19 results on '"R. Brosius"'
Search Results
2. Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014)
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Nicolette Borek, Stephen Arnstein, Erin L. Wade, Andrew Hyland, Kathryn C Edwards, Kevin P. Conway, Keegan J. Nicodemus, Brittany N. Pine, Yao Li, Dana Freeman, Tonya Guillot, Diane Choi, Dana M. van Bemmel, Heather L. Kimmel, Baoyun Xia, John T. Bernert, Cindy M. Chang, Gladys Ervies, John Lee, Lanqing Wang, Angel Cobos, B Rey de Castro, Justin L Brown, Maciej L. Goniewicz, Benjamin C. Blount, Stephen S. Hecht, Yang Xia, Dorothy K. Hatsukami, Charlie Lawrence, and Christina R Brosius
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Adult ,Male ,Nitrosamines ,Adolescent ,Population ,Original Investigations ,Urine ,Tobacco smoke ,Nicotine ,Tobacco Use ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,medicine ,Humans ,Tobacco-specific nitrosamines ,Longitudinal Studies ,030212 general & internal medicine ,Tobacco Use Epidemiology ,education ,Carcinogen ,education.field_of_study ,business.industry ,Public Health, Environmental and Occupational Health ,United States ,Smokeless tobacco ,030220 oncology & carcinogenesis ,Carcinogens ,Female ,business ,Biomarkers ,medicine.drug - Abstract
Introduction The tobacco-specific nitrosamines (TSNAs) are an important group of carcinogens found in tobacco and tobacco smoke. To describe and characterize the levels of TSNAs in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014), we present four biomarkers of TSNA exposure: N′-nitrosonornicotine, N′-nitrosoanabasine, N′-nitrosoanatabine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which is the primary urinary metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Methods We measured total TSNAs in 11 522 adults who provided urine using automated solid-phase extraction coupled to isotope dilution liquid chromatography–tandem mass spectrometry. After exclusions in this current analysis, we selected 11 004 NNAL results, 10 753 N′-nitrosonornicotine results, 10 919 N′-nitrosoanatabine results, and 10 996 N′-nitrosoanabasine results for data analysis. Geometric means and correlations were calculated using SAS and SUDAAN. Results TSNA concentrations were associated with choice of tobacco product and frequency of use. Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was highest for smokeless tobacco users (993.3; 95% confidence interval [CI: 839.2, 1147.3] ng/g creatinine), followed by all types of combustible tobacco product users (285.4; 95% CI: [267.9, 303.0] ng/g creatinine), poly tobacco users (278.6; 95% CI: [254.9, 302.2] ng/g creatinine), and e-cigarette product users (6.3; 95% CI: [4.7, 7.9] ng/g creatinine). TSNA concentrations were higher in every day users than in intermittent users for all the tobacco product groups. Among single product users, exposure to TSNAs differed by sex, age, race/ethnicity, and education. Urinary TSNAs and nicotine metabolite biomarkers were also highly correlated. Conclusions We have provided PATH Study estimates of TSNA exposure among US adult users of a variety of tobacco products. These data can inform future tobacco product and human exposure evaluations and related regulatory activities.
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- 2020
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3. COVID-19: Reflections from Entomologists Who Rose to the Occasion
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Isobel Ronai, Thomas J. Simonsen, Johnnie Van Den Berg, Ryan C Gott, Rebecca A. Schmidt-Jeffris, Frank Wessels, Melissa Siebert, Julien Saguez, Laura S. Higgins, Joseph L. Spencer, Ronda L. Hamm, David R. Coyle, Steve Thompson, Neil Spomer, Lieceng Zhu, Zachary C. DeVries, Tierney R. Brosius, Rosana Serikawa, Rory McDonnell, and Catherine Loudon
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AcademicSubjects/SCI01382 ,Rose (mathematics) ,2019-20 coronavirus outbreak ,History ,Coronavirus disease 2019 (COVID-19) ,Insect Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Virology ,Features ,Ecology, Evolution, Behavior and Systematics - Published
- 2020
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4. Behavioral niche partitioning in a sympatric tiger beetle assemblage and implications for the endangered Salt Creek tiger beetle
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Tierney R. Brosius and Leon G. Higley
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Cicindelidae ,Thermoregulation ,Ecophysiology ,Competitive exclusion ,Endangered species ,Conservation biology ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
How behavioral patterns are related to niche partitioning is an important question in understanding how closely related species within ecological communities function. Behavioral niche partitioning associated with thermoregulation is well documented in tiger beetles as a group. Co-occurring species of salt flat tiger beetles have adapted many thermoregulatory behaviors to cope with this harsh ecosystem. On first examination these beetles appear to occur in overlapping microhabitats and therefore compete for resources. To determine if behavioral niche partitioning is allowing multiple species to occur within the same harsh salt flat ecosystem we observed Cicindela nevadica lincolniana, Cicindela circumpicta, Cicindela fulgida, and Cicindela togata between 8:00 h and 21:00 h and recorded all behaviors related to thermoregulation using a digital voice recorder. Results of this study strongly indicate that competition among these species for resources has been reduced by the adaptation of different thermoregulatory behaviors such as spending time in shallow water, avoiding the sun during the hottest parts of the day, and by positioning their body against or away from the soil. The endangered C. n. lincolniana appears to rely most heavily on the shallow water of seeps for their diurnal foraging behavior (potentially limiting their foraging habitat), but with the advantage of allowing foraging during the hottest times of the day when potential competitors are less frequent. Ironically, this association also may help explain C. n. lincolniana’s susceptibility to extinction: beyond the loss of saline wetlands generally, limited seeps and pools even within remaining saline habitat may represent a further habitat limitation within an already limited habitat.
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- 2013
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5. Connecting Across Campus Through Cultural Entomology
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Connie Ghinazzi and Tierney R. Brosius
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010504 meteorology & atmospheric sciences ,Event (computing) ,Charismatic megafauna ,Media studies ,Cultural center ,Electronic information ,010502 geochemistry & geophysics ,Living room ,01 natural sciences ,The arts ,Insect Science ,Center (algebra and category theory) ,Cultural entomology ,Ecology, Evolution, Behavior and Systematics ,0105 earth and related environmental sciences - Abstract
Scientists who study large and charismatic megafauna have little trouble inspiring awe and love for their research subjects. As entomologists, we are often frustrated because we have the opposite experience. We are, however, keenly aware of one major advantage over our colleagues when interacting with the public: insects are everywhere. No one grows up without having some sort of interaction with insects. Insects are familiar, accessible, and often misunderstood. Misunderstanding has the potential to be converted into the mysterious and wonderful. Insects are a perfect tool to engage the public in science (Golick et al. 2010). As entomologists, we know that insects have the potential to reach out across and outside campus to engage faculty and community members from many backgrounds. Here, we provide an example of intersecting art and insects in a central location on a small college campus as a way to engage the public with insect biology. Libraries are a repository for print and electronic information, but they also serve important roles as a community center, cultural center, center for the arts, and lecture center. College libraries are increasingly seen as the center of college campus life, and as such provide the perfect location to host displays and events that foster interdisciplinary collaborations. Augustana College's Thomas Tredway library has served as the “living room of the campus” since it was built in 1992. Tredway Library hosts one major exhibit and corresponding event …
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- 2016
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6. Promoting the Conservation of the Salt Creek Tiger Beetle Using the Visual Arts
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Tierney R. Brosius, Lana Johnson, and Leon G. Higley
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Geography ,biology ,Ecology ,Insect Science ,biology.organism_classification ,Ecology, Evolution, Behavior and Systematics ,Tiger beetle - Published
- 2014
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7. Biotic and Abiotic Influences on Within-Plant Distribution of Soybean Aphid (Hemiptera: Aphididae: Aphis glycines)
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Thomas E. Hunt, Tierney R. Brosius, and Leon G. Higley
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Abiotic component ,Aphid ,education.field_of_study ,Population ,food and beverages ,Aphididae ,biochemical phenomena, metabolism, and nutrition ,Biology ,biology.organism_classification ,Population density ,Hemiptera ,Agronomy ,Insect Science ,Orius ,Soybean aphid ,education - Abstract
The within-plant distribution of soybean aphid, Aphis glycines Matsumura has been attributed to various causes, yet it is unclear which factor or combination of factors most influence aphid within-plant distribution. Understanding soybean aphid distribution within the soybean canopy is important both in developing sampling programs and in evaluating injury. Because natural enemies have the potential to alter aphid dispersion, we examined how within-plant distribution of soybean aphid was influenced by different natural enemies. Field cages of different mesh diameters were used to exclude different sizes of natural enemies from aphid infested plots. Plots were surveyed and both natural enemy density and soybean aphid density, by strata, were recorded twice weekly. Cages were found to have minimal effect on temperature and soybean plant development. Aphid densities were significantly different each year among dates, treatments, and strata. In 2004 aphid densities were concentrated on the top part of the plant and in 2005 aphid densities were concentrated in the middle of the canopy. Treatments had significant impacts on aphid density in both years of the study. The total exclusion treatment had the highest aphid densities in both years. Treatment also had a significant effect on which stratum aphids were most commonly found. The factor that was found to best explain the differences in aphid distribution was the abundance of natural enemies, primarily Orius insidosus (Say). In treatments left exposed to natural enemies the percentage of the total aphid population was found lower in the canopy. It is clear that aphid densities and distributions are being affected by the presence of natural enemies. Understanding how natural enemies affect the distribution of this economically damaging aphid species is an important component of its management, specifically the development of
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- 2010
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8. Population Dynamics of Soybean Aphid and Biotic Mortality at the Edge of Its Range
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Tierney R. Brosius, L. G. Higley, and T. E. Hunt
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Ecology ,Insect Science ,General Medicine - Published
- 2007
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9. Cleaning Puparia for Forensic Analysis
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David O. Carter, Leon G. Higley, Karl J. Reinhard, and Tierney R. Brosius
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Potassium hydroxide ,Chromatography ,Diptera ,Forensic Sciences ,Analytical chemistry ,Pupa ,Biology ,Adipocere ,Vial ,Pathology and Forensic Medicine ,Specimen Handling ,chemistry.chemical_compound ,chemistry ,Larva ,Postmortem Changes ,parasitic diseases ,Genetics ,Acetone ,Animals ,Entomology - Abstract
We tested procedures for removing adipocere from insect samples to allow identification. An acceptable procedure was determined: (i) Samples were sorted in petri dishes with 75% alcohol to remove any larvae, adult insects, or other soft-bodied material. (ii) Samples of up to 24 puparia were placed in a vial with 15 mL of 95% acetone, capped, and vortexed for a total of 30–90 sec in 10- to 15-sec bursts. This step removed large masses of adipocere or soil from specimen. (iii) Specimens were removed from acetone and placed in a vial of 15 mL of 2% potassium hydroxide (KOH) and vortexed in 10- to 15-sec bursts until all puparia appeared clean (with our samples this required a total of 60–120 sec). (iv) Specimens were removed from the 2% KOH, placed in 75% ethanol, and examined microscopically. (v) Material was stored in 75% ethanol for identification and long-term preservation.
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- 2015
10. Organic and synthetic fertility amendments influence soil microbial, physical and chemical properties on organic and conventional farms
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Jean B. Ristaino, M. R. Brosius, L. R. Bulluck, and G. K. Evanylo
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Ecology ,Soil biodiversity ,Soil organic matter ,fungi ,food and beverages ,Soil Science ,complex mixtures ,Agricultural and Biological Sciences (miscellaneous) ,Soil quality ,Manure ,Soil conditioner ,Agronomy ,Soil water ,Cation-exchange capacity ,Environmental science ,natural sciences ,Soil fertility - Abstract
Field experiments were conducted to examine the effects of organic and synthetic soil fertility amendments on soil microbial communities and soil physical and chemical properties at three organic and three conventional vegetable farms in Virginia and Maryland in 1996 and 1997. Two treatments, including either an alternative organic soil amendment (composted cotton-gin trash, composted yard waste, or cattle manure) or synthetic soil amendment (fertilizer) were applied to three replicated plots at each grower field location. Production history and time affected propagule densities of Trichoderma species which remained higher in soils from organic farms. Propagule densities of Trichoderma species, thermophilic microorganisms, and enteric bacteria were also detected in greater numbers in soils amended with alternative than synthetic amendments, whereas propagule densities of Phytophthora and Pythium species were lower in soils amended with alternative than synthetic fertility amendments. Concentrations of Ca, K, Mg, and Mn were higher in soils amended with alternative than synthetic fertility amendments. Canonical correlations and principle component analyses indicated significant correlation between these soil chemical factors and the biological communities. First-order canonical correlations were more negative in fields with a conventional history, and use of synthetic fertilizers, whereas canonical correlations were more positive in fields with a history of organic production and alternative soil amendments. In the first year, yields of corn or melon were not different in soil amended with either synthetic or organic amendments at four of six farms. In the second year, when all growers planted tomatoes, yields were higher on farms with a history of organic production, regardless of soil amendment type. Alternative fertility amendments, enhanced beneficial soil microorganisms reduced pathogen populations, increased soil organic matter, total carbon, and cation exchange capacity (CEC), and lowered bulk density thus improving soil quality.
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- 2002
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11. Pre- and post-irradiation performance of FBK 3D silicon pixel detectors for CMS
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John Perry Cumalat, Frank Jensen, A. Vilela Pereira, S. Terzo, Ada Solano, Maria Margherita Obertino, A. Krzywda, Ian Shipsey, Maurizio Boscardin, Roberto Mendicino, C. M. Lei, A. Kumar, Kirk Arndt, Luigi Moroni, Dario Menasce, S. Tentindo, Nhan Tran, M. Bubna, M. Povoli, Ilya Osipenkov, Lorenzo Uplegger, Suvadeep Bose, Daniela Bortoletto, Simon Kwan, Stephen Robert Wagner, G.-F. Dalla Betta, J. Ngadiuba, Ping Tan, Gino Bolla, L. Perera, J. Adreson, A. Prosser, R. Brosius, E. Alagoz, J. Chramowicz, and Ryan Rivera
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Radiation hardness ,Physics ,Nuclear and High Energy Physics ,Large Hadron Collider ,Luminosity (scattering theory) ,Silicon ,Pixel ,3D ,Silicon pixel detectors ,business.industry ,Physics::Instrumentation and Detectors ,Detector ,chemistry.chemical_element ,Particle detector ,Semiconductor detector ,Planar ,chemistry ,Optoelectronics ,High Energy Physics::Experiment ,business ,Instrumentation - Abstract
In preparation for the tenfold luminosity upgrade of the Large Hadron Collider (the HL-LHC) around 2020, three-dimensional (3D) silicon pixel sensors are being developed as a radiation-hard candidate to replace the planar ones currently being used in the CMS pixel detector. This study examines an early batch of FBK sensors (named ATLAS08) of three 3D pixel geometries: 1E, 2E, and 4E, which respectively contain one, two, and four readout electrodes for each pixel, passing completely through the bulk. We present electrical characteristics and beam test performance results for each detector before and after irradiation. The maximum fluence applied is 3.5×1015 n eq /cm2.
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- 2014
12. Comparison of Commercial Fertilizer and Organic By-Products on Soil Chemical and Biological Properties and Vegetable Yields
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L. R. Bulluck, M. R. Brosius, Jean B. Ristaino, and G. K. Evanylo
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chemistry.chemical_classification ,fungi ,food and beverages ,Mineralization (soil science) ,Biodegradable waste ,engineering.material ,complex mixtures ,Manure ,Horticulture ,Agronomy ,chemistry ,Soil pH ,Organic farming ,engineering ,Environmental science ,Organic matter ,Fertilizer ,Cover crop - Abstract
Organic wastes may substitute for commercial fertilizers and enhance soil chemical and biological properties. This study compared the effects of commercial fertilizer and organic wastes on soil properties and crop yields on three organic and three conventional vegetable farms in Virginia and Maryland. The organic farms produced sweet corn and the conventional farms produced muskmelon or watermelon in 1996. Commercial N, P and K fertilizers were applied according to Virginia Cooperative Extension (VCE) recommendations. The organic fertility sources, composted cotton gin trash (3 farms), composted yardwaste and livestock manure (2 farms), or beef manure (1 farm), were applied to meet the N needs of each crop according to estimated N mineralization rates of the waste after subtracting estimated cover crop N contributions. The concentrations of most nutrients and soil pH, organic matter, and total C were higher after amending with organic wastes than fertilizer. Populations of Trichoderma and thermophilic microorganisms, known antagonists of pathogenic soilborne fungi, were initially greater in the organically-managed soils, and Trichoderma was higher in organic waste-amended than commercially-fertilized soils at harvest. The beneficial species Trichoderma and Pseudomonas were higher and plant pathogenic oomycete fungi were lower in the organic waste-amended than the commercially-fertilized soils regardless of cultural history. The plant pathogenic fungi increased with time and were greater in plots treated with inorganic fertilizers than organic amendments at harvest. Beneficial soil microorganisms appear to be favored by long term organic amendments, but some groups can be increased with organic amendments within a single season. Yields were similar between treatments, which demonstrates that organic amendments can provide adequate amounts of required plant nutrients in addition to enhancing soil chemical and biological attributes.
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- 1998
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13. A New Catalytic Route for the Oxidative Halogenation of Cyclic Enol Ethers using Tungstate Exchanged on Takovite.
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B. Sels, P. Levecque, R. Brosius, D. De 4;Vos, P. Jacobs, D. 4;W. Gammon, and H. 4;H. Kinfe
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- 2005
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14. Secondary structure model for bacterial 16S ribosomal RNA: phylogenetic, enzymatic and chemical evidence
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J. Kop, R. Brosius, Linda J. Magrum, Robin R. Gutell, Carl R. Woese, Ramesh Gupta, David A. Stahl, Harry F. Noller, James J. Hogan, R. B. Siegel, and N. Crawford
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Base Sequence ,Sequence analysis ,RNase P ,Base pair ,RNA ,Bacillus ,Biology ,Ribosomal RNA ,Conserved sequence ,RNA, Bacterial ,Ribonucleases ,Models, Chemical ,Biochemistry ,RNA, Ribosomal ,Escherichia coli ,Genetics ,Nucleic Acid Conformation ,30S ,Protein secondary structure ,Phylogeny - Abstract
We have derived a secondary structure model for 16S ribosomal RNA on the basis of comparative sequence analysis, chemical modification studies and nuclease susceptibility data. Nucleotide sequences of the E. coli and B. brevis 16S rRNA chains, and of RNAse T1 oligomer catalogs from 16S rRNAs of over 100 species of eubacteria were used for phylogenetic comparison. Chemical modification of G by glyoxal, A by m-chloroperbenzoic acid and C by bisulfite in naked 16S rRNA, and G by kethoxal in active and inactive 30S ribosomal subunits was taken as an indication of single stranded structure. Further support for the structure was obtained from susceptibility to RNases A and T1. These three approaches are in excellent agreement. The structure contains fifty helical elements organized into four major domains, in which 46 percent of the nucleotides of 16S rRNA are involved in base pairing. Phylogenetic comparison shows that highly conserved sequences are found principally in unpaired regions of the molecule. No knots are created by the structure.
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- 1980
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15. Epidemic Phlebodynia
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GEORGE R. BROSIUS
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Internal Medicine - Published
- 1961
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16. Engineering of a novel anti-CD40L domain antibody for treatment of autoimmune diseases.
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Xie JH, Yamniuk AP, Borowski V, Kuhn R, Susulic V, Rex-Rabe S, Yang X, Zhou X, Zhang Y, Gillooly K, Brosius R, Ravishankar R, Waggie K, Mink K, Price L, Rehfuss R, Tamura J, An Y, Cheng L, Abramczyk B, Ignatovich O, Drew P, Grant S, Bryson JW, Suchard S, Salter-Cid L, Nadler S, and Suri A
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- Animals, Antibodies, Monoclonal adverse effects, Disease Models, Animal, HEK293 Cells, Humans, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Mice, Platelet Activation immunology, Receptors, IgG immunology, Single-Domain Antibodies immunology, Surface Plasmon Resonance, Thromboembolism etiology, Thromboembolism prevention & control, Transfection, Autoimmune Diseases immunology, CD40 Ligand immunology, Platelet Activation drug effects, Single-Domain Antibodies pharmacology
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CD40-CD40L interactions play a critical role in regulating immune responses. Blockade of CD40L by Abs, such as the anti-CD40L Ab 5c8, demonstrated positive clinical effects in patients with autoimmune diseases; however, incidents of thromboembolism (TE) precluded further development of these molecules. In this study, we examined the role of the Fc domain interaction with FcγRs in modulating platelet activation and potential for TE. Our results show that the interaction of the 5c8 wild-type IgG1 Fc domain with FcγRs is responsible for platelet activation, as measured by induction of PAC-1 and CD62P. A version of 5c8 with a mutated IgG1 tail was identified that showed minimal FcγR binding and platelet activation while maintaining full binding to CD40L. To address whether Fc effector function is required for immunosuppression, a potent Ab fragment, termed a "domain Ab" (dAb), against murine CD40L was identified and fused to a murine IgG1 Fc domain containing a D265A mutation that lacks Fc effector function. In vitro, this dAb-Fc demonstrated comparable potency to the benchmark mAb MR-1 in inhibiting B cell and dendritic cell activation. Furthermore, the anti-CD40L dAb-Fc exhibited a notable efficacy comparable to MR-1 in various preclinical models, such as keyhole limpet hemocyanin-induced Ab responses, alloantigen-induced T cell proliferation, "heart-to-ear" transplantation, and NZB × NZW F1 spontaneous lupus. Thus, our data show that immunosuppression and TE can be uncoupled and that a CD40L dAb with an inert Fc tail is expected to be efficacious for treating autoimmune diseases, with reduced risk for TE.
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- 2014
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17. A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety.
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Suchard SJ, Davis PM, Kansal S, Stetsko DK, Brosius R, Tamura J, Schneeweis L, Bryson J, Salcedo T, Wang H, Yang Z, Fleener CA, Ignatovich O, Plummer C, Grant S, and Nadler SG
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- Animals, Antibodies immunology, Antigen-Presenting Cells immunology, Autoimmune Diseases therapy, CTLA-4 Antigen immunology, Cell Proliferation, Humans, Lymphocyte Activation immunology, Macaca fascicularis, B7-1 Antigen immunology, B7-2 Antigen immunology, CD28 Antigens antagonists & inhibitors, CD28 Antigens immunology, T-Lymphocytes immunology
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Targeting the CD28-CD80/86 pathway with an anti-CD28 antagonist is a promising alternative to current therapies for autoimmunity. However, attempts at generating conventional anti-CD28 mAbs lacking stimulatory activity has been challenging. In this study, we describe anti-human CD28 receptor antagonist domain Abs (dAbs) that are specific for human CD28. These dAbs are potent inhibitors of T cell activation, with an EC50 of 35 ± 14 ng/ml for inhibition of proliferation. The EC50 of 53 ± 11 ng/ml in an ex vivo CD28 receptor occupancy assay corresponds with in vitro functional activity, suggesting a direct correlation. The anti-CD28 dAb is equipotent in the inhibition of CD80- and CD86-mediated T cell proliferation and does not interfere with CTLA-4-mediated downmodulation of CD86 expression on APCs. The anti-CD28 dAbs are monomeric and do not demonstrate any evidence of agonism or costimulatory activity. In cynomolgus monkeys, the anti-CD28 dAb demonstrated pharmacodynamic activity, as measured by the inhibition of a T cell-dependent Ab response, without evidence of T cell depletion or cytokine release. Furthermore, there was a strong correlation between systemic exposure, duration, and extent of CD28 receptor occupancy, and pharmacodynamic activity. Taken together, these data support clinical evaluation of this novel anti-CD28 dAb for the treatment of autoimmune diseases.
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- 2013
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18. Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries.
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Parry TJ, Brosius R, Thyagarajan R, Carter D, Argentieri D, Falotico R, and Siekierka J
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- Animals, Antibiotics, Antineoplastic pharmacology, Apoptosis drug effects, Carotid Artery Injuries complications, Carotid Artery Injuries pathology, Cell Cycle drug effects, Cell Movement drug effects, Cell Survival, Cells, Cultured, Coronary Vessels cytology, Coronary Vessels drug effects, Dose-Response Relationship, Drug, Drug Delivery Systems, Endothelial Cells cytology, Endothelial Cells drug effects, Hyperplasia etiology, Male, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular drug effects, Rats, Rats, Inbred Lew, Stents, Tunica Intima drug effects, Tunica Intima pathology, Carotid Artery Injuries prevention & control, Cell Proliferation drug effects, Paclitaxel pharmacology, Sirolimus pharmacology
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Sirolimus and paclitaxel eluted from stents inhibit cell proliferation and other cellular processes by dramatically different mechanisms. In this study, the effects of sirolimus and paclitaxel on cultured human coronary artery smooth muscle and endothelial cell function or cell cycle changes in balloon-injured arteries were directly compared. Both sirolimus and paclitaxel inhibited smooth muscle and endothelial cell proliferation. However, only paclitaxel inhibited smooth muscle and endothelial cell migration at low (nM) concentrations. Sirolimus arrested smooth muscle and endothelial cells in the G0/G1 phase of the cell cycle without inducing apoptosis while paclitaxel produced apoptosis in both cell types at low nanomolar concentrations. Although both agents blocked neointimal formation, sirolimus applied locally to injured rat carotid arteries increased the percentage of cycling vascular cells in G0/G1 without inducing apoptosis while paclitaxel increased the percentage of cycling cells in S and G2/M phases while inducing apoptosis. These results suggest that sirolimus reduces neointimal hyperplasia through a cytostatic mechanism while paclitaxel produces apoptotic cell death.
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- 2005
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19. Nitroarylhydroxymethylphosphonic acids as inhibitors of CD45.
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Beers SA, Malloy EA, Wu W, Wachter MP, Gunnia U, Cavender D, Harris C, Davis J, Brosius R, Pellegrino-Gensey JL, and Siekierka J
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- Amino Acid Sequence, Animals, Binding, Competitive, Models, Chemical, Molecular Sequence Data, Nitrobenzenes pharmacology, Organophosphonates pharmacology, Recombinant Proteins metabolism, Spectrometry, Mass, Fast Atom Bombardment, Spodoptera, Leukocyte Common Antigens metabolism, Nitrobenzenes chemical synthesis, Organophosphonates chemical synthesis
- Abstract
A series of nitroarylhydroxymethylphosphonic acids was synthesized and evaluated as inhibitors of CD45. It was discovered that both the alpha hydroxy and nitro groups are essential for activity. Potency is enhanced by the addition of a large lipophilic group on the aryl ring adjacent to the phosphonic acid moiety. Kinetics studies have shown that these compounds are competitive inhibitors and thus bind at the active site of this enzyme.
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- 1997
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