108 results on '"Rogers, Natasha M."'
Search Results
102. Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies.
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Yi, Zhengzi, Salem, Fadi, Menon, Madhav C., Keung, Karen, Xi, Caixia, Hultin, Sebastian, Haroon Al Rasheed, M. Rizwan, Li, Li, Su, Fei, Sun, Zeguo, Wei, Chengguo, Huang, Weiqing, Fredericks, Samuel, Lin, Qisheng, Banu, Khadija, Wong, Germaine, Rogers, Natasha M., Farouk, Samira, Cravedi, Paolo, Shingde, Meena, Smith, R. Neal, Rosales, Ivy A., O’Connell, Philip J., Colvin, Robert B., Murphy, Barbara, and Zhang, Weijia
- Abstract
Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to 789 whole slide images from baseline (478 pre-transplant and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores, but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies, and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.
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- 2021
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103. P1: CD47 drives pulmonary hypertension through coordinate regulation of c-Myc and endothelin-1.
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Rogers, Natasha M., Sharifi, Maryam S., Knupp, Heather E., Bauer, Eileen M., Bauer, Phillip M., Zukerbraun, Brian S., Novelli, Enrico M., and Champion, Hunter C.
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PULMONARY hypertension , *ENDOTHELINS , *GENETIC regulation , *ETIOLOGY of diseases , *MEMBRANE proteins , *LUNG transplantation - Abstract
Background: Pulmonary hypertension (PH), regardless of etiology, remains progressive and incurable despite intensive research for over half a century. Existing therapies have only modestly enhanced survival with the only available “cure” being lung transplantation. The reasons for lack of progress in this area remain unknown but suggest a deficit in understanding the overarching mechanism (s) that drive PH. Recently we reported that the thrombospondin-1 (TSP1)-CD47 ligand receptor pathway is induced in multiple pre-clinical models of PH and human disease. Mice lacking secreted TSP1 are protected from PH. Methods: Wild type and CD47 null mice were challenged with hypoxia and cardiopulmonary assessment performed. Likewise, in cell culture experiments pulmonary arterial vascular smooth muscle cells were exposed to hypoxia and molecular signal transduction assessed. Results: We know report that mice mutated to lack cell receptor CD47 are highly resistant to hypoxia-mediated PH with minimal evidence of pulmonary arterial overgrowth and no right ventricular hypertrophy compared to controls. Hypoxic CD47 null mice demonstrated increased stroke volume and cardiac output compared to a significant deterioration of these functional parameters in wild type controls. Hypoxic wild type animals also displayed concurrent loss of cMyc and upregulation of endothelin-1. In contrast, hypoxic CD47 null animals demonstrated cMyc-mediated suppression of endothelin-1 signaling. Impressively, under basal conditions endothelin-1 and the cognate receptors ETA and ETB where nearly undetectable in CD47 null lungs. Disrupting TSP1-mediated activation of CD47 in monocrotaline treated rats, and in hypoxic pulmonary arterial smooth muscle cell cultures, upregulated cMyc, inhibited endothelin-1 signaling and corrected established PH. Finally, antibody blocking CD47 in lungs from patients with end-stage PH normalized the vasodilation profile of distal pulmonary arteries to acetylcholine and sodium nitroprusside. Conclusions: The above preclinical results suggest CD47 is an important and proximate promoter of PH through cMyc-mediated inhibition of endothelin-1, while results in diseased human PH lung arterioles suggest that CD47 is a clinical target to restore end-stage pulmonary arteriole function. Disclosure: J.S.I. is Chair of the Scientific Advisory Boards and has equity interest in Vasculox, Inc. (St. Louis, MO) and Radiation Control Technologies, Inc. (Rockville, MD). [ABSTRACT FROM AUTHOR]
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- 2013
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104. Oral anticoagulation for hemodialysis patients with atrial fibrillation: The therapeutic conundrum remains
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Horowitz, John D and Rogers, Natasha M
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105. Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in healthy adults
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Natasha M. Rogers, Aaron L. Sverdlov, B. Assadi-Khansari, Marilyn Black, Greer Dymmott, Saifei Liu, Doan T.M. Ngo, Anjalee T Amarasekera, John D. Horowitz, Amarasekera, Anjalee T, Assadi-Khansari, Bahador, Liu, Saifei, Black, Marilyn, Dymmott, Greer, Rogers, Natasha M, Sverdlov, Aaron L, Horowitz, John D, and Ngo, Doan TM
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0301 basic medicine ,Male ,Physiology ,Organic chemistry ,lcsh:Medicine ,Blood Pressure ,030204 cardiovascular system & hematology ,Vascular Medicine ,Biochemistry ,Thrombospondin 1 ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Fibrosis ,Animal Cells ,South Australia ,Medicine and Health Sciences ,Medicine ,Insulin ,Vitamin D ,Enzyme-Linked Immunoassays ,lcsh:Science ,vitamin D insufficiency ,Multidisciplinary ,Neurochemistry ,Vitamins ,Middle Aged ,Healthy Volunteers ,Body Fluids ,Physical sciences ,Chemistry ,Blood ,Female ,medicine.symptom ,Anatomy ,Neurochemicals ,Cellular Types ,Research Article ,Adult ,Platelets ,medicine.medical_specialty ,Diastole ,inflammation and fibrosis ,Inflammation ,Nitric Oxide ,Research and Analysis Methods ,Blood Plasma ,Nitric oxide ,03 medical and health sciences ,Chemical compounds ,Internal medicine ,Organic compounds ,Vitamin D and neurology ,Humans ,cardio-metabolic dysfunction ,Immunoassays ,Diabetic Endocrinology ,Blood Cells ,business.industry ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,medicine.disease ,Hormones ,030104 developmental biology ,Blood pressure ,chemistry ,Immunologic Techniques ,lcsh:Q ,business ,Asymmetric dimethylarginine ,Plasminogen activator ,Biomarkers ,Neuroscience - Abstract
Introduction Vitamin D insufficiency, defined as 25-hydroxyVitamin D (25(OH)D) levels 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D insufficiency is associated with inflammation and fibrosis, but it remains uncertain whether these anomalies are readily reversible. Therefore, we aimed to determine the effects of Vitamin D supplementation on markers of: 1) nitric oxide (NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild hypovitaminosis. Methods Healthy volunteers (n = 35) (mean age: 45 ± 11 years) with 25(OH)D levels 75nmol/L, received Vitamin D supplementation (Ostelin capsules 2000IU) for 12 weeks. Resting systolic and diastolic blood pressures (BP) were assessed. Routine biochemistry was examined. Plasma concentrations of asymmetric dimethylarginine (ADMA), thrombospondin-1 (TSP-1), plasminogen activator inhibitor- 1 (PAI-1), hs-CRP, activin-A, and follistatin-like 3 (FSTL3) were quantitated. Results Vitamin D administration for 12 weeks significantly increased 25-(OH)D levels (48.8 ± 16 nmol/L to 100.8 ± 23.7 nmol/L, p0.001). There was significant lowering of systolic and diastolic BP, while there was no significant change in lipid profiles, or fasting insulin. Plasma concentrations of ADMA, hs-CRP, PAI-1, activin A, and FSTL-3 did not change with Vitamin D supplementation. However, there was a marked reduction of TSP-1 (522.7 ± 379.8 ng/mL vs 206.7 ± 204.5 ng/mL, p0.001). Conclusions Vitamin D supplementation in Vitamin D insufficient, but otherwise healthy individuals markedly decreased TSP-1 levels and blood pressure. Since TSP-1 suppresses signaling of NO, it is possible that the fall in BP is engendered by restoration of NO effect. Refereed/Peer-reviewed
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- 2017
106. Vascular TSP1-CD47 signaling promotes sickle cell-associated arterial vasculopathy and pulmonary hypertension in mice.
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Novelli EM, Little-Ihrig L, Knupp HE, Rogers NM, Yao M, Baust JJ, Meijles D, St Croix CM, Ross MA, Pagano PJ, DeVallance ER, Miles G, Potoka KP, Isenberg JS, and Gladwin MT
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- Anemia, Sickle Cell genetics, Animals, CD47 Antigen antagonists & inhibitors, CD47 Antigen genetics, Cells, Cultured, Endothelial Cells pathology, Humans, Hypertension, Pulmonary genetics, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Pulmonary Artery cytology, Reactive Oxygen Species metabolism, Ventricular Function, Right physiology, Anemia, Sickle Cell pathology, CD47 Antigen metabolism, Hypertension, Pulmonary pathology, Pulmonary Artery pathology, Thrombospondin 1 metabolism
- Abstract
Pulmonary hypertension (PH) is a leading cause of death in sickle cell disease (SCD) patients. Hemolysis and oxidative stress contribute to SCD-associated PH. We have reported that the protein thrombospondin-1 (TSP1) is elevated in the plasma of patients with SCD and, by interacting with its receptor CD47, limits vasodilation of distal pulmonary arteries ex vivo. We hypothesized that the TSP1-CD47 interaction may promote PH in SCD. We found that TSP1 and CD47 are upregulated in the lungs of Berkeley (BERK) sickling (Sickle) mice and patients with SCD-associated PH. We then generated chimeric animals by transplanting BERK bone marrow into C57BL/6J ( n = 24) and CD47 knockout (CD47KO, n = 27) mice. Right ventricular (RV) pressure was lower in fully engrafted Sickle-to-CD47KO than Sickle-to-C57BL/6J chimeras, as shown by the reduced maximum RV pressure ( P = 0.013) and mean pulmonary artery pressure ( P = 0.020). The afterload of the sickle-to-CD47KO chimeras was also lower, as shown by the diminished pulmonary vascular resistance ( P = 0.024) and RV effective arterial elastance ( P = 0.052). On myography, aortic segments from Sickle-to-CD47KO chimeras showed improved relaxation to acetylcholine. We hypothesized that, in SCD, TSP1-CD47 signaling promotes PH, in part, by increasing reactive oxygen species (ROS) generation. In human pulmonary artery endothelial cells, treatment with TSP1 stimulated ROS generation, which was abrogated by CD47 blockade. Explanted lungs of CD47KO chimeras had less vascular congestion and a smaller oxidative footprint. Our results show that genetic absence of CD47 ameliorates SCD-associated PH, which may be due to decreased ROS levels. Modulation of TSP1-CD47 may provide a new molecular approach to the treatment of SCD-associated PH.
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- 2019
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107. Seeing is believing: NO therapy for glaucoma? Focus on "Role of nitric oxide in murine conventional outflow physiology".
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Rogers NM and Isenberg JS
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- Animals, Female, Humans, Male, Aqueous Humor metabolism, Glaucoma metabolism, Intraocular Pressure physiology, Nitric Oxide physiology, Nitric Oxide Synthase Type III metabolism
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- 2015
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108. Endothelial cell global positioning system for pulmonary arterial hypertension: homing in on vascular repair.
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Rogers NM and Isenberg JS
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- Animals, Familial Primary Pulmonary Hypertension, Female, Endothelial Cells transplantation, Genetic Therapy methods, Hypertension, Pulmonary prevention & control, Monocrotaline, Pulmonary Artery metabolism, Receptors, Interleukin-8 biosynthesis
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- 2014
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