1,942 research outputs found
In vivo differences in leukotriene biosynthesis in zymosan-induced peritonitis: role of resident peritoneal macrophages.
No full textLeukotrienes (LTs) are lipid mediators implicated in inflammatory and autoimmune diseases, often characterized by a sex-
bias in the incidence (e.g., asthma). LTs derive from arachidonic acid through the action of 5-lipoxygenase (5-LO), which
is a soluble protein translocating to perinuclear membranes after activation. We have previously shown sex-differences in
LT formation in human whole blood and leukocytes, due to down-regulation of 5-LO product formation by androgens.
Here we show that LT synthesis is sex-biased
in vivo
, in a model of zymosan-induced peritonitis. After intraperitoneal
injection of zymosan in mice, an immediate production of LTs was observed within 30 min, which was significantly higher
in female then in male mice (about two times). These effects were followed by the recruitment of neutrophils into the
peritoneal cavity, and both infiltrating cell numbers and myeloperoxidase activity (marker for neutrophils) were
significantly higher in females than in males. Interestingly, orchidectomy of male mice resulted in a significant increase of
LT levels in the peritoneal exudates, while a decrease of LTs was observed in ovariectomized female mice, thus suggesting
significant effects of both male and female sex hormones. Mechanistically, we observed that
in vitro
stimulation of resident
peritoneal macrophages from female mice induced higher LTC
4
formation as compared to males, which was not due to
different AA release or 5-LO protein expression, but was accompanied by a different 5-LO subcellular localization. Taking
together, we here demonstrate that LT biosynthesis is sex-biased
in vivo
in mouse zymosan-induced peritonitis, seemingly
related to a different activation status of 5-LO in peritoneal macrophages, with profound consequences on the development
of the inflammatory reaction. These data further support the evaluation of a gender-tailored therapy with anti-LT
ERK-mediated regulation of leukotriene biosynthesis by androgens: a molecular basis for gender differences in inflammation and asthma.
No full text5-Lipoxygenase initiates the biosynthesis of leukotrienes, lipid mediators involved in normal host defense and in inflammatory
and allergic disorders. Despite an obvious gender bias in leukotriene-related diseases (e.g., asthma), gender aspects have been neglected in studies on leukotrienes and 5-alpha-lipoxygenase. Here, we show that leukotriene formation in stimulated whole blood or neutrophils from males is substantially lower compared with females, accompanied by changed 5-lipoxygenase trafficking. This is due to gender-specific differential activation of extracellular signal-regulated kinases (ERKs). The differences are directly related to variant male/female testosterone plus 5-alpha-dihydrotestosterone levels, and addition of 5-alpha-dihydrotestosterone to female blood or neutrophils reduced the high (female) LT biosynthesis capacity to low (male) levels. In conclusion, regulation of ERKs and leukotriene formation by androgens constitutes a molecular basis for gender differences in the inflammatory response, and in inflammatory diseases such as asthma
A Response to Honig and Samuelsson (2014)
No full textHonig and Samuelsson (2014) recently published an article in this outlet criticizing “Does business planning facilitate the development of new ventures? “ a paper I wrote with Scott Shane nearly 15 years ago. They claim that their effort adds to the discussion of (a) the merits of business planning, (b) data replication and extension, (c) sample selection bias, (d) evaluation of normative research and (e) publication standards. However, most of the claims they make are incorrect
A Response to Honig and Samuelsson (2014) [Elektronisk resurs]
No full textHonig and Samuelsson (2014) recently published an article in this outlet criticizing “Does business planning facilitate the development of new ventures? “ a paper I wrote with Scott Shane nearly 15 years ago. They claim that their effort adds to the discussion of (a) the merits of business planning, (b) data replication and extension, (c) sample selection bias, (d) evaluation of normative research and (e) publication standards. However, most of the claims they make are incorrect
The dynamics of neutron star crusts: Lagrangian perturbation theory for a relativistic superfluid-elastic system
No full textThe inner crust of a mature neutron star is composed of an elastic lattice of neutron-rich nuclei penetrated by free neutrons. These neutrons can flow relative to the crust once the star cools below the superfluid transition temperature. In order to model the dynamics of this system, which is relevant for a range of problems from pulsar glitches to magnetar seismology and continuous gravitational-wave emission from rotating deformed neutron stars, we need to understand general relativistic Lagrangian perturbation theory for elastic matter coupled to a superfluid component. This paper develops the relevant formalism to the level required for astrophysical applications
Are neutron stars with crystalline color-superconducting cores relevant for the LIGO experiment?
No full textWe estimate the maximal deformation that can be sustained by a rotating neutron star with a crystalline
color-superconducting quark core. Our results suggest that current gravitational-wave data from the Laser
Interferometer Gravitational-Wave Observatory have already reached the level where a detection would
have been possible over a wide range of the poorly constrained QCD parameters. This leads to the
nontrivial conclusion that compact objects do not contain maximally strained color crystalline cores
drawn from this range of parameter space. We discuss the uncertainties associated with our simple model
and how it can be improved in the future
Modelling magnetically deformed neutron stars
No full textRotating deformed neutron stars are important potential sources for ground-based gravitational wave interferometers such as LIGO, GEO600 and VIRGO. One mechanism that may lead to significant non-asymmetries is the internal magnetic field. It is well known that a magnetic star will not be spherical and, if the magnetic axis is not aligned with the spin axis, the deformation will lead to the emission of gravitational waves. The aim of this paper is to develop a formalism that would allow us to model magnetically deformed stars, using both realistic equations of state and field configurations. As a first step, we consider a set of simplified model problems. Focusing on dipolar fields, we determine the internal magnetic field which is consistent with a given neutron star model and calculate the associated deformation. We discuss the relevance of our results for current gravitational wave detectors and future prospects
Afrodite : Fragment av Sapfo. Kärlekstrilogi nr – 1
No full textFragment av Sapfo översatta av VP och M. W-O, tonsatta av Marie Samuelsson 2015.Uruppförande fred 11/3 19.30 lörd 12/3 15.00 Berwaldhallen Sveriges Radios Symfoniorkester Daniel Blendulf dirigent, Katija Dragojevic mezzosopran </p
Mesenchymal stromal/stem cells : expansion, engraftment and immune modulation
No full textDue to their production of hematopoietic growth factors and their immunomodulatory capacity, bone marrow-derived mesenchymal stromal/stem cells (MSC), are a promising tool in the procedure of hematopoietic stem cell transplantation (HSCT).Seven patients undergoing allogeneic HSCT were co-infused with MSC. Three of the patients were regrafted after a previous rejection. Either HLA-identical or haploidentical MSC were given at the time of HSC infusion. Engraftment was successful in all patients with no untowards effects.Large-scale expansion of MSC intended for clinical use, requires standardized and optimized handling of the cells ex vivo. For safety and regulatory reasons, we explored if fetal calf serum (FCS) in the culture medium could be replaced by human blood group AB serum. Characteristics and immune suppressive function of MSC were not affected by culturing MSC in the alternative serum, and the cell yield was slighlty improved.Cryopreservation of bone marrow derived mononuclear cells negatively influenced the final MSC yield. An increased number of MSC was achieved by increasing the FCS levels above 10% and decreasing the replating density. The suppressive effect of MSC was similar after repeated passaging. Cell viability and immunosuppression in vitro remained high even after several years storage in liquid nitrogen. Mixing MSC from several donors improved suppression. When selecting MSC for immunosuppressive therapy, it would be helpful to have defined markers relating MSC characteristics to their immunosuppressive function. We compared phenotype, growth characteristics and gene expression of MSC with differing immunosuppressive capacity, derived from two donors. MSC from donor 1 consistently suppressed proliferation of activated lymphocytes. This was in contrast to MSC from donor 2, where MSC had no or little inhibition or a stimulating effect. Furthermore, single cell derived cultures from the suppressive donor generated suppressive and non-suppressive clones, indicating that the suppressive phenotype is not inherent to the MSC donor. However, phenotypic differences between all cells from the two donors were too diverse to be efficient for prospective isolation of MSC with suppressive capacity. Thus, the only currently reliable means of validating MSC remain the proposed set of standards focusing on the cells adherence to plastic, the phenotype and trilineage potential. Functional testing by in vitro assays is required to assess the immunosuppressive function.List of scientific papersI. Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, Ljungman P, Lönnies H, Nava S, Ringden O (2007). "Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells." Leukemia 21(8): 1733-8. Epub 2007 May 31 https://pubmed.ncbi.nlm.nih.gov/17541394II. Le Blanc K, Samuelsson H, Lönnies L, Sundin M, Ringden O (2007). "Generation of immunosuppressive mesenchymal stem cells in allogeneic human serum." Transplantation 84(8): 1055-9 https://pubmed.ncbi.nlm.nih.gov/17989613III. Samuelsson H, Ringden O, Lönnies H, Le Blanc K (2009). "Optimizing in vitro conditions for immunomodulation and expansion of mesenchymal stromal cells." Cytotherapy 11(2): 129-36 https://pubmed.ncbi.nlm.nih.gov/19152151IV. Samuelsson H, Ringden O, Kumagai-Braesch M, Rosendahl K, Le Blanc K (2009). "Characterization of clonal and polyclonal mesenchymal stromal cells with different immunosuppressive capacity." (Manuscript)</p
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