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Search Results: 1 - 10 of 224263 matches for " Madeleine R?dinger "
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Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways
Zhi-Hua Cui, Madeleine Rdinger, Margareta Sj?strand, Jan L?tvall
Clinical and Translational Allergy , 2012, DOI: 10.1186/2045-7022-2-7
Abstract: A trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge.Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways.The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.Early phase airway response to allergen and airway plasma exudation are predominantly mediated by inflammatory mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2) [1-3] released from mast cells in the response to allergen challenge [4-7]. In asthmatic patients, the concentrations of cysLTs and TXA2 are increased in plasma, urine and BAL fluid during asthma exacerbation and after experimental allergen challenges [8-11]. Thus, these mediators can induce both airway constriction and airway plasma exudation in several species [3,12-14]. Production of these mediators needs the substrate arachidonic acid and enzymes such as 5-lipo
Airway allergen exposure stimulates bone marrow eosinophilia partly via IL-9
Brigita Sitkauskiene, Madeleine Rdinger, Apostolos Bossios, Anna-Karin Johansson, Raimundas Sakalauskas, Jan L?tvall
Respiratory Research , 2005, DOI: 10.1186/1465-9921-6-33
Abstract: OVA-sensitized Balb/c mice were intraperitoneally pretreated with a single dose (100 μg) of an anti-mouse IL-9 monoclonal antibody (clone D9302C12) or its vehicle. A third group was given 50 μg of a monoclonal anti-mouse IL-5 antibody (TRFK-5) or its vehicle. Animals were subsequently exposed to OVA on five days via airways. Newly produced eosinophils were labelled using 5-bromo-2'-deoxyuridine (BrdU). BrdU+ eosinophils and CD34+ cell numbers were examined by immunocytochemistry. After culture and stimulation with OVA or PMA+IC, intracellular staining of IL-9 in bone marrow cells from OVA-exposed animals was measured by Flow Cytometry. The Mann-Whitney U-test was used to determine significant differences between groups.Anti-IL-9 significantly reduced bone marrow eosinophilia, primarily by decrease of newly produced (BrdU+) and mature eosinophils. Anti-IL-9 treatment also reduced blood neutrophil counts, but did not affect BAL neutrophils. Anti-IL-5 was able to reduce eosinophil numbers in all tissue compartments, as well as BrdU+ eosinophils and CD34+ progenitor cells, and in all instances to a greater extent than anti-IL-9. Also, FACS analysis showed that IL-9 is over-expressed in bone marrow CD4+ cells after allergen exposure.Our data shows that a single dose of a neutralizing IL-9 antibody is not sufficient to reduce allergen-induced influx of newly produced cells from bone marrow to airways. However, in response to allergen, bone marrow cells over-express IL-9. This data suggest that IL-9 may participate in the regulation of granulocytopoiesis in allergic inflammation.Airway eosinophilic inflammation is a predominant feature of asthma. Eosinophils are believed to be involved in several features of asthma through the release of cationic granule proteins, reactive oxygen radicals, a variety of cytokines and bronchoconstrictive mediators [1-4]. The regulation of the eosinophil in asthma is considered to be orchestrated by the Th2-cell, which can release a range of
Expansion of CD4+CD25+ and CD25- T-Bet, GATA-3, Foxp3 and RORγt Cells in Allergic Inflammation, Local Lung Distribution and Chemokine Gene Expression
You Lu,Carina Malmh?ll,Margareta Sj?strand,Madeleine Rdinger,Serena E. O'Neil,Jan L?tvall,Apostolos Bossios
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019889
Abstract: Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2′-deoxyuridine (BrdU) together with 7-aminoactnomycin (7-AAD). The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet+, GATA-3+, RORγt+ and Foxp3+ cells in CD4+CD25+ and CD4+CD25- T cells, with the greatest expansion of GATA-3+ cells. The majority of CD4+CD25+ T-bet+, GATA-3+, RORγt+ and Foxp3+ cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet+, GATA-3+ and Foxp3+ cells in peribronchial and alveolar tissue, GATA-3+ and Foxp3+ cells in perivascular tissue, and RORγt+ cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu.
Immunophenotyping of Circulating T Helper Cells Argues for Multiple Functions and Plasticity of T Cells In Vivo in Humans - Possible Role in Asthma
Carina Malmh?ll, Apostolos Bossios, Madeleine Rdinger, Margareta Sj?strand, You Lu, Bo Lundb?ck, Jan L?tvall
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040012
Abstract: Background The immune process driving eosinophilic and non-eosinophilic asthma is likely driven by different subsets of T helper (Th) cells. Recently, in vitro studies and animal studies suggest that Th cell subsets displays plasticity by changing their transcription factor or by expressing multiple transcription factors. Our aim was to determine whether individuals with asthma and elevated circulating eosinophils express signs of different regulatory immune mechanisms compared with asthmatics with low blood eosinophils and non-asthmatic control subjects. In addition, determine the relationship between eosinophilia and circulating Th cell subsets. Methodology/Principal findings Participants were selected from a random epidemiological cohort, the West Sweden Asthma Study. Immunophenotypes of fresh peripheral blood cells obtained from stable asthmatics, with and without elevated eosinophilic inflammation (EOS high and EOS low respectively) and control subjects, were determined by flow cytometry. No differences in the number of Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt) or Treg (FOXP3) cells were observed between the groups when analysing each subset separately. However, in all groups, each of the Th subsets showed expression of additional canonical transcription factors T-bet, GATA-3, RORγt and FOXP3. Furthermore, by in vitro stimulation with anti-CD3/anti-CD28 there was a significant increase of single expressing GATA-3+ and co-expressing T-bet+GATA-3+ cells in the EOS high asthmatics in comparison with control subjects. In addition, T-bet?GATA-3+RORγt+FOXP3+ were decreased in comparison to the EOS low asthmatics. Finally, in a group of control subjects we found that the majority of proliferating Th cells (CD4+CD25+Ki67+) expressed three or four transcription factors. Conclusions The ability of human Th cells to express several regulatory transcription factors suggests that these cells may display plasticity in vivo.
Regulatory role of CD8+ T lymphocytes in bone marrow eosinophilopoiesis
Madeleine Rdinger, Svetlana Sergejeva, Anna-Karin Johansson, Carina Malmh?ll, Apostolos Bossios, Margareta Sj?strand, James J Lee, Jan L?tvall
Respiratory Research , 2006, DOI: 10.1186/1465-9921-7-83
Abstract: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3+ T lymphocytes (NJ.1638; CD3IL-5+ mice) were bred with gene knockout mice lacking either CD4+ T lymphocytes (CD4-/-) or CD8+ T lymphocytes (CD8-/-) to produce CD3IL-5+ knockout mice deficient in CD4+ T lymphocytes (CD3IL-5+/CD4-/-) and CD8+ T lymphocytes (CD3IL-5+/CD8-/-), respectively. Secondly, CD3+, CD4+ and CD8+ T lymphocytes from na?ve CD3IL-5+ and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3IL-5+, CD3IL-5+/CD8-/- and CD3IL-5+/CD4-/- mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments.The number of BM eosinophils was significantly reduced in CD3IL-5+/CD8-/- mice compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice. Serum IL-5 was significantly higher in CD3IL-5+/CD4-/- mice compared to CD3IL-5+ mice but there was no difference in serum IL-5 between CD3IL-5+/CD4-/- and CD3IL-5+/CD8-/- mice. Adoptive transfer of CD8+, but not CD4+ T lymphocytes from na?ve CD3IL-5+ and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3IL-5+/CD8-/- mice developed lower numbers of BM eosinophils compared to CD3IL-5+ mice and CD3IL-5+/CD4-/- mice.This study shows that CD8+ T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice.One important pathologic feature of allergic airway inflammation is associated with T lymphocyte activation and increase in eosinophil numbers in the airways [1-3]. Accumulation of eosinophils is considered to be the result of increased production and traffic of cells from the bone marrow (BM) into the airways via the circulation [4,5]. A substantial body of evidence suggests that BM eosinophilopoiesis is enhanced in allergic patients as well as in animal models of allergen-
Strengthening the Gauss-Lucas theorem for polynomials with Zeros in the interior of the convex hull
Andreas Rüdinger
Mathematics , 2014,
Abstract: According to the classical Gauss-Lucas theorem all zeros of the derivative of a complex non-constant polynomial p lie in the convex hull of the zeros of p. It is proved that for a polynomial p of degree four with four different zeros forming a concave quadrilateral, the zeros of the derivative lie in two of the three triangles formed by the zeros of p. Thus a strengthening of the classical Gauss-Lucas theorem is established for this case, which can be extended to the case of a polynomial of degree n for which the zeros do not form a convex n-polygon.
As investiga??es "leigas" e a dinamica das controvérsias em saúde ambiental
Barthe, Yannick;Akrich, Madeleine;Rémy, Catherine;
Sociologias , 2011, DOI: 10.1590/S1517-45222011000100005
Abstract: starting from the existing literature, this paper proposes an analytical framework to capture the general dynamics of the controversies in environmental health and, more particularly, the role of the 'layman' in this issue, within democratic societies. the article emphasizes the importance of a research work conducted by non-specialists to provide tangible demonstration of the existence of a health problem related to their environment. this research work provides for two processes that are at the center of the dynamics of these controversies: the victimization, i.e., the transformation of ill people into victims; and the questioning, i.e., the attribution of certain pathologies to environmental factors. the identification of these two processes, which may be concurrent, makes it possible to distinguish different settings and to understand how a controversy evolves over time.
Differentiating Protein-Coding and Noncoding RNA: Challenges and Ambiguities
Marcel E. Dinger ,Ken C. Pang ,Tim R. Mercer ,John S. Mattick
PLOS Computational Biology , 2008, DOI: 10.1371/journal.pcbi.1000176
Abstract: The assumption that RNA can be readily classified into either protein-coding or non-protein–coding categories has pervaded biology for close to 50 years. Until recently, discrimination between these two categories was relatively straightforward: most transcripts were clearly identifiable as protein-coding messenger RNAs (mRNAs), and readily distinguished from the small number of well-characterized non-protein–coding RNAs (ncRNAs), such as transfer, ribosomal, and spliceosomal RNAs. Recent genome-wide studies have revealed the existence of thousands of noncoding transcripts, whose function and significance are unclear. The discovery of this hidden transcriptome and the implicit challenge it presents to our understanding of the expression and regulation of genetic information has made the need to distinguish between mRNAs and ncRNAs both more pressing and more complicated. In this Review, we consider the diverse strategies employed to discriminate between protein-coding and noncoding transcripts and the fundamental difficulties that are inherent in what may superficially appear to be a simple problem. Misannotations can also run in both directions: some ncRNAs may actually encode peptides, and some of those currently thought to do so may not. Moreover, recent studies have shown that some RNAs can function both as mRNAs and intrinsically as functional ncRNAs, which may be a relatively widespread phenomenon. We conclude that it is difficult to annotate an RNA unequivocally as protein-coding or noncoding, with overlapping protein-coding and noncoding transcripts further confounding this distinction. In addition, the finding that some transcripts can function both intrinsically at the RNA level and to encode proteins suggests a false dichotomy between mRNAs and ncRNAs. Therefore, the functionality of any transcript at the RNA level should not be discounted.
Characterization of body weight and composition changes during the sophomore year of college
Holly R Hull, Michelle L Morrow, Mary K Dinger, Jennifer L Han, David A Fields
BMC Women's Health , 2007, DOI: 10.1186/1472-6874-7-21
Abstract: Body composition by dual energy X-ray absorptiometry was obtained in participants beginning during their freshman year and continued through their sophomore year.No difference was observed between sophomore year fall and spring visits for body weight (60.4 versus 60.6 kg) or fat mass (19.3 versus 18.7 kg). However, a significant (P ≤ 0.05) decrease was observed for body fat (31.9 versus 30.9 %fat) and a significant increase was observed for fat-free mass (37.7 versus 38.4 kg). Participants living off campus significantly (P ≤ 0.05) declined in body fat (33.0 versus 31.0 %fat) and fat mass (19.4 versus 18.2 kg) and increased in fat-free mass (36.1 versus 37.2 kg) with no differences in those living on campus.No change in body weight was observed in females during their sophomore year. However, an increase in fat-free mass accompanied with a decrease in fat mass resulted in a decrease in body fat. Participants living off campus had favorable changes in their body composition by means of decreasing %fat and fat mass while increasing fat-free mass. Participants living on campus did not demonstrate these favorable changes.It is widely accepted that substantial weight gain occurs during the first year of college therefore the phrase 'Freshman 15' is often echoed on college campuses. However no study has actually shown the purported 15 pound increase, instead an average of 1.9 kg (4.2 pound) has been reported between all studies completed [1-11]. Possibly more important and warranting further inquiry than weight gained in solely the first year of college is whether weight gained is lost, maintained or if additional weight is added. This information could provide a crucial model of slow weight gain thought to be at the root of our current obesity epidemic.Increases in obesity levels are commonly attributed to small prolonged increases in energy intake resulting in a gradual consistent yearly weight gain. In young adults this has been estimated to be approximately 0.2 to 0.8
The effect of the Thanksgiving Holiday on weight gain
Holly R Hull, Duncan Radley, Mary K Dinger, David A Fields
Nutrition Journal , 2006, DOI: 10.1186/1475-2891-5-29
Abstract: 94 college students (23.0 ± 4.6 yrs, 72.1 ± 14.0 kg, 172.6 ± 9.3 cm, 24.0 ± 3.9 kg/m2) reported to the human body composition laboratory at the University of Oklahoma following a 6-hour fast with testing occurring prior to, and immediately following the Thanksgiving holiday break (13 ± 3 days). Body weight (BW) was assessed using a balance beam scale while participants were dressed in minimal clothing. Paired t-tests were used to assess changes in BW pre and post Thanksgiving holiday with additional analysis by gender, body mass index (BMI), and class standing (i.e. undergraduate vs. graduate).Overall, a significant (P < 0.05) increase in BW was found between pre (72.1 kg) and post (72.6 kg) Thanksgiving holiday. When stratified by gender and class standing a significant (P < 0.05) increase in body weight was observed between the pre and post Thanksgiving holiday in males (0.6 kg), females (0.4 kg) and graduate students (0.8 kg). When participants were classified by BMI as normal or as overweight/obese, a significant 1.0 kg BW gain was found (P < 0.05) in the overweight/obese (≥25 kg/m2) group compared to a non significant 0.2 kg gain in the normal group (<25 kg/m2).These data indicate that participants in our study gained a significant amount of BW (0.5 kg) during the Thanksgiving holiday. While an increase in BW of half a kilogram may not be cause for alarm, the increase could have potential long-term health consequences if participants retained this weight gain throughout the college year. Additionally, because the overweight/obese participants gained the greatest amount of BW, this group may be at increased risk for weight gain and further obesity development during the holiday season.In the United States 1 in 5 college students are classified as obese [1]. Perhaps more alarming is that previous research indicates obesity rates rising fastest in 18 to 29 year olds and those with some college education [2]. These are grave statistics given that for the first time
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