1298A > C was studied separately in subjects with the 677CC and 677CT genotypes, and the 1298C allele was found to be associated with higher tHcy levels both when children were stratified according to 677C > T genotypes, and when using haplotype analyses and diplotype reconstructions. The 1793A allele was in complete linkage disequilibrium with the 1298C allele. It was still possible to show that the 1793A allele was associated with lower tHcy levels, statistically significant in the adolescents. In conclusion, a haplotype-based approach was slightly superior in explaining the genetic interaction on tHcy plasma levels in children and adolescents than a simple genotype based approach (R-2 adj 0.44 vs. 0.40). The major genetic impact on tHcy concentrations is attributable to the MTHFR 677C > T polymorphism. The common 1298A > C polymorphism had a minor elevating effect on tHcy, whereas the 1793G > A polymorphism had a lowering effect on tHcy.
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- Cunha, Sara I., et al.
(författare)
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Exposure to EGF and 17 beta-estradiol irreversibly affects the proliferation and transformation of MCF7 cells but is not sufficient to promote tumor growth in a xenograft mouse model upon withdrawal of exposure
- 2018
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Ingår i: International Journal of Molecular Medicine. - : SPANDIDOS PUBL LTD. - 1107-3756 .- 1791-244X. ; 42:3, s. 1615-1624
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Tidskriftsartikel (refereegranskat)abstract
- Epidermal growth factor (EGF) and estrogen are potent regulators of breast tumorigenesis. Their short-term actions on human breast epithelial cells have been investigated extensively. However, the consequence of a long-term exposure to EGF and estrogen remains to be fully elucidated. The present study examined the effects of long-term exposure to EGF and 17 beta-estradiol on the proliferation, transformation, expression of markers of stemness, and tumorigenesis of MCF7 human breast adenocarcinoma cells. Exposure to EGF and/or 17 beta-estradiol irreversibly enhanced the proliferation rate of MCF7 cells, even following withdrawal. However, in a mouse xenograft experiment, no significant difference in tumor volume was observed between tumors derived from cells exposed to EGF, 17 beta-estradiol or EGF + 17 beta-estradiol. Immunohistochemistry performed on tumors derived from 17 beta-estradiol-exposed cells revealed reduced cell proliferation and vessel scores, according to the results obtained using Ki67 and von Willebrand factor staining, respectively. The EGF-and/or 17 beta-estradiol-treated cells exhibited an increased ratio of cluster of differentiation (CD) 44(+)/CD24(-) cells and enhanced ability to form mammospheres. Furthermore, the long-term exposure of MCF7 cells to EGF and 17 beta-estradiol altered their responsiveness to short-term stimulatory or inhibitory treatments with EGF, 17 beta-estradiol, transforming growth factor-beta 1 (TGF beta 1), Iressa and SB431542. Therefore, the findings indicated that sustained exposure of MCF7 cells to EGF and/or 17 beta-estradiol resulted in enhanced cell proliferation and mammosphere formation, an increased ratio of CD 44(+)/CD24 cells, and altered responses to short-term treatments with EGF, 17 beta-estradiol, TGF beta 1, and drugs inhibiting these signaling pathways. However, this sustained exposure was not sufficient to affect tumor take or volume in a xenograft mouse model.
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