tbuckley/cabot-search huggingface dataset:
Abstract 11207: Global Longitudinal Left Ventricular Strain Assessed by Speckle Tracking Imaging Is an Independent Strongest Predictor of Plasma BNP Levels in Patients with Cardiac Amyloidosis
Authors: Jun Koyama, Ayako Minamisawa, Kazunori Aizawa, Hiroki Kasai, Megumi Koshikawa, Atsushi Izawa, Takeshi Tomita, Yusuke Miyashita, Setsuo Kumazaki, Uichi Ikeda
Journal: Circulation (2011)

Background:  Cardiac amyloidosis is characterized by an early impairment in longitudinal left ventricular (LV) systolic function at a time when fractional shortening remains normal. We examined which parameter by speckle tracking echocardiography (global LV longitudinal/circumferential strain, and LV torsion) is mostly associated with plasma BNP levels in patients with cardiac amyloidosis.   Methods:  We examined 312 consecutive patients with cardiac amyloidosis who underwent standard echocardiographic, Doppler flow, and 2 dimensional speckle tracking imaging examinations. Plasma BNP levels were measured on the day of echocardiography. Global longitudinal LV strain was obtained from apical 3 views by automatic functional imaging and global circumferential LV strains and LV torsion were measured in parasternal short axis views at basal, mid and apical LV levels (GE Echo Pac PC).   Results:  Univariate and multivariate analyses showed that the global longitudinal strain by automatic functional imaging was the most powerful and independent predictor of plasma BNP levels (R=0.699, P   Conclusions:  Global longitudinal LV strain rather than global circumferential strain and LV torsion is associated with elevated plasma BNP levels in patients with cardiac amyloidosis. Measurement of plasma BNP levels is useful for presuming the global longitudinal LV strain in patients with cardiac amyloidosis.
The novel thrombopoietic agent AMG 531 is effective in pre-clinical models of chemo/radiotherapy induced thrombocytopenia
Authors: Cynthia Hartley, Trish McElroy, Graham Molineux, Glenn Begley
Journal: Cancer Research (2005)

1233  AMG 531 is a novel thrombopoietic agent that engages c-mpl and has been demonstrated to elevate platelet counts in normal individuals and in patients with idiopathic thrombocytopenic purpura (ITP)1. Consistent with this clinical data, AMG 531 increases platelet counts in mice in a dose-related fashion. We sought to determine whether AMG 531 would be an effective agent in models of chemo/radiotherapy induced thrombocytopenia. We therefore employed a model combining chemotherapy with radiation (CRT) that results in severe thrombocytopenia2. The effects of a single injection of AMG 531 were examined in this mouse model.Mice were treated with the combination of carboplatin (62.5 mg/kg) and 4 hours later sub-lethal irradiation (5 Gy total body irradiation). Two hours post-irradiation, groups were treated with either placebo (n=20) or AMG531 (n=20). Platelet counts in mice treated with placebo fell to 10% of the initial platelet count by day 10 after CRT and returned to normal by day 21. Animals that received only placebo showed nadir platelet counts of   700X106/mL and the nadir was brought forward to between days 5 and 6. At the dose studied this was then followed by a substantial overshoot in platelets though dose reduction was not investigated. Platelet counts were significantly improved (AMG 531 vs. placebo) between days 7 and 19 (p= 0.001 on day 7) when platelets recovered in the unsupported group to pre-treatment values. We conclude that AMG531 reduces the severity and duration of the thrombocytopenia resulting from CRT when compared to placebo-treated mice. The beneficial effect was similar to that seen historically for mice treated with CRT and that received other mpl ligands. Further work is required to establish the optimal dose and schedule for administration of AMG531 in chemotherapy induced thrombocytopenia. 1 Bussel, et al An Open-Label, Dose-Finding Study Evaluating the Safety and Platelet Response of a Novel Thrombopoietic Protein (AMG 531) in Thrombocytopenic Adult Patients with Immune Thrombocytopenic Purpura (ITP). Blood. 102(11): 86a 2003, November 16 2 Hokom, et al Pegylated Megakaryocyte Growth and Development Factor Abrogates the Lethal Thrombocytopenia Associated With Carboplatin and Irradiation in Mice. Blood. 86(12): 4486-92, 1995 Dec 15
Symbionticism and the Origin of Species.
Authors: Ivan Emmanuel Wallin
Journal: JAMA (1927)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Control of Diastolic Calcium in the Heart
Authors: David A. Eisner, Jessica L. Caldwell, Andrew W. Trafford, David C. Hutchings
Journal: Circulation Research (2020)

Normal cardiac function requires that intracellular Ca2+ concentration be reduced to low levels in diastole so that the ventricle can relax and refill with blood. Heart failure is often associated with impaired cardiac relaxation. Little, however, is known about how diastolic intracellular Ca2+ concentration is regulated. This article first discusses the reasons for this ignorance before reviewing the basic mechanisms that control diastolic intracellular Ca2+ concentration. It then considers how the control of systolic and diastolic intracellular Ca2+ concentration is intimately connected. Finally, it discusses the changes that occur in heart failure and how these may result in heart failure with preserved versus reduced ejection fraction.
The Detection of Cardiac Adrenocorticotropic Hormone–Secreting Neuroendocrine Tumor With the Help of 68Ga-DOTATATE PET/CT
Authors: Guozhu Hou, Yuanyuan Jiang, Xin Cheng
Journal: Clinical Nuclear Medicine (2019)

Abstract Ectopic adrenocorticotropic hormone Cushing syndrome is a relatively rare condition. We present the case of a 39-year-old man with ectopic adrenocorticotropic hormone Cushing syndrome due to a cardiac neuroendocrine tumor (NET), which was localized with the help of 68 Ga-DOTATATE. 18 F-FDG PET/CT revealed a hypermetabolic lesion in the heart, while the distinction between physiological and pathological FDG uptake is difficult. 68 Ga-DOTATATE PET/CT revealed focal uptake corresponding to the cardiac focus found on FDG PET/CT, providing evidence of cardiac NET. This case illustrates that 68 Ga-DOTATATE could play a role in the evaluation of cardiac NET as it lacks significant physiological myocardial uptake.
Wnt-Induced Stabilization of KDM4C Is Required for Wnt/β-Catenin Target Gene Expression and Glioblastoma Tumorigenesis
Authors: Yaohui Chen, Runping Fang, Chen Yue, Guoqiang Chang, Peng Li, Qing Guo, Jing Wang, Aidong Zhou, Sicong Zhang, Gregory N. Fuller, Xiaobing Shi, Suyun Huang
Journal: Cancer Research (2019)

Wnt/β-catenin signaling activates the transcription of target genes to regulate stem cells and cancer development. However, the contribution of epigenetic regulation to this process is unknown. Here, we report that Wnt activation stabilizes the epigenetic regulator KDM4C that promotes tumorigenesis and survival of human glioblastoma cells by epigenetically activating the transcription of Wnt target genes. KDM4C protein expression was upregulated in human glioblastomas, and its expression directly correlated with Wnt activity and Wnt target gene expression. KDM4C was essential for Wnt-induced gene expression and tumorigenesis of glioblastoma cells. In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation. Wnt3a stabilized KDM4C through inhibition of GSK3-dependent protein kinase R activity. Stabilized KDM4C accumulated in the nucleus and bound to and demethylated TCF4-associated histone H3K9 by interacting with β-catenin, promoting HP1γ removal and transcriptional activation. These findings reveal that Wnt-KDM4C-β-catenin signaling represents a novel mechanism for the transcription of Wnt target genes and regulation of tumorigenesis, with important clinical implications. SIGNIFICANCE: These findings identify the Wnt-KDM4C-β-catenin signaling axis as a critical mechanism for glioma tumorigenesis that may serve as a new therapeutic target in glioblastoma.
Reducing invasion potential of cervical cancer cells via targeted knockdown of c-Jun.
Authors: Grace Pei Chien Yee, Paul L. De Souza, Levon M. Khachigian
Journal: Journal of Clinical Oncology (2013)

e22005 Background: Despite recent advent of vaccines for human papillomaviruses (HPV) in cervical cancer and increasing efforts to improve therapy, deaths still average 275,000 annually worldwide, with most women succumbing to recurrent or metastatic disease. The c-Jun oncogene is a subunit of the activating protein-1 (AP-1) transcription factor and is strongly expressed in cervical cancer, regulating the expression of HPV16 and 18 genes. AP-1 plays a major role in cell growth, migration and apoptosis in many cell types. This study examined the role of c-Jun in modulating HeLa proliferation, migration, apoptosis and invasion as well as susceptibility to cisplatin. Methods: Transient knockdown and over-expression of c-Jun was performed in HeLa cervical cancer cells using Dharmacon c-Jun siRNA and Origene Jun expression vector. c-Jun and downstream gene/protein expression was confirmed by western blot and real-time PCR and cells subject to proliferation, in vitro wound and matrigel dual-chamber transwell assays. Flow cytometry was used for analysis of cell cycle and apoptosis. Results: c-Jun protein and mRNA levels were reduced by c-Jun siRNA. c-Jun silencing inhibited cervical cancer cell proliferation. Significantly, c-Jun suppression dramatically reduced HeLa migration and invasion and targeted down-regulation of cyclooxygenase-2 (Cox2), interleukin-6 (IL-6), metalloproteinases (MMP)-1, -9 and -13 as well as HPV18 E6 and E7, genes highly expressed in cervical cancer and associated with metastatic growth. Direct siRNA knockdown of Cox2 in HeLa also reduced MMP1 and MMP9 expression suggesting an intermediary link. In HeLa cells over-expressing c-Jun, cell proliferation was not significantly increased but cell invasiveness was markedly enhanced in parallel with enhanced MMP-1 expression. Modulation of c-Jun expression did not interfere with susceptibility of HeLa cells to apoptosis in the presence of cisplatin. Conclusions: Reduced invasion potential of HeLa cells after c-Jun knockdown suggests a potential target in treatment of metastatic and recurrent cervical cancer. Data suggest a mechanism involving down-regulation of Cox2 and MMP-1 and -9 expression.
Be Ready to Talk With Parents About Direct-to-Consumer Genetic Testing
Authors: Ellen Wright Clayton
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
Microphthalmia transcription factor expression contributes to bone marrow failure in Fanconi anemia
Authors: Alessia Oppezzo, Julie Bourseguin, Emilie Renaud, Patrycja Pawlikowska, Filippo L Rosselli
Journal: Journal of Clinical Investigation (2019)

Hematopoietic stem cell (HSC) attrition is considered the key event underlying progressive BM failure (BMF) in Fanconi anemia (FA), the most frequent inherited BMF disorder in humans. However, despite major advances, how the cellular, biochemical, and molecular alterations reported in FA lead to HSC exhaustion remains poorly understood. Here, we demonstrated in human and mouse cells that loss-of-function of FANCA or FANCC, products of 2 genes affecting more than 80% of FA patients worldwide, is associated with constitutive expression of the transcription factor microphthalmia (MiTF) through the cooperative, unscheduled activation of several stress-signaling pathways, including the SMAD2/3, p38 MAPK, NF-κB, and AKT cascades. We validated the unrestrained Mitf expression downstream of p38 in Fanca-/- mice, which display hallmarks of hematopoietic stress, including loss of HSC quiescence, DNA damage accumulation in HSCs, and reduced HSC repopulation capacity. Importantly, we demonstrated that shRNA-mediated downregulation of Mitf expression or inhibition of p38 signaling rescued HSC quiescence and prevented DNA damage accumulation. Our data support the hypothesis that HSC attrition in FA is the consequence of defects in the DNA-damage response combined with chronic activation of otherwise transiently activated signaling pathways, which jointly prevent the recovery of HSC quiescence.
Outcomes of combined modality treatment in elderly patients with stage III non-small cell lung cancer.
Authors: Ludimila Cavalcante, Flavia Kutwak, Ana L. Ruiz, Tiffany Fan, Judith Samuels, Michael Samuels, Estelamari Rodriguez
Journal: Journal of Clinical Oncology (2012)

7049 Background: The use of combined modality treatment (CMT) has been demonstrated to improve survival in patients with inoperable, locally advanced NSCLC. Elderly patients have been traditionally excluded from prospective clinical trials investigating CMT and thus the optimal treatment strategy for these patients remains unclear. We retrospectively evaluated the outcomes of elderly patients who received concurrent and sequential chemoradiation. Methods: All lung cancer patients age 70 or older who received chemotherapy and radiation treatment at Mt. Sinai Medical Center for stage III NSCLC between 1997 and 2010 were analyzed from tumor registry data. Among 282 lung cancer elderly patients diagnosed with stage III disease, 64 patients (22.7 %) received CMT as part of their treatment. Patients who underwent surgery and palliative radiation were excluded. Statistical analysis was performed by log-rank, Kaplan-Meier methods, and t-test. Results: Median age at diagnosis for the CMT group was 75 years (70-87), male/female: 34/30, TNM: T4N0-1: 12, T3N1: 1, TXN2: 41, TXN3: 10. Concurrent chemoradiation was delivered in 43 cases and sequential in 21 cases. RT doses ranged from 50 to 63 Gy. The most common chemotherapy regimens used were carboplatin and taxol (44 %) and carboplatin and etoposide (15%). The most common treatment-related toxicities were esophagitis (42%), anemia (39%), and pneumonia (24%). Median survival (MST) was 19 months and 11 months in the concurrent and sequential chemoradiation groups (p=0.67). Observed two, three and five-year overall survival (OS) in the CMT group was 49.1%, 27.5%, and 12.5%, respectively. Conclusions: Although CMT is not commonly used in elderly patients with lung cancer, the treatment is feasible and beneficial for selected patients in the community setting. Interestingly, the MST of elderly patients who received CMT in this cohort was comparable to that of younger historical controls with CMT. There was also a trend for increased survival in the concurrent versus sequential chemoradiation group.
Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration
Authors: Yao Xiao, Jinrong Peng, Qingya Liu, Lijuan Chen, Kun Shi, Ruxia Han, Qian Yang, Lin Zhong, Ruoyu Zha, Ying Qu, Zhiyong Qian
Journal: Theranostics (2020)

Mesenchymal stem cell (MSC)-based therapies have been used in skin regeneration due to their ability to differentiate into many cells, promote cytokine secretion and participate in collagen deposition.In this study, we concluded that a CuS@BSA nanoparticles exhibited similar potential in inducing MSCs differentiation to fibroblasts as Cu ions for wound healing.Methods: First, we verified the photothermal efficiency of CuS@BSA in vivo and vitro and had no cytotoxicity for MSCs when the temperature was controlled at 42 °C by adjusting the power of irradiation at 980 nm.And then we detected the expression of vimentin in MSCs, which further directed the MSCs to fibroblasts through Western blotting and Immunofluorescence when treated with CuS@BSA or pre-heat at 42 °C.In addition, we implanted MSCs into the Matrigel or electrospun PLA nanofiber membrane in vitro to evaluating the effect of heating or CuS@BSA on the morphological change of MSCs by SEM.Finally, we evaluated improving skin regeneration by the combination of preheated-MSCs and CuS@BSA nanoparticles that were encapsulated in Matrigel.Results: The CuS@BSA nanoparticles have good photothermal conversion efficiency.Not only CuS nanoparticles itself or after irradiation at 980 nm stimulated the expressioin of vimentin in MSCs.Besides, the CuS@BSA can promote cell proliferation as Cu ion through the expression of ERK.The combination of the CuS@BSA nanoparticles and thermal treatment synergistically improved the closure of an injured wound in an injured wound model.Conclusions: MSCs combined with CuS@BSA are a promising wound dressing for the reconstruction of full-thickness skin injuries.
Platelet-derived growth factor-AB improves scar mechanics and vascularity after myocardial infarction
Authors: Sujitha Thavapalachandran, Stuart M. Grieve, Robert D. Hume, Thi Yen Loan Le, Kalyan Raguram, James E. Hudson, Jim Pouliopoulos, Gemma A. Figtree, Rafael P. Dye, Anthony M. Barry, Paula Brown, Juntang Lu, Sean Coffey, Scott H. Kesteven, Richard J. Mills, Fairooj N. Rashid, Elena Taran, Pramesh Kovoor, Liza Thomas, Alan Robert Denniss, Eddy Kizana, Naisana S. Asli, Munira Xaymardan, Michael P. Feneley, Robert M. Graham, Richard P. Harvey, James J. H. Chong
Journal: Science Translational Medicine (2020)

Recombinant human platelet-derived growth factor-AB improves cardiac function and survival after myocardial infarction in a porcine model.
Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer: a case-control study
Authors: Valerio De Stefano, Arianna Ghirardi, Arianna Masciulli, Alessandra Carobbio, Francesca Palandri, Nicola Vianelli, Elena Rossi, Silvia Betti, Ambra Di Veroli, Alessandra Iurlo, Daniele Cattaneo, Guido Finazzi, Massimiliano Bonifacio, Luigi Scaffidi, Andrea Patriarca, Elisa Rumi, Ilaria Carola Casetti, Clemency Stephenson, Paola Guglielmelli, Elena Maria Elli, Miroslava Palova, Davide Rapezzi, Daniel Erez, Montse Gomez, Kai Wille, Manuel Perez-Encinas, Francesca Lunghi, Anna Angona, Maria Laura Fox, Eloise Beggiato, Giulia Benevolo, Giuseppe Carli, Rossella Cacciola, Mary Frances McMullin, Alessia Tieghi, Valle Recasens, Susanne Isfort, Monia Marchetti, Martin Griesshammer, Alberto Alvarez-Larran, Alessandro Maria Vannucchi, Alessandro Rambaldi, Tiziano Barbui
Journal: Blood (2019)
Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells
Authors: Jie Zhang, Jiefang Huang, Yuting Gu, Mingxing Xue, Fengtao Qian, Bei Wang, Wanlin Yang, Hongshuang Yu, Qiwei Wang, Xin Guo, Xinyuan Ding, Jina Wang, Min Jin, Yanyun Zhang
Journal: Cellular and Molecular Immunology (2020)

Abstract Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells (MSCs). However, the biological function of chaperone-mediated autophagy (CMA) in MSCs remains elusive. Here, we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2 (LAMP-2A) in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation, and as expected, LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation. This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10 (CXCL10), which recruits inflammatory cells, especially T cells, to MSCs, and inducible nitric oxide synthase (iNOS), which leads to the subsequent inhibition of T cell proliferation via nitric oxide (NO). Mechanistically, CMA inhibition dramatically promoted IFN-γ plus TNF-α-induced activation of NF-κB and STAT1, leading to the enhanced expression of CXCL10 and iNOS in MSCs. Furthermore, we found that IFN-γ plus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs. More interestingly, CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury. Taken together, our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines and highlighted a previously unknown function of CMA.
Psychosocial Stressors and Telomere Length: A Current Review of the Science
Authors: Kelly E. Rentscher, Judith E. Carroll, Colter Mitchell
Journal: Annual Review of Public Health (2020)

A growing literature suggests that exposure to adverse social conditions may accelerate biological aging, offering one mechanism through which adversity may increase risk for age-related disease. As one of the most extensively studied biological markers of aging, telomere length (TL) provides a valuable tool to understand potential influences of social adversity on the aging process. Indeed, a sizeable literature now links a wide range of stressors to TL across the life span. The aim of this article is to review and evaluate this extant literature with a focus on studies that investigate psychosocial stress exposures and experiences in early life and adulthood. We conclude by outlining potential biological and behavioral mechanisms through which psychosocial stress may influence TL, and we discuss directions for future research in this area.