1,763 research outputs found
Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus
BACKGROUND: IL-33 has recently been found to be the specific ligand of ST2, an IL-1 receptor family member that is selectively expressed on Th2 cells and mediates Th2 response. This study aimed to measure serum levels of soluble form of ST2 (sST2) and IL-33 in patients with systemic lupus erythematosus (SLE) and to examine its association with disease activity. METHODS: Seventy SLE patients were evaluated for disease activity determined by SLE disease activity index (SLEDAI), serological features (anti-dsDNA antibody, C3 and C4) and 57 patients were evaluated longitudinally on a second occasion. IL-33 and sST2 were measured by sandwich ELISA in the 127 SLE serum samples and compared to 28 age- and sex-matched healthy controls. RESULTS: Serum sST2 level was significantly higher in SLE patients with active disease (0.51+0.18 ng/mL) compared to those with inactive disease (0.42+0.08 ng/mL) [P=0.006] and to normal controls (0.36+0.13 ng/mL) [P<0.001]. sST2 level correlated significantly and positively with SLEDAI, level of anti-dsDNA antibody and prednisolone dosage and negatively with C3 and remained significantly predictive of active disease after adjustment for prednisolone use in logistic regression analysis (odds ratio=4.6, P=0.01). sST2 level was sensitive to change in disease activity in longitudinal evaluation and not influenced by age, gender, and renal function. Elevated serum IL-33 was comparable in frequency (4.3% vs 7.1%, P=0.62) and levels (P=0.53) between SLE patients and controls. CONCLUSION: Elevated serum sST2 level in SLE patients was found to correlate with disease activity and was sensitive to change, suggesting a potential role as surrogate marker of disease activity.published_or_final_versionThe 15th Medical Research Conference (15th MRC), Department of Medicine, University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 n. 1, suppl. 1, p. 46, abstract no. 7
Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood
OBJECTIVE:
Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance.
METHODS:
Foxp3 and IL-17 coexpression were evaluated in CD4 T lymphocytes from RA patients. An in vitro T cell polarisation assay was performed to investigate the role of proinflammatory cytokines in IL-17-producing Treg polarisation. The suppressive function of IL-17-producing Tregs in RA was assessed by an in vitro suppression assay. The relationship between this Treg subset and clinical features in RA patients was analysed using Spearman's rank correlation test.
RESULTS:
A higher frequency of IL-17-producing Tregs was present in the peripheral blood of RA patients compared with healthy subjects. These cells from peripheral blood showed phenotypic characteristics of Th17 and Treg cells, and suppressed T cell proliferation in vitro. Tregs in RA synovial fluid lost suppressive function. The Th17 plasticity of Tregs could be induced by IL-6 and IL-23. An increased ratio of this Treg subset was associated with decreased levels of inflammatory markers, including the erythrocyte sedimentation rate and C-reactive protein level, in patients with RA.
CONCLUSIONS:
Increased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic.postprin
Instantons and Killing spinors
We investigate instantons on manifolds with Killing spinors and their cones.
Examples of manifolds with Killing spinors include nearly Kaehler 6-manifolds,
nearly parallel G_2-manifolds in dimension 7, Sasaki-Einstein manifolds, and
3-Sasakian manifolds. We construct a connection on the tangent bundle over
these manifolds which solves the instanton equation, and also show that the
instanton equation implies the Yang-Mills equation, despite the presence of
torsion. We then construct instantons on the cones over these manifolds, and
lift them to solutions of heterotic supergravity. Amongst our solutions are new
instantons on even-dimensional Euclidean spaces, as well as the well-known
BPST, quaternionic and octonionic instantons.Comment: 40 pages, 2 figures v2: author email addresses and affiliations adde
Understanding the nature of "superhard graphite"
Numerous experiments showed that on cold compression graphite transforms into
a new superhard and transparent allotrope. Several structures with different
topologies have been proposed for this phase. While experimental data are
consistent with these models, the only way to solve this puzzle is to find
which structure is kinetically easiest to form. Using state-of-the-art
molecular-dynamics transition path sampling simulations, we investigate kinetic
pathways of the pressure-induced transformation of graphite to various
superhard candidate structures. Unlike hitherto applied methods for elucidating
nature of superhard graphite, transition path sampling realistically models
nucleation events necessary for physically meaningful transformation kinetics.
We demonstrate that nucleation mechanism and kinetics lead to -carbon as the
final product. -carbon, initially competitor to -carbon, is ruled out by
phase growth. Bct-C structure is not expected to be produced by cold
compression due to less probable nucleation and higher barrier of formation
The skeletal phenotype of chondroadherin deficient mice
Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3â6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth
Wet Granular Materials
Most studies on granular physics have focused on dry granular media, with no
liquids between the grains. However, in geology and many real world
applications (e.g., food processing, pharmaceuticals, ceramics, civil
engineering, constructions, and many industrial applications), liquid is
present between the grains. This produces inter-grain cohesion and drastically
modifies the mechanical properties of the granular media (e.g., the surface
angle can be larger than 90 degrees). Here we present a review of the
mechanical properties of wet granular media, with particular emphasis on the
effect of cohesion. We also list several open problems that might motivate
future studies in this exciting but mostly unexplored field.Comment: review article, accepted for publication in Advances in Physics;
tex-style change
Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay
The decay channel
is studied using a sample of events collected
by the BESIII experiment at BEPCII. A strong enhancement at threshold is
observed in the invariant mass spectrum. The enhancement can be fit
with an -wave Breit-Wigner resonance function with a resulting peak mass of
and a
narrow width that is at the 90% confidence level.
These results are consistent with published BESII results. These mass and width
values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics
Association of ICAM3 genetic variant with severe acute respiratory syndrome
Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3, were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS infection caused by the novel coronavirus (SARS-CoV) was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P = .0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P = .022; OR, 0.30 [95% CI, 0.10-0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio
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