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排序方式: 共有404条查询结果,搜索用时 875 毫秒
31.
The involvement of CD44 and its novel ligand galectin-8 in apoptotic regulation of autoimmune inflammation 总被引:1,自引:0,他引:1
Eshkar Sebban L Ronen D Levartovsky D Elkayam O Caspi D Aamar S Amital H Rubinow A Golan I Naor D Zick Y Golan I 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(2):1225-1235
The synovial fluid (SF) cells of rheumatoid arthritis (RA) patients express a specific CD44 variant designated CD44vRA. Using a cellular model of this autoimmune disease, we show in this study that the mammalian lectin, galectin-8 (gal-8), is a novel high-affinity ligand of CD44vRA. By affinity chromatography, flow cytometry, and surface plasmon resonance, we demonstrate that gal-8 interacts with a high affinity (K(d), 6 x 10(-9) M) with CD44vRA. We further demonstrate that SF cells from RA patients express and secrete gal-8, to a concentration of 25-65 nM, well within the concentration of gal-8 required to induce apoptosis of SF cells. We further show that not all gal-8 remains freely soluble in the SF and at least part forms triple complexes with CD44 and fibrinogen that can be detected, after fibrinogen immunoprecipitation, with Abs against fibrinogen, gal-8 and CD44. These triple complexes may therefore increase the inflammatory reaction by sequestering the soluble gal-8, thereby reducing its ability to induce apoptosis in the inflammatory cells. Our findings not only shed light on the receptor-ligand relationships between CD44 and gal-8, but also underline the biological significance of these interactions, which may affect the extent of the autoimmune inflammatory response in the SF of RA patients. 相似文献
32.
Chapoval SP Al-Garawi A Lora JM Strickland I Ma B Lee PJ Homer RJ Ghosh S Coyle AJ Elias JA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(10):7030-7041
IL-13 is a major Th2 cytokine that is capable of inducing inflammation, excessive mucus production, airway hyperresponsiveness, alveolar remodeling, and fibrosis in the murine lung. Although IL-13 through its binding to IL-4Ralpha/IL-13Ralpha1 uses the canonical STAT6-signaling pathway to mediate these tissue responses, recent studies have demonstrated that other signaling pathways may also be involved. Previous studies from our laboratory demonstrated that IL-13 mediates its tissue effects by inducing a wide variety of downstream genes many of which are known to be regulated by NF-kappaB. As a result, we hypothesized that NF-kappaB activation plays a critical role in the pathogenesis of IL-13-induced tissue alterations. To test this hypothesis, we compared the effects of transgenic IL-13 in mice with normal and diminished levels of NF-kappaB activity. Three pharmacologic approaches were used to inhibit NF-kappaB including 1) PS1145, a small molecule inhibitor of IkappaBalpha kinase (IKK2), 2) antennapedia-linked NF-kappaB essential modulator-binding domain (NBD) peptide (wild-type NBD), and 3) an adenoviral construct expressing a dominant-negative version of IKK2. We also crossed IL-13-transgenic mice with mice with null mutations of p50 to generate mice that overproduced IL-13 in the presence and absence of this NF-kappaB component. These studies demonstrate that all these interventions reduced IL-13-induced tissue inflammation, fibrosis and alveolar remodeling. In addition, we show that both PS1145 and wild-type NBD inhibit lung inflammatory and structural cell apoptosis. PS1145 inhibits caspase activation and up-regulates inhibitor of apoptosis protein cellular-inhibitor of apoptosis protein 1 (c-IAP-1). Therefore, NF-kappaB is an attractive target for immunotherapy of IL-13-mediated diseases. 相似文献
33.
Billings L Schwartz IB Shaw LB McCrary M Burke DS Cummings DA 《Journal of theoretical biology》2007,246(1):18-27
This paper investigates the complex dynamics induced by antibody-dependent enhancement (ADE) in multiserotype disease models. ADE is the increase in viral growth rate in the presence of immunity due to a previous infection of a different serotype. The increased viral growth rate is thought to increase the infectivity of the secondary infectious class. In our models, ADE induces the onset of oscillations without external forcing. The oscillations in the infectious classes represent outbreaks of the disease. In this paper, we derive approximations of the ADE parameter needed to induce oscillations and analyze the associated bifurcations that separate the types of oscillations. We then investigate the stability of these dynamics by adding stochastic perturbations to the model. We also present a preliminary analysis of the effect of a single serotype vaccination in the model. 相似文献
34.
Multistrain diseases have multiple distinct coexisting serotypes (strains). For some diseases, such as dengue fever, the serotypes interact by antibody-dependent enhancement (ADE), in which infection with a single serotype is asymptomatic, but contact with a second serotype leads to higher viral load and greater infectivity. We present and analyze a dynamic compartmental model for multiple serotypes exhibiting ADE. Using center manifold techniques, we show how the dynamics rapidly collapses to a lower dimensional system. Using the constructed reduced model, we can explain previously observed synchrony between certain classes of primary and secondary infectives (Schwartz et al. in Phys Rev E 72:066201, 2005). Additionally, we show numerically that the center manifold equations apply even to noisy systems. Both deterministic and stochastic versions of the model enable prediction of asymptomatic individuals that are difficult to track during an epidemic. We also show how this technique may be applicable to other multistrain disease models, such as those with cross-immunity. 相似文献
35.
Glaros AG Kim-Weroha N Lausten L Franklin KL 《Applied psychophysiology and biofeedback》2007,32(3-4):149-154
This study tested the hypothesis that a habit reversal program emphasizing awareness and reduction of masticatory muscle activity
would significantly reduce pain in patients diagnosed with chronic temporomandibular disorder (TMD) and would be a competitive
alternative to a behaviorally-modified dental intervention. Eight individuals diagnosed with TMD were randomly assigned to
a splint therapy or habit reversal group. Patients in the splint group received an interocclusal appliance (splint) fabricated
from acrylic and were instructed to wear the splint day and night up to a maximum of 20 h per day. Patients in the habit reversal
group were given a pager and instructed to check tooth position and masticatory muscle tension when paged. Paging occurred
approximately once every 2 h during the day, but not at night. Both groups were instructed to avoid tooth contact and relax
the masticatory muscles during the 4 weeks of active treatment. Outcome data were collected at 1 month and 1 year post-treatment
intervals. Pain decreased significantly for both groups and did not differ between groups. Habit reversal may be as effective
as a behaviorally-modified splint therapy for TMD-related pain. 相似文献
36.
37.
Charles-André Couture Stéphane Bancelin Jarno Van?der?Kolk Konstantin Popov Maxime Rivard Katherine Légaré Gabrielle Martel Hélène Richard Cameron Brown Sheila Laverty Lora Ramunno Fran?ois Légaré 《Biophysical journal》2015,109(12):2501-2510
In this work, we report the implementation of interferometric second harmonic generation (SHG) microscopy with femtosecond pulses. As a proof of concept, we imaged the phase distribution of SHG signal from the complex collagen architecture of juvenile equine growth cartilage. The results are analyzed in respect to numerical simulations to extract the relative orientation of collagen fibrils within the tissue. Our results reveal large domains of constant phase together with regions of quasi-random phase, which are correlated to respectively high- and low-intensity regions in the standard SHG images. A comparison with polarization-resolved SHG highlights the crucial role of relative fibril polarity in determining the SHG signal intensity. Indeed, it appears that even a well-organized noncentrosymmetric structure emits low SHG signal intensity if it has no predominant local polarity. This work illustrates how the complex architecture of noncentrosymmetric scatterers at the nanoscale governs the coherent building of SHG signal within the focal volume and is a key advance toward a complete understanding of the structural origin of SHG signals from tissues. 相似文献
38.
Stigmatellin Probes the Electrostatic Potential in the QB Site of the Photosynthetic Reaction Center
László Gerencsér Bogáta Boros Valerie Derrien Deborah?K. Hanson Colin?A. Wraight Pierre Sebban Péter Maróti 《Biophysical journal》2015,108(2):379-394
The electrostatic potential in the secondary quinone (QB) binding site of the reaction center (RC) of the photosynthetic bacterium Rhodobacter sphaeroides determines the rate and free energy change (driving force) of electron transfer to QB. It is controlled by the ionization states of residues in a strongly interacting cluster around the QB site. Reduction of the QB induces change of the ionization states of residues and binding of protons from the bulk. Stigmatellin, an inhibitor of the mitochondrial and photosynthetic respiratory chain, has been proven to be a unique voltage probe of the QB binding pocket. It binds to the QB site with high affinity, and the pK value of its phenolic group monitors the local electrostatic potential with high sensitivity. Investigations with different types of detergent as a model system of isolated RC revealed that the pK of stigmatellin was controlled overwhelmingly by electrostatic and slightly by hydrophobic interactions. Measurements showed a high pK value (>11) of stigmatellin in the QB pocket of the dark-state wild-type RC, indicating substantial negative potential. When the local electrostatics of the QB site was modulated by a single mutation, L213Asp→Ala, or double mutations, L213Asp-L212Glu→Ala-Ala (AA), the pK of stigmatellin dropped to 7.5 and 7.4, respectively, which corresponds to a >210 mV increase in the electrostatic potential relative to the wild-type RC. This significant pK drop (ΔpK > 3.5) decreased dramatically to (ΔpK > 0.75) in the RC of the compensatory mutant (AA+M44Asn→AA+M44Asp). Our results indicate that the L213Asp is the most important actor in the control of the electrostatic potential in the QB site of the dark-state wild-type RC, in good accordance with conclusions of former studies using theoretical calculations or light-induced charge recombination assay. 相似文献
39.
Review of Florida Red Tide and Human Health Effects 总被引:1,自引:0,他引:1
Fleming LE Kirkpatrick B Backer LC Walsh CJ Nierenberg K Clark J Reich A Hollenbeck J Benson J Cheng YS Naar J Pierce R Bourdelais AJ Abraham WM Kirkpatrick G Zaias J Wanner A Mendes E Shalat S Hoagland P Stephan W Bean J Watkins S Clarke T Byrne M Baden DG 《Harmful algae》2011,10(2):224-233
This paper reviews the literature describing research performed over the past decade on the known and possible exposures and human health effects associated with Florida red tides. These harmful algal blooms are caused by the dinoflagellate, Karenia brevis, and similar organisms, all of which produce a suite of natural toxins known as brevetoxins. Florida red tide research has benefited from a consistently funded, long term research program, that has allowed an interdisciplinary team of researchers to focus their attention on this specific environmental issue-one that is critically important to Gulf of Mexico and other coastal communities. This long-term interdisciplinary approach has allowed the team to engage the local community, identify measures to protect public health, take emerging technologies into the field, forge advances in natural products chemistry, and develop a valuable pharmaceutical product. The Review includes a brief discussion of the Florida red tide organisms and their toxins, and then focuses on the effects of these toxins on animals and humans, including how these effects predict what we might expect to see in exposed people. 相似文献
40.
Global patterns of leaf mechanical properties 总被引:1,自引:0,他引:1
Onoda Y Westoby M Adler PB Choong AM Clissold FJ Cornelissen JH Díaz S Dominy NJ Elgart A Enrico L Fine PV Howard JJ Jalili A Kitajima K Kurokawa H McArthur C Lucas PW Markesteijn L Pérez-Harguindeguy N Poorter L Richards L Santiago LS Sosinski EE Van Bael SA Warton DI Wright IJ Wright SJ Yamashita N 《Ecology letters》2011,14(3):301-312
Leaf mechanical properties strongly influence leaf lifespan, plant-herbivore interactions, litter decomposition and nutrient cycling, but global patterns in their interspecific variation and underlying mechanisms remain poorly understood. We synthesize data across the three major measurement methods, permitting the first global analyses of leaf mechanics and associated traits, for 2819 species from 90 sites worldwide. Key measures of leaf mechanical resistance varied c. 500-800-fold among species. Contrary to a long-standing hypothesis, tropical leaves were not mechanically more resistant than temperate leaves. Leaf mechanical resistance was modestly related to rainfall and local light environment. By partitioning leaf mechanical resistance into three different components we discovered that toughness per density contributed a surprisingly large fraction to variation in mechanical resistance, larger than the fractions contributed by lamina thickness and tissue density. Higher toughness per density was associated with long leaf lifespan especially in forest understory. Seldom appreciated in the past, toughness per density is a key factor in leaf mechanical resistance, which itself influences plant-animal interactions and ecosystem functions across the globe. 相似文献