A major concern for cancer vaccines targeting self-tumor antigens is the risk of autoimmune sequelae. Although antitumor immunity correlates with autoimmune disease in some preclinical models, the mechanism(s) linking antitumor immunity and subsequent autoimmune pathology remain(s) to be determined. In the current study, we demonstrated that intradermal (i. d

The role of oxygen radicals in causing ozone-induced airway hyperresponsiveness in dogs was examined by pretreating dogs with allopurinol and/or deferoxamine mesylate (desferal), which are inhibitors of oxygen radical generation, before ozone inhalation. Acetylcholine airway responsiveness was measured before and after either air or ozone inhalation (3 ppm for 20 min) on 5 experimental days separated by at least 2 wk. On each day, the dogs were pretreated intravenously with allopurinol (50 mg/kg) followed by inhaled desferal (1,000 mg inhalation) or with allopurinol followed by the diluent for desferal or with the diluent for allopurinol and desferal or with both diluents. The effect of ozone on acetylcholine airway responsiveness was expressed as the differences in the log-transformed preozone-postozone acetylcholine provocative concentrations. When dogs received both diluents or either treatment alone, ozone inhalation caused airway hyperresponsiveness. The mean log differences for the preozone-postozone acetylcholine provocative concentration were 0.804 (SEM, 0.17) for both diluents, 0.524 (SEM, 0.16) for allopurinol alone, and 0.407 (SEM, 0.22) for desferal alone. However, the combination of allopurinol and desferal significantly inhibited the development of ozone-induced airway hyperresponsiveness, the log difference being 0.195 (SEM, 0.11) (p less than 0.05), without inhibiting ozone-induced neutrophil influx into the airways. The results suggest that the production of oxygen radicals is important in the pathogenesis of ozone-induced airway hyperresponsiveness.

Previously, we compared the efficiency of direct injection with an adenovirus (Ad) expressing human gp100 (hgp100) to immunization with dendritic cells (DC) loaded with the same vector ex vivo. The DC vaccine provided the greatest protection against challenge with B16F10 melanoma, and antitumor immunity was found to be CD8+ T cell-independent. In the current study, we sought to determine whether lack of CD8+ T cell-mediated antitumor immunity was a function of the vaccine platform or the tumor line. Both Ad and DC/Ad vaccines elicited CD8+ CTL reactive against hgp100 and provided protection against B16F10 engineered to express hgp100 demonstrating that both vaccination platforms can effectively generate protective CD8+ T cell-mediated immunity. The hgp100-induced CTL cross-reacted with murine gp100 (mgp100) and lysed B16F10 cells pulsed with mgp100 peptide indicating that the resistance of B16F10 cells to CTL elicited by hgp100 vaccination may be due to a defect in processing of the endogenous mgp100. Indeed, introduction of the TAP-1 cDNA into B16F10 rendered the cells sensitive to lysis by gp100-specific CTL. Furthermore, gp100-immunized mice were protected from challenge with B16F10-TAP1 cells through a mechanism dependent upon CD8+ T cells. These results demonstrate that tumor phenotype, not the vaccination platform, ultimately determines CD8+ or CD4+ T cell-mediated tumor clearance.

Ozone inhalation causes neutrophil migration into the airway and airway hyperresponsiveness in dogs. The leukocyte adhesion molecule Mo1 (CD11b/CD18) is a heterodimeric glycoprotein the expression of which is necessary for neutrophil adhesion to endothelium. To evaluate the contribution of Mo1 to ozone-induced neutrophil influx and airway hyperresponsiveness, six dogs were treated intravenously with an Anti-Mo1 monoclonal antibody (3.75 mg/kg in normal saline) that binds to both human and canine Mo1, or the diluent alone, 1.5 h before inhaling ozone (3 ppm for 30 min), or dry air. Airway responses to doubling doses of inhaled acetylcholine (ACh) were measured before and after inhalation of ozone. Neutrophil influx was assessed by bronchoalveolar lavage (BAL) performed after the second ACh inhalation. Treatment with anti-Mo1 prevented the ozone-induced influx of neutrophils into BAL. After diluent and inhaled dry air, the neutrophil count in BAL was 1.49 +/- 1.26 (SE) x 10(4) (5.0% of total cells). After diluent and inhaled ozone, the neutrophil count increased to 7.27 +/- 3.22 (SE) x 10(4) (22.6% of total cells) (P < 0.05). After anti-Mo1 and inhaled ozone, the neutrophil count was 1.48 +/- 0.62 (SE) x 10(4) (8.5% of total cells). Treatment with anti-Mo1 also significantly reduced the number of eosinophils in BAL after ozone. Ozone-induced ACh airway hyperresponsiveness was not prevented by treatment with anti-Mo1. These results indicate that expression of Mo1 is necessary for ozone-induced neutrophil migration into the airway lumen.

No abstract

The role of the eosinophil in the development of allergen-induced airway hyperresponsiveness is uncertain. We examined whether the development of airway hyperresponsiveness in 17 dogs after inhalation of Ascaris suum allergen (10(-6) to 10(-2) weight/volume [w/v]) was associated with increases in the number and level of activation of eosinophils before and after allergen inhalation. Airway responsiveness to inhaled acetylcholine was measured before and 24 h after Ascaris inhalation. Eosinophil number was assessed by bronchoalveolar lavage performed 1 wk before allergen inhalation and 15 min after the 24 h acetylcholine challenge. Dogs that developed Ascaris-induced airway hyperresponsiveness (n = 8) had a significantly greater number of bronchoalveolar lavage eosinophils before allergen inhalation (mean +/- SEM: 4.6 +/- 1.94 x 10(4) cells/ml) than dogs that did not become hyperresponsive (n = 9) (1.2 +/- 0.81 x 10(4) cells/ml) (p = 0.03). Ascaris-induced airway hyperresponsiveness, measured 24 h after allergen inhalation, was not associated with increases in eosinophil number after allergen challenge. These results suggest that the presence of airway eosinophils before allergen inhalation is necessary for the development of allergen-induced airway hyperresponsiveness.

The presence of airway eosinophils before allergen inhalation may contribute to the development of allergen-induced airway responses. We examined whether a reduction in airway eosinophil numbers before allergen inhalation as a result of inhalation of the corticosteroid budesonide would prevent allergen-induced airway hyperresponsiveness in seven dogs. Acetylcholine airway responsiveness was measured before and 24 h after inhalation of Ascaris suum allergen (10(-6)-10(-2) wt/vol) or its diluent on 4 test days separated by > or = 4 wk. Dogs were pretreated for 7 days before and on the morning of each test day with inhaled budesonide (2.69 mg/day) or a placebo (lactose). Airway eosinophil numbers were assessed by bronchoalveolar lavage. Inhaled budesonide significantly reduced the number of airway eosinophils before allergen inhalation from 3.6 +/- 2.38 x 10(4) (SE) cells/ml after inhaled lactose to 0.3 +/- 0.21 x 10(4) cells/ml after inhaled budesonide (P = 0.028). The decrease in eosinophil number was associated with a significant reduction in allergen-induced airway hyperresponsiveness (P = 0.005). These results support the hypothesis that the number of eosinophils in the airways before allergen inhalation is an important determinant in the development of allergen-induced airway hyperresponsiveness in dogs.

For more information on the USGS-the Federal source for science about the Earth, its natural and living resources, natural hazards, and the environment, visit http://www.usgs.gov or call 1-888-ASK-USGS. For an overview of USGS information products, including maps, imagery, and publications, visit http://www.usgs.gov/pubprodTo order this and other USGS information products, visit http://store.usgs.gov Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Although this information product, for the most part, is in the public domain, it also may contain copyrighted materials as noted in the text. Permission to reproduce copyrighted items must be secured from the copyright owner.Suggested citation: Cappiella, Karen, Stack, W.P., Fraley-McNeal, Lisa, Lane, Cecilia, and McMahon, Gerard, 2012, Strategies for managing the effects of urban development on streams: U.S. Geological Survey Circular 1378, 69 p. Available online at http://pubs.usgs.gov/circ/1378/ Library of Congress Cataloging-in-Publication DataStrategies for managing the effects of urban development on streams / by Karen Cappiella ... [et al.].p. cm. Urban development remains an important agent of environmental change in the United States. The U.S. population grew by 17 percent from 1982 to 1997, while urbanized land area grew by 47 percent, suggesting that urban land consumption far outpaced population growth (Fulton and others, 2001; Sierra Club, 2003;American Farmland Trust, 2009) Nowhere are the environmental changes associated with urban development more evident than in urban streams. The U.S. Geological Survey's National Water-Quality Assessment (NAWQA) Program investigation of the effects of urban development on stream ecosystems (EUSE) during 1999-2004 provides the most spatially comprehensive analysis of stream impacts of urban development that has been completed in the United States. A nationally consistent study design was used in nine metropolitan areas of the United States-Portland, Oregon; Salt Lake City, Utah; Birmingham, Alabama; Atlanta, Georgia; Raleigh, North Carolina; Boston, Massachusetts; Denver, Colorado; Dallas, Texas; and Milwaukee, Wisconsin ( fig. 1; see Effects of Urbanization on Stream Ecosystems).A summary report published as part of the EUSE study describes several of these impacts on urban streams (Coles and others, 2012):• Urban streams are affected by multiple stressorsAnalyses of how urban-related changes in stream hydrology, habitat, and chemistry relate to the species composition of biological communities indicate that no single environmental factor was universally important across all the study areas in explaining the effects of urban development on stream ecosystems. Even within a single study area, the three biological communities that were surveyed-algal, invertebrate, and fish-had different responses to urban development and changing environmental factors.• Response of stream biota to urban development varied across the country-Stream ecosys...