Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan- And dose-dependent. At concentrations ≤0.25 μM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1-induced migration. Exposure to concentrations ≥1 μM resulted in ERK(1/2)- dependent apoptosis and disruption of the F- Actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1-deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.Fil: Ge, Xiao Na. University of Minnesota; Estados UnidosFil: Ha, Sung Gil. University of Minnesota; Estados UnidosFil: Greenberg, Yana G.. University of Minnesota; Estados UnidosFil: Rao, Amrita. University of Minnesota; Estados UnidosFil: Bastan, Idil. University of Minnesota; Estados UnidosFil: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rao, Savita P.. University of Minnesota; Estados UnidosFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sriramarao, P.. University of Minnesota; Estados Unido

Spin dependent extension of Calogero-Sutherland model through anyon like representations of permutation operators

We consider a $A_{N-1}$ type of spin dependent Calogero-Sutherland model, containing an arbitrary representation of the permutation operators on the combined internal space of all particles, and find that such a model can be solved as easily as its standard $su(M)$ invariant counterpart through the diagonalisation of Dunkl operators. A class of novel representations of the permutation operator $P_{ij}$, which pick up nontrivial phase factors along with interchanging the spins of $i$-th and $j$-th particles, are subsequently constructed. These `anyon like' representations interestingly lead to different variants of spin Calogero-Sutherland model with highly nonlocal interactions. We also explicitly derive some exact eigenfunctions as well as energy eigenvalues of these models and observe that the related degeneracy factors crucially depend on the choice of a few discrete parameters which characterise such anyon like representations.Comment: 25 pages, plain LaTex file, the results of sec.4 are presented in a more explicit way, to appear in Nucl. Phys.

Evaluation of the MODS Culture Technique for the Diagnosis of Tuberculous Meningitis

Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropraite chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratories and PCR requires expertise with advanced infrastructure and has sensitivity of only around 60% under optimal conditions. Neither technique allows for the microbiological isolation of M. tuberculosis and subsequent drug susceptibility testing. We evaluated the recently developed microscopic observation drug susceptibility (MODS) assay format for speed and accuracy in diagnosing TBM.Two hundred and thirty consecutive CSF samples collected from 156 patients clinically suspected of TBM on presentation at a tertiary referal hospital in Vietnam were enrolled into the study over a five month period and tested by Ziehl-Neelsen (ZN) smear, MODS, Mycobacterial growth Indicator tube (MGIT) and Lowenstein-Jensen (LJ) culture. Sixty-one samples were from patients already on TB therapy for >1day and 19 samples were excluded due to untraceable patient records. One hundred and fifty samples from 137 newly presenting patients remained. Forty-two percent (n = 57/137) of patients were deemed to have TBM by clinical diagnostic and microbiological criteria (excluding MODS). Sensitivity by patient against clinical gold standard for ZN smear, MODS MGIT and LJ were 52.6%, 64.9%, 70.2% and 70.2%, respectively. Specificity of all microbiological techniques was 100%. Positive and negative predictive values for MODS were 100% and 78.7%, respectively for HIV infected patients and 100% and 82.1% for HIV negative patients. The median time to positive was 6 days (interquartile range 5-7), significantly faster than MGIT at 15.5 days (interquartile range 12-24), and LJ at 24 days (interquartile range 18-35 days) (P<0.01).We have shown MODS to be a sensitive, rapid technique for the diagnosis of TBM with high sensitivity, ease of performance and low cost (0.53 USD/sample)

Correlation Between Tumor Necrosis Factor Alpha and Proteinuria in Type-2 Diabetic Patients

Introduction: Diabetic Nephropathy (DN) is the single most common cause of end stage renal disease (ESRD) in many countries. Inflammation is a potential factor in the development and progression of DN and recent data indicate that diabetes includes an inflammatory component which may contribute to diabetic complications. Methods: This study was conducted at Ain Shams University Hospital on 95 patients with type-2 diabetes mellitus complicated with retinopathy and fifteen age- and sex-matched healthy volunteers. Diabetic patients were divided into 4 groups according to the degree of proteinuria. Serum tumor necrosis factor-α (TNF-α), urine TNF-α and C-reactive protein (CRP) levels were measured in all subjects. Correlations between these inflammatory parameters and degree of proteinuria, duration of diabetes and degree of glycemic control were examined. Results: Levels of the three inflammatory parameters were significantly higher in diabetic patients when compared to control subjects, and they were positively correlated to urinary protein excretion. There was significant positive correlation between serum and urine TNF-α and duration of diabetes, as well as between serum TNF-α and glycemic control. Serum and urine TNF-α remained as independent predictors of urine protein excretion in diabetic patients with overt proteinuria after forward stepwise multiple regression analysis. Conclusion: Serum and urine TNF-α and CRP levels are significantly elevated in this group of diabetic patients, and correlate positively with severity of proteinuria. This suggests a significant role for TNF-α in the pathogenesis and progression of renal injury in diabetes mellitus. Keywards: Diabetic nephropathy; Proteinuria; Tumor necrosis factor-

Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities

Acute myocardial infarction (AMI) and the heart failure that often follows, are major causes of death and disability worldwide. As such, new therapies are required to limit myocardial infarct (MI) size, prevent adverse left ventricular (LV) remodeling, and reduce the onset of heart failure following AMI. The inflammatory response to AMI, plays a critical role in determining MI size, and a persistent pro-inflammatory reaction can contribute to adverse post-MI LV remodeling, making inflammation an important therapeutic target for improving outcomes following AMI. In this article, we provide an overview of the multiple players (and their dynamic roles) involved in the complex inflammatory response to AMI and subsequent LV remodeling, and highlight future opportunities for targeting inflammation as a therapeutic strategy for limiting MI size, preventing adverse LV remodeling, and reducing heart failure in AMI patients

Long Range Interaction Models and Yangian Symmetry

The generalized Sutherland-Romer models and Yan models with internal spin degrees are formulated in terms of the Polychronakos' approach and RTT relation associated to the Yang-Baxter equation in consistent way. The Yangian symmetry is shown to generate both models. We finally introduce the reflection algebra K(u) to the long range models.Comment: 13 pages, preprint of Nankai Institute of Mathematics ( Theoretical Physics Division ), published in Physical Review E of 1995. For hard copy, write to Prof. Mo-lin GE directly. Do not send emails to this accoun

Numerical Investigation of the Performance of Three Hinge Designs of Bileaflet Mechanical Heart Valves

Thromboembolic complications (TECs) of bileaflet mechanical heart valves (BMHVs) are believed to be due to the nonphysiologic mechanical stresses imposed on blood elements by the hinge flows. Relating hinge flow features to design features is, therefore, essential to ultimately design BMHVs with lower TEC rates. This study aims at simulating the pulsatile three-dimensional hinge flows of three BMHVs and estimating the TEC potential associated with each hinge design. Hinge geometries are constructed from micro-computed tomography scans of BMHVs. Simulations are conducted using a Cartesian sharp-interface immersed-boundary methodology combined with a second-order accurate fractional-step method. Leaflet motion and flow boundary conditions are extracted from fluid–structure-interaction simulations of BMHV bulk flow. The numerical results are analyzed using a particle-tracking approach coupled with existing blood damage models. The gap width and, more importantly, the shape of the recess and leaflet are found to impact the flow distribution and TEC potential. Smooth, streamlined surfaces appear to be more favorable than sharp corners or sudden shape transitions. The developed framework will enable pragmatic and cost-efficient preclinical evaluation of BMHV prototypes prior to valve manufacturing. Application to a wide range of hinges with varying design parameters will eventually help in determining the optimal hinge design

Elementary Excitations and Dynamical Correlation Functions of the Calogero-Sutherland Model with Internal Symmetry

We consider the physical properties of elementary excitations of the Calogero-Sutherland (CS) model with SU(K) internal symmetry. From the results on the thermodynamics of this model, we obtain the charge, spin, and statistics of elementary excitations. Combining this knowledge and the known results on the dynamics in the spinless CS model, we propose the expression for the dynamical correlation functions of the SU(K) CS model. In the asymptotic region, we confirm the consistency of our results with predictions from conformal field theory.Comment: 22 pages, REVTe

Interpolated sequences and critical LL-values of modular forms

Recently, Zagier expressed an interpolated version of the Ap\'ery numbers for $\zeta(3)$ in terms of a critical $L$-value of a modular form of weight 4. We extend this evaluation in two directions. We first prove that interpolations of Zagier's six sporadic sequences are essentially critical $L$-values of modular forms of weight 3. We then establish an infinite family of evaluations between interpolations of leading coefficients of Brown's cellular integrals and critical $L$-values of modular forms of odd weight.Comment: 23 pages, to appear in Proceedings for the KMPB conference: Elliptic Integrals, Elliptic Functions and Modular Forms in Quantum Field Theor