tbuckley/cabot-search huggingface dataset:
Abstract 16434: IL-6 Signaling is Crucial for Cardiomyocyte Hypertrophy and Left Ventricular Dysfunction Induced by Pressure Overload
Authors: Lin Zhao, Guangming Cheng, Yanjuan Yang, Anweshan Samanta, Rizwan R Afzal, Magdy Girgis, Xing Chen, Sheng Ye, Samuel Asante, Patrick McEnulty, Robert J Vincent, Jeryl Hauptman, Runming Jin, Buddhadeb Dawn
Journal: Circulation (2015)

Introduction: Interleukin-6 (IL-6), a proinflammatory cytokine, has been implicated in ischemic cardiac pathologies. Very little is currently known regarding the role of IL-6 signaling in pathological cardiomyocyte hypertrophy and LV dysfunction. Hypothesis: We hypothesized that IL-6 signaling plays a central role in cardiomyocyte hypertrophy and exerts a deleterious impact on LV remodeling induced by pressure overload. Methods: In vitro, adult cardiomyocytes from C57BL/6 (WT, control) and IL-6 knockout (KO) mice were stimulated by IL-6 and pro-hypertrophic agent angiotensin II (Ang II). The expression of hypertrophy markers and related signaling molecules were examined by real-time quantitative RT-PCR. In vivo, weight-matched male WT and IL-6 KO mice underwent transverse aortic constriction (TAC) or a sham procedure. Serial echocardiograms and a terminal hemodynamic study were performed. Results: After exposure to IL-6 and hypertrophic agonists, the expression of hypertrophy related genes, BNP, GATA-4, αSK actin, and β-MHC increased significantly in WT cardiomyocytes (Fig). These effects were significantly attenuated in IL-6 knockout cardiomyocytes (Fig), indicating an essential role of IL-6 in cardiomyocyte hypertrophy. In vivo, the worsening in LV contraction as well as relaxation after TAC was significantly attenuated in IL-6 KO mice, indicating superior preservation of LV function in the setting of pressure overload in the absence of IL-6 signaling. Conclusions: The protection against Ang II-induced hypertrophy observed in IL-6 KO adult cardiomyocytes in vitro, and in hearts of IL-6 KO mice after TAC in vivo illustrates a crucial role played by IL-6 in pathogenesis of pressure overload-induced LV hypertrophy. Modulation of IL-6 signaling may have preventive therapeutic potential for countless hypertensive patients at risk for LV hypertrophy and failure.
Vision-Related Quality of Life Associated with Unilateral and Bilateral Ocular Conditions
Authors: Gary C. Brown, Melissa M. Brown, Joshua D. Stein, William E. Smiddy, Gary C. Brown, Melissa M. Brown, Lynn Geiger, Heidi B. Lieske, Philip A. Lieske, Sanjay Sharma, William E. Smiddy, Joshua D. Stein, Woody Stevens
Journal: Ophthalmology (2018)
Elevated serum TSLP, IL-33, 6Ckine and MCP-3 levels in school children or older patients with eosinophilic gastroenteritis
Authors: Ichiro Nomura, Hideaki Morita, Akio Matsuda, Miori Sato, Motoko Mitsui, Yumiko Miyaji, Shinichiro Inagaki, Tatsuki Fukuie, Masami Narita, Yukihiro Ohya, Hirohisa Saito, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2018)
P102 S100A9 hampers osteoclast differentiation from circulating precursors by reducing the expression of rank
Authors: M van den Bosch, I Di Ceglie, T Vogl, J Roth, C Goodyear, P van der Kraan, A Blom, P van Lent
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The alarmins S100A8/A9 are produced in high levels in the synovium during both experimental and human rheumatoid arthritis (RA) and have been implicated in inflammation-induced bone resorption. We and others have previously shown that stimulation of mature osteoclasts with S100A8/A9 results in increased numbers and resorptive activity. In agreement, reduced bone destruction was observed after induction of experimental RA models in <i>S100a9<sup>-/-</sup></i> mice. However, the effects of S100A8/A9 on monocyte-to-osteoclast differentiation remain elusive. <h3>Objectives</h3> Here, we investigated the effects of S100A9 on CD14<sup>+</sup> monocytes and their potential to differentiate into osteoclasts. <h3>Methods</h3> CD14<sup>+</sup> monocytes were isolated from buffy coats of healthy donors using density gradient centrifugation and magnetic cell sorting. Cells were differentiated into osteoclasts with macrophage colony-stimulating factor (M-CSF) and Receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL) in the presence or absence of S100A9. mRNA expression was determined by RT-qPCR and protein expression was determined using Luminex analysis. Moreover, osteoclast differentiation was assessed using Tartrate-resistant acid phosphatase (TRAP) staining and the resorptive capacity was determined using mineral-coated plates. RANK protein expression was assessed using FACS. <h3>Results</h3> We observed that S100A9 stimulation of monocytes resulted in a strong induction of various pro-inflammatory factors, such as interleukin (IL)1β, IL6, IL8, and tumour necrosis factor (TNF)α after 24 hour, both on the mRNA and protein level. Interestingly, we observed a strong decrease in the number of multinucleated osteoclasts as determined by TRAP staining, at day 6 and 8 after start of the cultures. In agreement with this, the cells showed a strongly reduced resorptive capacity. We demonstrated that already a 24 hour stimulation with S100A9 strongly reduced the osteoclastogenic potential of the CD14<sup>+</sup> monocytes. Finally, we observed that S100A9 stimulation hampered the M-CSF-induced upregulation of RANK, which could be reversed by addition of the TNFα-inhibitor etanercept, but not the interleukin 1 receptor antagonist. <h3>Conclusions</h3> Whereas S100A8/A9 have been previously shown to stimulate the numbers and resorptive capacity of mature osteoclasts, we here show that stimulation of monocytes with S100A9 strongly inhibits their osteoclastogenic potential, possibly via TNFα-induced reduction of RANK expression. This suggests that the timing of exposure to S100A8/A9 is an important determinant for monocyte-to-osteoclast differentiation. <h3>Disclosure of interest</h3> None declared
Abstract 12314: β-2-Hydroxyglutarate Inhibits Glycolysis in Pulmonary Vascular Cells
Authors: William Oldham, Joseph Loscalzo
Journal: Circulation (2015)

β-2-hydroxyglutarate (L2HG) is a metabolite of unknown function that we have found to increase in pulmonary arterial endothelial cells, smooth muscle cells, and lung fibroblasts (PAEC, PASMC, LF) in response to hypoxia. L2HG is produced from the reduction of mitochondrial 2-oxoglutarate (2OG) and is oxidized back to 2OG by L2HG dehydrogenase (L2HGDH) in a redox cycle coupled to the oxidation of NADH and reduction of FAD, respectively. As these are the only known reactions in which L2HG participates, we hypothesized that L2HG metabolism plays an important role in cellular redox homeostasis. To test this hypothesis, we measured the effect of L2HGDH levels on cellular NADH/NAD + in LF using an enzymatic cycling assay. L2HGDH knockdown potentiated hypoxia-mediated increases in cellular NADH/NAD + (138 ± 10% v. 169 ± 14%, siCTL v. siL2HGDH, p = 0.08) while L2HGDH overexpression had the opposite effect (139 ± 10% v. 127 ± 7%, Vector v. L2HGDH, p = 0.08). Given these results, we next examined the effect of L2HGDH knockdown on mitochondrial electron transport and glycolysis using the Seahorse Extracellular Flux Analyzer. We found that siL2HGDH decreased maximal, FCCP-stimulated oxygen consumption rate in LF (10.8 ± 1.0 v. 9.8 ± 0.9 nmol O2/min/10 6 cells, p &lt; 0.001) and inhibited maximal, oligomycin-stimulated glycolytic flux (790 ± 42 v. 519 ± 61 mpH/min/10 6 cells, p = 0.02). The effects of siL2HGDH on glycolysis were confirmed in PAEC and PASMC, where the knockdown decreased oligomycin-stimulated extracellular acidification rate (ECAR) by 24% and 16%, respectively. Cell-permeable L2HG inhibited ECAR to a similar degree. Metabolomic profiling of LF treated with siL2HGDH identified increases in the pentose phosphate pathway intermediates 6-phosphogluconate and pentose monophosphate, suggesting phosphofructokinase as a potential target of L2HG. Together, these data indicate that L2HG accumulation in hypoxia reduces mitochondrial reductant stress.
Road traffic injuries: Cross-sectional cluster randomized countrywide population data from 4 low-income countries
Authors: Syed Nabeel Zafar, Joseph K. Canner, Neeraja Nagarajan, Adam L. Kushner, Shailvi Gupta, Joseph K. Canner, Tu M. Tran, Neeraja Nagarajan, Barclay T. Stewart, Thaim B. Kamara, Patrick Kyamanywa, Kapendra S. Amatya, Moses Galukande, Robin T. Petroze, Benedict C. Nwomeh, Emily R. Smith, Michael M. Haglund, Benedict Nwomeh, Reinou S. Groen, Adam L. Kushner
Journal: International Journal of Surgery (2018)
Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells
Authors: John L. Johnson, Georgios Georgakilas, Jelena Petrovic, Makoto Kurachi, Stanley Cai, Christelle Harly, Warren S. Pear, Avinash Bhandoola, E. John Wherry, Golnaz Vahedi
Journal: Immunity (2018)
Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors
Authors: Eleonora De Martin, Jean-Marie Michot, Barbara Papouin, Stéphane Champiat, Christine Mateus, Olivier Lambotte, Bruno Roche, Teresa Maria Antonini, Audrey Coilly, Salim Laghouati, Caroline Robert, Aurélien Marabelle, Catherine Guettier, Didier Samuel
Journal: Journal of Hepatology (2018)
Comparison of the Hemostatic Efficacy of Pathogen-Reduced Platelets vs Untreated Platelets in Patients With Thrombocytopenia and Malignant Hematologic Diseases
Authors: Frédéric Garban, Audrey Guyard, Helene Labussière, Claude-Eric Bulabois, Tony Marchand, Christiane Mounier, Denis Caillot, Jacques-Olivier Bay, Valérie Coiteux, Aline Schmidt-Tanguy, Catherine Le Niger, Christine Robin, Patrick Ladaique, Simona Lapusan, Eric Deconinck, Carole Rolland, Alison M. Foote, Anne François, Chantal Jacquot, René Tardivel, Pierre Tiberghien, Jean-Luc Bosson
Journal: JAMA Oncology (2018)

Pathogen reduction of platelet concentrates may reduce transfusion-transmitted infections but is associated with qualitative impairment, which could have clinical significance with regard to platelet hemostatic capacity.
Abstract 18845: Induced Cardiac Progenitor Cells Differentiate Into Cardiac Lineage Cells in vivo and Improve Survival in Mice post Myocardial Infarction
Authors: Pratik A Lalit, Max R Salick, Daryl O Nelson, Jayne M Squirrell, Christina M Shafer, Eric G Shmuck, Yogananda S Markandeya, Kevin W Eliceiri, Timothy A Hacker, Wendy C Crone, Michael Kyba, Daniel J Garry, Ron Stewart, James A Thomson, Karen M Downs, Gary E Lyons, Timothy J Kamp
Journal: Circulation (2015)

Several studies have reported reprogramming of fibroblasts (Fibs) to induced cardiomyocytes, and we have recently reprogrammed mouse Fibs to induced cardiac progenitor cells (iCPCs), which may be more favorable for cardiac repair because of their expandability and multipotency. Adult cardiac (AC), lung and tail-tip Fibs from an Nkx2.5-EYFP reporter mouse were reprogrammed using a combination of five defined factors into iCPCs. Transcriptome and immunocytochemistry analysis revealed that iCPCs were cardiac mesoderm-restricted progenitors that expressed CPC markers including Nkx2.5, Gata4, Irx4, Tbx5, Cxcr4, Flk1 etc. iCPCs could be extensively expanded (over 30 passages) while maintaining multipotency to differentiate in vitro into cardiac lineage cells including cardiomyocytes (CMs), smooth muscle cells and endothelial cells. iCPC derived CMs upon co-culture with mESC-derived CMs formed intercellular gap junctions, exhibited calcium transients, and contractions. The purpose of this study was to determine the in vivo potency of iCPCs. Given that the Nkx2.5-EYFP reporter identifies embryonic CPCs, we first tested the embryonic potency of iCPCs using an ex vivo whole embryo culture model injecting cells into the cardiac crescent (CC) of E8.5 mouse embryos and culturing for 24 to 48 hours. GFP labeled AC Fibs were first tested and live imaging revealed that after 24 hours these cells were rejected from the embryo proper and localized to the ecto-placental cone. In contrast, iCPCs reprogrammed from AC Fibs when injected into the CC localized to the developing heart tube and differentiated into MLC2v, αMHC and cardiac actin expressing CMs. Further we injected iCPCs into infarcted adult mouse hearts and determined their regenerative potential after 1-4 wks. The iCPCs significantly improved survival (p&lt;0.01 Mantel-Cox test) in treated animals (75%) as compared to control (11%). Immunohistochemistry revealed that injected iCPCs localized to the scar area and differentiated into cardiac lineage cells including CMs (cardiac actin). These results indicate that lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for cardiac regenerative therapy as well as drug discovery and disease modeling.
Evaluating Readmission—Need for More Clarity on Methods—Reply
Authors: Ankur Gupta, Clyde W. Yancy, Gregg C. Fonarow
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
The role of matrix metalloproteinase-2 in transforming growth factor-beta2 mediated glioma cell migration
Authors: Peter Hau, Fuesun Arslan, Anja-Kathrin Bosserhoff, Anett Doerfelt, Dagmar Beier, Petra Leukel, Thomas Nickl-Jockschat, Ulrich Bogdahn
Journal: Cancer Research (2008)

3527   Transforming growth factor-beta2 (TGF-beta2) is known to contribute to a malignant course in gliomas partially by inducing a mesenchymal phenotype and by modulating the microenviroment including the extracellular matrix. Matrix metalloproteinase 2 (MMP-2) also correlates with the malignant progression of human gliomas together with cell surface adhesion receptors like integrin alphav beta3. We have described elsewhere that the V0/V1-isoforms of the proteoglycan versican interact with TGF-beta2 and enhance glioma migration. In this study, we aimed to investigate possible interactions of TGF-beta2 with MMP-2 and integrin alphav beta3 that might contribute to glioma migration. Using real-time qPCR to screen for expressional changes in response to TGF-beta2, we showed that TGF-beta2 enhances the expression of MMP-2 and of integrin alphav beta3. Additionally, TGF-beta2 increased the MMP-2 secretion detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA) and the activation of MMP-2 in glioma cells as measured by gelatin zymography.  In vitro  migration assays demonstrated that the inhibition of MMP-2 activity using a MMP-2 inhibitor suppresses TGF-beta2 stimulated glioma cell-migration. This effect can be enhanced by additional blockade of integrin alphav beta3. We also found that MMP-2 interacts with and cleaves versican V0/V1. Taken together, we outline a new set of interactions involving TGF-beta2, MMP-2, integrin alphav beta3 and the proteoglycan versican which might constitute a crucial network for glioma migration. This molecular cascade may further elucidate the diffuse parenchyma-infiltrating character of glioma invasion and thus be a target for new approaches to anti-tumor therapy.
The farnesyltransferase inhibitor Zarnestra synergizes with paclitaxel to induce mitotic arrest and apoptosis in multiple myeloma cells
Authors: Kuichun Zhu, Melissa Alsina, Said M. Sebti
Journal: Cancer Research (2004)

3865   Despite significant recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease with a median survival of 3 to 6 years. Recently, we conducted a phase II clinical trial with the farnesyltransferase inhibitor Zarnestra in patients with relapsed MM and demonstrated that Zarnestra as a single agent induces disease stabilization in about 50% of the patients. In the present study, Zarnestra was found to synergyze with paclitaxel (taxol) to induce mitotic arrest and apoptosis in 8226 MM cells. Zarnestra synergized with taxol to inhibit proliferation (MTT analysis), to induce apoptosis (TUNEL assay and Cyt. C release) and to cause G2/M arrest (flow cytometric analysis). Taxol also synergyzed with a PI-3K, but not a Mek, inhibitor. Neither taxol nor Zarnestra affected P-Erk levels, but both decreased P-AKT levels. VEGF levels in the cells as well as in the culture medium decreased only when both Zarnestra and taxol were used with or without IL-6 stimulation. The combination of Zarnestra and taxol also blocked the stimulation of Bcl-XL expression by IL-6. Finally, taxol was shown to enhance the antitumor activity of Zarnestra in vivo with the 8226 myeloma SCID-hu mouse model. Our results provide the basis to evaluate combination therapy of Zarnestra and taxol in myeloma patients.
H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers
Authors: Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney, Michael Thomas, Anant A Agrawal, Benjamin Caleb, Alfredo Csibi, Eckley Sean, Peter Fekkes, Craig Karr, Virginia Klimek, George Lai, Linda Lee, Pavan Kumar, Stanley Chun-Wei Lee, Xiang Liu, Crystal Mackenzie, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Shouyong Peng, Sudeep Prajapati, Justin Taylor, Teng Teng, John Wang, Markus Warmuth, Huilan Yao, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith, Silvia Buonamici
Journal: Nature Medicine (2018)
Prognostic Accuracy of the Quick Sequential Organ Failure Assessment for Mortality in Patients With Suspected Infection
Authors: Shannon M. Fernando, Alexandre Tran, Monica Taljaard, Wei Cheng, Bram Rochwerg, Andrew J.E. Seely, Jeffrey J. Perry
Journal: Annals of Internal Medicine (2018)

The quick Sequential Organ Failure Assessment (qSOFA) has been proposed for prediction of mortality in patients with suspected infection.To summarize and compare the prognostic accuracy of qSOFA and the systemic inflammatory response syndrome (SIRS) criteria for prediction of mortality in adult patients with suspected infection.Four databases from inception through November 2017.English-language studies using qSOFA for prediction of mortality (in-hospital, 28-day, or 30-day) in adult patients with suspected infection in the intensive care unit (ICU), emergency department (ED), or hospital wards.Two investigators independently extracted data and assessed study quality using standard criteria.Thirty-eight studies were included (n = 385 333). qSOFA was associated with a pooled sensitivity of 60.8% (95% CI, 51.4% to 69.4%) and a pooled specificity of 72.0% (CI, 63.4% to 79.2%) for mortality. The SIRS criteria were associated with a pooled sensitivity of 88.1% (CI, 82.3% to 92.1%) and a pooled specificity of 25.8% (CI, 17.1% to 36.9%). The pooled sensitivity of qSOFA was higher in the ICU population (87.2% [CI, 75.8% to 93.7%]) than the non-ICU population (51.2% [CI, 43.6% to 58.7%]). The pooled specificity of qSOFA was higher in the non-ICU population (79.6% [CI, 73.3% to 84.7%]) than the ICU population (33.3% [CI, 23.8% to 44.4%]).Potential risk of bias in included studies due to qSOFA interpretation and patient selection.qSOFA had poor sensitivity and moderate specificity for short-term mortality. The SIRS criteria had sensitivity superior to that of qSOFA, supporting their use for screening of patients and as a prompt for treatment initiation.Canadian Association of Emergency Physicians. (PROSPERO: CRD42017075964).
Transparency and Dermatologic Device Approval by the US Food and Drug Administration
Authors: Harib H. Ezaldein, Jeffrey F. Scott, Emily S. Yin, Alessandra Ventura, Nicholaas P. DeRuyter, David J. Leffell
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> The US Food and Drug Administration approves Class III medical devices via the premarket approval pathway, often requiring clinical data on safety and efficacy. Manufacturers can submit incremental device changes via supplemental applications, which are not subjected to such vetting measures and can cause understudied changes that lead to drift from a device’s original design. <h3>Objectives</h3> To characterize the postapproval changes to Class III dermatologic devices and to evaluate inconsistencies in the use of the premarket approval pathway. <h3>Design, Setting, and Participants</h3> This study was a cross-sectional retrospective cohort analysis of a public US Food and Drug Administration database for premarket approval of devices. Included were dermatologic devices approved by the US Food and Drug Administration between January 1, 1980, and November 1, 2016, through the premarket pathway for device approval. <h3>Main Outcomes and Measures</h3> Original devices were identified, and their supplements were characterized chronologically, by review track, and by modification category. <h3>Results</h3> The 27 dermatologic devices studied consisted of 14 injectables, 11 photodynamic therapies, a dermal replacement matrix, and a diagnostic imaging instrument. Supplemental applications are increasingly used: the data-requiring panel-track pathway was the least common approach (2.8% [16 of 562 supplements]), while the 30-day track, which does not require clinical data, was most frequently used (42.5% [239 of 562 supplements]). Four devices (14.8%) underwent low-risk recalls (Class II or Class III), and 10 devices (37.0%) were voluntarily withdrawn. <h3>Conclusions and Relevance</h3> As manufacturers make increasing use of supplemental applications, minor device changes may occur without supporting clinical data, which could pose a safety risk to patients.