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Regulation of CD23 in the chronic inflammatory response in asthma: a role for interferon-gamma and heat shock protein 70 in the TH2 environment. 总被引:2,自引:0,他引:2
Michelle S Harkins Pope L Moseley Gary K Iwamoto 《Annals of allergy, asthma & immunology》2003,91(6):567-574
BACKGROUND: Monocytic cells and alveolar macrophages (AMs) are activated in patients with asthma, producing inflammatory cytokines. This occurs despite a TH2 environment that consists of the cytokines interleukin (IL) 4, IL-10, and IL-13. The mechanism by which this occurs may involve cross-linking of the low-alphaffinity IgE receptor CD23. OBJECTIVE: To determine the effect of the TH2 environment with interferon-gamma (IFN-gamma) and heat shock protein 70 (HSP 70) on CD23 receptor expression and tumor necrosis factor alpha (TNF-alpha) production. METHODS: We examined the effect of IL-4 and IL-13 in culture with IFN-gamma and HSP 70 on CD23 expression in both THP-1 cells and AMs from healthy controls via flow cytometry. AMs from mild asthmatic patients and THP-1 cells were evaluated for TNF-alpha production after cross-linking CD23 with immune complexes. RESULTS: Asthmatic AMs stimulated with anti-IgE exhibited a 5.7- +/- 1.9-fold increase in TNF-alpha protein. AMs from healthy controls increased the geometric mean +/- SD of CD23 2.00- +/- 0.50-fold in IL-4 and 2.14- +/- 0.50-fold in IL-13. THP-1 cells cultured with IL-4 and IL-13 then stimulated with IFN-gamma or HSP 70 increased CD23 expression above baseline as follows: IL-4, 2.16- +/- 0.31-fold; IL-13, 2.66- +/- 0.43-fold; IFN-gamma, 2.03- +/- 0.34-fold; IL-4/IFN-gamma, 9.14- to 4.02-fold; IL-13/IFN-gamma, 11.51- +/- 5.51-fold; IL-4/HSP, 5.20- +/- 0.61-fold; and IL-13/HSP, 5.60- +/- 0.79-fold. Stimulating the CD23 receptor with immune complexes significantly increased TNF-alpha production by THP-1 cells stimulated with IFN-gamma, IL-4, IL-13, or a combination of these. CONCLUSIONS: Both IFN-gamma and HSP 70, in the TH2 environment, up-regulate CD23 expression and thus may play an important role in maintaining the chronic inflammatory state in asthma. 相似文献
3.
Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology 总被引:8,自引:0,他引:8
Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism. 相似文献
4.
Harkins KM Mattacola CG Uhl TL Malone TR McCrory JL 《Journal of Athletic Training》2005,40(3):191-194
Context: Muscle fatigue is generally categorized in 2 ways: that caused by peripheral weakness (peripheral fatigue) and that caused by a progressive failure of voluntary neural drive (central fatigue). Numerous variables have been studied in conjunction with fatigue protocols, including postural stability, maximum voluntary contraction force, and reaction time. When torque recordings fall below 50% of a maximum voluntary contraction, the muscle is described as fatigued, but whether this value is a good indicator of fatigue has not been studied.Objective: To compare the effects of 2 ankle musculature fatigue protocols (30% and 50%) on the duration of postural stability dysfunction.Design: To assess differences between the 30% and 50% fatigue protocols, we calculated a 1 between-groups factor (subjects) and 2 within-groups factors (fatigue, test) analysis of variance.Setting: E.J. Nutter Athletic Training Facility.Patients or Other Participants: Twenty subjects (10 men, 10 women; age = 21.15 ± 2.23 years; height = 172.97 ± 9.86 cm; mass = 70.62 ± 14.60 kg) volunteered for this study. Subjects had no history of lower extremity injury, vestibular or balance disorders, functional ankle instability, or head injury in the past 6 months.Intervention(s): On separate days, subjects performed isokinetic fatiguing contractions of the plantar flexors and dorsiflexors in a 30% protocol (70% decrease in strength) and a 50% protocol (50% decrease in strength).Main Outcome Measure(s): Baseline and postfatigue postural stability scores were determined before and after the isokinetic fatiguing contractions. Plantar-flexion peak-torque measurements were obtained for the 2 fatiguing protocols. Three prefatigue and 12 postfatigue postural stability trials were recorded. Velocities for testing were 60°/s for plantar flexion and 120°/s for dorsiflexion.Results: Sway velocity was significantly greater when the ankle was fatigued to 30% (1.56°/s) than in the 50% condition (1.36°/s). For the 30% protocol, sway was significantly impaired when the pretest condition (1.19°/s) was compared with posttest trial 1 (2.34°/s), trial 2 (2.37°/s), and trial 3 (1.71°/s). For the 50% protocol, sway was significantly impaired when the pretest condition (1.27°/s) was compared with posttest trial 1 (2.02°/s).Conclusions: The 30% fatigue protocol resulted in significantly longer impairment of postural stability than the 50% protocol. Because the 30% protocol resulted in a greater effect but was relatively short-lived (approximately 75 to 90 s), it is more useful for research purposes. 相似文献
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Group relations conferences and 12-Step recovery thrive on the participants working in groups. This article is an inquiry into the integration of these traditions, in the Loyola Group Relations Conference, January 14–16, 2011. This conference recruited staff and members from the recovery community. 12-Step meetings were integrated into the conference design. The authors discuss the similarities and differences of the two models and examine the learning of conference staff and members. The authors conclude that Group Relations Conferences focusing on leadership, authority, and recovery from addiction can bring important group relations learning to the recovery community and vice versa. 相似文献
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Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes
Gilbert MT Drautz DI Lesk AM Ho SY Qi J Ratan A Hsu CH Sher A Dalén L Götherström A Tomsho LP Rendulic S Packard M Campos PF Kuznetsova TV Shidlovskiy F Tikhonov A Willerslev E Iacumin P Buigues B Ericson PG Germonpré M Kosintsev P Nikolaev V Nowak-Kemp M Knight JR Irzyk GP Perbost CS Fredrikson KM Harkins TT Sheridan S Miller W Schuster SC 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(24):8327-8332
We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximately 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the (14)C ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep. 相似文献
9.
Objectives: There is growing evidence indicating a connection between vitamin D deficiency and the severity of asthma exacerbations. This study seeks to assess the relationship between vitamin D deficiency and the number and severity of asthma exacerbation in adults. Methods: A retrospective analysis was conducted in 92 patients being treated for asthma at the University of New Mexico Adult Asthma Clinic. Serum 25-hydroxyvitamin D3 levels were analyzed in adults with mild to severe persistent asthma. Using multi-variant modeling, the relationship was examined between serum vitamin D levels and the odds of asthma exacerbations ranging in severity from moderate to severe over the span of five years. Results: This study demonstrates that vitamin D sufficiency was significantly associated with a decreased total number of asthma exacerbations (incidence rate ratio [IRR]: 0.61, 95% confidence interval [CI]: 0.44–0.84, p?=?0.002), decreased total severe asthma exacerbations (IRR: 0.41, 95% CI: 0.24–0.72, p?=?0.002) and decreased emergency room visits (IRR: 0.42, 95% CI: 0.20–0.88, p?=?0.023). Conclusion: Vitamin D deficiency may be linked to the risk of severe asthma exacerbations in adults. 相似文献
10.
Marlous Hoogstraat Mirjam S. de Pagter Geert A. Cirkel Markus J. van Roosmalen Timothy T. Harkins Karen Duran Jennifer Kreeftmeijer Ivo Renkens Petronella O. Witteveen Clarence C. Lee Isaac J. Nijman Tanisha Guy Ruben van ’t Slot Trudy N. Jonges Martijn P. Lolkema Marco J. Koudijs Ronald P. Zweemer Emile E. Voest Edwin Cuppen Wigard P. Kloosterman 《Genome research》2014,24(2):200-211