tbuckley/cabot-search huggingface dataset:
A novel C19MC amplified cell line links Lin28/let-7 to mTOR signaling in embryonal tumor with multilayered rosettes
Authors: Tara Spence, Christian Perotti, Patrick Sin-Chan, Daniel Picard, Wei Wu, Anjali Singh, Colleen Anderson, Michael D. Blough, J. Gregory Cairncross, Lucie Lafay-Cousin, Douglas Strother, Cynthia Hawkins, Aru Narendran, Annie Huang, Jennifer A. Chan
Journal: Neuro-Oncology (2013)

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive central nervous system primitive neuroectodermal tumor (CNS-PNET) variant. ETMRs have distinctive histology, amplification of the chromosome 19 microRNA cluster (C19MC) at chr19q13.41-42, expression of the RNA binding protein Lin28, and dismal prognosis. Functional and therapeutic studies of ETMR have been limited by a lack of model systems.We have established a first cell line, BT183, from a case of ETMR and characterized its molecular and cellular features. LIN28 knockdown was performed in BT183 to examine the potential role of Lin28 in regulating signaling pathway gene expression in ETMR. Cell line findings were corroborated with immunohistochemical studies in ETMR tissues. A drug screen of 73 compounds was performed to identify potential therapeutic targets.The BT183 line maintains C19MC amplification, expresses C19MC-encoded microRNAs, and is tumor initiating. ETMRs, including BT183, have high LIN28 expression and low let-7 miRNA expression, and show evidence of mTOR pathway activation. LIN28 knockdown increases let-7 expression and decreases expression of IGF/PI3K/mTOR pathway components. Pharmacologic inhibition of the mTOR pathway reduces BT183 cell viability.BT183 retains key genetic and histologic features of ETMR. In ETMR, Lin28 is not only a diagnostic marker but also a regulator of genes involved in growth and metabolism. Our findings indicate that inhibitors of the IGF/PI3K/mTOR pathway may be promising novel therapies for these fatal embryonal tumors. As the first patient-derived cell line of these rare tumors, BT183 is an important, unique reagent for investigating ETMR biology and therapeutics.
Modern Surgery: General and Operative.
Authors: John Chalmers Da Costa
Journal: JAMA (1920)

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
Adiponectin protects against Toll-like receptor 4-mediated cardiac inflammation and injury
Authors: Alexander Jenke, Sabrina Wilk, Wolfgang Poller, Urs Eriksson, Alan Valaperti, Bernhard Hermann Rauch, Andrea Stroux, Peter Liu, Heinz-Peter Schultheiss, Carmen Scheibenbogen, Carsten Skurk
Journal: Cardiovascular Research (2013)

Adiponectin (APN) is an immunomodulatory and cardioprotective adipocytokine. Toll-like receptor (TLR) 4 mediates autoimmune reactions that cause myocarditis resulting in inflammation-induced cardiac injury. Here, we investigated whether APN inhibits inflammation and injury in autoimmune myocarditis by interfering with TLR4 signalling. APN overexpression in murine experimental autoimmune myocarditis (EAM) down-regulated cardiac expression of TLR4 and its downstream targets tumour necrosis factor (TNF)α, interleukin (IL)-6, IL-12, CC chemokine ligand (CCL)2, and intercellular adhesion molecule (ICAM)-1 resulting in reduced infiltration with cluster of differentiation (CD)3+, CD14+, and CD45+ immune cells as well as diminished myocardial apoptosis. Expression of TLR4 signalling pathway components was unchanged in hearts and spleens of APN-knockout (APN-KO) mice. In vitro APN had no effect on TLR4 expression in cardiac and immune cells but induced dissociation of APN receptors from the activated TLR4/CD14 signalling complex. APN inhibited the expression of a TLR4-mediated inflammatory phenotype induced by exogenous and endogenous TLR4 ligands as assessed by attenuated nuclear factor (NF)-κB activation and reduced expression of TNFα, IL-6, CCL2, and ICAM-1. Accordingly, following TLR4 ligation, splenocytes from APN-KO mice showed enhanced expression of TNFα, IL-6, IL-12, CCL2, and ICAM-1, whereas dendritic cells (DCs) from APN-KO mice demonstrated increased activation and T-cell priming capacity. Moreover, APN diminished TLR4-mediated splenocyte migration towards cardiac cells as well as cardiomyocyte apoptosis after co-cultivation with splenocytes. Mechanistically, APN inhibited TLR4 signalling through cyclooxygenase (COX)-2, protein kinase A (PKA), and meiosis-specific serine/threonine kinase (MEK)1. Our observations indicate that APN protects against inflammation and injury in autoimmune myocarditis by diminishing TLR4 signalling thereby attenuating inflammatory activation and interaction of cardiac and immune cells.
Soy diet worsens heart disease in mice
Authors: Brian L. Stauffer, John P. Konhilas, Elizabeth D. Luczak, Leslie A. Leinwand
Journal: Journal of Clinical Investigation (2005)

We report that dietary modification from a soy-based diet to a casein-based diet radically improves disease indicators and cardiac function in a transgenic mouse model of hypertrophic cardiomyopathy. On a soy diet, males with a mutation in the alpha-myosin heavy chain gene progress to dilation and heart failure. However, males fed a casein diet no longer deteriorate to severe, dilated cardiomyopathy. Remarkably, their LV size and contractile function are preserved. Further, this diet prevents a number of pathologic indicators in males, including fibrosis, induction of beta-myosin heavy chain, inactivation of glycogen synthase kinase 3beta (GSK3beta), and caspase-3 activation.
Diaphragmatic Fatigue and High-intensity Exercise in Patients with Chronic Obstructive Pulmonary Disease
Authors: M. JEFFERY MADOR, THOMAS J. KUFEL, LILIBETH A. PINEDA, GYANENDRA K. SHARMA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Patients with chronic obstructive pulmonary disease (COPD) are at a mechanical disadvantage and should be predisposed to the development of diaphragmatic fatigue when the ventilatory system is stressed by exercise. The purpose of this study was to determine whether patients with moderately severe COPD develop contractile fatigue of the diaphragm after cycle exercise to the limits of tolerance. Twelve male patients with COPD, age 61.4 ± 3.0 yr, participated. Their forced expiratory volume in 1 s (FEV1) was 1.79 ± 0.14 L, 49.6 ± 3.4% of predicted. Patients cycled at 60–70% of their predetermined maximal work capacity until they had to stop because of intolerable symptoms. Twitch transdiaphragmatic pressure (Pdi,tw) was measured during cervical magnetic stimulation before and 10, 30, and 60 min after exercise. A persistent fall in Pdi,tw postexercise of ⩾ 10% was considered potentially indicative of contractile fatigue of the diaphragm. Patients cycled for 10.2 ± 2.0 min at a workload of 59.9 ± 4.3 W. Patients exercised maximally relative to their capacity reaching a peak oxygen consumption (V˙ o 2) of 108.1 ± 2.8% of the peak V˙ o 2 obtained during a preliminary maximal incremental exercise test. Pdi,tw was not significantly different from baseline at any time postexercise. Pdi,tw was 19.9 ± 1.6 cm H2O at baseline, 19.6 ± 2.0 cm H2O at 10 min postexercise, 18.6 ± 2.0 cm H2O at 30 min postexercise, and 19.5 ± 1.7 cm H2O at 60 min postexercise. In the individual patients, two of the patients had a persistent ⩾ 10% fall in Pdi,tw postexercise, potentially indicative of contractile fatigue of the diaphragm. In conclusion, the majority of patients with moderately severe COPD do not develop contractile fatigue of the diaphragm after high-intensity constant workload cycle exercise to the limits of tolerance. Mador MJ, Kufel TJ, Pineda LA, Sharma GK. Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive pulmonary disease.
Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
Authors: Georg Lenz, Inga Nagel, Reiner Siebert, Anna V. Roschke, Warren Sanger, George W. Wright, Sandeep S. Dave, Bruce Tan, Hong Zhao, Andreas Rosenwald, Hans Konrad Muller-Hermelink, Randy D. Gascoyne, Elias Campo, Elaine S. Jaffe, Erlend B. Smeland, Richard I. Fisher, W. Michael Kuehl, Wing C. Chan, Louis M. Staudt
Journal: The Journal of Experimental Medicine (2007)

To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell–like (ABC), germinal center B cell–like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch μ (Sμ) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sγ and other illegitimate switch recombinations. Sequence analysis revealed ongoing Sμ deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase–dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Sμ in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB.
Molecular characterization of the human macrophage mannose receptor: demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells.
Authors: R A Ezekowitz, K Sastry, P Bailly, A Warner
Journal: The Journal of Experimental Medicine (1990)

The macrophage mannose receptor is an integral membrane protein expressed on the surface of tissue macrophages. After ligation of mannose-rich glycoconjugates or pathogens, the receptor mediates endocytosis and phagocytosis of the bound ligands by macrophages. The cDNA-derived primary structure of the mannose receptor predicts a cysteine-rich NH2-terminal domain, followed by a fibronectin type II region. The remainder of the ectodomain is comprised of eight carbohydrate recognition-like domains, followed by a transmembrane region, and a cytoplasmic tail. Transfection of the mannose receptor cDNA into Cos-I cells is necessary for receptor-mediated endocytosis of mannose-rich glycoconjugate as well as phagocytosis of yeasts. Deletion of the cytoplasmic tail results in a mutant receptor that is able to bind but not ingest the ligated pathogens, suggesting that the signal for phagocytosis is contained in the cytoplasmic tail.
Fetal antigens on the surface of human lymphoid cells.
Authors: A K Sullivan, L M Jerry, G Rowden, M G Lewis, R Pitzele, T Law, L S Adams, H Le Thi, M Shea
Journal: The Journal of Experimental Medicine (1976)

Human B-lymphoblastoid cells established in long-term culture from healthy adults carry surface components that are normally found in human fetal tissues at about 10 wk of age. These antigens are strongly expressed on neoplastic B lymphocytes but not on thymocytes or a cultured T-cell line. They are carried by a small subpopulation of normal adult peripheral blood lymphocytes as well.
The ‘Senshu’ method often used to detect citrullinated proteins does not discriminate between citrullination and carbamylation
Authors: J Shi, G M C Janssen, P A van Veelen, A Cerami, T WJ Huizinga, R E Toes, L A Trouw
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Anticitrullinated protein antibodies (ACPA) play an important role in the diagnosis and prognosis of rheumatoid arthritis (RA). ACPA have been implicated in disease pathogenesis partially based on the argument that citrullinated proteins are present in the joint. The ‘Senshu’-method is one of the most frequently used methods to detect citrullinated proteins. Recently, the authors observed the presence of antibodies against carbamylated proteins (anti-CarP) and the authors wished to address the question whether the ‘Senshu’-method could discriminate between citrullinated and carbamylated proteins since citrulline and homocitrulline have a high degree of homology. <h3>Materials and methods</h3> The authors analysed the reactivity of the ‘Senshu’-method on westernblots targeting citrullinated, carbamylated or non-modified fetal calf serum (FCS) and fibrinogen (Fib). As control, the authors used patients9 sera to stain the same proteins with or without specific inhibition to verify whether human autoantibodies are able to distinguish the two modifications. <h3>Results</h3> The ‘Senshu’-method does not reveal staining on non-modified FCS or Fib but strongly stains both the citrullinated and the carbamylated forms of FCS and Fib. Using selected patient sera the authors demonstrate that an anti-CarP Fib single-positive serum only binds to the carbamylated Fib and an anti-Cit-Fib single-positive serum only to the citrullinated Fib. An anti-Cit-Fib and anti-CarP-Fib double positive serum could be specifically inhibited by Cit-Fib or Carb-Fib. These data show that in contrast to the ‘Senshu’-method, human autoantibodies can discriminate between citrullinated and carbamylated proteins. <h3>Conclusions</h3> In conclusion, the ‘Senshu’-method, the method most frequently used to detect citrullinated antigens is not specific for citrullination as it also identifies carbamylated proteins. In light of the recently identified anti-CarP antibodies, the extent and nature of citrullination and carbamylation in the joint should be re-evaluated.
Empirical Validation of Primary Negative Symptoms: Independence From Effects of Medication and Psychosis
Authors: Mary E. Kelley, Daniel P. van Kammen, Daniel N. Allen
Journal: American Journal of Psychiatry (1999)

Recent studies of negative symptoms in schizophrenia-specifically, those involving the deficit syndrome-have focused on uncovering the symptoms that are primary to the disease rather than secondary to the psychotic process. One of the foremost concerns in this effort is establishing whether the negative symptoms observed are the result of medication effects.This study used negative symptom ratings obtained in a drug withdrawal paradigm to compare symptom profiles in the same schizophrenic patients when they were on and off antipsychotic drug treatment. The study group consisted of 93 physically healthy male patients with DSM-III-R-defined schizophrenia. Principal components analysis was performed on negative symptom data obtained separately during haloperidol treatment and again when the patients were drug free to determine whether there were meaningful factor scores that were consistent across medication conditions. Drug withdrawal effects on negative symptom factors were then tested for associations with secondary sources of variance including extrapyramidal side effects, anxiety/depression, and psychosis.Two factors, termed affective flattening and diminished motivation, exhibited similar loadings when the patients were both on and off medication. Changes in motivation were associated with changes in anxiety/depression and psychosis, while changes in affective flattening were associated with changes in extrapyramidal side effects.The documented secondary sources of negative symptoms are related to different and distinct aspects of negative symptoms; this finding will aid in the identification of primary negative symptoms.
The monophasic action potential upstroke: a means of characterizing local conduction.
Authors: J H Levine, E N Moore, A H Kadish, T Guarnieri, J F Spear
Journal: Circulation (1986)

The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.
RIP-seq analysis of eukaryotic Sm proteins identifies three major categories of Sm-containing ribonucleoproteins
Authors: Zhipeng Lu, Xiaojun Guan, Casey A Schmidt, A Gregory Matera
Journal: Genome biology (2014)

Abstract Background Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. Results We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. Conclusions This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism.
Progressive Exercise for Anabolism in Kidney Disease (PEAK)
Authors: Bobby Cheema, Haifa Abas, Benjamin Smith, Anthony O'Sullivan, Maria Chan, Aditi Patwardhan, John Kelly, Adrian Gillin, Glen Pang, Brad Lloyd, Maria Fiatarone Singh
Journal: Journal of the American Society of Nephrology (2007)

Skeletal muscle wasting is common and insidious in patients who receive maintenance hemodialysis treatment for the management of ESRD. The objective of this study was to determine whether 12 wk of high-intensity, progressive resistance training (PRT) administered during routine hemodialysis treatment could improve skeletal muscle quantity and quality versus usual care. Forty-nine patients (62.6 ± 14.2 yr; 0.3 to 16.7 yr on dialysis) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital (Sydney, Australia). Patients were randomized to PRT + usual care (n = 24) or usual care control only (n = 25). The PRT group performed two sets of 10 exercises at a high intensity (15 to 17/20 on the Borg Scale) using free weights, three times per week for 12 wk during routine hemodialysis treatment. Primary outcomes included thigh muscle quantity (cross-sectional area [CSA]) and quality (intramuscular lipid content via attenuation) evaluated by computed tomography scan. Secondary outcomes included muscle strength, exercise capacity, body circumference measures, proinflammatory cytokine C-reactive protein, and quality of life. There was no statistically significant difference in muscle CSA change between groups. However, there were statistically significant improvements in muscle attenuation, muscle strength, mid-thigh and mid-arm circumference, body weight, and C-reactive protein in the PRT group relative to the nonexercising control group. These findings suggest that patients with ESRD can improve skeletal muscle quality and derive other health-related adaptations solely by engaging in a 12-wk high-intensity PRT regimen during routine hemodialysis treatment sessions. Longer training durations or more sensitive analysis techniques may be required to document alterations in muscle CSA.
Global implementation of genomic medicine: We are not alone
Authors: Teri A. Manolio, Marc Abramowicz, Fahd Al-Mulla, Warwick Anderson, Rudi Balling, Adam C. Berger, Steven Bleyl, Aravinda Chakravarti, Wasun Chantratita, Rex L. Chisholm, Vajira H. W. Dissanayake, Michael Dunn, Victor J. Dzau, Bok-Ghee Han, Tim Hubbard, Anne Kolbe, Bruce Korf, Michiaki Kubo, Paul Lasko, Erkki Leego, Surakameth Mahasirimongkol, Partha P. Majumdar, Gert Matthijs, Howard L. McLeod, Andres Metspalu, Pierre Meulien, Satoru Miyano, Yaakov Naparstek, P. Pearl O’Rourke, George P. Patrinos, Heidi L. Rehm, Mary V. Relling, Gad Rennert, Laura Lyman Rodriguez, Dan M. Roden, Alan R. Shuldiner, Sukdeb Sinha, Patrick Tan, Mats Ulfendahl, Robyn Ward, Marc S. Williams, John E. L. Wong, Eric D. Green, Geoffrey S. Ginsburg
Journal: Science Translational Medicine (2015)

Human-genomics programs work together worldwide to speed the translation of genomic medicine to the clinic.