| 1. |
- Sandén, Emma, et al.
(författare)
-
Aberrant immunostaining pattern of the CD24 glycoprotein in clinical samples and experimental models of pediatric medulloblastomas
- 2015
-
Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 123:1, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- The CD24 glycoprotein is a mediator of neuronal proliferation, differentiation and immune suppression in the normal CNS, and a proposed cancer biomarker in multiple peripheral tumor types. We performed a comparative analysis of CD24 gene expression in a large cohort of pediatric and adult brain tumors (n = 813), and further characterized protein expression in tissue sections (n = 39), primary brain tumor cultures (n = 12) and a novel orthotopic group 3 medulloblastoma xenograft model. Increased CD24 gene expression was demonstrated in ependymomas, medulloblastomas, anaplastic astrocytomas and glioblastomas, although medulloblastomas displayed higher expression than all other tumor entities. Preferential expression of CD24 in medulloblastomas was confirmed at protein level by immunostaining and computerized image analysis of cryosections. Morphologies and immunophenotyping of CD24(+) cells in tissue sections tentatively suggested disparate functions in different tumor subsets. Notably, protein staining of medulloblastoma cells was associated with prominent cytoplasmic and membranous granules, enabling rapid and robust identification of medulloblastoma cells in clinical tissue samples, as well as in experimental model systems. In conclusion, our results implicate CD24 as a clinically and experimentally useful medulloblastoma immunomarker. Although our results encourage further functional studies of CD24 as a potential molecular target in subsets of brain tumors, the promiscuous expression of CD24 in vivo highlights the importance of specificity in the future design of such targeted treatment.
|
|
| 2. |
- Andersson, Lena, 1965-, et al.
(författare)
-
Respiratory health and inflammatory markers : Exposure to respirable dust and quartz and chemical binders in Swedish iron foundries
- 2019
-
Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 14:11
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the relationship between respirable dust, quartz and chemical binders in Swedish iron foundries and respiratory symptoms, lung function (as forced expiratory volume FEV1 and vital capacity FVC), fraction of exhaled nitric oxide (FENO) and levels of club cell secretory protein 16 (CC16) and CRP.METHODS: Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Full shift sampling and examination were performed on the second or third day of a working week after a work free weekend, with additional sampling on the fourth or fifth day. Logistic, linear and mixed model analyses were performed including, gender, age, smoking, infections, sampling day, body mass index (BMI) and chemical binders as covariates.RESULTS: The adjusted average respirable quartz and dust concentrations were 0.038 and 0.66 mg/m3, respectively. Statistically significant increases in levels of CC16 were associated with exposure to chemical binders (p = 0.05; p = 0.01) in the regression analysis of quartz and respirable dust, respectively. Non-significant exposure-responses were identified for cumulative quartz and the symptoms asthma and breathlessness. For cumulative chemical years, non-significant exposure-response were observed for all but two symptoms. FENO also exhibited a non significant exposure-response for both quartz and respirable dust. No exposure-response was determined for FEV1 or FVC, CRP and respirable dust and quartz.CONCLUSIONS: Our findings suggest that early markers of pulmonary effect, such as increased levels of CC16 and FENO, are more strongly associated with chemical binder exposure than respirable quartz and dust in foundry environments.
|
|
| 3. |
- Andersson, Lena, 1965-, et al.
(författare)
-
Respiratory Health and Inflammatory Markers : Exposure to Cobalt in the Swedish Hard Metal Industry
- 2020
-
Ingår i: Journal of Occupational and Environmental Medicine. - : Lippincott Williams & Wilkins. - 1076-2752 .- 1536-5948. ; 62:10, s. 820-829
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the relationship between inhalable dust and cobalt and respiratory symptoms, lung function, exhaled nitric oxide in expired air and CC16 in the Swedish hard metal industry.METHODS: Personal sampling of inhalable dust and cobalt, medical examination including blood sampling was performed for 72 workers. Exposure-response relationships was determined using logistic, linear and mixed model analysis.RESULTS: The average inhalable dust and cobalt concentrations were 0.079 and 0.0017 mg/m, respectively. Statistically significant increased serum levels of CC16 were determined when the high and low cumulative exposures for cobalt were compared. Non-significant exposure-response relationships was observed between cross-shift inhalable dust or cobalt exposures and asthma, nose dripping and bronchitis.CONCLUSIONS: Our findings suggest an exposure-response relationship between inhalable cumulative cobalt exposure and CC16 levels in blood, which may reflect an injury or a reparation process in the lungs.
|
|
| 4. |
|
|
| 5. |
- Burguillos Garcia, Miguel, et al.
(författare)
-
Caspase signalling controls microglia activation and neurotoxicity.
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 472, s. 214-319
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-δ-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson's disease (PD) and the frontal cortex of individuals with Alzheimer's disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves.
|
|
| 6. |
- Burguillos Garcia, Miguel, et al.
(författare)
-
Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.
- 2015
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 10:9, s. 1626-1638
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.
|
|
| 7. |
|
|
| 8. |
- Chen, Dongfeng, et al.
(författare)
-
Better Prognosis of Patients with Glioma Expressing FGF2-Dependent PDGFRA Irrespective of Morphological Diagnosis.
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- Signaling of platelet derived growth factor receptor alpha (PDGFRA) is critically involved in the development of gliomas. However, the clinical relevance of PDGFRA expression in glioma subtypes and the mechanisms of PDGFRA expression in gliomas have been controversial. Under the supervision of morphological diagnosis, analysis of the GSE16011 and the Repository of Molecular Brain Neoplasia Data (Rembrandt) set revealed enriched PDGFRA expression in low-grade gliomas. However, gliomas with the top 25% of PDGFRA expression levels contained nearly all morphological subtypes, which was associated with frequent IDH1 mutation, 1p LOH, 19q LOH, less EGFR amplification, younger age at disease onset and better survival compared to those gliomas with lower levels of PDGFRA expression. SNP analysis in Rembrandt data set and FISH analysis in eleven low passage glioma cell lines showed infrequent amplification of PDGFRA. Using in vitro culture of these low passage glioma cells, we tested the hypothesis of gliogenic factor dependent expression of PDGFRA in glioma cells. Fibroblast growth factor 2 (FGF2) was able to maintain PDGFRA expression in glioma cells. FGF2 also induced PDGFRA expression in glioma cells with low or non-detectable PDGFRA expression. FGF2-dependent maintenance of PDGFRA expression was concordant with the maintenance of a subset of gliogenic genes and higher rates of cell proliferation. Further, concordant expression patterns of FGF2 and PDGFRA were detected in glioma samples by immunohistochemical staining. Our findings suggest a role of FGF2 in regulating PDGFRA expression in the subset of gliomas with younger age at disease onset and longer patient survival regardless of their morphological diagnosis.
|
|
| 9. |
- Chen, Dongfeng, et al.
(författare)
-
Glioma Cell Proliferation Controlled by ERK Activity-Dependent Surface Expression of PDGFRA.
- 2014
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Increased PDGFRA signaling is an essential pathogenic factor in many subtypes of gliomas. In this context the cell surface expression of PDGFRA is an important determinant of ligand sensing in the glioma microenvironment. However, the regulation of spatial distribution of PDGFRA in glioma cells remains poorly characterized. Here, we report that cell surface PDGFRA expression in gliomas is negatively regulated by an ERK-dependent mechanism, resulting in reduced proliferation of glioma cells. Glioma tumor tissues and their corresponding cell lines were isolated from 14 patients and analyzed by single-cell imaging and flow cytometry. In both cell lines and their corresponding tumor samples, glioma cell proliferation correlated with the extent of surface expression of PDGFRA. High levels of surface PDGFRA also correlated to high tubulin expression in glioma tumor tissue in vivo. In glioma cell lines, surface PDGFRA declined following treatment with inhibitors of tubulin, actin and dynamin. Screening of a panel of small molecule compounds identified the MEK inhibitor U0126 as a potent inhibitor of surface PDGFRA expression. Importantly, U0126 inhibited surface expression in a reversible, dose- and time-dependent manner, without affecting general PDGFRA expression. Treatment with U0126 resulted in reduced co-localization between PDGFRA and intracellular trafficking molecules e.g. clathrin, RAB11 and early endosomal antigen-1, in parallel with enhanced co-localization between PDGFRA and the Golgi cisternae maker, Giantin, suggesting a deviation of PDGFRA from the endosomal trafficking and recycling compartment, to the Golgi network. Furthermore, U0126 treatment in glioma cells induced an initial inhibition of ERK1/2 phosphorylation, followed by up-regulated ERK1/2 phosphorylation concomitant with diminished surface expression of PDGFRA. Finally, down-regulation of surface PDGFRA expression by U0126 is concordant with reduced glioma cell proliferation. These findings suggest that manipulation of spatial expression of PDGFRA can potentially be used to combat gliomas.
|
|
| 10. |
- de Bont, Jeroen, et al.
(författare)
-
Mixtures of long-term exposure to ambient air pollution, built environment and temperature and stroke incidence across Europe
- 2023
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 179
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The complex interplay of multiple environmental factors and cardiovascular has scarcely been studied. Within the EXPANSE project, we evaluated the association between long-term exposure to multiple environmental indices and stroke incidence across Europe.Methods: Participants from three traditional adult cohorts (Germany, Netherlands and Sweden) and four administrative cohorts (Catalonia [region Spain], Rome [city-wide], Greece and Sweden [nationwide]) were followed until incident stroke, death, migration, loss of follow-up or study end. We estimated exposures at residential addresses from different exposure domains: air pollution (nitrogen dioxide (NO2), particulate matter < 2.5 μm (PM2.5), black carbon (BC), ozone), built environment (green/blue spaces, impervious surfaces) and meteorology (seasonal mean and standard deviation of temperatures). Associations between environmental exposures and stroke were estimated in single and multiple-exposure Cox proportional hazard models, and Principal Component (PC) Analyses derived prototypes for specific exposures domains. We carried out random effects meta-analyses by cohort type.Results: In over 15 million participants, increased levels of NO2 and BC were associated with increased higher stroke incidence in both cohort types. Increased Normalized Difference Vegetation Index (NDVI) was associated with a lower stroke incidence in both cohort types, whereas an increase in impervious surface was associated with an increase in stroke incidence. The first PC of the air pollution domain (PM2.5, NO2 and BC) was associated with an increase in stroke incidence. For the built environment, higher levels of NDVI and lower levels of impervious surfaces were associated with a protective effect [%change in HR per 1 unit = −2.0 (95 %CI, −5.9;2.0) and −1.1(95 %CI, −2.0; −0.3) for traditional adult and administrative cohorts, respectively]. No clear patterns were observed for distance to blue spaces or temperature parameters.Conclusions: We observed increased HRs for stroke with exposure to PM2.5, NO2 and BC, lower levels of greenness and higher impervious surface in single and combined exposure models.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Ericson Lindquist, Kajsa, et al.
(författare)
-
Immunohistochemical Loss of the DNA Mismatch Repair Proteins MSH2 and MSH6 in Malignant Fibrous Histiocytomas.
- 2004
-
Ingår i: Sarcoma. - 1357-714X. ; 8:4, s. 123-127
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Soft tissue sarcomas (STS) account for less than 1% of all malignancies and constitute a heterogeneous tumor entity in which malignant fibrous histiocytomas (MFH) represent one-third and are characterized by a lack of type-specific differentiation. A defective mismatch repair (MMR) system cause the familial cancer syndrome hereditary non-polyposis colorectal cancer (HNPCC), and since occasional MFH have been described in HNPCC patients we assessed the contribution of defective MMR to the development of MFH.Methods: MMR status was characterized in a series of 209 histopathologically reviewed MFH. Tissue microarray sections from the tumors were immunohistochemically stained for the MMR proteins MLH1, MSH2 and MSH6, and cases with aberrant staining were further characterized for microsatellite instability.Results and Discussion: Two of the 209 STS-a storiform-pleomorphic MFH and a myxofibrosarcoma-showed concomitant loss of MSH2 and MSH6, but retained staining for MLH1 on both cases. The myxoid tumor also had a microsatellite unstable phenotype. These findings, together with previous observations of defective MMR in pleomorphic STS, indicate that these tumors may be part of the HNPCC-associated tumor spectrum and demonstrate that MMR defects occur in a small subset of STS.
|
|
| 14. |
|
|
| 15. |
- Fernebro, Josefin, et al.
(författare)
-
Standardizing evaluation of sarcoma proliferation - higher Ki-67 expression in the tumor periphery than the center
- 2007
-
Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 115:6, s. 707-712
-
Tidskriftsartikel (refereegranskat)abstract
- Soft tissue sarcomas often present as large and histopathologically heterogenous tumors. Proliferation has repeatedly been identified as a prognostic factor and immunostaining for Ki-67 represents the most commonly used proliferation marker. There is, however, a lack of consensus on how to evaluate Ki-67 staining regarding optimal cut-off levels, selection of tumor areas, and the number of tumor cells to evaluate. We assessed the impact of targeting peripheral versus central tumor areas using tissue microarray-based staining for Ki-67 throughout the tumor diameter in 25 leiomyosarcomas. In 18/25 tumors, Ki-67 expression was higher in the tumor periphery. If 10% staining tumor nuclei was used as cut-off and the maximal Ki-67 staining section in the tumor periphery was considered, 21/25 tumors would have been classified as highly proliferative compared to 14/25 if the tumor center had been analyzed. Similar results were obtained also when higher cut-off levels were used and if the mean expression rather than the maximal expression was considered and the differences were neither caused by necrosis nor by hypoxia (assessed as HIF-1 alpha expression). Our findings suggest that the determination of proliferation in soft tissue sarcomas should be standardized for clinical application of Ki-67 as a prognostic marker.
|
|
| 16. |
|
|
| 17. |
- Freitag, C., et al.
(författare)
-
Visualizing the entire DNA from a chromosome in a single frame
- 2015
-
Ingår i: Biomicrofluidics. - : AIP Publishing. - 1932-1058. ; 9:4
-
Tidskriftsartikel (refereegranskat)abstract
- The contiguity and phase of sequence information are intrinsic to obtain complete understanding of the genome and its relationship to phenotype. We report the fabrication and application of a novel nanochannel design that folds megabase lengths of genomic DNA into a systematic back-and-forth meandering path. Such meandering nanochannels enabled us to visualize the complete 5.7 Mbp (1mm) stained DNA length of a Schizosaccharomyces pombe chromosome in a single frame of a CCD. We were able to hold the DNA in situ while implementing partial denaturation to obtain a barcode pattern that we could match to a reference map using the Poland-Scheraga model for DNA melting. The facility to compose such long linear lengths of genomic DNA in one field of view enabled us to directly visualize a repeat motif, count the repeat unit number, and chart its location in the genome by reference to unique barcode motifs found at measurable distances from the repeat. Meandering nanochannel dimensions can easily be tailored to human chromosome scales, which would enable the whole genome to be visualized in seconds. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.
|
|
| 18. |
- Frykholm, Karolin, 1977, et al.
(författare)
-
Probing concentration-dependent behavior of DNA-binding proteins on a single-molecule level illustrated by Rad51
- 2013
-
Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 443:2, s. 261-268
-
Tidskriftsartikel (refereegranskat)abstract
- Low throughput is an inherent problem associated with most single-molecule biophysical techniques. We have developed a versatile tool for high-throughput analysis of DNA and DNA-binding molecules by combining microfluidic and dense DNA arrays. We use an easy-to-process microfluidic flow channel system in which dense DNA arrays are prepared for simultaneous imaging of large amounts of DNA molecules with single-molecule resolution. The Y-shaped microfluidic design, where the two inlet channels can be controlled separately and precisely, enables the creation of a concentration gradient across the microfluidic channel as well as rapid and repeated addition and removal of substances from the measurement region. A DNA array stained with the fluorescent DNA-binding dye YOYO-1 in a gradient manner illustrates the method and serves as a proof of concept. We have applied the method to studies of the repair protein Rad51 and could directly probe the concentration-dependent DNA-binding behavior of human Rad51 (HsRad51). In the low-concentration regime used (100 nM HsRad51 and below), we detected binding to double-stranded DNA (dsDNA) without positive cooperativity. (C) 2013 Elsevier Inc. All rights reserved.
|
|
| 19. |
- Hoibakk, Ralph, et al.
(författare)
-
A New Development of the Classical Single Ladder Problem via Converting the Ladder to a Staircase
- 2021
-
Ingår i: Mathematics. - : MDPI. - 2227-7390. ; 9:4
-
Tidskriftsartikel (refereegranskat)abstract
- Our purpose is to shed some new light on problems arising from a study of the classical Single Ladder Problem (SLP). The basic idea is to convert the SLP to a corresponding Single Staircase Problem. The main result (Theorem 1) shows that this idea works fine and new results can be obtained by just calculating rational solutions of an algebraic equation. Some examples of such concrete calculations are given and examples of new results are also given. In particular, we derive a number of integer SLPs with congruent ladders, where a set of rectangular boxes with integer sides constitutes a staircase along a common ladder. Finally, the case with a regular staircase along a given ladder is investigated and illustrated with concrete examples.
|
|
| 20. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 21. |
- Hudson, Lawrence N., et al.
(författare)
-
The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
-
Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
-
Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
|
|
| 22. |
- Høibakk, Ralph, et al.
(författare)
-
A New Look at the Single Ladder Problem (SLP) via Integer Parametric Solutions to the Corresponding Quartic Equation
- 2020
-
Ingår i: Mathematics. - : MDPI. - 2227-7390. ; 8:2, s. 1-21
-
Tidskriftsartikel (refereegranskat)abstract
- The aim is to put new light on the single ladder problem (SLP). Some new methods for finding complete integer solutions to the corresponding quartic equation z(4) - 2Lz(3) + ( L-2 - a(2) - b(2))z(2) + 2La(2)z - L(2)a(2) = 0 are developed. For the case L >= L-min, these methods imply a complete parametric representation for integer solutions of SLP in the first quadrant. Some corresponding (less complete) results for the case L > L-min are also pointed out.
|
|
| 23. |
- Høibakk, Ralph, et al.
(författare)
-
On some power means and their geometric constructions
- 2018
-
Ingår i: Mathematica Æterna. - : Hilaris Ltd. - 1314-3336 .- 1314-3344. ; 8:3, s. 139-158
-
Tidskriftsartikel (refereegranskat)abstract
- The main aim of this paper is to further develop the recently initiatedresearch concerning geometric construction of some power means wherethe variables are appearing as line segments. It will be demonstratedthat the arithmetic mean, the harmonic mean and the quadratic meancan be constructed for any number of variables and that all power meanswhere the number of variables are n = 2m, m 1 2 N for all powersk = 2?q and k = 2q; q 2 N can be geometrically constructed.
|
|
| 24. |
- Igra, Annachiara Malin, et al.
(författare)
-
Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy and timing of pubertal onset in a longitudinal mother-child cohort in rural Bangladesh
- 2024
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 189
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In experimental studies, several polycyclic aromatic hydrocarbons (PAHs) have shown endocrine disrupting properties, but very few epidemiological studies have examined their impact on pubertal development and results have been heterogenous. Objective: To explore if maternal PAH exposure during pregnancy was associated with the offspring's timing of pubertal onset. Methods: We studied 582 mother-daughter dyads originating from a population-based cohort in a rural setting in Bangladesh. Maternal urinary samples, collected in early pregnancy (on average, gestational week 8), were analyzed for monohydroxylated metabolites of phenanthrene (1-OH-Phe, E2-,3-OH-Phe, and 4-OH-Phe), fluorene (E2-,3-OH-Flu), and pyrene (1-OH-Pyr) using liquid chromatography with tandem mass spectrometry (LCMS/MS). The girls were interviewed on two separate occasions concerning date of menarche, as well as breast and pubic hair development according to Tanner. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox proportional hazards regression or ordered logistic regression. Results: In early pregnancy, the mothers' median urinary concentrations of E1-,2-,3-,4-OH-Phe, E2-,3-OH-Flu, and 1-OH-Pyr were 3.25 ng/mL, 2.0 ng/mL, and 2.3 ng/mL respectively. At the second follow-up, 78 % of the girls had reached menarche, and the median age of menarche was 12.7 +/- 0.81 years. Girls whose mothers belonged to the second and third quintiles of EOH-Phe metabolites had a higher rate of menarche, indicating a younger menarcheal age (HR 1.39; 95 % CI 1.04, 1.86, and HR 1.41; 95 % CI 1.05, 1.88, respectively), than girls of mothers in the lowest quintile. This trend was not observed in relation to either breast or pubic hair development. None of the other maternal urinary PAH metabolites or the sum of all thereof in early pregnancy were associated with age at menarche or pubertal stage. Conclusions: Indications of non-monotonic associations of prenatal phenanthrene exposure with the daughters' age of menarche were found, warranting further investigation.
|
|
| 25. |
- Karlsson, Christine, et al.
(författare)
-
Genetic intratumour heterogeneity in high-grade brain tumours is associated with telomere-dependent mitotic instability.
- 2007
-
Ingår i: Neuropathology & Applied Neurobiology. - : Wiley. - 1365-2990 .- 0305-1846. ; 33:4, s. 440-454
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) and other high-grade brain tumours are typically characterized by complex chromosome abnormalities and extensive intratumour cytogenetic heterogeneity. The mechanisms behind this diversity have been little explored. In this study, we analysed the pattern of chromosome segregation at mitosis in 20 brain tumours. We found an abnormal segregation of chromatids at mitosis through anaphase bridging (10-25% of anaphase cells) in all 10 GBMs. Anaphase bridging was also found in two medulloblastomas (7-15%), one anaplastic astrocytoma (17%) and one oligodendroglioma (6%). These tumours showed a relatively high degree of cytogenetic complexity and heterogeneity. In contrast, cell division abnormalities were not found in low-grade brain tumours with less complex karyotypes, including two pilocytic astrocytomas and two ependymomas. Further analysis of two GBMs by fluorescence in situ hybridization with telomeric repeat probes revealed excessive shortening of TTAGGG repeats, indicating dysfunctional protection of chromosome ends. In xenografts established from these GBMs, there was a gradual reduction in cytogenetic heterogeneity through successive passages as the proportion of abnormally short telomeres was reduced and the frequency of anaphase bridges decreased from >25% to 0. However, bridging could be reintroduced in late-passage xenograft cells by pharmacological induction of telomere shortening, using a small-molecule telomerase inhibitor. Telomere-dependent abnormal segregation of chromosomes at mitosis is thus a common phenomenon in high-grade brain tumours and may be one important factor behind cytogenetic intratumour diversity in GBM.
|
|
| 26. |
- Karlsson, Johanna, et al.
(författare)
-
Att ta tillvara och bygga vidare på tidigare kunskaper (ämnesspecifik text: bild)
- 2018
-
Annan publikation (populärvet., debatt m.m.)abstract
- För att kunna utmana elever på åldersadekvat nivå behöver lärare känna till elevernas tidigare kunskaper och erfarenheter. Resultatet från den inledande bedömningen (Kartläggningsmaterialet steg 1 och 2) ger en del information, men bedömningen behöver kompletteras med korta inledande kartläggningar inför varje arbetsmoment. För en bildlärare med nyanlända elever i elevgruppen handlar det om att bygga vidare på den ämneskunskap som eleven har med sig in i klassrummet och att med den som utgångspunkt kunna bedriva en språk- och kunskapsutvecklande undervisning som är kognitivt utmanande för alla elever.
|
|
| 27. |
- Karlsson, Johanna, et al.
(författare)
-
Skrivutveckling i alla ämnen (ämnesspecifik text: bild)
- 2018
-
Annan publikation (populärvet., debatt m.m.)abstract
- För att stötta nyanlända elever i skriftliga uppgifter i bildämnet kan läraren använda sig av cirkelmodellens fyra steg i textframställningen. Genom att gemensamt bygga upp ämneskunskaper, studera den texttyp som ska skrivas och formulera en första text ges eleven bättre möjligheter att klara en individuell skrivuppgift. Andra konkreta redskap som skrivmallar och begreppslistor fungerar också stöttande i skrivundervisningen
|
|
| 28. |
|
|
| 29. |
- Kaufmann, Tobias, et al.
(författare)
-
Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
-
Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
-
Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
|
|
| 30. |
- Lambe, Mats, et al.
(författare)
-
Reductions in use of hormone replacement therapy: effects on Swedish breast cancer incidence trends only seen after several years.
- 2010
-
Ingår i: Breast cancer research and treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 121:3, s. 679-83
-
Tidskriftsartikel (refereegranskat)abstract
- Studies from Western countries have found evidence of a recent decline in breast cancer incidence rates in postmenopausal women, findings which have been hypothesized to reflect a reduced use of hormonal replacement therapy (HRT). We examined breast cancer incidence trends in Sweden between 1997 and 2007, a period characterized by a drop in the use of HRT. Incidence trends were assessed using data from three population-based Regional Clinical Registries on breast cancer covering 2/3 of the Swedish population. Information on HRT sales was obtained from national pharmacy data. The prevalence of HRT use in age group 50-59 years decreased from a peak of 36% in 1999 to 27% in 2002 and further to 9% in 2007. Incidence rates of breast cancer in women 50 years and older increased between 1997 and 2003. A significant decrease in incidence between 2003 and 2007 was confined to women 50-59 years of age, the group in which the prevalence of HRT use has been highest and the decrease in use most pronounced. As opposed to the immediate effects reported from the United States and other regions, there was a time lag between the drop in HRT use and clear reductions in breast cancer incidence. This may reflect between country differences with regard to types of HRT used, and the rate, magnitude and pattern of change in use. The present findings give further support to the notion that HRT use is a driver of breast cancer incidence trends on the population level.
|
|
| 31. |
- Lindberg, Eva, et al.
(författare)
-
Concurrent gain of 17q and the MYC oncogene in a medullomyoblastoma
- 2007
-
Ingår i: Neuropathology. - : Wiley. - 0919-6544 .- 1440-1789. ; 27:6, s. 556-560
-
Tidskriftsartikel (refereegranskat)abstract
- Medullomyoblastoma (MMB) is a rare cerebellar childhood tumor containing both myoblastic and primitive neuroectodermal components. Similar to the scenario in classical medulloblastoma, which contains the primitive neuroectodermal component only, gain of sequences from the long arm of chromosome 17 (17q) and gain of the MYC gene in 8q have been implicated in the pathogenesis of MMB. Because karyotypic analysis has not previously been performed for MMB, the mechanisms behind genomic imbalances in this tumor have remained unknown. Several other central aspects of this tumor, such as histocytogenetic origin, clinical characteristics, tumor behavior and prognosis, also remain unknown. We here report neuropathological and cytogenetic features of an MMB in a 3-year-old boy. Chromosome banding analysis and multicolor karyotyping revealed a hyperdiploid karyotype including an unbalanced 1; 17 translocation and isochromosome 17q formation, both leading to gain of 17q. There were also two extra copies of chromosome 8, leading to gain of the MYC oncogene, trisomies 5 and 13, and monosomy 9. Clonal chromosome changes were present in both the myoblastic and neuroectodermal components. Our findings support the notion that MMB and classical medulloblastoma arise through similar genetic mechanisms and that the two main tissue components in MMB are clonally related.
|
|
| 32. |
- Lukkassen, Dag, et al.
(författare)
-
Nonlinear variational methods for estimating effective properties of multiscale materials
- 2010
-
Ingår i: Nonlinear analysis and variational problems. - Berlin : Encyclopedia of Global Archaeology/Springer Verlag. - 9781441901583 ; , s. 367-414
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- We consider homogenization of sequences of integral functionals with natural growth conditions. Some means are analyzed and used to discuss some fairly new bounds for the homogenized integrand corresponding to integrands which are periodic in the spatial variable. These bounds, which are obtained by variational methods, are compared with the nonlinear bounds of Wiener and Hashin-Shtrikman type. We also point out conditions that make our bounds sharp. Several applications are presented. Moreover, we also discuss bounds for some linear reiterated two-phase problems with m different micro-levels in the spatial variable. In particular, the results imply that the homogenized integrand becomes optimal as m turns to infinity. Both the scalar case (the conductivity problem) and the vector-valued case (the elasticity problem) are considered. In addition, we discuss bounds for estimating the effective behavior described by homogenizing a problem which is a generalization of the Reynold equation.
|
|
| 33. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
|
|
| 34. |
|
|
| 35. |
- Nilsson, Madeleine, 1964, et al.
(författare)
-
Coping in relation to perceived threat of the risk of graft rejection and Health-Related Quality of Life of organ transplant recipients
- 2013
-
Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 1471-6712 .- 0283-9318. ; 27:4, s. 935-944
-
Tidskriftsartikel (refereegranskat)abstract
- The most serious risk connected with transplantations besides infection is graft rejection. Organ transplant recipients (OTRs) perceive graft rejection as a stress factor and a threat. The primary aim of the present study was to examine types of coping used to handle the threat of the risk of graft rejection among OTRs and to investigate relations between coping and perceived threat as well as Health-Related Quality of Life (HRQoL). A second aim was to test the General Coping Questionnaire (GCQ) for reliability in relation to the threat of the risk of graft rejection. Three different questionnaires, the Perceived Threat of the Risk of Graft Rejection (PTGR), GCQ and the SF-36, were mailed to 229 OTRs between 19 and 65years old. Patients were transplanted with a kidney, a liver or a heart and/or a lung. All patients with follow-up time of 1year +/- 3months and 3years +/- 3months were included. With an 81% response rate, the study comprised of 185 OTRs. The differences between the transplanted organ groups in their use of coping were small. Likewise, coping related weakly with sex, age, time since transplantation and whether they had experienced graft rejections or not. The respondents tended in general to use more of the positive' coping (strategies related to positive well-being). The measured coping in relation to the perceived threat of the risk of graft rejection seem to be relatively stable over time and quite independent of demographic and clinical variables.
|
|
| 36. |
- Nilsson, Madeleine, et al.
(författare)
-
The perceived threat of the risk for graft rejection and health-related quality of life among organ transplant recipients
- 2011
-
Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 20:1-2, s. 274-282
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. This study was primarily aimed for developing and testing a valid and reliable instrument that measures perceived threat of the risk for graft rejection after organ transplantation. A second aim was to report descriptive data regarding graft rejection and Health-Related Quality of Life. Background. The most serious risk connected with transplantations besides infection is graft rejection. Design. Non experimental, descriptive involving instrument development and psychometric assessment. Method. Questionnaires about perceived threat of the risk for graft rejection and Health-Related Quality of Life were mailed to 229 OTRs between 19-65 years old. The items were formed from a previous interview study. Patients were transplanted with a kidney, a liver or a heart and/or a lung. All patients with follow-up time of one year +/- three months and three years +/- three months were included. Results. With an 81% response rate, the study comprised of 185 OTRs, who had received either a kidney (n = 117), a liver (n = 39) or heart or lung (n = 29). Three homogenous factors of perceived threat for graft rejection were revealed, labelled 'intrusive anxiety', 'graft-related threat' and 'lack of control'. Tests of internal consistency showed good item-scale convergent and discriminatory validity. A majority of the OTRs scored low levels for 'intrusive anxiety'. The kidney transplant recipients experienced more 'graft-related threat' by acute graft rejection than those transplanted with a liver, heart or lung. Conclusion. In conclusion, this study suggests that it is possible to measure the perceived threat of the risk for graft rejection in three homogenous factors. Relevance to clinical practice. The instrument perceived threat of the risk for graft rejection, might be usable to measure the impact of fear of graft rejection, to predict needs of pedagogical intervention strategies to reduce fear and to improve Health-Related Quality of Life related to graft rejection.
|
|
| 37. |
|
|
| 38. |
- Persson, Annette, et al.
(författare)
-
Cell type- and region- dependent coxsackie adenovirus receptor expression in the central nervous system.
- 2006
-
Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 1573-7373 .- 0167-594X. ; 78:1, s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- Model systems have shown that adenoviral vector mediated transient gene expression can potentially be applied for the treatment of brain tumours, neurodegenerative diseases and brain injuries. Most studies utilized adenovirus serotype 5 (Ad5) based vectors, which as adhesion molecules require the coxsackie adenovirus receptor (CAR) as a critical determinant for cellular infection. In this report, we have systematically characterized CAR expression in the adult human central nervous system (CNS) by using immunohistochemistry. A total of 85 specimens from various CNS regions were investigated for CAR expression in a cell type-dependent context. The most marked staining positivity was found in the choroid plexus and the pituitary gland. The neocortex had scattered positive neurons, while the white matter was mainly negative. We need to consider the possible adverse effects and the possible damage caused by adenoviral gene therapy if the virus-vector also binds to normal brain cells.
|
|
| 39. |
|
|
| 40. |
- Persson, Annette, et al.
(författare)
-
Different assessments of immunohistochemically stained Ki-67 and hTERT in glioblastoma multiforme yield variable results: a study with reference to survival prognosis.
- 2008
-
Ingår i: Clinical Neuropathology. - 0722-5091. ; 27:4, s. 224-233
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate a marker of tumor proliferation, Ki-67, and telomerase expression in glioblastoma multiforme and to compare the results of different mainly quantitative assessments, in relation to age and survival rates. METHODS: Immunohistochemical stainings of Ki-67 and hTERT were evaluated in 39 formaldehyde-fixed, paraffin-embedded surgical samples of glioblastoma multiforme diagnosed during 2004, comprising all specimens with sufficient amount of vital tissue sent to the Department of Pathology during this year. Ki-67 counting and hTERT evaluation was assessed on whole tumor sections and on selected areas within each section. Age and length of survival were analyzed in relation to these parameters. RESULTS: We found that different methods of evaluating the stained sections yielded different results regarding Ki-67, but less marked differences for hTERT. With Ki-67 counting on whole sections (non-selected areas), we found a statistically significant correlation with length of survival. There was no corresponding information in the hTERT assessment. We could also confirm a significant inverse correlation between age and length of survival, as previously published. CONCLUSION: Our data demonstrate that different methods of Ki-67 evaluation may give markedly dissimilar results. The significant correlation found between survival and one but not with two other methods of Ki-67 assessment, implicate the value of standardized quantification methods. Our data indicate a possible prognostic use of immunohistochemical Ki-67 proliferation index in glioblastoma multiforme.
|
|
| 41. |
- Persson, Annette
(författare)
-
Glioblastoma multiforme in the microscope: Diagnostic features of importance for prognosis and treatment.
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glioblastoma multiforme (GBM) is the most malignant and also the most common form of brain tumour in humans. The overall aim of this thesis was to investigate morphological and diagnostics features in human GBM that may be of importance for prognosis and treatment. Immunohistochemically stained tissue sections have been microscopically analysed regarding immuno-reactive cells, cell proliferation, telomerase activity and presence of coxsackie adenovirus receptor (CAR). While telomerase activity reflects inherent life prolongation, CAR act as adhesion molecules on target cells in adenoviral based gene therapy. We found that cytotoxic T-lymfocytes (CTL) occurred spontaneously in GBM but also that a transient increase was detected after immunotherapy. Macrophage positive cells were in general plentiful. GBM as well as other grades of gliomas, expressed low levels of CAR while neuroblastomas and medulloblastomas exhibited a high CAR expression. However, various regions and cell types of the normal brain also expressed CAR. Proliferation activity (Ki-67) showed a significant correlation to longer survival if index was below 10 %, while telomerase activity (hTERT) showed no relation to length of survival. Different methods of assessment of Ki-67 are of relevance for histopathological diagnostics. This project indicates that morphological features of importance for prognosis and treatment can be identified by the use of established and simple, reliable methods, routinely applied in clinical pathological diagnostics.
|
|
| 42. |
|
|
| 43. |
- Persson, Annette, et al.
(författare)
-
Neuroblastomas and medulloblastomas exhibit more Coxsackie adenovirus receptor expression than gliomas and other brain tumors.
- 2007
-
Ingår i: Neuropathology. - : Wiley. - 0919-6544 .- 1440-1789. ; 27:3, s. 233-236
-
Tidskriftsartikel (refereegranskat)abstract
- Adenoviral vector-mediated treatment is a potential therapy for tumors of the central nervous system. To obtain a significant therapeutic effect by adenoviral vectors, a sufficient infection is required, the power of which depends predominantly on the level of Coxsackie adenovirus receptors. We stained surgical biopsies of central nervous system tumors and neuroblastomas for Coxsackie adenovirus receptors. For gliomas, the level of the receptor was low and markedly variable among individual tumors. By contrast, neuroblastomas and medulloblastomas exhibited a higher degree of Coxsackie adenovirus receptor expression than gliomas and other brain tumors. We conclude that neuroblastomas and medulloblastomas could be suitable for adenovirus-mediated gene therapy. Adverse effects of the treatment, however, must be considered because neurons and reactive astrocytes also express a significant amount of the receptor.
|
|
| 44. |
- Persson, Annette, et al.
(författare)
-
Phagocytic properties in tumor astrocytes.
- 2012
-
Ingår i: Neuropathology. - : Wiley. - 0919-6544. ; 32, s. 252-260
-
Tidskriftsartikel (refereegranskat)abstract
- In glioblastoma multiforme (GBM), the pathophysiological events preceding and promoting an uncontrolled and remarkable growth is largely unknown. Studies on gliomas and macrophage expression have shown high levels of phagocytic cells, that is, microglial cells. It has also been demonstrated that human astrocytic cells and rat glioma cells are capable of phagocytosis. The purpose of this study was to investigate a potential phagocytic property in human GBM cells in tumor biopsies from surgery. With an immunhistochemical double staining using macrophage markers (CD68 and CD163) and human telomerase reverse transcriptase (hTERT) as a marker for neoplastic cells, we found high levels of double positive cells in human GBM. In hematoxylin-erythrosin stained sections, we also identified fragmented cell components in the cytoplasm of tumor cells. In our judgement, many neoplastic cells in GBM are also positive for macrophage markers. We suggest that human astroglial tumor cells may have phagocytic properties or phagocyte-like properties. This may represent a latent capacity of self-defence, evoked under certain circumstances. It is likely that these properties substantially help the tumors thrive and expand.
|
|
| 45. |
|
|
| 46. |
- Persson, Annette, et al.
(författare)
-
The glioma cell edge - winning by engulfing the enemy?
- 2009
-
Ingår i: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 73, s. 336-337
-
Tidskriftsartikel (refereegranskat)abstract
- Malignant glioma and glioblastoma multiforme form the largest group of highly malignant brain tumours, for which there is yet no definitive cure. Different approaches to treatment have been tried, in vain or with minimal benefit for the patient. In addition to surgery, radiation and chemotherapy, immunotherapy aiming at evoking an inflammatory reaction against the tumour itself has been tried. Immunotherapy has shown good results in an experimental mouse model, but no convincing efficacy/success in patients. Why are the gliomas always winning, how do they take the lead? The following phenomena lead us to propose an hypothesis about the reason for the glioma lead: the reported findings of phagocytic activity in reactive and neoplastic astrocytes in animal models and humans; the frequently observed ingested "non-self material"/debris in glioma cells; the markedly high contents of tumour cells with phagocytic phenotype in gliomas and the signs of only limited and temporary inflammatory reactions in different immunotherapy attempts. Whether it being a true phagocytosis, an engulfing or comparable activity by the glioma cells, contributing to the tumour's self defense against e.g. antitumoural therapies, it should be beneficial to attempt hampering these self defense properties e.g. by blocking their engulfing capacity.
|
|
| 47. |
- Persson, Karin, et al.
(författare)
-
LDL and UV-oxidized LDL induce upregulation of iNOS and NO in unstimulated J774 macrophages and HUVEC
- 2009
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 117:1, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- Oxidized low-density lipoprotein (LDL) diminishes NO production from activated macrophages. The interaction between LDL and inactivated macrophages is neglected and controversial. This study examines the effect of LDL, 7-oxysterols and iron compounds on NO production in unstimulated J774 macrophages. J774 cells and human umbilical vein endothelial cells (HUVEC) were either incubated for 24 h with native LDL (LDL) or ultraviolet (UV)-oxidized LDL (UVoxLDL), in the absence or presence of an inducible nitric oxide synthase (iNOS)- or an endothelial constitutive nitric oxide synthase (eNOS)-inhibitor. J774 cells were also incubated with lipopolysaccharide (LPS), in the absence or presence of an iNOS- or an eNOS-inhibitor. Nitrite was analysed as a marker of NO production. The mRNA levels of iNOS were evaluated by reverse transcriptase polymerase chain reaction. LDL and UVoxLDL significantly increased NO production from unstimulated J774 macrophages. This increase in NO was accompanied by enhanced expression of iNOS mRNA, and was inhibited by the iNOS inhibitor. Furthermore, NO production was elevated and angiotensin-converting enzyme (ACE) activity was reduced in HUVEC following the exposure to LDL and UVoxLDL. In conclusion, LDL may serve as an important inflammatory activator of macrophages and HUVEC, inducing inducible nitric oxide production but diminishing ACE. After its oxidation, this function of LDL may be further enhanced and may contribute to the regulation and progression of atheroma formation.
|
|
| 48. |
- Persson Skare, Tor, et al.
(författare)
-
Novel anti-VEGF therapeutics
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Excessive and chronic vascular leakage in pathologies such as eye diseases leads to edema, tissue ischemia and disease progression. To suppress vascular leakage by blocking vascular endothelial growth factor (VEGF) function is clinically beneficial. However, development of new, topically applied therapeutic options is important as intravitreal injections currently carried out to deliver anti-VEGF therapeutics is expensive and may have serious side effects. VEGF receptor-2 (VEGFR2) activates Src family kinases via binding the T cell specific adaptor (TSAd) to its phosphotyrosine residue Y951. These molecular interactions are required for gap formation at endothelial junctions and vascular leakage. Here, we describe the identification from a high throughput screen, of a small molecular weight inhibitor (LC1) which blocks the interaction between the phosphorylated VEGFR2 kinase domain and TSAd. LC1 binds to TSAd in surface plasmon resonance analysis. In intact cells, LC1 suppresses VEGFR2 kinase activity while if fails to inhibit kinase activity in an in vitro biochemical kinase screen of 35 kinases including VEGFR2. Superfusion of retinal explants blocks vascular leakage from retinal vessels. In conclusion, we have identified a compound which specifically blocks VEGFR2 function in endothelial cells.
|
|
| 49. |
|
|
| 50. |
- Rebetz, Johan, et al.
(författare)
-
Glial Progenitor-Like Phenotype in Low-Grade Glioma and Enhanced CD133-Expression and Neuronal Lineage Differentiation Potential in High-Grade Glioma
- 2008
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6, s. 1107-1107
-
Tidskriftsartikel (refereegranskat)abstract
- Background: While neurosphere-as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified. Methodology/Principal Findings: Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFR alpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRa, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype. Conclusions/Significance: This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas.
|
|
