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Search Results: 1 - 10 of 217255 matches for " Heidi W?h?maa "
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High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts
Heidi Whmaa, Hanna Schierbeck, Hulda S Hreggvidsdottir, Karin Palmblad, Anne-Charlotte Aveberger, Ulf Andersson, Helena Harris
Arthritis Research & Therapy , 2011, DOI: 10.1186/ar3450
Abstract: Synovial fibroblasts obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients were stimulated with HMGB1 alone or in complex with LPS, IL-1α or IL-1β. Tumour necrosis factor (TNF) production was determined by enzyme-linked immunospot assay (ELISPOT) assessment. Levels of IL-10, IL-1-β, IL-6 and IL-8 were measured using Cytokine Bead Array and matrix metalloproteinase (MMP) 3 production was determined by ELISA.Stimulation with HMGB1 in complex with LPS, IL-1α or IL-1β enhanced production of TNF, IL-6 and IL-8. HMGB1 in complex with IL-1β increased MMP production from both RASF and OASF. The cytokine production was inhibited by specific receptor blockade using detoxified LPS or IL-1 receptor antagonist, indicating that the synergistic effects were mediated through the partner ligand-reciprocal receptors TLR4 and IL-1RI, respectively.HMGB1 in complex with LPS, IL-1α or IL-1β boosted proinflammatory cytokine- and MMP production in synovial fibroblasts from RA and OA patients. A mechanism for the pathogenic role of HMGB1 in arthritis could thus be through enhancement of inflammatory and destructive mechanisms induced by other proinflammatory mediators present in the arthritic joint.The highly conserved protein high mobility group box protein 1 (HMGB1) exerts vital functions in the nucleus of all eukaryotic cells. When tissue injury is inflicted and inflammation is induced, HMGB1 can be released extracellularly and can then convey inflammatory functions. Extracellular HMGB1 may induce cytokine production, up-regulation of adhesion molecules on endothelial cells and activation of dendritic cells and T cells [1-11]. The reported presence of extracellular HMGB1 in multiple inflammatory conditions and the beneficial effects of HMGB1 blockade in preclinical models of inflammatory diseases have thus led to the acknowledgement of HMGB1 as an inflammatory mediator with pathogenic functions in several inflammatory diseases (reviewed in [12]).HMGB1 interacts with th
Oxaliplatin retains HMGB1 intranuclearly and ameliorates collagen type II-induced arthritis
Therese ?stberg, Heidi Whmaa, Karin Palmblad, Norimasa Ito, Pernilla Stridh, Maria Shoshan, Michael T Lotze, Helena Harris, Ulf Andersson
Arthritis Research & Therapy , 2008, DOI: 10.1186/ar2347
Abstract: Oxaliplatin-based therapy was evaluated in collagen type II-induced arthritis in DBA/1 mice by clinical scoring and immunostaining of articular tissue. Oxaliplatin is an antineoplastic platinum-based compound that generates DNA adducts which tightly bind HMGB1. Secretion and intracellular location of HMGB1 were assessed by a novel HMGB1-specific ELISPOT assay and immunofluorescent staining.Intraperitoneal injections of oxaliplatin in early collagen type II-induced arthritis trapped HMGB1 with a distinct biphasic response pattern. Oxaliplatin therapy showed beneficial results for approximately 1 week. Microscopic evaluation of synovitis during this period showed strong nuclear HMGB1 staining in the oxaliplatin treated animals with much lower quantities of extracellular HMGB1 when compared to control treated animals. Furthermore, cellular infiltration, as well as cartilage and bone damage, were all reduced in the oxaliplatin treated group. A dramatic and as yet unexplained clinical relapse occurred later in the oxaliplatin exposed animals, which coincided with a massive synovial tissue expression of extracellular HMGB1 in all treated animals. This rebound-like reaction was also accompanied by a significantly increased incidence of arthritis in the oxaliplatin treated group. These results indicate a distinct temporal and spatial relationship between the clinical course of disease and the cellular localization of HMGB1. Beneficial effects were noted when extracellular HMGB1 expression was low, while severe inflammation coincided with substantial extracellular synovial HMGB1 expression.Therapeutic compounds like oxaliplatin and gold salts share a capacity to inhibit nuclear HMGB1 release and to ameliorate the course of synovial inflammation. These observations support the hypothesis that HMGB1 plays an important functional role in the pathogenesis of arthritis and may represent a novel target molecule for therapy.Major progress has been achieved during the last decade in
A multilevel layout algorithm for visualizing physical and genetic interaction networks, with emphasis on their modular organization
Johannes Tuikkala, Heidi V?hmaa, Pekka Salmela, Olli S Nevalainen, Tero Aittokallio
BioData Mining , 2012, DOI: 10.1186/1756-0381-5-2
Abstract: We implemented a modified layout plug-in, named Multilevel Layout, which applies the conventional layout algorithms within a multilevel optimization framework to better capture the hierarchical modularity of many biological networks. Using a wide variety of real life biological networks, we carried out a systematic evaluation of the method in comparison with other layout algorithms in Cytoscape.The multilevel approach provided both biologically relevant and visually pleasant layout solutions in most network types, hence complementing the layout options available in Cytoscape. In particular, it could improve drawing of large-scale networks of yeast genetic interactions and human physical interactions. In more general terms, the biological evaluation framework developed here enables one to assess the layout solutions from any existing or future graph drawing algorithm as well as to optimize their performance for a given network type or structure.By making use of the multilevel modular organization when visualizing biological networks, together with the biological evaluation of the layout solutions, one can generate convenient visualizations for many network biology applications.Network graphs provide a valuable conceptual framework for representing and mining high-throughput experimental datasets, as well as for extracting and interpreting their biological information by the means of graph-based analysis approaches [1-8]. In cellular systems, network nodes typically refer to biomolecules, such as genes or proteins, and the edge connections the type of relationships the network is encoding, including physical or functional information. Network visualization aims to organize the complex network structures in a way that provides the user with readily apparent insights into the most interesting biological patterns and relationships within the data, such as components of biological pathways, processes or complexes, which can be further investigated by follow-up computation
PolyAlign: A Versatile LC-MS Data Alignment Tool for Landmark-Selected and -Automated Use
Heidi V?hmaa,Ville R. Koskinen,Waltteri Hosia,Robert Moulder,Olli S. Nevalainen,Riitta Lahesmaa,Tero Aittokallio,Jussi Salmi
International Journal of Proteomics , 2011, DOI: 10.1155/2011/450290
Abstract: We present a versatile user-friendly software tool, PolyAlign, for the alignment of multiple LC-MS signal maps with the option of manual landmark setting or automated alignment. One of the spectral images is selected as a reference map, and after manually setting the landmarks, the program warps the images using either polynomial or Hermite transformation. The software provides an option for automated landmark finding. The software includes a very fast zoom-in function synchronized between the images, which facilitate detecting correspondences between the adjacent images. Such an interactive visual process enables the analyst to decide when the alignment is satisfactory and to correct known irregularities. We demonstrate that the software provides significant improvements in the alignment of LC-MALDI data, with 10–15 landmark pairs, and it is also applicable to correcting electrospray LC-MS data. The results with practical data show substantial improvement in peak alignment compared to MZmine, which was among the best analysis packages in a recent assessment. The PolyAlign software is freely available and easily accessible as an integrated component of the popular MZmine software, and also as a simpler stand-alone Perl implementation to preview data and apply landmark directed polynomial transformation. 1. Introduction With the emergence of liquid chromatography coupled to mass spectrometry (LC-MS) as a predominant method for bioanalysis, a number of software packages have been tailored for the alignment of data sets from multiple LC-MS analyses. In particular these and related algorithms have targeted comparative metabolomic and proteomics applications and have been widely demonstrated to provide an improved level of comparison for complex samples. Several of these methods have been recently reviewed by Katajamaa and Oresic [1], Vandenbogaert et al. [2], America and Cordewener [3], and Lange et al. [4]. The methods can be divided into two specific groups as follows. There are methods which identify and select significant features from the raw data that are used as a reference for alignment; here we refer to these as feature-based methods. Alternatively, there are those that use the whole data, which we refer to as profile-based methods. The data points from LC-MS analyses can be defined by their mass-to-charge ratios ( ), retention times, and intensities. This combination of numeric attributes is often referred to as a feature vector and when one of these attributes (usually intensity) is expressed by color scale, these features can be conveniently
Monkey Steering Responses Reveal Rapid Visual-Motor Feedback
Seth W. Egger,Heidi R. Engelhardt,Kenneth H. Britten
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011975
Abstract: The neural mechanisms underlying primate locomotion are largely unknown. While behavioral and theoretical work has provided a number of ideas of how navigation is controlled, progress will require direct physiolgical tests of the underlying mechanisms. In turn, this will require development of appropriate animal models. We trained three monkeys to track a moving visual target in a simple virtual environment, using a joystick to control their direction. The monkeys learned to quickly and accurately turn to the target, and their steering behavior was quite stereotyped and reliable. Monkeys typically responded to abrupt steps of target direction with a biphasic steering movement, exhibiting modest but transient overshoot. Response latencies averaged approximately 300 ms, and monkeys were typically back on target after about 1 s. We also exploited the variability of responses about the mean to explore the time-course of correlation between target direction and steering response. This analysis revealed a broad peak of correlation spanning approximately 400 ms in the recent past, during which steering errors provoke a compensatory response. This suggests a continuous, visual-motor loop controls steering behavior, even during the epoch surrounding transient inputs. Many results from the human literature also suggest that steering is controlled by such a closed loop. The similarity of our results to those in humans suggests the monkey is a very good animal model for human visually guided steering.
Short- and Long-Term Biomarkers for Bacterial Robustness: A Framework for Quantifying Correlations between Cellular Indicators and Adaptive Behavior
Heidy M. W. den Besten,Aarathi Arvind,Heidi M. S. Gaballo,Roy Moezelaar,Marcel H. Zwietering,Tjakko Abee
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013746
Abstract: The ability of microorganisms to adapt to changing environments challenges the prediction of their history-dependent behavior. Cellular biomarkers that are quantitatively correlated to stress adaptive behavior will facilitate our ability to predict the impact of these adaptive traits. Here, we present a framework for identifying cellular biomarkers for mild stress induced enhanced microbial robustness towards lethal stresses. Several candidate-biomarkers were selected by comparing the genome-wide transcriptome profiles of our model-organism Bacillus cereus upon exposure to four mild stress conditions (mild heat, acid, salt and oxidative stress). These candidate-biomarkers—a transcriptional regulator (activating general stress responses), enzymes (removing reactive oxygen species), and chaperones and proteases (maintaining protein quality)—were quantitatively determined at transcript, protein and/or activity level upon exposure to mild heat, acid, salt and oxidative stress for various time intervals. Both unstressed and mild stress treated cells were also exposed to lethal stress conditions (severe heat, acid and oxidative stress) to quantify the robustness advantage provided by mild stress pretreatment. To evaluate whether the candidate-biomarkers could predict the robustness enhancement towards lethal stress elicited by mild stress pretreatment, the biomarker responses upon mild stress treatment were correlated to mild stress induced robustness towards lethal stress. Both short- and long-term biomarkers could be identified of which their induction levels were correlated to mild stress induced enhanced robustness towards lethal heat, acid and/or oxidative stress, respectively, and are therefore predictive cellular indicators for mild stress induced enhanced robustness. The identified biomarkers are among the most consistently induced cellular components in stress responses and ubiquitous in biology, supporting extrapolation to other microorganisms than B. cereus. Our quantitative, systematic approach provides a framework to search for these biomarkers and to evaluate their predictive quality in order to select promising biomarkers that can serve to early detect and predict adaptive traits.
TNFR1 Deficiency Protects Mice from Colitis-Associated Colorectal Cancer Coupled with a Decreased Level of Oxidative Damage in the Colon: Implications for Anti-TNF Therapy of Unremitting Colitis  [PDF]
Rose Marie Stillie, Heidi L. Sapp, Andrew W. Stadnyk
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.326119
Abstract: It has long been appreciated that there is a direct relationship between the intensity and duration of inflammatory bowel diseases (IBD) and increasing intestinal cancer risk but which elements of the inflammatory response are responsible have not been identified. Anti-TNF drugs have been successful at treating IBD but considering the presumed anti-tumor activity of TNF, it is important to understand whether the treatment impacts on the patients’ intestinal cancer risk. We modeled this relationship by “treating mice lacking TNF receptors with a colon cancer causing combination of azoxymethane followed by repeated dextran sulphate sodium exposures (AOM + DSS regime). TNF receptor type1 gene deficient (TNFR1-/-) and TNFR2-/- mice experienced similar clinical illnesses and colonic inflammation as C57BL/6 wildtype controls during the AOM + DSS regime. Despite the inflammation, TNFR1-/- mice developed significantly fewer colon tumors than the other strains. The reduced tumor incidence was a product of the combined lack of receptor expression on hematopoietic and nonhematopoietic cells, shown using bone marrow cell chimeras of wildtype and TNFR1-/- mice. As oxidative damage is a potent contributing factor to tumorigenesis and inflammatory leukocytes make copious amounts of reactive oxygen radicals, we measured oxidative damage in the animals’ colons. TNFR1-/- mice showed less damage compared to the other strains. We subsequently examined mice deficient in their leukocyte NADPH oxidative pathway (Nox2-/-) for their cancer incidence using the AOM + DSS regime. Nox2-/- mice became inflamed but had fewer tumors than wildtype mice. We conclude that TNF promotes colon cancer including through promoting oxidative processes utilizing TNFR1 in leukocytes. Moreover, the C57BL/6 strain can be used to dissociate mechanisms of colon inflammation from tumorigenic processes. We interpret our results to mean that IBD patients on TNF antagonist therapies will potentially benefit with reduced colon cancer risk even if they do not respond with reduced inflammation.
Improving the use of health data for health system strengthening
Tara Nutley,Heidi W. Reynolds
Global Health Action , 2013, DOI: 10.3402/gha.v6i0.20001
Abstract: Background: Good quality and timely data from health information systems are the foundation of all health systems. However, too often data sit in reports, on shelves or in databases and are not sufficiently utilised in policy and program development, improvement, strategic planning and advocacy. Without specific interventions aimed at improving the use of data produced by information systems, health systems will never fully be able to meet the needs of the populations they serve. Objective: To employ a logic model to describe a pathway of how specific activities and interventions can strengthen the use of health data in decision making to ultimately strengthen the health system. Design: A logic model was developed to provide a practical strategy for developing, monitoring and evaluating interventions to strengthen the use of data in decision making. The model draws on the collective strengths and similarities of previous work and adds to those previous works by making specific recommendations about interventions and activities that are most proximate to affect the use of data in decision making. The model provides an organizing framework for how interventions and activities work to strengthen the systematic demand, synthesis, review, and use of data. Results: The logic model and guidance are presented to facilitate its widespread use and to enable improved data-informed decision making in program review and planning, advocacy, policy development. Real world examples from the literature support the feasible application of the activities outlined in the model. Conclusions: The logic model provides specific and comprehensive guidance to improve data demand and use. It can be used to design, monitor and evaluate interventions, and to improve demand for, and use of, data in decision making. As more interventions are implemented to improve use of health data, those efforts need to be evaluated.
In vitro inhibition of camel hepatic glutathione transferases by selected organic azides
MAA Sarhan
Egyptian Journal of Biology , 2010,
Abstract: Glutathione S-transferases (GST) are a group of multifunctional enzymes, widely distributed in both animal and plant kingdom. The present study was carried out to investigate the inhibitory potential of three structurally related organic azides (n-propyl azide, n-butyl azide, and heptyl azide) on camel hepatic GST activity in vitro. The mean inhibition constants (Ki) were estimated to be 0.419 ± 0.068, 0.501 ± 0.068, and 0.563 ± 0.036 mM for n-propyl azide, n-butyl azide, and heptyl azide respectively, using Lineweaver-Burk plots. These results indicated that hepatic GST was sensitive to the organic azides used.
Giant mesenteric cystic lymphangioma presenting with abdominal pain and masquerading as a gynecologic malignancy
John Maa
Rare Tumors , 2009, DOI: 10.4081/rt.2009.e48
Abstract: Lymphangiomas are congenital malformations of the lymphatic system that account for about 5% of all benign tumors in infants and children.1 The most common sites are the neck and axilla, which account for 95% of cases.2 Abdominal cystic lymphangiomas are quite rare, and can arise from either the retroperitoneum, gastrointestinal tract, or the mesentery of the abdominal viscera.3 The presenting symptoms are painless abdominal distension, a palpable mass, or secondary complications in the abdomen such as intestinal obstruction, volvulus, intestinal infarction, or bleeding.4 Typically diagnosed during childhood, these tumors prompt surgical intervention. We describe an atypical case of an abdominal cystic lymphangioma, which did not manifest until adulthood, with atypical symptoms of a rapidly expanding and symptomatic mass.
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