198 results on '"Rubin, M."'
Search Results
2. Cell-Free DNA genomic profiling and its clinical implementation in advanced prostate cancer
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Roma, L., primary, Bratic Hench, I., additional, Conticelli, F., additional, Bubendorf, L., additional, Calgua, B., additional, Le Magnen, C., additional, Piscuoglio, S., additional, Rubin, M., additional, Chirindel, A., additional, Nicolas, G.P., additional, Vlajnic, T., additional, Zellweger, T., additional, Templeton, A.J., additional, Stenner, F., additional, Ruiz, C., additional, and Rentsch, C., additional
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- 2024
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3. A nanolander for a space mission to an active asteroid in the main belt
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Ho, T.M., primary, Kührt, E., additional, Zhang, X.J., additional, Auster, U., additional, Biele, J., additional, Grott, M., additional, Grundmann, J.T., additional, He, H., additional, Hördt, A., additional, Huang, J.C., additional, Ma, T., additional, Mottola, S., additional, Otto, K., additional, Plettemeier, D., additional, Qin, L., additional, Rubin, M., additional, Schmitz, N., additional, Ulamec, S., additional, and Vincent, J.B., additional
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- 2023
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4. Further evidence that system justification amongst the disadvantaged is positively related to superordinate group identification
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Owuamalam, C, Caricati, L, Spears, R, Rubin, M, Marinucci, M, Ferrari, A, Owuamalam C. K., Caricati L., Spears R., Rubin M., Marinucci M., Ferrari A., Owuamalam, C, Caricati, L, Spears, R, Rubin, M, Marinucci, M, Ferrari, A, Owuamalam C. K., Caricati L., Spears R., Rubin M., Marinucci M., and Ferrari A.
- Abstract
Members of disadvantaged groups sometimes support societal systems that enable the very inequalities that disadvantaged them. Is it possible to explain this puzzling system-justifying orientation in terms of rational group-interested motives, without recourse to a separate system motive? The social identity model of system attitudes (SIMSA) claims that it is. SIMSA proposes that the system justification shown by a disadvantaged group (e.g., African American women) can sometimes support identity needs that are tied to a more inclusive (superordinate) in-group (e.g., Americans). There is already some supportive evidence for this proposition, but it is not yet clear whether: (1) such trends are visible in a wider range of disadvantaged contexts, and (2) this explanation also applies to those who are strongly invested in their subgroup (e.g., feminists). In two waves of a large nationally representative survey from 21 to 23 European states (Ntotal = 84,572) and two controlled experiments (Ntotal = 290 women), we found that: (a) system justification was positively associated with superordinate ingroup identification across multiple cases of disadvantage (Studies 1–3), (b) system justification increased when this inclusive identity was made more salient (Studies 2 & 3), and (c) system justification was visible even amongst feminists when they activated their superordinate (Italian) identity (Study 3).
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- 2023
5. Evaluation of daily environmental cleaning and disinfection practices in veterans affairs acute and long-term care facilities: A mixed methods study
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McKinley, L., primary, Goedken, C.C., additional, Balkenende, E., additional, Clore, G., additional, Hockett, Sherlock S., additional, Bartel, R., additional, Bradley, S., additional, Judd, J., additional, Lyons, Goedken, additional, Rock, C., additional, Rubin, M., additional, Shaughnessy, C., additional, Reisinger, H.S., additional, Perencevich, E., additional, and Safdar, N., additional
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- 2023
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6. Post-acute sequelae of COVID-19 in a longitudinal cohort in New Orleans, Louisiana
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Rubin, M, primary, Immel, S, additional, Chatwani, B, additional, Katz, JL, additional, Moreida, M, additional, Montes, J, additional, Drouin, A, additional, and Fusco, D, additional
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- 2023
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7. A Unified Continuum Constitutive Model for Granular Materials
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Rubin, M. B., primary, Ciambella, Jacopo, additional, and Nadler, Ben, additional
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- 2023
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8. Matrix-Degrading Enzyme Expression and Aortic Fibrosis During Continuous-Flow Left Ventricular Mechanical Support
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Joseph C. Cleveland, Timothy A. McKinsey, Amrut V. Ambardekar, BS Philip D. Tatman, Madeleine E. Lemieux, Matthew S. Stratton, Evgenia Dobrinskikh, Kendall S. Hunter, Karen S. Moulton, Mary C.M. Weiser-Evans, and Rubin M. Tuder
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chemistry.chemical_classification ,Aorta ,medicine.medical_specialty ,Messenger RNA ,business.industry ,Matrix (biology) ,equipment and supplies ,medicine.disease ,Enzyme ,chemistry ,Fibrosis ,medicine.artery ,Internal medicine ,medicine ,Cardiology ,Extracellular ,Immunohistochemistry ,Implant ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The effects of nonphysiological flow generated by continuous-flow (CF) left ventricular assist devices (LVADs) on the aorta remain poorly understood. Objectives The authors sought to quantify indexes of fibrosis and determine the molecular signature of post–CF-LVAD vascular remodeling. Methods Paired aortic tissue was collected at CF-LVAD implant and subsequently at transplant from 22 patients. Aortic wall morphometry and fibrillar collagen content (a measure of fibrosis) was quantified. In addition, whole-transcriptome profiling by RNA sequencing and follow-up immunohistochemistry were performed to evaluate CF-LVAD–mediated changes in aortic mRNA and protein expression. Results The mean age was 52 ± 12 years, with a mean duration of CF-LVAD of 224 ± 193 days (range 45-798 days). There was a significant increase in the thickness of the collagen-rich adventitial layer from 218 ± 110 μm pre-LVAD to 410 ± 209 μm post-LVAD (P Conclusions There is aortic remodeling and fibrosis after CF-LVAD that correlates with the duration of support. This fibrosis is due, at least in part, to suppression of extracellular matrix–degrading enzyme expression. Further research is needed to examine the contribution of nonphysiological flow patterns on vascular function and whether modulation of pulsatility may improve vascular remodeling and long-term outcomes.
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- 2021
9. 471 Ecg Gating Matters: Thoracic Aortic Size Varies By Cardiac Phase
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Rubin, M., primary, Healy, A., additional, Horn, B., additional, and Jarrett, H., additional
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- 2022
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10. Matrix-Degrading Enzyme Expression and Aortic Fibrosis During Continuous-Flow Left Ventricular Mechanical Support
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Ambardekar, Amrut V., primary, Stratton, Matthew S., additional, Dobrinskikh, Evgenia, additional, Hunter, Kendall S., additional, Tatman, Philip D., additional, Lemieux, Madeleine E., additional, Cleveland, Joseph C., additional, Tuder, Rubin M., additional, Weiser-Evans, Mary C.M., additional, Moulton, Karen S., additional, and McKinsey, Timothy A., additional
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- 2021
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11. New constraints on the chemical composition and outgassing of 67P/Churyumov-Gerasimenko
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Herny, C., primary, Mousis, O., additional, Marschall, R., additional, Thomas, N., additional, Rubin, M., additional, Pinzón-Rodríguez, O., additional, and Wright, I.P., additional
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- 2021
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12. An Eulerian model for orthotropic elasticity and inelasticity applied to injection-moulded low-density polyethylene
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Kroon, Martin and Rubin, M. B.
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Orthotropic ,Plasticity ,Applied Mechanics ,Teknisk mekanik ,Polyethylene ,Mechanics of Materials ,Anisotropic ,Plastic spin ,General Materials Science ,Instrumentation - Abstract
Anisotropic elasticity and inelasticity is of relevance in many practical applications. The Eulerian formulation for anisotropic elastic and inelastic response based on microstructural vectors is used here to model an injection-moulded low-density polyethylene. In contrast with Lagrangian models of inelasticity, the Eulerian formulation is insensitive to arbitrariness of the reference and intermediate configurations as well as to measures of total and inelastic deformations. A specific strain-space-type anisotropic yield function is proposed that depends on anisotropic measures of elastic deformation and anisotropic hardening variables. Use is also made of a rate-independent model with a smooth elastic-inelastic transition. The material parameters were calibrated to reproduce uniaxial test data for loading in three directions in the moulding plane. In addition, a strongly objective numerical implementation is presented and used to simulate stretching of a plate with a circular hole. In contrast with metals, this polyethylene experiences elastic deformations of about 10%. Although the inelastic spin rate could not be determined by the available test data, simulations of loadings in different material directions yield observable influences of inelastic spin rate.
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- 2022
13. Targeted phage display-based pulmonary vaccination in mice and non-human primates
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Staquicini, Daniela I., primary, Barbu, E. Magda, additional, Zemans, Rachel L., additional, Dray, Beth K., additional, Staquicini, Fernanda I., additional, Dogra, Prashant, additional, Cardó-Vila, Marina, additional, Miranti, Cindy K., additional, Baze, Wallace B., additional, Villa, Luisa L., additional, Kalil, Jorge, additional, Sharma, Geetanjali, additional, Prossnitz, Eric R., additional, Wang, Zhihui, additional, Cristini, Vittorio, additional, Sidman, Richard L., additional, Berman, Andrew R., additional, Panettieri, Reynold A., additional, Tuder, Rubin M., additional, Pasqualini, Renata, additional, and Arap, Wadih, additional
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- 2021
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14. Advanced Microengineered Lung Models for Translational Drug Discovery
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Kambez H. Benam, Brian F. Niemeyer, Rubin M. Tuder, and Peng Zhao
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Lung Diseases ,0301 basic medicine ,medicine.medical_specialty ,Cell Culture Techniques ,Drug Evaluation, Preclinical ,02 engineering and technology ,Biochemistry ,Analytical Chemistry ,Human lung ,Tissue Culture Techniques ,Translational Research, Biomedical ,03 medical and health sciences ,Lab-On-A-Chip Devices ,Drug Discovery ,medicine ,Animals ,Humans ,Biomarker discovery ,Intensive care medicine ,Lung ,Tissue Engineering ,Drug discovery ,business.industry ,Reproducibility of Results ,respiratory system ,021001 nanoscience & nanotechnology ,Pre-clinical development ,Respiratory Medicine ,030104 developmental biology ,medicine.anatomical_structure ,Drug development ,Molecular Medicine ,Personalized medicine ,0210 nano-technology ,business ,Biomarkers ,Biotechnology - Abstract
Lung diseases impose a significant socioeconomic burden and are a leading cause of morbidity and mortality worldwide. Moreover, respiratory medicine, unlike several other therapeutic areas, faces a disappointingly low number of new approved therapies. This is partly due to lack of reliable in vitro or in vivo models that can reproduce organ-level complexity and pathophysiological responses of human lung. Here, we examine new opportunities in application of recently emerged organ-on-chip technology to model human lung alveolus and small airway in preclinical drug development and biomarker discovery. We also discuss challenges that need to be addressed in coming years to further enhance the physiological and clinical relevance of these microsystems, enable their increased accessibility, and support their leap into personalized medicine.
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- 2018
15. Pulmonary Arteries and Microcirculation in COPD With Pulmonary Hypertension
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Carlyne D. Cool and Rubin M. Tuder
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,COPD ,Lung ,business.industry ,Pulmonary disease ,Critical Care and Intensive Care Medicine ,medicine.disease ,Culprit ,Pulmonary hypertension ,Microcirculation ,medicine.anatomical_structure ,Internal medicine ,medicine.artery ,Pulmonary artery ,Bystander effect ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Published
- 2019
16. Electron dynamics near diamagnetic regions of comet 67P/Churyumov- Gerasimenko
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Madanian, H., primary, Burch, J.L., additional, Eriksson, A.I., additional, Cravens, T.E., additional, Galand, M., additional, Vigren, E., additional, Goldstein, R., additional, Nemeth, Z., additional, Mokashi, P., additional, Richter, I., additional, and Rubin, M., additional
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- 2020
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17. Position-dependent microchannel plate gain correction in Rosetta's ROSINA/DFMS mass spectrometer
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De Keyser, J., primary, Altwegg, K., additional, Gibbons, A., additional, Dhooghe, F., additional, Balsiger, H., additional, Berthelier, J.-J., additional, Fuselier, S.A., additional, Gombosi, T.I., additional, Neefs, E., additional, and Rubin, M., additional
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- 2019
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18. Calibration of parent and fragment ion detection rates in Rosettas ROSINA/DFMS mass spectrometer
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De Keyser, J., primary, Gibbons, A., additional, Dhooghe, F., additional, Altwegg, K., additional, Balsiger, H., additional, Berthelier, J.-J., additional, Fuselier, S.A., additional, Gombosi, T.I., additional, Neefs, E., additional, and Rubin, M., additional
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- 2019
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19. Th2 Cd4 + T Cells are Necessary and Sufficient for Schistosoma-Pulmonary Hypertension
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Brian B. Graham, Rajesh Kumar, Andrew P. Fontenot, Claudia Mickael, Biruk Kassa, Daniel Morales-Cano, Ghazwan Butrous, Amy S. McKee, Linda Sanders, Daniel Hernandez-Saavedra, Rubin M. Tuder, Scott R. Freeman, Dan Koyanagi, and Angel Cogolludo
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Adoptive cell transfer ,medicine.diagnostic_test ,biology ,Parabiosis ,business.industry ,Institutional Animal Care and Use Committee ,Inflammation ,medicine.disease ,biology.organism_classification ,Pulmonary hypertension ,Flow cytometry ,Andrology ,medicine ,Animal studies ,medicine.symptom ,business ,Schistosoma - Abstract
Background: Inflammation underlies many forms of pulmonary hypertension (PH), including that resulting from Schistosoma infection, a major cause of PH worldwide. Schistosomiasis-associated PH is proximately triggered by embolization of parasite eggs into the lungs, resulting in localized Type 2 inflammation. However, the role of CD4+ T cells in this disease is not well defined. Methods: We used a mouse model of schistosomiasis-associated PH, induced by intraperitoneal egg sensitization followed by intravenous egg challenge, with outcomes including right ventricle systolic pressure measured by cardiac catheterization, and cell density and phenotype assessed by flow cytometry. Parabiosis and Rag-/- mice reconstituted with CD4 T cells were used to determine the role of CD4 T cells. Findings: We identified that embolization of Schistosoma eggs into the lungs of egg-sensitized mice increased the perivascular density of Th2 CD4+ T cells by recruitment of cells from the circulation, and triggered Type 2 inflammation. Parabiosis confirmed that egg embolization is required for the localized Type 2 immunity. We found Th2 CD4+ T cells were necessary for Schistosoma-induced PH, as deletion of CD4+ T cells or inhibiting their Th2 function protected against Type 2 inflammation and PH following Schistosoma exposure. We also observed adoptive transfer of Schistosoma-sensitized CD4+ Th2 cells was sufficient to drive Type 2 inflammation and PH. Interpretation: Th2 CD4+T cells are a necessary and sufficient component for the Type 2 inflammation-induced PH following Schistosoma exposure. Funding Statement: Grant funding was provided by the American Heart Association Grants 17POST33670045 (RK), 19CDA34730030 (RK); NIH Grants P01HL014985 (RMT and BBG), R03HL133306 (BBG), and R01HL135872 (BBG). Ministerio de Economia y Competitividad (SAF2016-77222-R to AC), with funds co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”, and the Cardiovascular Medical Research and Education Fund (AC and GB). Declaration of Interests: The authors declare that no conflict of interest exists. Ethics Approval Statement: All animal studies were approved by the University of Colorado Institutional Animal Care and Use Committee.
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- 2019
20. A comparison of multiple Rosetta data sets and 3D model calculations of 67P/Churyumov-Gerasimenko coma around equinox (May 2015)
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Marschall, R., primary, Rezac, L., additional, Kappel, D., additional, Su, C.C., additional, Gerig, S.-B., additional, Rubin, M., additional, Pinzón-Rodríguez, O., additional, Marshall, D., additional, Liao, Y., additional, Herny, C., additional, Arnold, G., additional, Christou, C., additional, Dadzie, S.K., additional, Groussin, O., additional, Hartogh, P., additional, Jorda, L., additional, Kührt, E., additional, Mottola, S., additional, Mousis, O., additional, Preusker, F., additional, Scholten, F., additional, Theologou, P., additional, Wu, J.-S., additional, Altwegg, K., additional, Rodrigo, R., additional, and Thomas, N., additional
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- 2019
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21. Pulmonary Arteries and Microcirculation in COPD With Pulmonary Hypertension
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Tuder, Rubin M., primary and Cool, Carlyne D., additional
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- 2019
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22. Th2 Cd4 + T Cells are Necessary and Sufficient for Schistosoma-Pulmonary Hypertension
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Kumar, Rahul, primary, Mickael, Claudia, additional, Kassa, Biruk, additional, Sanders, Linda, additional, Koyanagi, Dan, additional, Hernandez-Saavedra, Daniel, additional, Freeman, Scott, additional, Morales-Cano, Daniel, additional, Cogolludo, Angel, additional, McKee, Amy S., additional, Fontenot, Andrew P., additional, Butrous, Ghazwan, additional, Tuder, Rubin M., additional, and Graham, Brian B., additional
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- 2019
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23. Rtp801 Suppression of Epithelial mTORC1 Augments Endotoxin-Induced Lung Inflammation
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Daniel E. Koyanagi, Eric P. Schmidt, Brian B. Graham, Aaron M. Nadon, Daniel Hernandez-Saavedra, Mario J. Perez, Jacob J. Chabon, Lynelle P. Smith, Aneta Gandjeva, Linda Sanders, Yimu Yang, and Rubin M. Tuder
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Male ,Lipopolysaccharide ,Fluorescent Antibody Technique ,mTORC1 ,Medical and Health Sciences ,Transgenic ,chemistry.chemical_compound ,Mice ,Pathology ,2.1 Biological and endogenous factors ,Aetiology ,Lung ,Acute Respiratory Distress Syndrome ,Mice, Knockout ,biology ,TOR Serine-Threonine Kinases ,Adaptor Proteins ,3. Good health ,DNA-Binding Proteins ,medicine.anatomical_structure ,Respiratory ,medicine.symptom ,biological phenomena, cell phenomena, and immunity ,Short Communication ,Knockout ,Mice, Transgenic ,Inflammation ,Lung injury ,Mechanistic Target of Rapamycin Complex 1 ,Real-Time Polymerase Chain Reaction ,Proinflammatory cytokine ,Pathology and Forensic Medicine ,Rare Diseases ,medicine ,Animals ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,Animal ,Inflammatory and immune system ,Signal Transducing ,Pneumonia ,Endotoxins ,Disease Models, Animal ,chemistry ,Multiprotein Complexes ,Immunology ,Disease Models ,biology.protein ,Cancer research ,Transcription Factors - Abstract
The mechanistic target of rapamycin (mTOR) is a central regulator of cellular responses to environmental stress. mTOR (and its primary complex mTORC1) is, therefore, ideally positioned to regulate lung inflammatory responses to an environmental insult, a function directly relevant to disease states such as the acute respiratory distress syndrome. Our previous work in cigarette smoke-induced emphysema identified a novel protective role of pulmonary mTORC1 signaling. However, studies of the impact of mTORC1 on the development of acute lung injury are conflicting. We hypothesized that Rtp801, an endogenous inhibitor of mTORC1, which is predominantly expressed in alveolar type II epithelial cells, is activated during endotoxin-induced lung injury and functions to suppress anti-inflammatory epithelial mTORC1 responses. We administered intratracheal lipopolysaccharide to wild-type mice and observed a significant increase in lung Rtp801 mRNA. In lipopolysaccharide-treated Rtp801(-/-) mice, epithelial mTORC1 activation significantly increased and was associated with an attenuation of lung inflammation. We reversed the anti-inflammatory phenotype of Rtp801(-/-) mice with the mTORC1 inhibitor, rapamycin, reassuring against mTORC1-independent effects of Rtp801. We confirmed the proinflammatory effects of Rtp801 by generating a transgenic Rtp801 overexpressing mouse, which displayed augmented inflammatory responses to intratracheal endotoxin. These data suggest that epithelial mTORC1 activity plays a protective role against lung injury, and its inhibition by Rtp801 exacerbates alveolar injury caused by endotoxin.
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- 2014
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24. The Castalia mission to Main Belt Comet 133P/Elst-Pizarro
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Snodgrass, C., primary, Jones, G.H., additional, Boehnhardt, H., additional, Gibbings, A., additional, Homeister, M., additional, Andre, N., additional, Beck, P., additional, Bentley, M.S., additional, Bertini, I., additional, Bowles, N., additional, Capria, M.T., additional, Carr, C., additional, Ceriotti, M., additional, Coates, A.J., additional, Della Corte, V., additional, Donaldson Hanna, K.L., additional, Fitzsimmons, A., additional, Gutiérrez, P.J., additional, Hainaut, O.R., additional, Herique, A., additional, Hilchenbach, M., additional, Hsieh, H.H., additional, Jehin, E., additional, Karatekin, O., additional, Kofman, W., additional, Lara, L.M., additional, Laudan, K., additional, Licandro, J., additional, Lowry, S.C., additional, Marzari, F., additional, Masters, A., additional, Meech, K.J., additional, Moreno, F., additional, Morse, A., additional, Orosei, R., additional, Pack, A., additional, Plettemeier, D., additional, Prialnik, D., additional, Rotundi, A., additional, Rubin, M., additional, Sánchez, J.P., additional, Sheridan, S., additional, Trieloff, M., additional, and Winterboer, A., additional
- Published
- 2018
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25. Advanced Microengineered Lung Models for Translational Drug Discovery
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Niemeyer, Brian F., primary, Zhao, Peng, additional, Tuder, Rubin M., additional, and Benam, Kambez H., additional
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- 2018
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26. Comprehensive molecular profiling of multifocal prostate cancer challenges the robustness of prostate cancer prognostic signatures
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Salami, S., primary, Hovelson, D., additional, Kaplan, J., additional, Mathieu, R., additional, Udager, A., additional, Curci, N., additional, Lee, M., additional, Lazo De La Vega, L.N., additional, Susani, M., additional, Rioux-Leclercq, N., additional, Spratt, D., additional, Morgan, T., additional, Davenport, M., additional, Rubin, M., additional, Shariat, S., additional, Tomlins, S., additional, and Palapattu, G., additional
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- 2018
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27. Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational Derepression of HIF2α
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Anamika Singh, Brian B. Graham, Kavitha Ramaswamy, Daniel R. Crooks, De-Liang Zhang, Tiffany Tu, Thomas Senecal, Wing Hang Tong, Jaekwon Lee, Gabrielle Robinson, Tracey A. Rouault, Hayden Ollivierre-Wilson, Michael Eckhaus, Manik C. Ghosh, Zu Xi Yu, Suh Young Jeong, Danielle A. Springer, Gennadiy Kovtunovych, Rubin M. Tuder, and Audrey Noguchi
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Physiology ,Ferroportin ,Medical Biochemistry and Metabolomics ,Cardiovascular ,Mice ,0302 clinical medicine ,Models ,hemic and lymphatic diseases ,Basic Helix-Loop-Helix Transcription Factors ,2.1 Biological and endogenous factors ,Extramedullary ,Aetiology ,Lung ,0303 health sciences ,Endothelin-1 ,biology ,Pulmonary ,Hematology ,Iron deficiency ,3. Good health ,Organ Specificity ,Hematopoiesis, Extramedullary ,030220 oncology & carcinogenesis ,Hypertension ,Erythropoiesis ,Gastrointestinal Hemorrhage ,medicine.drug ,Transcriptional Activation ,medicine.medical_specialty ,Anemia ,Hypertension, Pulmonary ,Iron ,Longevity ,Transferrin receptor ,Polycythemia ,Models, Biological ,Article ,Endocrinology & Metabolism ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Iron Regulatory Protein 1 ,Erythropoietin ,Iron Regulatory Protein 2 ,Molecular Biology ,030304 developmental biology ,Endothelial Cells ,Cell Biology ,Biological ,medicine.disease ,Pulmonary hypertension ,Hematopoiesis ,Diet ,Ferritin ,Endocrinology ,Protein Biosynthesis ,Nerve Degeneration ,biology.protein ,Biochemistry and Cell Biology ,Gene Deletion - Abstract
SummaryIron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia, and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension.
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- 2013
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28. Schistosomiasis-Induced Experimental Pulmonary Hypertension
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Hazim El-Haddad, Rubin M. Tuder, Brian B. Graham, Angela Bandeira, Margaret M. Mentink-Kane, Elizabeth F. Redente, Hunter C. Champion, David W. H. Riches, Li Zhang, Paul M. Hassoun, Thomas A. Wynn, Ari L. Zaiman, Ghazwan Butrous, and Shawn M. Purnell
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medicine.medical_specialty ,Lung ,biology ,medicine.medical_treatment ,Respiratory disease ,Interleukin ,biology.organism_classification ,medicine.disease ,Pulmonary hypertension ,Pathology and Forensic Medicine ,Cytokine ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Interleukin 13 ,Immunology ,medicine ,Schistosoma mansoni ,Transforming growth factor - Abstract
The mechanisms underlying schistosomiasis-induced pulmonary hypertension (PH), one of the most common causes of PH worldwide, remain unclear. We sought to determine whether Schistosoma mansoni causes experimental PH associated with pulmonary vascular remodeling in an interleukin (IL)-13-dependent manner. IL-13Rα1 is the canonical IL-13 signaling receptor, whereas IL-13Rα2 is a competitive nonsignaling decoy receptor. Wild-type, IL-13Rα1−/−, and IL-13Rα2−/− C57BL/6J mice were percutaneously infected with S. mansoni cercariae, followed by i.v. injection of eggs. We assessed PH with right ventricular catheterization, histological evaluation of pulmonary vascular remodeling, and detection of IL-13 and transforming growth factor-β signaling. Infected mice developed pulmonary peri-egg granulomas and arterial remodeling involving predominantly the vascular media. In addition, gain-of-function IL-13Rα2−/− mice had exacerbated vascular remodeling and PH. Mice with loss of IL-13Rα1 function did not develop PH and had reduced pulmonary vascular remodeling. Moreover, the expression of resistin-like molecule-α, a target of IL-13 signaling, was increased in infected wild-type and IL-13Rα2−/− but not IL-13Rα1−/− mice. Phosphorylated Smad2/3, a target of transforming growth factor-β signaling, was increased in both infected mice and humans with the disease. Our data indicate that experimental schistosomiasis causes PH and potentially relies on up-regulated IL-13 signaling.
- Published
- 2010
29. Schistosomiasis-Associated Pulmonary Hypertension
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Rubin M. Tuder, Angela Bandeira, Brian B. Graham, Ghazwan Butrous, and Nicholas W. Morrell
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Portopulmonary hypertension ,Lung ,biology ,business.industry ,Helminthiasis ,Schistosomiasis ,Inflammation ,Critical Care and Intensive Care Medicine ,medicine.disease ,biology.organism_classification ,Pulmonary hypertension ,medicine.anatomical_structure ,Immunology ,medicine ,Portal hypertension ,Schistosoma mansoni ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Inflammation is likely a critical underlying etiology in many forms of severe pulmonary hypertension (PH), and schistosomiasis-associated PH, one of the most common causes of PH worldwide, is likely driven by the host response to parasite antigens. More than 200 million people are infected with schistosomiasis, the third most common parasitic disease, and approximately 1% of those chronically infected develop PH. Acute cutaneous infection causes inflammation at the site of parasite penetration followed by a subacute immune complex-mediated hypersensitivity response as the parasite migrates through the lungs. Chronic schistosomiasis infection induces a granulomatous inflammation around ova deposited in the tissue. In particular, Schistosoma mansoni migrates to the portal venous system and causes preportal fibrosis in a subset of individuals and appears to be a prerequisite for PH. Portal hypertension facilitates shunting of ova from the portal system to the pulmonary arterial tree, resulting in localized periovular pulmonary granulomas. The pulmonary vascular remodeling is likely a direct consequence of the host inflammatory response, and portopulmonary hypertension may be a significant contributor. New specific therapies available for PH have not been widely tested in patients with schistosomiasis and often are unavailable for those infected in resource-poor areas of the world where schistosomiasis is endemic. Furthermore, the current PH therapies in general target vasodilation rather than vascular remodeling and inflammation. Further research is needed into the pathogenic mechanism by which this parasitic infection results in pulmonary vascular remodeling and PH, which also may be informative regarding the etiology of other types of PH.
- Published
- 2010
30. Genomics of Pulmonary Arterial Hypertension: Implications for Therapy
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Rubin M. Tuder, Todd M. Bull, and Mark W. Geraci
- Subjects
Proteomics ,Pathology ,medicine.medical_specialty ,Microarray ,Hypertension, Pulmonary ,Gene Expression ,Genomics ,Disease ,Bone Morphogenetic Protein Receptors, Type II ,Nitric Oxide ,Bioinformatics ,Article ,medicine ,Animals ,Humans ,Oligonucleotide Array Sequence Analysis ,Endothelin-1 ,business.industry ,Disease progression ,General Medicine ,medicine.disease ,Pulmonary hypertension ,BMPR2 ,Vasodilation ,Heart failure ,Disease Progression ,Etiology ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
Pulmonary arterial hypertension (PAH) remains a vexing clinical disease with no cure. Despite advances and the discovery of a gene (BMPR2) associated with many of the hereditary forms of the disease, and some cases not previously known to be inherited, the reasons for mutations in this gene as a cause remain somewhat elusive. Clearly, a complex interplay exists between genetic alterations, environmental exposures (including infections), and disease development. This article addresses the advances in the genetics of PAH, including the identification of genetic etiologies and modulators, and the role of genetics in predicting disease progression and targeting therapeutics.
- Published
- 2010
31. Vascular endothelial growth factor of the lung: friend or foe
- Author
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Rubin M. Tuder and Jeong H. Yun
- Subjects
Vascular Endothelial Growth Factor A ,Angiogenesis ,Hypertension, Pulmonary ,Morphogenesis ,Biology ,Article ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Humans ,Lung ,Emphysema ,Pharmacology ,Respiratory Distress Syndrome ,Endothelial Cells ,Phenotype ,Asthma ,Vascular endothelial growth factor ,Vascular endothelial growth factor B ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,chemistry ,Vascular endothelial growth factor C ,Immunology ,Cancer research - Abstract
The discovery of vascular endothelial growth factor (VEGF) changed the field of angiogenesis. We have learned that VEGF has broader actions than merely a driver of tumor angiogenesis, particularly that VEGF controlled several fundamental functions and properties of endothelial cells and non-endothelial cells. The lung is one of the main organs where VEGF controls several critical physiological functions. These actions rely on tightly regulated temporal and concentration gradients of VEGF and VEGF receptor expression in the lung. Excessive or diminished VEGF have been linked to abnormal lung phenotypes and, in humans, linked to several diseases. The beneficial and detrimental actions of VEGF underscore that therapeutic targeting of VEGF in disease has to carefully consider the lung biology of VEGF.
- Published
- 2008
32. Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension
- Author
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Jacqueline Sharp, Lauren Licina, Lan Huang, Serpil C. Erzurum, Suzy A. A. Comhair, Judith A. Drazba, Amit Vasanji, Carol Farver, Mervin C. Yoder, Weiling Xu, Micheala A. Aldred, Rubin M. Tuder, Kewal Asosingh, and Bela Anand-Apte
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Hypertension, Pulmonary ,Bone Morphogenetic Protein 2 ,Antigens, CD34 ,Bone Marrow Cells ,Pathology and Forensic Medicine ,Mice ,Antigens, CD ,Cell Movement ,Mice, Inbred NOD ,Transforming Growth Factor beta ,medicine.artery ,medicine ,Animals ,Humans ,AC133 Antigen ,Cells, Cultured ,Cell Proliferation ,Glycoproteins ,Matrigel ,business.industry ,Stem Cells ,Endothelial Cells ,Middle Aged ,Hematopoietic Stem Cells ,medicine.disease ,Pulmonary hypertension ,medicine.anatomical_structure ,Bone Morphogenetic Proteins ,Pulmonary artery ,Circulatory system ,Female ,Bone marrow ,Peptides ,business ,Regular Articles ,Blood vessel ,Artery - Abstract
Vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistant pulmonary artery endothelial cells. In this study, we evaluated the relative contribution of bone marrow-derived proangiogenic precursors and tissue-resident endothelial progenitors to vascular remodeling in IPAH. Levels of circulating CD34 + CD133 + bone marrow-derived proangiogenic precursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated with pulmonary artery pressure, whereas levels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of healthy controls. Colony-forming units of endothelial-like cells (CFU-ECs) derived from CD34 + CD133 + bone marrow precursors of IPAH patients secreted high levels of matrix metalloproteinase-2, had greater affinity for angiogenic tubes, and spontaneously formed disorganized cell clusters that increased in size in the presence of transforming growth factor-β or bone morphogenetic protein-2. Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control CFU-ECs, produced cell clusters in the Matrigel and proliferative lesions in surrounding murine tissues. Thus, mobilization of high levels of proliferative bone marrow-derived proangiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remodeling process.
- Published
- 2008
33. Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury
- Author
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McClendon, Jazalle, primary, Jansing, Nicole L., additional, Redente, Elizabeth F., additional, Gandjeva, Aneta, additional, Ito, Yoko, additional, Colgan, Sean P., additional, Ahmad, Aftab, additional, Riches, David W.H., additional, Chapman, Harold A., additional, Mason, Robert J., additional, Tuder, Rubin M., additional, and Zemans, Rachel L., additional
- Published
- 2017
- Full Text
- View/download PDF
34. The impact of bariatric surgery on nonalcoholic fatty liver disease and cardiovascular risk utilizing non-invasive measures
- Author
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Netanel, C., primary, Goitein, D., additional, Rubin, M., additional, Shechter, M., additional, Kleinbaum, Y., additional, Katsherginsky, S., additional, Hermon, H., additional, Hemi, R., additional, Tsaraf, K., additional, Donuzi, A., additional, Safran, M., additional, Tachlytski, I., additional, Herman, A., additional, Ortiz, P., additional, and Ben-Ari, Z., additional
- Published
- 2017
- Full Text
- View/download PDF
35. The diagnostic yield of ultrasound of the head in healthy infants presenting with the clinical diagnosis of benign macrocrania
- Author
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Naffaa, L., primary, Rubin, M., additional, Stamler, A.C., additional, Haddad, M., additional, and Saade, C., additional
- Published
- 2017
- Full Text
- View/download PDF
36. Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations
- Author
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Roy G. Brower, Gianfranco Umberto Meduri, Rubin M. Tuder, Jaideep Moitra, Edmund J. Miller, Shwu Fan-Ma, Raj Wadgaonkar, C. Ryan Yates, Li Gao, Shui Qing Ye, Jonathan E. Sevransky, Carl Shanholtz, Marc Moss, Joe G.N. Garcia, Kathleen C. Barnes, Liliana Moreno, Brett A. Simon, Carlos Flores, and James P. Maloney
- Subjects
Adult ,Male ,Candidate gene ,ARDS ,animal diseases ,medicine.medical_treatment ,Lung injury ,Polymorphism, Single Nucleotide ,White People ,Article ,Sepsis ,Mice ,Risk Factors ,Physiology (medical) ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Macrophage Migration-Inhibitory Factors ,Aged ,Respiratory Distress Syndrome ,business.industry ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,General Medicine ,Middle Aged ,respiratory system ,medicine.disease ,respiratory tract diseases ,Black or African American ,Intramolecular Oxidoreductases ,Mice, Inbred C57BL ,Cytokine ,Haplotypes ,Case-Control Studies ,Immunology ,Biomarker (medicine) ,Female ,Tumor necrosis factor alpha ,Macrophage migration inhibitory factor ,business ,Bronchoalveolar Lavage Fluid ,Biomarkers - Abstract
The macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine central to the response to endotoxemia, is a putative biomarker in acute lung injury (ALI). To explore MIF as a molecular target and candidate gene in ALI, the MIF gene and protein expression were examined in murine and canine models of ALI (high tidal volume mechanical ventilation, endotoxin exposure) and in patients with either sepsis or sepsis-induced ALI. MIF gene expression and protein levels were significantly increased in each ALI model, with serum MIF levels significantly higher in patients with either sepsis or ALI compared with healthy controls (African- and European-descent). The association of 8 MIF gene polymorphisms (single-nucleotide polymorphisms (SNPs)) (within a 9.7-kb interval on chromosome 22q11.23) with the development of sepsis and ALI in European-descent and African-descent populations was studied next. Genotyping in 506 DNA samples (sepsis patients, sepsis-associated ALI patients, and healthy controls) revealed haplotypes located in the 3' end of the MIF gene, but not individual SNPs, associated with sepsis and ALI in both populations. These data, generated via functional genomic and genetic approaches, suggest that MIF is a relevant molecular target in ALI.
- Published
- 2007
37. VEGF receptor 2 blockade leads to renal cyst formation in mice
- Author
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Roshni R. Molls, D.J. Hicklin, Rubin M. Tuder, Melissa Burne-Taney, Sharon A. McGrath-Morrow, Mark Haas, Chung Cho, and Hamid Rabb
- Subjects
Nephrology ,medicine.medical_specialty ,Time Factors ,Kidney development ,Mice, Inbred Strains ,Biology ,urologic and male genital diseases ,Kidney cysts ,renal cysts ,Mice ,chemistry.chemical_compound ,Internal medicine ,medicine ,Polycystic kidney disease ,Animals ,Cyst ,VEGFR-2 blockade ,DC101 ,urogenital system ,Antibodies, Monoclonal ,Kinase insert domain receptor ,Kidney Diseases, Cystic ,medicine.disease ,Immunohistochemistry ,Vascular Endothelial Growth Factor Receptor-2 ,Vascular endothelial growth factor ,Endocrinology ,Animals, Newborn ,chemistry ,medicine.symptom ,Signal Transduction ,Kidney disease - Abstract
Polycystic kidney disease (PKD) is associated with mutations in PKD1 and PKD2 and vascular abnormalities. The links between the epithelial and vascular defects, however, are poorly understood. Vascular endothelial growth factor (VEGF) has been shown to be critical for normal kidney development. In animal models, blockade of VEGF in the perinatal period can lead to abnormal glomerular development, impaired nephrogenesis, proteinuria, and renal failure. We hypothesized that brief blockade of VEGF signaling during early postnatal kidney development can lead to renal cyst development. On days 2 and 4 of life, CD-1 mice were treated with antibodies generated against the extracellular portion of the VEGF receptor 2 (DC101), the area of the receptor where VEGF binding occurs. Mice developed renal cysts between 2 and 3 weeks. The DC101-treated mice also had increased cell proliferation in the renal tubule epithelium. In addition, mice receiving DC101 developed abnormal glomeruli, proteinuria, and patchy cellular infiltrates. Early disruption of VEGFR-2 signaling during the perinatal period results in renal cyst formation, impaired glomerulogenesis, and inflammation. VEGF could be a key link between vascular and cystic changes in kidney cyst formation.
- Published
- 2006
38. Emphysema – a vascular disease?
- Author
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Norbert F. Voelkel, Rubin M. Tuder, and Laima Taraseviciene-Stewart
- Subjects
medicine.medical_specialty ,Pathology ,COPD ,Lung ,Vascular disease ,business.industry ,Disease ,respiratory system ,medicine.disease ,respiratory tract diseases ,medicine.anatomical_structure ,Immune system ,Feature (computer vision) ,Internal medicine ,Drug Discovery ,medicine ,Cardiology ,Molecular Medicine ,Entire lung ,business ,Lung function - Abstract
Chronic obstructive pulmonary disease (COPD), of which emphysema is a feature, encompasses several diseases characterized by a progressive loss of lung function and is a huge health problem with many needs for new treatments. It is likely to be a disease of the entire lung including airways, lung vasculature and the components of the immune system. Early detection markers for emphysema are badly needed.
- Published
- 2004
39. Pathologic assessment of vasculopathies in pulmonary hypertension
- Author
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Frédérique Capron, Marc Humbert, Lynne Reid, Susan Stewart, Rubin M. Tuder, Giuseppe G. Pietra, Ivan M. Robbins, and Ornella Leone
- Subjects
Pulmonary Circulation ,Pathology ,medicine.medical_specialty ,Vascular disease ,business.industry ,Hypertension, Pulmonary ,Respiratory disease ,Pulmonary capillary hemangiomatosis ,Pulmonary Artery ,medicine.disease ,Pulmonary hypertension ,Muscle, Smooth, Vascular ,Vasoconstriction ,Pulmonary venoocclusive disease ,Circulatory system ,medicine ,Humans ,Vascular Resistance ,Vascular Diseases ,Pulmonary Veno-Occlusive Disease ,Pulmonary pathology ,Tunica Intima ,Cardiology and Cardiovascular Medicine ,business ,Lung - Abstract
Pulmonary arterial hypertension (PAH) includes various forms of pulmonary hypertension of different etiology but similar clinical presentation and functional derangement. Histopathological vascular changes in all forms of PAH are qualitatively similar but with quantitative differences in the distribution and prevalence of pathological changes in various portions of the pulmonary vascular bed. The documentation of these topographic variations in the response of the pulmonary vasculature to injury may be important to understand the pathogenesis of the various subsets of PAH. To standardize the precise histopathological documentation of the pulmonary vasculopathy in PAH we propose a histopathological classification that includes both the predominant segment of the pulmonary vasculature affected and the possible coexistence of pathological changes in other vascular segments.
- Published
- 2004
40. The pathobiological mechanisms of emphysema models: What do they have in common?
- Author
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Enid Neptune, Rubin M. Tuder, and Sharon A. McGrath
- Subjects
Pulmonary and Respiratory Medicine ,Lung ,business.industry ,Smoking ,Biochemistry (medical) ,Pulmonary disease ,Inflammation ,respiratory system ,respiratory tract diseases ,Pathogenesis ,Disease Models, Animal ,Pulmonary Disease, Chronic Obstructive ,medicine.anatomical_structure ,Pulmonary Emphysema ,Endopeptidases ,Immunology ,medicine ,Animals ,Humans ,Pharmacology (medical) ,medicine.symptom ,Lung tissue ,business - Abstract
Emphysema results from a multi-step, complex, process of lung destruction. This review aims at organizing the available information concerning the animal models of emphysema as to which step of the pathogenesis they address. The experimental models have been classified as to whether they are based on: (a) pharmacological, (b) environmental, or (c) genetic manipulations to induce emphysema and whether they are: (a) triggers or initiators of emphysema, (b) modifiers of lung predisposition to further damage by trigger factors, or (c) mediators of lung tissue destruction.
- Published
- 2003
41. Pulmonary Eosinophilia Following Lung Transplantation for Sarcoidosis in Two Patients*
- Author
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Reda E. Girgis, Jonathan B. Orens, John V. Conte, Susan G. Gerhardt, Rubin M. Tuder, and Stephen C. Yang
- Subjects
Graft Rejection ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Biopsy ,medicine.medical_treatment ,Bronchiolitis obliterans ,Critical Care and Intensive Care Medicine ,Postoperative Complications ,Sarcoidosis, Pulmonary ,hemic and lymphatic diseases ,medicine ,Humans ,Transplantation, Homologous ,Lung transplantation ,Eosinophilia ,Pulmonary pathology ,Pulmonary Eosinophilia ,Bronchiolitis Obliterans ,Lung ,business.industry ,Respiratory disease ,Middle Aged ,respiratory system ,medicine.disease ,humanities ,respiratory tract diseases ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Lung Transplantation - Abstract
Pulmonary eosinophilia is an uncommon problem in lung transplant recipients. We report the unique occurrence of two cases of pulmonary eosinophilia in pulmonary allografts for sarcoidosis. Both patients rapidly acquired bronchiolitis obliterans syndrome (BOS) after resolution of pulmonary eosinophilia. It is known that peripheral eosinophilia is a marker for pulmonary allograft rejection, but its potential in the pathogenesis of BOS is unclear.
- Published
- 2003
42. THE PATHOBIOLOGY OF PULMONARY HYPERTENSION
- Author
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Laimute Taraseviciene-Stewart, Rubin M. Tuder, Carlyne D. Cool, Michael E. Yeager, Todd M. Bull, and Norbert F. Voelkel
- Subjects
Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung ,Endothelium ,Angiogenesis ,Cell growth ,business.industry ,medicine.disease ,Pulmonary hypertension ,Endothelial stem cell ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,medicine ,Progenitor cell ,business - Abstract
Dysfunctional endothelial cells have a central and critical role in the initiation and progression of severe pulmonary hypertension. The elucidation of the mechanisms involved in the control of endothelial cell proliferation and cell death in the pulmonary vasculature, therefore, is fundamentally important in the pathogenesis of severe pulmonary hypertension and of great interest for a better understanding of endothelial cell biology. Because the intravascular growth of endothelial cells resulting in tumorlets is unique to severe pulmonary hypertension, this phenomenon can teach researchers about the factors involved in the formation and maintenance of the normal endothelial cell monolayer. Clearly, in severe pulmonary hypertension, the "law of the endothelial cell monolayer" has been broken. The ultimate level of such a control is at the altered gene expression pattern that is conducive to endothelial cell growth and disruption of pulmonary blood flow. Secondary pulmonary hypertension certainly also is associated with proliferated pulmonary endothelial cells and plexiform lesions that are histologically indistinguishable from those in PPH. What is then the difference in the mechanisms of endothelial cell proliferation between primary and secondary pulmonary hypertension? The authors believe that PPH is a disease caused by somatic mutations in key angiogenesis- or apoptosis-related genes such as the TGF-beta receptor-2 and Bax. The loss of these important cell growth control mechanisms allows for the clonal expansion of endothelial cells from a single cell that has acquired a selective growth advantage. On the other hand, the proliferated endothelial cells in secondary pulmonary hypertension are polyclonal. It follows from this finding that local (vascular) factor(s) (such as increased shear stress), rather than mutations, play a major role in triggering endothelial cell proliferation. In PPH and secondary pulmonary hypertension, the researcher can postulate that the pulmonary vascular bed contains progenitor-like cells with the capacity of dysregulated growth. The main difference in the pathogenesis of primary and secondary pulmonary endothelial cell proliferation therefore may be the initial mechanism involved in the recruitment of an endothelial progenitor-like cell. In PPH, anorexigen-associated, and familial PPH, the proliferation of endothelial cells occurs from a mutated single cell, whereas in secondary pulmonary hypertension, several progenitor-like cells would be activated to grow. The abnormal endothelial cells in both forms of severe pulmonary hypertension expand because of the expression of angiogenesis-related molecules such as VEGF, VEGFR-2, HIF-1 alpha, and HIF-beta. Also important for the expansion of these cells is the down-regulation of expression of apoptosis-related mediators such as TGF-beta receptor-2 or Bax. The success of any therapy for severe pulmonary hypertension requires that the underlying process of endothelial cell proliferation could be controlled or reversed.
- Published
- 2001
43. HOX Genes in Human Lung
- Author
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Heidi L. Miller, Mark D. Moore, Heiko A. Golpon, Gary J. Miller, Mark W. Geraci, Rubin M. Tuder, and Norbert F. Voelkel
- Subjects
Pathology ,medicine.medical_specialty ,Lung ,Respiratory disease ,In situ hybridization ,respiratory system ,Biology ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,Pathology and Forensic Medicine ,medicine.anatomical_structure ,embryonic structures ,medicine ,Homeobox ,Hox gene ,Gene ,Transcription factor - Abstract
HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3′ end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases.
- Published
- 2001
44. Transforming Growth Factor-β1 Induces Endothelin-1 in a Bovine Pulmonary Artery Endothelial Cell Line and Rat Lungs via cAMP
- Author
-
DS Kim, Rubin M. Tuder, SD Lee, DS Lee, SH Paik, WD Kim, Norbert F. Voelkel, YG Chun, and WS Kim
- Subjects
Male ,Transcriptional Activation ,Pulmonary and Respiratory Medicine ,Pulmonary Artery ,Biology ,Rats, Sprague-Dawley ,Transforming Growth Factor beta1 ,Transforming Growth Factor beta ,Gene expression ,Cyclic AMP ,Protein biosynthesis ,Animals ,Pharmacology (medical) ,Endothelium ,Lung ,Regulation of gene expression ,Messenger RNA ,Endothelin-1 ,Biochemistry (medical) ,MRNA stabilization ,Endothelin 1 ,Molecular biology ,Rats ,Endothelial stem cell ,Gene Expression Regulation ,Cattle ,Transforming growth factor - Abstract
We investigated the mechanism of Endothelin-1 regulation by transforming growth factor-beta1 (TGF-beta1) in bovine pulmonary artery endothelial cells (BPAECs) and in isolated perfused rat lungs. Our data show that TGF-beta1 induces ET-1 gene expression and ET-1 peptide synthesis in BPAECs. The induction of preproET-1 mRNA level was due to de novo transcription, as well as mRNA stabilization, and new protein synthesis was not required for this induction. To investigate the role of cAMP-protein kinase A pathway in TGF-beta1-stimulated-ET-1 induction, we exposed BPAECs to various compounds which modulate this pathway. Dibutyryl-cAMP led to an increase in preproET-1 mRNA and Rp-cAMP abolished the induction of preproET-1 mRNA and ET-1 peptide by TGF-beta1. TGF-beta1 increased cAMP in BPAECs. Dexamethasone up-regulated preproET-1 mRNA expression and ET-1 peptide synthesis under basal and TGF-beta1-stimulated conditions. In isolated perfused rat lungs, TGF-beta1 increased preproET-1 mRNA abundance whereas Rp-cAMP inhibited the TGF-beta1-induced ET-1 gene activation. Thus our data suggest that TGF-beta1 stimulates ET-1 gene expression in BPAECs and in rat lungs via a cAMP dependent mechanism.
- Published
- 2000
45. Three-Dimensional Reconstruction of Pulmonary Arteries in Plexiform Pulmonary Hypertension Using Cell-Specific Markers
- Author
-
Priya N. Werahera, Carlyne D. Cool, Norbert F. Voelkel, J. Scott Stewart, Rubin M. Tuder, Randy L. Williams, and Gary J. Miller
- Subjects
Pathology ,medicine.medical_specialty ,Lung ,Endothelium ,Anatomy ,Biology ,medicine.disease ,Pulmonary hypertension ,Pathology and Forensic Medicine ,Endothelial stem cell ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,chemistry.chemical_compound ,medicine.anatomical_structure ,nervous system ,chemistry ,medicine.artery ,Pulmonary artery ,medicine ,sense organs ,Blood vessel - Abstract
The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in five patients with severe PH demonstrate that plexiform (n = 14) and concentric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change--it may represent one stage in an ongoing, angiogenic endothelial cell growth process.
- Published
- 1999
46. Mycoplasma pneumoniae-Associated Bronchiolitis Causing Severe Restrictive Lung Disease in Adults
- Author
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Tul Kalayanamit, Edward D. Chan, David A. Lynch, Marvin I. Schwarz, Rubin M. Tuder, Patrick G. Arndt, and Robert A. Winn
- Subjects
Pulmonary and Respiratory Medicine ,Mycoplasma pneumoniae ,medicine.medical_specialty ,Pediatrics ,business.industry ,Respiratory disease ,Bronchiolitis obliterans organizing pneumonia ,Critical Care and Intensive Care Medicine ,Constrictive Bronchiolitis ,medicine.disease ,medicine.disease_cause ,3. Good health ,03 medical and health sciences ,Pneumonia ,0302 clinical medicine ,030228 respiratory system ,Bronchiolitis ,medicine ,Restrictive lung disease ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Intensive care medicine ,Cryptogenic Organizing Pneumonia - Abstract
Study objectives To characterize adult Mycoplasma pneumoniae -induced bronchiolitis requiring hospitalization. Design We encountered an adult patient with severe bronchiolitis in the absence of pneumonia due to M pneumoniae. To determine the relative frequency of such a condition, we retrospectively reviewed the medical records of adults over a 4-year period with a hospital discharge diagnosis of “bronchiolitis” from a university hospital. Setting University Hospital of the University of Colorado Health Sciences Center, Denver, CO. Study subjects From 1994 to 1998, 10 adult inpatients were identified with a diagnosis of bronchiolitis. There were two with respiratory bronchiolitis, one with panbronchiolitis, one patient with bronchiolitis obliterans organizing pneumonia (BOOP), and six with acute inflammatory bronchiolitis. Including the initial patient, three had a definitive clinical diagnosis of Mycoplasma-associated bronchiolitis. Results The three adult patients with bronchiolitis due to M pneumoniae are unusual because they occurred in the absence of radiographic features of a lobar or patchy alveolar pneumonia. Hospital admission was occasioned by the severity of symptoms and gas exchange abnormalities. One patient had bronchiolitis as well as organizing pneumonia (BOOP) that responded favorably to corticosteroid treatment. The other two had high-resolution CT findings diagnostic of an acute inflammatory bronchiolitis. One of the patients with inflammatory bronchiolitis had an unusual pattern of marked ventilation and perfusion defects localized predominantly to the left lung. All three had restrictive ventilatory impairment on physiologic testing. Conclusions In adults, Mycoplasma-associated bronchiolitis without pneumonia is rarely reported, but in hospitalized patients, it may be more common than expected and may be associated with severe physiologic disturbances.
- Published
- 1999
47. A phase 2 study of the aurora kinase A inhibitor alisertib for patients with neuroendocrine prostate cancer (NEPC)
- Author
-
Beltran, H., primary, Danila, D., additional, Montgomery, B., additional, Szmulewitz, R., additional, Vaishampayan, U., additional, Armstrong, A., additional, Stein, M., additional, Hoimes, C., additional, Pinski, J., additional, Scher, H., additional, Puca, L., additional, Bareja, R., additional, Wong, W., additional, Rubin, M., additional, Mosquera, J.M., additional, Sboner, A., additional, Oromendia, C., additional, Nanus, D., additional, Ballman, K., additional, and Tagawa, S.T., additional
- Published
- 2016
- Full Text
- View/download PDF
48. 386 PCA3 and T2-ERG add further predictive and clinical benefit to the detection of prostate cancer in men of various ages in the early detection research network (EDRN)
- Author
-
O'Malley, P., primary, Golombos, D., additional, Lewicki, P., additional, Al Hussein Al Awamlh, B., additional, Christos, P., additional, Sanda, M., additional, Thompson, IM, additional, Wei, J., additional, Rubin, M., additional, Barbieri, C., additional, and Scherr, D., additional
- Published
- 2016
- Full Text
- View/download PDF
49. 138 Exploring a novel therapeutic target for neuroendocrine prostate cancer using a xenograft model of trans-differentiation
- Author
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Akamatsu, S., primary, Wyatt, A., additional, Lin, D., additional, Lysakowski, S., additional, Zhang, F., additional, Kawai, Y., additional, Fazli, L., additional, Ogawa, O., additional, Lotan, T., additional, Rubin, M., additional, Beltran, H., additional, Zoubeidi, A., additional, Wang, Y., additional, Gleave, M., additional, and Collins, C., additional
- Published
- 2016
- Full Text
- View/download PDF
50. Correcting peak deformation in Rosetta's ROSINA/DFMS mass spectrometer
- Author
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De Keyser, J., primary, Dhooghe, F., additional, Gibbons, A., additional, Altwegg, K., additional, Balsiger, H., additional, Berthelier, J.-J., additional, Briois, Ch., additional, Calmonte, U., additional, Cessateur, G., additional, Equeter, E., additional, Fiethe, B., additional, Fuselier, S.A., additional, Gombosi, T.I., additional, Gunell, H., additional, Hässig, M., additional, Le Roy, L., additional, Maggiolo, R., additional, Neefs, E., additional, Rubin, M., additional, and Sémon, Th., additional
- Published
- 2015
- Full Text
- View/download PDF
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