28 results on '"Dwyer JE"'
Search Results
2. Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development.
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Rana VS, Kitsou C, Dutta S, Ronzetti MH, Zhang M, Bernard Q, Smith AA, Tomás-Cortázar J, Yang X, Wu MJ, Kepple O, Li W, Dwyer JE, Matias J, Baljinnyam B, Oliver JD, Rajeevan N, Pedra JHF, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, and Pal U
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- Animals, Interferon-gamma metabolism, Signal Transduction, Ixodes genetics, Ixodes immunology, Janus Kinases genetics, Janus Kinases metabolism, STAT Transcription Factors genetics, STAT Transcription Factors metabolism, Host-Parasite Interactions immunology, Receptors, Cytokine metabolism, Arachnid Vectors immunology
- Abstract
Ancestral signaling pathways serve critical roles in metazoan development, physiology, and immunity. We report an evolutionary interspecies communication pathway involving a central Ixodes scapularis tick receptor termed Dome1, which acquired a mammalian cytokine receptor motif exhibiting high affinity for interferon-gamma (IFN-γ). Host-derived IFN-γ facilitates Dome1-mediated activation of the Ixodes JAK-STAT pathway. This accelerates tick blood meal acquisition and development while upregulating antimicrobial components. The Dome1-JAK-STAT pathway, which exists in most Ixodid tick genomes, regulates the regeneration and proliferation of gut cells-including stem cells-and dictates metamorphosis through the Hedgehog and Notch-Delta networks, ultimately affecting Ixodes vectorial competence. We highlight the evolutionary dependence of I. scapularis on mammalian hosts through cross-species signaling mechanisms that dually influence arthropod immunity and development.
- Published
- 2023
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3. Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.
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Sanchez VC, Yang HH, Craig-Lucas A, Dubois W, Carofino BL, Lack J, Dwyer JE, Simpson RM, Cataisson C, Lee MP, Luo J, Hunter KW, and Yuspa SH
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- Animals, Female, Humans, Mice, Neoplasm Metastasis, Proteomics, Transforming Growth Factor beta metabolism, Tumor Microenvironment, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Chloride Channels biosynthesis, Chloride Channels genetics
- Abstract
The TGF-β-regulated Chloride Intracellular Channel 4 (CLIC4) is an essential participant in the formation of breast cancer stroma. Here, we used data available from the TCGA and METABRIC datasets to show that CLIC4 expression was higher in breast cancers from younger women and those with early-stage metastatic disease. Elevated CLIC4 predicted poor outcome in breast cancer patients and was linked to the TGF-β pathway. However, these associations did not reveal the underlying biological contribution of CLIC4 to breast cancer progression. Constitutive ablation of host Clic4 in two murine metastatic breast cancer models nearly eliminated lung metastases without reducing primary tumor weight, while tumor cells ablated of Clic4 retained metastatic capability in wildtype hosts. Thus, CLIC4 was required for host metastatic competence. Pre- and post-metastatic proteomic analysis identified circulating pro-metastatic soluble factors that differed in tumor-bearing CLIC4-deficient and wildtype hosts. Vascular abnormalities and necrosis increased in primary tumors from CLIC4-deficient hosts. Transcriptional profiles of both primary tumors and pre-metastatic lungs of tumor-bearing CLIC4-deficient hosts were consistent with a microenvironment where inflammatory pathways were elevated. Altogether, CLIC4 expression in human breast cancers may serve as a prognostic biomarker; therapeutic targeting of CLIC4 could reduce primary tumor viability and host metastatic competence., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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4. Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response.
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Amin R, Shukla A, Zhu JJ, Kim S, Wang P, Tian SZ, Tran AD, Paul D, Cappell SD, Burkett S, Liu H, Lee MP, Kruhlak MJ, Dwyer JE, Simpson RM, Hager GL, Ruan Y, and Hunter KW
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- Animals, Breast Neoplasms genetics, Breast Neoplasms metabolism, CCCTC-Binding Factor metabolism, Cell Line, Tumor, Cell Movement genetics, Cytoskeleton metabolism, Enhancer of Zeste Homolog 2 Protein metabolism, Focal Adhesions genetics, Gene Expression Regulation, Neoplastic, Histones metabolism, Humans, Methyltransferases metabolism, Mice, Neoplasm Metastasis, Neoplastic Cells, Circulating metabolism, Nuclear Envelope metabolism, Nuclear Pore Complex Proteins genetics, Nuclear Proteins metabolism, Polymorphism, Genetic, Prognosis, Promoter Regions, Genetic, Protein Binding, Repressor Proteins metabolism, Transcription Factors metabolism, Tumor Microenvironment, Breast Neoplasms pathology, Heterochromatin metabolism, Mechanotransduction, Cellular genetics, Nuclear Pore Complex Proteins metabolism
- Abstract
Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2021
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5. Selective targeting of the αC and DFG-out pocket in p38 MAPK.
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Röhm S, Schröder M, Dwyer JE, Widdowson CS, Chaikuad A, Berger BT, Joerger AC, Krämer A, Harbig J, Dauch D, Kudolo M, Laufer S, Bagley MC, and Knapp S
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- Allosteric Regulation, Allosteric Site, Animals, Cell Line, Tumor, Fluorometry, HEK293 Cells, Humans, Mice, Microsomes, Liver metabolism, Phenylurea Compounds chemical synthesis, Phenylurea Compounds metabolism, Protein Binding, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors metabolism, p38 Mitogen-Activated Protein Kinases chemistry, p38 Mitogen-Activated Protein Kinases metabolism, Phenylurea Compounds pharmacology, Protein Kinase Inhibitors pharmacology, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
- Abstract
The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we have explored the highly dynamic back pocket of p38 MAPK with allosteric urea fragments. However, screening against known off-targets showed that these fragments maintained the selectivity issues of their parent compound BIRB-796, while combination with the hinge-binding motif of VPC-00628 greatly enhanced inhibitor selectivity. Further efforts focused therefore on the exploration of the αC-out pocket of p38 MAPK, yielding compound 137 as a highly selective type-II inhibitor. Even though 137 is structurally related to a recent p38 type-II chemical probe, SR-318, the data presented here provide valuable insights into back-pocket interactions that are not addressed in SR-318 and it provides an alternative chemical tool with good cellular activity targeting also the p38 back pocket., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
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- 2020
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6. Efficacy, Tolerability, and Pharmacokinetics of Combined Targeted MEK and Dual mTORC1/2 Inhibition in a Preclinical Model of Mucosal Melanoma.
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Wei BR, Hoover SB, Peer CJ, Dwyer JE, Adissu HA, Shankarappa P, Yang H, Lee M, Peat TJ, Figg WD, and Simpson RM
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- Animals, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Disease Models, Animal, Drug Monitoring, Female, Humans, Melanoma etiology, Mice, Mucous Membrane metabolism, Treatment Outcome, Xenograft Model Antitumor Assays, Mechanistic Target of Rapamycin Complex 1 antagonists & inhibitors, Mechanistic Target of Rapamycin Complex 2 antagonists & inhibitors, Melanoma drug therapy, Melanoma pathology, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mucous Membrane drug effects, Mucous Membrane pathology, Protein Kinase Inhibitors pharmacology
- Abstract
Melanomas arising in the mucous membranes are a rare and aggressive subtype. New treatment approaches are needed, yet accumulating sufficient evidence to improve patient outcomes is difficult. Clinical and pathological correlates between human and canine mucosal melanomas are substantial, and the relatively greater incidence of spontaneous naturally occurring mucosal melanoma in dogs represents a promising opportunity for predictive modeling. The genomic landscapes of human and canine mucosal melanoma appear highly diverse and generally lack recurring hotspot mutations associated with cutaneous melanomas. Although much remains to be determined, evidence indicates that Ras/MAPK and/or PI3K/AKT/mTOR signaling pathway activations are common in both species and may represent targets for therapeutic intervention. Sapanisertib, an mTORC1/2 inhibitor, was selected from a PI3K/mTOR inhibitor library to collaborate with MEK inhibition; the latter preclinical efficacy was demonstrated previously for canine mucosal melanoma. Combined inhibition of MEK and mTORC1/2, using trametinib and sapanisertib, produced apoptosis and cell-cycle alteration, synergistically reducing cell survival in canine mucosal melanoma cell lines with varying basal signaling activation levels. Compared with individual inhibitors, a staggered sapanisertib dose, coupled with daily trametinib, was optimal for limiting primary mucosal melanoma xenograft growth in mice, and tumor dissemination in a metastasis model, while minimizing hematologic and renal side effects. Inhibitors downmodulated respective signaling targets and the combination additionally suppressed pathway reciprocal crosstalk. The combination did not significantly change plasma sapanisertib pharmacokinetics; however, trametinib area under the curve was increased in the presence of sapanisertib. Targeting Ras/MAPK and PI3K/AKT/mTOR signal transduction pathways appear rational therapies for canine and human mucosal melanoma., (©2020 American Association for Cancer Research.)
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- 2020
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7. Inter-Institutional Partnerships to Develop Veterinarian-Investigators through the NIH Comparative Biomedical Scientist Training Program Benefit One Health Goals.
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Simpson RM, Hoover SB, Davis BJ, Hickerson J, Miller MA, Kiupel M, Cullen JM, Dwyer JE, Wei BR, Rosol TJ, Kornegay JN, and Samal SK
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- Animals, Goals, Humans, National Institutes of Health (U.S.), United States, Biomedical Research, Education, Veterinary, One Health, Veterinarians
- Abstract
Limitations in workforce size and access to resources remain perennial challenges to greater progress in academic veterinary medicine and engagement between human and veterinary medicine (One Health). Ongoing resource constraints occur in part due to limited public understanding of the role veterinarians play in improving human health. One Health interactions, particularly through interdisciplinary collaborations in biomedical research, present constructive opportunities to inform resource policies and advance health care. To this end, inter-institutional partnerships between individual veterinary medical education programs (VMEPs) and several National Institutes of Health (NIH) intramural research programs have created synergies beyond those provided by individual programs. In the NIH Comparative Biomedical Scientist Training Program (CBSTP), interdisciplinary cross-training of veterinarians consisting of specialty veterinary medicine coupled with training in human disease research leading to a PhD, occurs collaboratively on both VMEP and NIH campuses. Pre-doctoral veterinary student research opportunities have also been made available. Through the CBSTP, NIH investigators and national biomedical science policy makers gain access to veterinary perspective and expertise, while veterinarians obtain additional opportunities for NIH-funded research training. CBSTP Fellows serve as de facto ambassadors enhancing visibility for the profession while in residence at NIH, and subsequently through a variety of university, industry, and government research appointments, as graduates. Thus, the CBSTP represents an inter-institutional opportunity that not only addresses critical needs for veterinarian-scientists in the biomedical workforce, but also simultaneously exposes national policy makers to veterinarian-scientists' specialized training, leading to more effective realization of One Health goals to benefit human and animal health.
- Published
- 2020
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8. In vivo localization and postmortem stability of benzo[a]pyrene-DNA adducts.
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Poirier MC, Beland FA, Divi KV, Damon AL, Ali M, Vanlandingham MM, Churchwell MI, Von Tungeln LS, Dwyer JE, Divi RL, Beauchamp G, and Martineau D
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- Animals, Benzo(a)pyrene administration & dosage, Carcinogens, Environmental administration & dosage, Chromatography, High Pressure Liquid, DNA Adducts administration & dosage, Intestine, Small chemistry, Luminescent Measurements, Male, Mice, Stomach chemistry, Tandem Mass Spectrometry, Tissue Distribution, Benzo(a)pyrene analysis, Carcinogens, Environmental analysis, DNA Adducts analysis
- Abstract
DNA adducts of carcinogenic polycyclic aromatic hydrocarbons (PAHs) play a critical role in the etiology of gastrointestinal tract cancers in humans and other species orally exposed to PAHs. Yet, the precise localization of PAH-DNA adducts in the gastrointestinal tract, and the long-term postmortem PAH-DNA adduct stability are unknown. To address these issues, the following experiment was performed. Mice were injected intraperitoneally with the PAH carcinogen benzo[a]pyrene (BP) and euthanized at 24 h. Tissues were harvested either at euthanasia (0 time), or after 4, 8, 12, 24, 48, and 168 hr (7 days) of storage at 4°C. Portions of mouse tissues were formalin-fixed, paraffin-embedded, and immunohistochemically (IHC) evaluated by incubation with r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA antiserum and H-scoring. The remaining tissues were frozen, and DNA was extracted and assayed for the r7,t8,t9-trihydroxy-c-10-(N
2 -deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG) adduct using two quantitative assays, the BPDE-DNA chemiluminescence immunoassay (CIA), and high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ES-MS/MS). By IHC, which required intact nuclei, BPdG adducts were visualized in forestomach basal cells, which included gastric stem cells, for up to 7 days. In proximal small intestine villus epithelium BPdG adducts were visualized for up to 12 hr. By BPDE-DNA CIA and HPLC-ES-MS/MS, both of which used DNA for analysis and correlated well (P= 0.0001), BPdG adducts were unchanged in small intestine, forestomach, and lung stored at 4°C for up to 7 days postmortem. In addition to localization of BPdG adducts, this study reveals the feasibility of examining PAH-DNA adduct formation in wildlife species living in colder climates. Environ. Mol. Mutagen. 61:216-223, 2020. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)- Published
- 2020
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9. Agreement in Histological Assessment of Mitotic Activity Between Microscopy and Digital Whole Slide Images Informs Conversion for Clinical Diagnosis.
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Wei BR, Halsey CH, Hoover SB, Puri M, Yang HH, Gallas BD, Lee MP, Chen W, Durham AC, Dwyer JE, Sánchez MD, Traslavina RP, Frank C, Bradley C, McGill LD, Esplin DG, Schaffer PA, Cramer SD, Lyle LT, Beck J, Buza E, Gong Q, Hewitt SM, and Simpson RM
- Abstract
Validating digital pathology as substitute for conventional microscopy in diagnosis remains a priority to assure effectiveness. Intermodality concordance studies typically focus on achieving the same diagnosis by digital display of whole slide images and conventional microscopy. Assessment of discrete histological features in whole slide images, such as mitotic figures, has not been thoroughly evaluated in diagnostic practice. To further gauge the interchangeability of conventional microscopy with digital display for primary diagnosis, 12 pathologists examined 113 canine naturally occurring mucosal melanomas exhibiting a wide range of mitotic activity. Design reflected diverse diagnostic settings and investigated independent location, interpretation, and enumeration of mitotic figures. Intermodality agreement was assessed employing conventional microscopy (CM40×), and whole slide image specimens scanned at 20× (WSI20×) and at 40× (WSI40×) objective magnifications. An aggregate 1647 mitotic figure count observations were available from conventional microscopy and whole slide images for comparison. The intraobserver concordance rate of paired observations was 0.785 to 0.801; interobserver rate was 0.784 to 0.794. Correlation coefficients between the 2 digital modes, and as compared to conventional microscopy, were similar and suggest noninferiority among modalities, including whole slide image acquired at lower 20× resolution. As mitotic figure counts serve for prognostic grading of several tumor types, including melanoma, 6 of 8 pathologists retrospectively predicted survival prognosis using whole slide images, compared to 9 of 10 by conventional microscopy, a first evaluation of whole slide image for mitotic figure prognostic grading. This study demonstrated agreement of replicate reads obtained across conventional microscopy and whole slide images. Hence, quantifying mitotic figures served as surrogate histological feature with which to further credential the interchangeability of whole slide images for primary diagnosis., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2019
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10. Automated Computational Detection, Quantitation, and Mapping of Mitosis in Whole-Slide Images for Clinically Actionable Surgical Pathology Decision Support.
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Puri M, Hoover SB, Hewitt SM, Wei BR, Adissu HA, Halsey CHC, Beck J, Bradley C, Cramer SD, Durham AC, Esplin DG, Frank C, Lyle LT, McGill LD, Sánchez MD, Schaffer PA, Traslavina RP, Buza E, Yang HH, Lee MP, Dwyer JE, and Simpson RM
- Abstract
Background: Determining mitotic index by counting mitotic figures (MFs) microscopically from tumor areas with most abundant MF (hotspots [HS]) produces a prognostically useful tumor grading biomarker. However, interobserver concordance identifying MF and HS can be poorly reproducible. Immunolabeling MF, coupled with computer-automated counting by image analysis, can improve reproducibility. A computational system for obtaining MF values across digitized whole-slide images (WSIs) was sought that would minimize impact of artifacts, generate values clinically relatable to counting ten high-power microscopic fields of view typical in conventional microscopy, and that would reproducibly map HS topography., Materials and Methods: Relatively low-resolution WSI scans (0.50 μm/pixel) were imported in grid-tile format for feature-based MF segmentation, from naturally occurring canine melanomas providing a wide range of proliferative activity. MF feature extraction conformed to anti-phospho-histone H3-immunolabeled mitotic (M) phase cells. Computer vision image processing was established to subtract key artifacts, obtain MF counts, and employ rotationally invariant feature extraction to map MF topography., Results: The automated topometric HS (TMHS) algorithm identified mitotic HS and mapped select tissue tiles with greatest MF counts back onto WSI thumbnail images to plot HS topographically. Influence of dye, pigment, and extraneous structure artifacts was minimized. TMHS diagnostic decision support included image overlay graphics of HS topography, as well as a spreadsheet and plot of tile-based MF count values. TMHS performance was validated examining both mitotic HS counting and mapping functions. Significantly correlated TMHS MF mapping and metrics were demonstrated using repeat analysis with WSI in different orientation ( R
2 = 0.9916) and by agreement with a pathologist ( R2 = 0.8605) as well as through assessment of counting function using an independently tuned object counting algorithm (OCA) ( R2 = 0.9482). Limits of agreement analysis support method interchangeability. MF counts obtained led to accurate patient survival prediction in all ( n = 30) except one case. By contrast, more variable performance was documented when several pathologists examined similar cases using microscopy (pair-wise correlations, rho range = 0.7597-0.9286)., Conclusions: Automated TMHS MF segmentation and feature engineering performance were interchangeable with both observer and OCA in digital mode. Moreover, enhanced HS location accuracy and superior method reproducibility were achieved using the automated TMHS algorithm compared to the current practice employing clinical microscopy., Competing Interests: There are no conflicts of interest.- Published
- 2019
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11. Intestinal polycyclic aromatic hydrocarbon-DNA adducts in a population of beluga whales with high levels of gastrointestinal cancers.
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Poirier MC, Lair S, Michaud R, Hernández-Ramon EE, Divi KV, Dwyer JE, Ester CD, Si NN, Ali M, Loseto LL, Raverty SA, St Leger JA, Van Bonn WG, Colegrove K, Burek-Huntington KA, Suydam R, Stimmelmayr R, Wise JP, Wise SS, Beauchamp G, and Martineau D
- Subjects
- Animals, Arctic Regions, Beluga Whale, Fibroblasts drug effects, Fibroblasts pathology, Intestinal Mucosa cytology, Mice, Water Pollutants, Chemical toxicity, Carcinogenesis chemically induced, DNA Adducts toxicity, DNA Damage drug effects, Epithelial Cells pathology, Gastrointestinal Neoplasms etiology, Gastrointestinal Neoplasms pathology, Intestinal Mucosa pathology, Polycyclic Aromatic Hydrocarbons toxicity
- Abstract
Carcinogenic polycyclic aromatic hydrocarbons (PAHs) were disposed directly into the Saguenay River of the St. Lawrence Estuary (SLE) by local aluminum smelters (Quebec, Canada) for 50 years (1926-1976). PAHs in the river sediments are likely etiologically related to gastrointestinal epithelial cancers observed in 7% of 156 mature (>19-year old) adult beluga found dead along the shorelines. Because DNA adduct formation provides a critical link between exposure and cancer induction, and because PAH-DNA adducts are chemically stable, we hypothesized that SLE beluga intestine would contain PAH-DNA adducts. Using an antiserum specific for DNA modified with several carcinogenic PAHs, we stained sections of paraffin-embedded intestine from 51 SLE beluga (0-63 years), 4 Cook Inlet (CI) Alaska beluga (0-26 years), and 20 beluga (0-46 years) living in Arctic areas (Eastern Beaufort Sea, Eastern Chukchi Sea, Point Lay Alaska) and aquaria, all with low PAH contamination. Stained sections showed nuclear light-to-dark pink color indicating the presence of PAH-DNA adducts concentrated in intestinal crypt epithelial lining cells. Scoring of whole tissue sections revealed higher values for the 51 SLE beluga, compared with the 20 Arctic and aquarium beluga (P = 0.003). The H-scoring system, applied to coded individual photomicrographs, confirmed that SLE beluga and CI beluga had levels of intestinal PAH-DNA adducts significantly higher than Arctic and aquarium beluga (P = 0.003 and 0.02, respectively). Furthermore, high levels of intestinal PAH-DNA adducts in four SLE beluga with gastrointestinal cancers, considered as a group, support a link of causality between PAH exposure and intestinal cancer in SLE beluga. Environ. Mol. Mutagen. 60:29-41, 2019. Published 2018. This article is a U.S. Government work and is in the public domain in the USA., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)
- Published
- 2019
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12. Direct molecular dissection of tumor parenchyma from tumor stroma in tumor xenograft using mass spectrometry-based glycoproteomics.
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Ye X, Luke BT, Wei BR, Kaczmarczyk JA, Loncarek J, Dwyer JE, Johann DJ, Saul RG, Nissley DV, McCormick F, Whiteley GR, and Blonder J
- Abstract
The most widely used cancer animal model is the human-murine tumor xenograft. Unbiased molecular dissection of tumor parenchyma versus stroma in human-murine xenografts is critical for elucidating dysregulated protein networks/pathways and developing therapeutics that may target these two functionally codependent compartments. Although antibody-reliant technologies (e.g., immunohistochemistry, imaging mass cytometry) are capable of distinguishing tumor-proper versus stromal proteins, the breadth or extent of targets is limited. Here, we report an antibody-free targeted cross-species glycoproteomic (TCSG) approach that enables direct dissection of human tumor parenchyma from murine tumor stroma at the molecular/protein level in tumor xenografts at a selectivity rate presently unattainable by other means. This approach was used to segment/dissect and obtain the protein complement phenotype of the tumor stroma and parenchyma of the metastatic human lung adenocarcinoma A549 xenograft, with no need for tissue microdissection prior to mass-spectrometry analysis. An extensive molecular map of the tumor proper and the associated microenvironment was generated along with the top functional N-glycosylated protein networks enriched in each compartment. Importantly, immunohistochemistry-based cross-validation of selected parenchymal and stromal targets applied on human tissue samples of lung adenocarcinoma and normal adjacent tissue is indicative of a noteworthy translational capacity for this unique approach that may facilitate identifications of novel targets for next generation antibody therapies and development of real time preclinical tumor models., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.
- Published
- 2018
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13. Plasticity in early immune evasion strategies of a bacterial pathogen.
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Bernard Q, Smith AA, Yang X, Koci J, Foor SD, Cramer SD, Zhuang X, Dwyer JE, Lin YP, Mongodin EF, Marques A, Leong JM, Anguita J, and Pal U
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- Animals, Antigens, Bacterial immunology, Antimicrobial Cationic Peptides biosynthesis, Antimicrobial Cationic Peptides genetics, Arachnid Vectors microbiology, Bacterial Proteins genetics, Borrelia burgdorferi genetics, Borrelia burgdorferi pathogenicity, Cells, Cultured, Complement System Proteins immunology, Cytokines biosynthesis, Cytokines genetics, Female, Gene Expression Regulation, Bacterial, Humans, Ixodes microbiology, Lipoproteins genetics, Lyme Disease immunology, Lyme Disease microbiology, Membrane Proteins genetics, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, SCID, Specific Pathogen-Free Organisms, Virulence, Bacterial Proteins physiology, Borrelia burgdorferi immunology, Immune Evasion, Lipoproteins physiology, Membrane Proteins physiology
- Abstract
Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy of B. burgdorferi , orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
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14. Synergistic targeted inhibition of MEK and dual PI3K/mTOR diminishes viability and inhibits tumor growth of canine melanoma underscoring its utility as a preclinical model for human mucosal melanoma.
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Wei BR, Michael HT, Halsey CH, Peer CJ, Adhikari A, Dwyer JE, Hoover SB, El Meskini R, Kozlov S, Weaver Ohler Z, Figg WD, Merlino G, and Simpson RM
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- Animals, Apoptosis drug effects, Cell Proliferation drug effects, Dogs, Drug Synergism, Female, Humans, MAP Kinase Kinase Kinases metabolism, MAP Kinase Signaling System drug effects, Melanoma metabolism, Melanoma pathology, Mice, Mice, Nude, Mucous Membrane metabolism, Mucous Membrane pathology, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic drug effects, MAP Kinase Kinase Kinases antagonists & inhibitors, Melanoma drug therapy, Mucous Membrane drug effects, Phosphoinositide-3 Kinase Inhibitors, Protein Kinase Inhibitors pharmacology, TOR Serine-Threonine Kinases antagonists & inhibitors
- Abstract
Human mucosal melanoma (MM), an uncommon, aggressive and diverse subtype, shares characteristics with spontaneous MM in dogs. Although BRAF and N-RAS mutations are uncommon in MM in both species, the majority of human and canine MM evaluated exhibited RAS/ERK and/or PI3K/mTOR signaling pathway activation. Canine MM cell lines, with varying ERK and AKT/mTOR activation levels reflective of naturally occurring differences in dogs, were sensitive to the MEK inhibitor GSK1120212 and dual PI3K/mTOR inhibitor NVP-BEZ235. The two-drug combination synergistically decreased cell survival in association with caspase 3/7 activation, as well as altered expression of cell cycle regulatory proteins and Bcl-2 family proteins. In combination, the two drugs targeted their respective signaling pathways, potentiating reduction of pathway mediators p-ERK, p-AKT, p-S6, and 4E-BP1 in vitro, and in association with significantly inhibited solid tumor growth in MM xenografts in mice. These findings provide evidence of synergistic therapeutic efficacy when simultaneously targeting multiple mediators in melanoma with Ras/ERK and PI3K/mTOR pathway activation., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
- Published
- 2016
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15. The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells.
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Bagley MC, Dwyer JE, Baashen M, Dix MC, Murziani PG, Rokicki MJ, Kipling D, and Davis T
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- Cell Line, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Fibroblasts drug effects, Fibroblasts pathology, Humans, Ketones chemical synthesis, Ketones chemistry, Microwaves, Molecular Structure, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Pyrazoles chemical synthesis, Pyrazoles chemistry, Small Molecule Libraries chemical synthesis, Small Molecule Libraries chemistry, Structure-Activity Relationship, Werner Syndrome drug therapy, Werner Syndrome metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Ketones pharmacology, Protein Kinase Inhibitors pharmacology, Pyrazoles pharmacology, Small Molecule Libraries pharmacology, Werner Syndrome pathology, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
- Abstract
Microwave-assisted synthesis of the pyrazolyl ketone p38 MAPK inhibitor RO3201195 in 7 steps and 15% overall yield, and the comparison of its effect upon the proliferation of Werner Syndrome cells with a library of pyrazolyl ketones, strengthens the evidence that p38 MAPK inhibition plays a critical role in modulating premature cellular senescence in this progeroid syndrome and the reversal of accelerated ageing observed in vitro on treatment with SB203580.
- Published
- 2016
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16. Microwave-assisted synthesis of 3-aminobenzo[b]thiophene scaffolds for the preparation of kinase inhibitors.
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Bagley MC, Dwyer JE, Molina MD, Rand AW, Rand HL, and Tomkinson NC
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- Amination, Humans, Lim Kinases antagonists & inhibitors, MAP Kinase Kinase 2 antagonists & inhibitors, Microwaves, Protein Kinase Inhibitors chemistry, Proto-Oncogene Proteins c-pim-1 antagonists & inhibitors, Thiophenes chemistry, Protein Kinase Inhibitors chemical synthesis, Thiophenes chemical synthesis
- Abstract
Microwave irradiation of 2-halobenzonitriles and methyl thioglycolate in the presence of triethylamine in DMSO at 130 °C provides rapid access to 3-aminobenzo[b]thiophenes in 58-96% yield. This transformation has been applied in the synthesis of the thieno[2,3-b]pyridine core motif of LIMK1 inhibitors, the benzo[4,5]thieno[3,2-e][1,4]diazepin-5(2H)-one scaffold of MK2 inhibitors and a benzo[4,5]thieno[3,2-d]pyrimidin-4-one inhibitor of the PIM kinases.
- Published
- 2015
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17. Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells.
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Bagley MC, Baashen M, Chuckowree I, Dwyer JE, Kipling D, and Davis T
- Abstract
Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells.
- Published
- 2015
- Full Text
- View/download PDF
18. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.
- Author
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Simpson RM, Bastian BC, Michael HT, Webster JD, Prasad ML, Conway CM, Prieto VM, Gary JM, Goldschmidt MH, Esplin DG, Smedley RC, Piris A, Meuten DJ, Kiupel M, Lee CC, Ward JM, Dwyer JE, Davis BJ, Anver MR, Molinolo AA, Hoover SB, Rodriguez-Canales J, and Hewitt SM
- Subjects
- Animals, Disease Models, Animal, Dogs, Humans, MAP Kinase Signaling System genetics, Neoplasm Metastasis, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Dog Diseases genetics, Dog Diseases metabolism, Dog Diseases pathology, Melanoma genetics, Melanoma metabolism, Melanoma pathology, Melanoma veterinary, Mouth Neoplasms genetics, Mouth Neoplasms metabolism, Mouth Neoplasms pathology, Mouth Neoplasms veterinary, Skin Neoplasms genetics, Skin Neoplasms metabolism, Skin Neoplasms pathology, Skin Neoplasms veterinary
- Abstract
Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model., (© 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
19. The role of voltage dependence of the NMDA receptor in cellular and network oscillation.
- Author
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Martell AL, Ramirez JM, Lasky RE, Dwyer JE, Kohrman M, and van Drongelen W
- Subjects
- Action Potentials, Animals, Magnesium metabolism, Mice, Mice, Inbred Strains, Models, Neurological, Neocortex cytology, Neocortex physiology, Nerve Net physiology, Periodicity, Pyramidal Cells cytology, Sodium Channel Blockers pharmacology, Sodium Channels drug effects, Tetrodotoxin pharmacology, Pyramidal Cells physiology, Receptors, N-Methyl-D-Aspartate metabolism
- Abstract
Unraveling the mechanisms underlying oscillatory behavior is critical for understanding normal and pathological brain processes. Here we used electrophysiology in mouse neocortical slices and principles of nonlinear dynamics to demonstrate how an increase in the N-methyl-d-aspartic acid receptor (NMDAR) conductance can create a nonlinear whole-cell current-voltage (I-V) relationship which leads to changes in cellular stability. We discovered two behaviorally and morphologically distinct pyramidal cell populations. Under control conditions, both cell types responded to depolarizing current injection with regular spiking patterns. However, upon NMDAR activation, an intrinsic oscillatory (IO) cell type (n = 44) showed a nonlinear whole-cell I-V relationship, intrinsic voltage-dependent oscillations plus amplification of alternating input current, and these properties persisted after disabling action potential generation with tetrodotoxin (TTX). The other non-oscillatory (NO) neuronal population (n = 24) demonstrated none of these behaviors. Simultaneous intra- and extracellular recordings demonstrated the NMDAR's capacity to promote low-frequency seizure-like network oscillations via its effects on intrinsic neuronal properties. The two pyramidal cell types demonstrated different relationships with network oscillation--the IO cells were leaders that were activated early in the population activity cycle while the activation of the NO cell type was distributed across network bursts. The properties of IO neurons disappeared in a low-magnesium environment where the voltage dependence of the receptor is abolished; concurrently, the cellular contribution to network oscillation switched to synchronous firing. Thus, depending upon the efficacy of NMDAR in altering the linearity of the whole-cell I-V relationship, the two cell populations played different roles in sustaining network oscillation., (© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)
- Published
- 2012
- Full Text
- View/download PDF
20. Proteomic profiling of H-Ras-G12V induced hypertrophic cardiomyopathy in transgenic mice using comparative LC-MS analysis of thin fresh-frozen tissue sections.
- Author
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Wei BR, Simpson RM, Johann DJ, Dwyer JE, Prieto DA, Kumar M, Ye X, Luke B, Shive HR, Webster JD, Hoover SB, Veenstra TD, and Blonder J
- Subjects
- Amino Acid Sequence, Animals, Cardiomyopathy, Hypertrophic genetics, Chromatography, Liquid, Cluster Analysis, Gene Expression, Gene Expression Regulation, Mice, Mice, Transgenic, Molecular Sequence Data, Mutation, Missense, Peptide Fragments chemistry, Protein Precursors chemistry, Protein Precursors genetics, Protein Precursors metabolism, Proteome genetics, Proteomics, Proto-Oncogene Proteins p21(ras) chemistry, Proto-Oncogene Proteins p21(ras) metabolism, Vimentin metabolism, Wnt3A Protein metabolism, beta Catenin metabolism, Cardiomyopathy, Hypertrophic metabolism, Myocardium metabolism, Proteome metabolism, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Determination of disease-relevant proteomic profiles from limited tissue specimens, such as pathological biopsies and tissues from small model organisms, remains an analytical challenge and a much needed clinical goal. In this study, a transgenic mouse disease model of cardiac-specific H-Ras-G12V induced hypertrophic cardiomyopathy provided a system to explore the potential of using mass spectrometry (MS)-based proteomics to obtain a disease-relevant molecular profile from amount-limited specimens that are routinely used in pathological diagnosis. Our method employs a two-stage methanol-assisted solubilization to digest lysates prepared from 8-μm-thick fresh-frozen histological tissue sections of diseased/experimental and normal/control hearts. Coupling this approach with a nanoflow reversed-phase liquid chromatography (LC) and a hybrid linear ion trap/Fourier transform-ion cyclotron resonance MS resulted in the identification of 704 and 752 proteins in hypertrophic and wild-type (control) myocardium, respectively. The disease driving H-Ras protein along with vimentin were unambiguously identified by LC-MS in hypertrophic myocardium and cross-validated by immunohistochemistry and western blotting. The pathway analysis involving proteins identified by MS showed strong association of proteomic data with cardiovascular disease. More importantly, the MS identification and subsequent cross-validation of Wnt3a and β-catenin, in conjunction with IHC identification of phosphorylated GSK-3β and nuclear localization of β-catenin, provided evidence of Wnt/β-catenin canonical pathway activation secondary to Ras activation in the course of pathogenic myocardial hypertrophic transformation. Our method yields results indicating that the described proteomic approach permits molecular discovery and assessment of differentially expressed proteins regulating H-Ras induced hypertrophic cardiomyopathy. Selected proteins and pathways can be further investigated using immunohistochemical techniques applied to serial tissue sections of similar or different origin.
- Published
- 2012
- Full Text
- View/download PDF
21. Investigation into diagnostic agreement using automated computer-assisted histopathology pattern recognition image analysis.
- Author
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Webster JD, Michalowski AM, Dwyer JE, Corps KN, Wei BR, Juopperi T, Hoover SB, and Simpson RM
- Abstract
The extent to which histopathology pattern recognition image analysis (PRIA) agrees with microscopic assessment has not been established. Thus, a commercial PRIA platform was evaluated in two applications using whole-slide images. Substantial agreement, lacking significant constant or proportional errors, between PRIA and manual morphometric image segmentation was obtained for pulmonary metastatic cancer areas (Passing/Bablok regression). Bland-Altman analysis indicated heteroscedastic measurements and tendency toward increasing variance with increasing tumor burden, but no significant trend in mean bias. The average between-methods percent tumor content difference was -0.64. Analysis of between-methods measurement differences relative to the percent tumor magnitude revealed that method disagreement had an impact primarily in the smallest measurements (tumor burden <3%). Regression-based 95% limits of agreement indicated substantial agreement for method interchangeability. Repeated measures revealed concordance correlation of >0.988, indicating high reproducibility for both methods, yet PRIA reproducibility was superior (C.V.: PRIA = 7.4, manual = 17.1). Evaluation of PRIA on morphologically complex teratomas led to diagnostic agreement with pathologist assessments of pluripotency on subsets of teratomas. Accommodation of the diversity of teratoma histologic features frequently resulted in detrimental trade-offs, increasing PRIA error elsewhere in images. PRIA error was nonrandom and influenced by variations in histomorphology. File-size limitations encountered while training algorithms and consequences of spectral image processing dominance contributed to diagnostic inaccuracies experienced for some teratomas. PRIA appeared better suited for tissues with limited phenotypic diversity. Technical improvements may enhance diagnostic agreement, and consistent pathologist input will benefit further development and application of PRIA.
- Published
- 2012
- Full Text
- View/download PDF
22. Natriuretic response to increased pressure is preserved with COX-2 inhibitors.
- Author
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Gross JM, Dwyer JE, and Knox FG
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Dinoprostone urine, Male, Meloxicam, Nitrobenzenes pharmacology, Piroxicam pharmacology, Rats, Rats, Sprague-Dawley, Sulfonamides pharmacology, Thiazines pharmacology, Thiazoles pharmacology, Blood Pressure, Cyclooxygenase Inhibitors pharmacology, Isoenzymes drug effects, Kidney physiology, Natriuresis drug effects, Prostaglandin-Endoperoxide Synthases drug effects
- Abstract
Elevation of renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion increases sodium excretion. This natriuretic response is blunted by the nonspecific inhibition of the cyclooxygenase (COX) enzymes. The present study tested the hypothesis that the natriuretic response to increased RIHP during direct renal interstitial volume expansion is dependent on COX-1 but not COX-2. RIHP and fractional excretion of sodium (FE(Na)) were measured before and after direct renal interstitial volume expansion in control rats (n=7), rats infused with the COX-1 inhibitor piroxicam (n=6, 1.5 mg/kg), and rats infused with the COX-2 inhibitors NS-398 (n=5, 1.5 mg/kg) and meloxicam (n=6, 0.3 mg/kg). In control animals, direct renal interstitial volume expansion significantly increased RIHP (Delta2.3+/-0.5 mm Hg, P<0. 05) and FE(Na) (Delta1.1+/-0.3%, P<0.05). Likewise, in animals infused with NS-398 or meloxicam, direct renal interstitial volume expansion significantly increased RIHP (Delta1.8+/-0.6 mm Hg, P<0.05, and Delta1.7+/-0.3 mm Hg, P<0.05) and FE(Na) (Delta1.5+/-0.4%, P<0. 05, and Delta1.1+/-0.3%, P<0.05), respectively. In contrast, infusion of piroxicam significantly blunted the natriuretic response to direct renal interstitial volume expansion (DeltaFE(Na) 0.3+/-0. 2%), even though RIHP was increased (Delta1.9+/-0.6 mm Hg, P<0.05). Infusion of piroxicam but not NS-398 or meloxicam blunted the natriuretic response to increased renal interstitial hydrostatic pressure, suggesting that the natriuretic response to increased blood pressure may be preserved during inhibition of COX-2.
- Published
- 1999
- Full Text
- View/download PDF
23. Home management of the adult patient with leukemia.
- Author
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Dwyer JE and Held DM
- Subjects
- Adaptation, Psychological, Environment, Female, Humans, Leukemia psychology, Middle Aged, Nursing Assessment, Patient Care Planning, Patient Care Team, Home Care Services, Home Nursing, Leukemia nursing
- Abstract
The many changes that have occurred within the medical profession and among the public are taking long-term care out of the hospital and placing it back into the home. Attitudes toward cancer have altered, as seen by the rapid growth of the oncology specialty as well as the willingness of the community to allow those with cancer to return to a viable status. Even the individual who must face end-stage disease can now rest comfortably in the privacy of his or her own home, surrounded by loved ones. Improved nutritional efforts during periods of active therapy are reducing the side effects and improving the tolerance of highly cytotoxic drugs. Thus, acute episodes of treatment are shortened, allowing for earlier discharge. Individuals are demanding accurate information regarding their disease and its treatment. Patients are catalysts for their own recovery as they become more active participants in their care. Some are even choosing not to undergo suggested therapies and are returning home to put their lives in order and let disease processes take their natural course, even until death. As for leukemia, more supportive measures such as blood component therapy and evaluative work-ups are being offered on an outpatient basis. Patients are learning self-care measures to counteract or minimize side effects to chemotherapy or radiation therapy. Thus, overwhelming infection is of less risk and hospitalization is shortened. Infection, especially from Staphylococcus aureus, still remains a major cause of death of patients with leukemia. However, one must consider how prevalent this organism is in the hospital environment. Home care management is improving; care can be as comprehensive as one might need or receive in the hospital setting.
- Published
- 1982
24. Implementing the small group process.
- Author
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Dwyer JE
- Subjects
- Education, Nursing, Diploma Programs, Group Processes, Teaching methods
- Published
- 1977
25. Studies in Infarction: IV. Experimental bland Infarction of the Myocardium, Myocardial Regeneration and Cicatrization.
- Author
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Karsner HT and Dwyer JE
- Published
- 1916
26. Intestinal IgA neutralizing antibodies in newborn infants following poliovirus immunization.
- Author
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Keller R, Dwyer JE, Oh W, and D'Amodio M
- Subjects
- Feces analysis, Female, Humans, Immunoglobulin G analysis, Injections, Male, Neutralization Tests, Virus Cultivation, Antibody Formation, Infant, Newborn, Infant, Premature, Intestines immunology, Poliovirus Vaccine, Inactivated, Poliovirus Vaccine, Oral, gamma-Globulins analysis
- Published
- 1969
27. Studies on the neutralization of poliovirus by fecal immunoglobulins. The development of intestinal IgA antibodies following oral poliovirus immunization.
- Author
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Keller R and Dwyer JE
- Subjects
- Adolescent, Adult, Antibodies analysis, Child, Child, Preschool, Feces, Humans, Immune Sera, Immunodiffusion, Immunoglobulin M analysis, Immunoglobulins analysis, Infant, Poliovirus immunology, Poliovirus pathogenicity, Vaccination, Antibody Formation, Immunoglobulin G analysis, Poliomyelitis immunology, Poliovirus Vaccine, Oral
- Published
- 1970
28. Neutralization of poliovirus by IgA coproantibodies.
- Author
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Keller R and Dwyer JE
- Subjects
- Adult, Antibodies, Cellulose, Child, Preschool, Chromatography, Chromatography, Gel, Dialysis, Feces immunology, Hot Temperature, Humans, Hydrogen-Ion Concentration, Immunodiffusion, Immunoelectrophoresis, Infant, Newborn, Poliovirus Vaccine, Inactivated, Virus Cultivation, Poliovirus immunology, gamma-Globulins
- Published
- 1968
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