tbuckley/cabot-search huggingface dataset:
Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL
Authors: Philippe Rousselot, Marie Magdelaine Coudé, Nicola Gokbuget, Carlo Gambacorti Passerini, Sandrine Hayette, Jean-Michel Cayuela, Françoise Huguet, Thibaut Leguay, Patrice Chevallier, Celia Salanoubat, Caroline Bonmati, Magda Alexis, Mathilde Hunault, Sylvie Glaisner, Philippe Agape, Christian Berthou, Eric Jourdan, José Fernandes, Laurent Sutton, Anne Banos, Oumedaly Reman, Bruno Lioure, Xavier Thomas, Norbert Ifrah, Marina Lafage-Pochitaloff, Anne Bornand, Laure Morisset, Valérie Robin, Heike Pfeifer, Andre Delannoy, Josep Ribera, Renato Bassan, Marc Delord, Dieter Hoelzer, Herve Dombret, Oliver G. Ottmann
Journal: Blood (2016)
Heat shock factor-1 knockout enhances cholesterol 7α-hydroxylase (CYP7A1) and multidrug transporter (MDR1) gene expressions to attenuate atherosclerosis
Authors: Karthikeyan Krishnamurthy, Shannon Glaser, Gianfranco D. Alpini, Arturo J. Cardounel, Zhenguo Liu, Govindasamy Ilangovan
Journal: Cardiovascular Research (2016)

Stress response, in terms of activation of stress factors, is known to cause obesity and coronary heart disease such as atherosclerosis in human. However, the underlying mechanism(s) of these pathways are not known. Here, we investigated the effect of heat shock factor-1 (HSF-1) on atherosclerosis. HSF-1 and low-density lipoprotein receptor (LDLr) double knockout (HSF-1−/−/LDLr−/−) and LDLr knockout (LDLr−/−) mice were fed with atherogenic western diet (WD) for 12 weeks. WD-induced weight gain and atherosclerotic lesion in aortic arch and carotid regions were reduced in HSF-1−/−/LDLr−/− mice, compared with LDLr−/− mice. Also, repression of PPAR-γ2 and AMPKα expression in adipose tissue, low hepatic steatosis, and lessened plasma adiponectins and lipoproteins were observed. In HSF-1−/−/LDLr−/− liver, higher cholesterol 7α-hydroxylase (CYP7A1) and multidrug transporter [MDR1/P-glycoprotein (P-gp)] gene expressions were observed, consistent with higher bile acid transport and larger hepatic bile ducts. Luciferase reporter gene assays with wild-type CYP7A1 and MDR1 promoters showed lesser luminescence than with mutant promoters (HSF-1 binding site deleted), indicating that HSF-1 binding is repressive of CYP7A1 and MDR1 gene expressions. HSF-1 ablation not only eliminates heat shock response, but it also transcriptionally up-regulates CYP7A1 and MDR1/P-gp axis in WD-diet fed HSF-1−/−/LDLr−/− mice to reduce atherosclerosis.
Composition of TWIST1 dimers regulates fibroblast activation and tissue fibrosis
Authors: Katrin Palumbo-Zerr, Alina Soare, Pawel Zerr, Andrea Liebl, Rossella Mancuso, Michal Tomcik, Barbora Sumova, Clara Dees, Chih-Wei Chen, Thomas Wohlfahrt, Tatjana Mallano, Alfiya Distler, Andreas Ramming, Kolja Gelse, Carina Mihai, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2016)

TWIST1 is a member of the class B of basic helix-loop-helix transcription factors that regulates cell lineage determination and differentiation and has been implicated in epithelial-to-mesenchymal transition. Here, we aimed to investigate the role of TWIST1 for the activation of resident fibroblasts in systemic sclerosis (SSc).The expression of Twist1 in fibroblasts was modulated by forced overexpression or siRNA-mediated knockdown. Interaction of Twist1, E12 and inhibitor Of differentiation (Id) was analysed by co-immunoprecipitation. The role of Twist1 in vivo was evaluated using inducible, conditional knockout mice with either ubiquitous or fibroblast-specific depletion of Twist1. Mice were either challenged with bleomycin or overexpressing a constitutively active transforming growth factor (TGF)β receptor I.The expression of TWIST1 was increased in fibroblasts in fibrotic human and murine skin in a TGFβ/SMAD3-dependent manner. TWIST1 in turn enhanced TGFβ-induced fibroblast activation in a p38-dependent manner. The stimulatory effects of TWIST1 on resident fibroblasts were mediated by TWIST1 homodimers. TGFβ promotes the formation of TWIST1 homodimers by upregulation of TWIST1 and by induction of inhibitor of DNA-binding proteins, which have high affinity for E12/E47 and compete against TWIST1 for E12/E47 binding. Mice with selective depletion of Twist1 in fibroblasts are protected from experimental skin fibrosis in different murine models to a comparable degree as mice with ubiquitous depletion of Twist1.Our data identify TWIST1 as a central pro-fibrotic factor in SSc, which facilitates fibroblast activation by amplifying TGFβ signalling. Targeting of TWIST1 may thus be a novel approach to normalise aberrant TGFβ signalling in SSc.
<i>Notes from the Field</i>: Primary Amebic Meningoencephalitis Associated with Exposure to Swimming Pool Water Supplied by an Overland Pipe — Inyo County, California, 2015
Authors: Richard O. Johnson, Jennifer R. Cope, Marvin Moskowitz, Amy Kahler, Vincent Hill, Kaleigh Behrendt, Louis Molina, Kathleen E. Fullerton, Michael J. Beach
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On June 17, 2015, a previously healthy woman aged 21 years went to an emergency department after onset of headache, nausea, and vomiting during the preceding 24 hours. Upon evaluation, she was vomiting profusely and had photophobia and nuchal rigidity. Analysis of cerebrospinal fluid was consistent with meningitis.* She was empirically treated for bacterial and viral meningoencephalitis. Her condition continued to decline, and she was transferred to a higher level of care in another facility on June 19, but died shortly thereafter. Cultures of cerebrospinal fluid and multiple blood specimens were negative, and tests for West Nile, herpes simplex, and influenza viruses were negative. No organisms were seen in the cerebrospinal fluid; however, real-time polymerase chain reaction testing by CDC was positive for Naegleria fowleri, a free-living thermophilic ameba found in warm freshwater that causes primary amebic meningoencephalitis, an almost universally fatal infection.
Insertion DNA Accelerates Meiotic Interchromosomal Recombination inArabidopsis thaliana
Authors: Xiao-Qin Sun, Ding-Hong Li, Jia-Yu Xue, Si-Hai Yang, Yan-Mei Zhang, Mi-Mi Li, Yue-Yu Hang
Journal: Molecular Biology and Evolution (2016)

Nucleotide insertions/deletions are ubiquitous in eukaryotic genomes, and the resulting hemizygous (unpaired) DNA has significant, heritable effects on adjacent DNA. However, little is known about the genetic behavior of insertion DNA. Here, we describe a binary transgenic system to study the behavior of insertion DNA during meiosis. Transgenic Arabidopsis lines were generated to carry two different defective reporter genes on nonhomologous chromosomes, designated as "recipient" and "donor" lines. Double hemizygous plants (harboring unpaired DNA) were produced by crossing between the recipient and the donor, and double homozygous lines (harboring paired DNA) via self-pollination. The transfer of the donor's unmutated sequence to the recipient generated a functional β-glucuronidase gene, which could be visualized by histochemical staining and corroborated by polymerase chain reaction amplification and sequencing. More than 673 million seedlings were screened, and the results showed that meiotic ectopic recombination in the hemizygous lines occurred at a frequency >6.49-fold higher than that in the homozygous lines. Gene conversion might have been exclusively or predominantly responsible for the gene correction events. The direct measurement of ectopic recombination events provided evidence that an insertion, in the absence of an allelic counterpart, could scan the entire genome for homologous counterparts with which to pair. Furthermore, the unpaired (hemizygous) architectures could accelerate ectopic recombination between itself and interchromosomal counterparts. We suggest that the ectopic recombination accelerated by hemizygous architectures may be a general mechanism for interchromosomal recombination through ubiquitously dispersed repeat sequences in plants, ultimately contributing to genetic renovation and eukaryotic evolution.
Clinical Concepts of Infectious Diseases.
Journal: Annals of Internal Medicine (1974)

This volume is an update and expanded sequel to the first edition, published in 1972.It tries to offer a "perspective of the approaches important for thinking about problems in infectious diseases and caring for patients".In keeping with this objective, this book is not a "cookbook" dealing with all the eventualities of the field of clinical infectious disease.The editors have devoted the first eight chapters to basic host defences, microbial virulence factors, and the interaction of the two that leads to clinically apparent disease.A new chapter on clinical epidemiology clarifies this approach to disease states for the nonepidemiologist.The ensuing six chapters deal with the signs and symptoms by which various infectious agents may be suspected clinically, including acute and prolonged fever, septic shock, and the dermatologic and hematologic manifestations of infection.A review of the many factors that influence the rate of recovery from infection raises useful points for evaluation of patients' response to therapy.Thirteen chapters detail selected problems in clinical infectious diseases, which include viral respiratory infections, infectious mononucleosis, acute and chronic pulmonary infections, urinary tract infections, hepatitis, meningitis and endocarditis.New to this volume are chapters
The 12;21 translocation involving TEL and deletion of the other TEL allele: two frequently associated alterations found in childhood acute lymphoblastic leukemia
Authors: S Raynaud, H Cave, M Baens, C Bastard, V Cacheux, J Grosgeorge, C Guidal-Giroux, C Guo, E Vilmer, P Marynen, B Grandchamp
Journal: Blood (1996)
Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction
Authors: Lin Zhao, Guangming Cheng, Runming Jin, Muhammad R. Afzal, Anweshan Samanta, Yu-Ting Xuan, Magdy Girgis, Harold K. Elias, Yanqing Zhu, Arash Davani, Yanjuan Yang, Xing Chen, Sheng Ye, Ou-Li Wang, Lei Chen, Jeryl Hauptman, Robert J. Vincent, Buddhadeb Dawn
Journal: Circulation Research (2016)

The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial.To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy and to elucidate the underlying molecular pathways.Wild-type and IL-6 knockout (IL-6(-/-)) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6(-/-) mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6(-/-) hearts after TAC. Transcriptional and protein assays of myocardial tissue identified Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 3 (STAT3) activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from wild-type and IL-6(-/-) mice exposed to prohypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together, these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling.Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension.
<i>Akkermansia Muciniphila</i> Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in <i>Apoe</i> <sup>−/−</sup> Mice
Authors: Jin Li, Shaoqiang Lin, Paul M. Vanhoutte, Connie W. Woo, Aimin Xu
Journal: Circulation (2016)

Background— Altered composition of the gut microbiota is involved in both the onset and progression of obesity and diabetes mellitus. However, the link between gut microbiota and obesity-related cardiovascular complications has not been explored. The present study was designed to investigate the role of Akkermansia muciniphila , a mucin-degrading bacterium with beneficial effects on metabolism, in the pathogenesis of atherosclerosis in apolipoprotein E–deficient ( Apoe −/− ) mice. Methods and Results— Apoe −/− mice on normal chow diet or a Western diet were treated with A muciniphila by daily oral gavage for 8 weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time polymerase chain reaction analysis demonstrated that the fecal abundance of A muciniphila was significantly reduced by Western diet. Replenishment with A muciniphila reversed Western diet–induced exacerbation of atherosclerotic lesion formation without affecting hypercholesterolemia. A muciniphila prevented Western diet–induced inflammation in both the circulation and local atherosclerotic lesion, as evidenced by reduced macrophage infiltration and expression of proinflammatory cytokines and chemokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia. A muciniphila –mediated reduction in circulating endotoxin level could be attributed to the induction of intestinal expression of the tight junction proteins (zona occuldens protein-1 and occludin), thereby reversing Western diet–induced increases in gut permeability. Long-term infusion of endotoxin to Apoe −/− mice reversed the protective effect of A muciniphila against atherosclerosis. Conclusion— A muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.
Clinical Utility of Feno in Preschool Children with Allergic Rhinitis
Authors: Keum Hee Hwang, Jisun Yoon, Yean Jung Choi, Eun Lee, Hyun-Ju Cho, Song I. Yang, Young Ho Kim, Young-Ho Ho Jung, Ju-Hee Seo, Ji-Won Kwon, So Yeon Lee, Bong-Seong Kim, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2016)
STUDIES ON HERPETIC INFECTION IN MICE
Authors: George Packer Berry, Howard B. Slavin
Journal: The Journal of Experimental Medicine (1943)

Passive immunity, naturally acquired from immune mothers or artificially induced through the administration of immune rabbit serum, conferred on suckling mice of the albino Swiss strain a high degree of resistance against herpetic infection following the intranasal instillation of the virus. Antibodies, which could be readily demonstrated in the blood of 2-week-old mice, were received by the offspring of immune mothers primarily by the mammary route. Naturally acquired immunity declined rapidly when suckling was interrupted. Herpes virus was not recovered from the fetuses of either immune or infected, non-immune mothers.
Abstract P120: Prevalence of Ventricular Premature Beats Decreases With Serum Magnesium in Adults with Type 2 Diabetes
Authors: Liana C Del Gobbo, Yiqing Song, Ronald J Elin, Eric Dewailly, Paul Poirier, Grace M Egeland
Journal: Circulation (2012)

Introduction: Ventricular premature beats (VPB) predict cardiovascular mortality among several adult populations. Controlled dietary magnesium (Mg) depletion studies demonstrated that diminished Mg intake and status induced VPB and other arrhythmias. Thus, we hypothesized that the prevalence of VPB is closely associated with serum Mg concentrations in a general adult population at high cardiovascular risk. Methods: Anthropometric, demographic and lifestyle characteristics were assessed in 750 Cree adults, &gt;18yrs, who participated in an age-stratified, cross-sectional health survey in Quebec, Canada. Holter electrocardiograms recorded heart rate variability and cardiac arrhythmias for two consecutive hours. Multivariate logistic regression was used to evaluate potential associations between serum Mg and VPB. Results: VPB prevalence in adults with hypomagnesaemia (serum Mg ≤ 0.70mmol/L) was over twice that of adults without hypomagnesaemia (50% vs. 21%, p =0.015); results were not materially altered when adults with cardiovascular disease history were excluded. All hypomagnesaemic adults with VPB had type 2 diabetes. Prevalence of VPB declined across the serum Mg concentration gradient in adults with type 2 diabetes only ( p &lt;0.001). In multivariate logistic regressions adjusted for age, sex, community, body mass index, smoking, physical activity, alcohol consumption, kidney disease, antihypertensive and cholesterol lowering drug use, and blood docosahexaenoic acid concentrations, the odds of VPB among diabetics with serum Mg &gt; 0.70 mmol/L was 0.24 (95%CI: 0.06-0.98; p =0.046). Conclusions: Prevalence of VPB significantly declined across the serum Mg concentration gradient in adults with type 2 diabetes, indicating that future interventions to increase levels of serum Mg among adults with type 2 diabetes may confer protection against cardiac arrhythmia.
Case 25-1974
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, David A. Rytand, Benjamin Castleman
Journal: New England Journal of Medicine (1974)

Presentation of Case*A 56-year-old man was admitted to the hospital because of peripheral edema.He was well until one year previously, when there was the onset of episodes of anterior chest pain that radiated down both arms. He went to another hospital, where an electrocardiogram (Fig. 1) was interpreted as showing complete heart block at a ventricular rate of 25, and he was admitted. Serial electrocardiograms showed changes believed consistent with acute inferior myocardial infarction. A transvenous pacemaker was inserted and was removed before discharge on the twenty-fourth hospital day. Three days later he returned to the hospital because . . .
Aggravation of Er Stress By Combination of Proteasome Inhibitors and Hiv Protease Inhibitors Results in Preferencial Killing of Triple-Negative Breast Cancer Cells in Vitro
Authors: J. Gibbons Marsico, T. Heger, M. Kraus, M. Joerger, C. Driessen, T. Cerny
Journal: Annals of Oncology (2014)
Coagulation parameters and major bleeding in critically ill patients with cirrhosis
Authors: Andreas Drolz, Thomas Horvatits, Kevin Roedl, Karoline Rutter, Katharina Staufer, Nikolaus Kneidinger, Ulrike Holzinger, Christian Zauner, Peter Schellongowski, Gottfried Heinz, Thomas Perkmann, Stefan Kluge, Michael Trauner, Valentin Fuhrmann
Journal: Hepatology (2016)

Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d-dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d-dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 10(9) /L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One-year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P < 0.05 between groups).Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (Hepatology 2016;64:556-568).
Frequency of L858R and D746-750 EGFR mutations in 411 Caucasian patients with non-small cell lung cancer measured by mutation-specific antibodies.
Authors: A. T. Dimou, K. N. Syrigos, S. Agarwal, L. Lozovatsky, V. Zolota, V. K. Anagnostou, D. Rimm
Journal: Journal of Clinical Oncology (2010)

1587 Background: Mutations in the tyrosine kinase (TK) domain of EGFR have been associated with clinical benefit from EGFR TK inhibitors. Traditionally, their detection is based on direct DNA sequencing and their frequency has been reported to be 8-10% in the Caucasian non-small cell lung cancer (NSCLC) population with 90% of these being the exon 21 L858R point mutation and exon 19 D746-750 deletion. Here, we assess the frequency of these two mutations with immunohistochemistry in two large NSCLC Caucasian cohorts. Methods: Cohorts were analyzed in a tissue microarray format including 145 cases from Yale Cancer Center and 266 cases from Sotiria General Hospital, Athens, and Patras Hospital, Rion, Greece. D746-750 and L858R mutation specific antibodies (Cell Signaling Technologies) were used and detection was measured with quantitative immunofluorescence (AQUA). Results: The Yale cohort included 71 adenocarcinoma (AC) and 30 squamous cell carcinoma (SCC) cases, 67 females and 78 males. One SCC was a L858R carrier and one large cell carcinoma specimen was found D746-750 positive, yielding a frequency of mutated EGFR of 1.37%. The Greek cohort included 104 AC and 132 SCC cases, 33 females and 218 males, 203 smokers and 21 never-smokers. Three mutations were detected (3/266, 1.12%), 1 D746-750 AC and 2 L858R SCCs. For the majority of cases in both cohorts, the staining pattern was either clearly positive or negative; rare cases with minimal expression above background by quantitative assessment proved negative for mutation by DNA sequencing for the Yale cohort. The positive cases all showed a homogeneous pattern throughout the spot. There were no cases that showed a few positive cells admixed with negative cells. Conclusions: Although these antibodies are estimated to detect only 90% of the mutated forms, the frequencies of EGFR mutations in these NSCLC Caucasian cohorts are much lower than previously reported. This immunohistochemistry-based test is easily applicable and could be valuable for screening large populations for EGFR mutation status. Cohorts Cases Females Adenocarcinoma EGFR mutations EGFR mutation rate Yale 145 67 (46%) 71 (49%) 2 1.37% Greek 266 33 (12%) 104 (39%) 3 1.12% No significant financial relationships to disclose.