Determining the Contribution of Epidermal Cell Shape to Petal Wettability Using Isogenic Antirrhinum Lines

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Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa

BACKGROUND: Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI). We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa. METHODS: We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosa monomicrobial nBSI. RESULTS: The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiologic Score (SAPS II), were calculated daily from 2 days prior through 2 days after the first positive blood culture. Calculation of the area under the receiver operating characteristic (ROC) curve confirmed that APACHE II and SAPS II at day -1 and SOFA at day +1 were better predictors of outcome than days -2, 0 and day 2 of BSI. By stepwise logistic regression analysis of these three scoring systems, SAPS II (OR: 13.03, CI95% 2.51–70.49) and APACHE II (OR: 12.51, CI95% 3.12–50.09) on day -1 were the best predictors for mortality. CONCLUSION: SAPS II and APACHE II are more accurate than the SOFA score for predicting mortality in this group of patients at day -1 of BSI

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Emerging therapies for severe asthma

Many patients with asthma have poorly controlled symptoms, and particularly for those with severe disease, there is a clear need for improved treatments. Two recent therapies licensed for use in asthma are omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, and bronchial thermoplasty, which involves the delivery of radio frequency energy to the airways to reduce airway smooth muscle mass. In addition, there are new therapies under development for asthma that have good potential to reach the clinic in the next five years. These include biological agents targeting pro-inflammatory cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting β2-agonists and once daily inhaled corticosteroids. In addition, drugs that block components of the arachidonic acid pathway that targets neutrophilic asthma and CRTH2 receptor antagonists that inhibit the proinflammatory actions of prostaglandin D2 may become available. We review the recent progress made in developing viable therapies for severe asthma and briefly discuss the idea that development of novel therapies for asthma is likely to increasingly involve the assessment of genotypic and/or phenotypic factors

Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV

We use 106 \ipb of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an anti-top quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to \ttbar are presented. At the 95% confidence level, we exclude the existence of a leptophobic \zpr boson in a model of topcolor-assisted technicolor with mass M_{\zpr} $<$ 480 \gev for natural width $\Gamma$ = 0.012 M_{\zpr}, and M_{\zpr} $<$ 780 \gev for $\Gamma$ = 0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200

Double Diffraction Dissociation at the Fermilab Tevatron Collider

We present results from a measurement of double diffraction dissociation in $\bar pp$ collisions at the Fermilab Tevatron collider. The production cross section for events with a central pseudorapidity gap of width $\Delta\eta^0>3$ (overlapping $\eta=0$) is found to be $4.43\pm 0.02{(stat)}{\pm 1.18}{(syst) mb}$ [$3.42\pm 0.01{(stat)}{\pm 1.09}{(syst) mb}$] at $\sqrt{s}=1800$ [630] GeV. Our results are compared with previous measurements and with predictions based on Regge theory and factorization.Comment: 10 pages, 4 figures, using RevTeX. Submitted to Physical Review Letter