tbuckley/cabot-search huggingface dataset:
Abstract 4565: Bet bromodomain inhibitors affects replication &amp; cell cycle progression
Authors: Somsundar Veppil Muralidharan, Joydeep Bhadury, Lydia Green, Lisa M. Nilsson, Kevin G. Mclure, Jonas A. Nilsson
Journal: Cancer Research (2014)

Abstract Myc family of transcription factors contribute to pathogenesis in most cancers and their expression projects a poor prognosis. Genetic and pharmacological inhibition of Myc and several Myc targets leads to apoptosis and tumor regression. Recently, inhibitors of BET Bromodomain proteins (BETi) were shown to have anti-tumor properties and this has been attributed to Myc down-regulation. In this study, we show that two structurally distinct BETi affects replication and cell cycle progression at low concentrations where the transcriptome remains largely unaltered. At these concentrations, S-phase progression is hindered, as assessed by thymidine incorporation and flow cytometry analyses. However, in a cell-free system replication is not impaired suggesting that BETi-mediated block of replication is linked to effects on chromatin. Furthermore, at higher concentration of BET, S-phase entry of cells is completely abrogated. Ectopic expression of Myc fails to rescue these phenotypes, suggesting a novel function of BET bromodomain proteins in replication and cell cycle regulation. Citation Format: Somsundar Veppil Muralidharan, Joydeep Bhadury, Lydia Green, Lisa M. Nilsson, Kevin G. Mclure, Jonas A. Nilsson. Bet bromodomain inhibitors affects replication &amp; cell cycle progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4565. doi:10.1158/1538-7445.AM2014-4565
Abstract 443: Synergistic inhibition of HER2 positive breast cancer by triptolide and lapatinib
Authors: Paweena Chalugun, Joong Sup Shim, Preethi C. Korangath, Saraswati Sukumar, Jun O. Liu
Journal: Cancer Research (2014)

Abstract HER2-positive breast cancers are poorly differentiated and have a higher potential for metastasis. Although trastuzumab and lapatinib have been used for the treatment of HER2-positive breast cancer, resistance to both drugs has dampened the long-term benefit of those drugs. As cancer has multiple genetic aberrations and can readily develop resistance to individual drugs with specific targets, we employed synergistic drug combination as a strategy to overcome drug resistance and to enhance the efficacy of existing drugs. From a screen of the Johns Hopkins Drug Library, we identified triptolide as a strong synergistic hit with lapatinib in HCC1954, a drug-resistant HER2-positive breast cancer cell line. The combination of lapatinib and nontoxic doses of triptolide synergistically inhibited the HER2 signaling pathway. We found that lapatinib increased both mRNA expression and the half-life of HER2 protein, whereas triptolide countered the effects of lapatinib by downregulating the expression of HER2, leading to synergistic inhibition of the HER2 signaling pathway. The synergy in cell proliferation was observed in all HER2-positive breast cancer cell lines regardless of drug resistance status, but was absent in HER2-negative ones. In mouse xenograft models, the combination of lapatinib and triptolide at their minimum effective doses almost completely inhibited the growth of the drug-resistant HER2-positive breast cancer cells. Together, these findings suggest that the combination of triptolide and lapatinib could be a promising new therapeutic regimen for drug-resistant HER2-positive breast cancer. Citation Format: Paweena Chalugun, Joong Sup Shim, Preethi C. Korangath, Saraswati Sukumar, Jun O. Liu. Synergistic inhibition of HER2 positive breast cancer by triptolide and lapatinib. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 443. doi:10.1158/1538-7445.AM2014-443
Oral Anticoagulant and Antiplatelet Therapy and Peripheral Arterial Disease
Authors: Sonia Anand, Salim Yusuf, Changchun Xie, Janice Pogue, John Eikelboom, Andrzej Budaj, Bruce Sussex, Lisheng Liu, Randy Guzman, Claudio Cina, Richard Crowell, Matyas Keltai, Gilbert Gosselin
Journal: New England Journal of Medicine (2007)

Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear.We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normalized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary outcome was myocardial infarction, stroke, or death from cardiovascular causes; the second coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardiovascular causes.A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% confidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001).In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding. (ClinicalTrials.gov number, NCT00125671 [ClinicalTrials.gov].).
Abstract 5470: Cardiomyocyte-specific Overexpression of Nox4 Attenuates Adverse Cardiac Remodeling After Myocardial Infarction
Authors: Min Zhang, Yee H Looi, Alison C Brewer, Ajay M Shah
Journal: Circulation (2009)

Background. Reactive oxygen species (ROS) production is implicated in the development of cardiac remodeling after myocardial infarction (MI). NADPH oxidases are major sources of cardiovascular ROS, with cardiomyocytes expressing both Nox2 and Nox4 isoforms. We previously showed that Nox2 contributes significantly to the processes underlying adverse cardiac remodeling and contractile dysfunction post-MI, but the effect of Nox4 remains unclear. The aim of this study was to investigate the role of Nox4 in cardiac remodelling after MI. Methods and Results. We generated transgenic mice (TG) with cardiomyocyte-specific overexpression of Nox4, expressing the mouse full-length Nox4 cDNA under control of the α -MHC promoter. TG were backcrossed onto a C57BL6/J background and wild-type littermates (WT) used as controls. Nox4 TG mice were grossly similar to WT in terms of body weight, growth, activity, fertility and basal cardiac function. TG displayed heart-specific expression of the Nox4 transgene, had significantly higher Nox4 protein expression, over 60% higher heart NADPH oxidase activity and 42% increased hydrogen peroxide production (all P&lt;0.05). Compared with WT, p22 phox protein expression was increased by 2.4-fold, which may be related to an increased protein stability. There was no change in protein expression level of Nox2 or eNOS. MI was achieved by permanent left coronary ligation for 4 weeks. Compared with WT/MI, TG/MI groups displayed significantly high survival rate (72 % vs 95%) and less hypertrophy at 4 weeks post MI in terms of heart/body weight ratio (6.95±0.16 vs 6.44±0.14, p&lt;0.01), although the infarct size was similar (38.3±2.0 vs 39.9±2.8%). TG mice also exhibited less apoptosis and interstitial cardiac fibrosis (0.52±0.03 vs 0.65±0.05%, p&lt;0.05), and lower increases in expression of fibronectin and procollagen III mRNA. Both echocardiography and cardiac catheterization demonstrated less left ventricular cavity dilatation and a preservation of cardiac function in TG than WT mice. Conclusions. In contrast to Nox2, which contributes to cardiac dilation, contractile dysfunction and fibrosis, cardiomyocyte Nox4 was found to exert protective effects against adverse remodelling post-MI.
Alternative (complementary) medicine: a cuckoo in the nest of empiricist reed warblers Commentary: A warning to complementary medicine practitioners: get empirical or else
Authors: L. Leibovici, R B. Haynes
Journal: BMJ (1999)

# Alternative (complementary) medicine: a cuckoo in the nest of empiricist reed warblers {#article-title-2}

Proponents of alternative medicine can be compared to cuckoo chicks in that they are using false signals to gain nourishment from a legitimate scientific and medical frame. Rather like the reed warbler parent,1 the guardians of this frame are not equipped to recognise loud signals as false.

Warbler chicks increase both their gapes and calling rates as they grow hungry. When the parent is a reed warbler and the nestling is a cuckoo chick, the cuckoo produces a loud begging signal. The sound not only matches the total calling rate of four warbler nestlings but rises so fast as the cuckoo grows that it soon sounds like eight little warblers. This signal fits overwhelmingly with what the warblers want to hear, if only imperfectly with what they expect to see. Still, it is so clamorous that the warbler parents ignore the missing visual cues and feed the cuckoo chick—to the detriment (and ultimately death) of their own offspring. 1 2

#### Summary points

Empiricists are not equipped to recognise the loud signals of alternative medicine as false

A deep model of the physical world is essential for choosing hypotheses to be tested and for learning from failures

Practices of alternative medicine that do not fit even at the far fringes of the model should not be tested in humans

Our decisions on which practices to test and which to adopt should be based on three things: empirical evidence; our deep model of physical world; and our commitment to the wellbeing of our patients

Two conceptual frames are relevant to the present discussion. One (the empirical-social construct) is ill equipped to deal with the clamour of alternative medicine. Like the warbler, it ignores the absence of vital cues because of the loud signal. The other frame (the “deep model” empirical one) has deficiencies …
Lesson of the week: hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum
Authors: G. J de Klerk, M. G Nieuwenhuis, J. J Beutler
Journal: BMJ (1997)

Prolonged ingestion of substances containing glycyrrhizinic acid, such as liquorice, is a well known cause of exogenously induced hypermineralocorticoidism. This is characterised by sodium retention, hypokalaemia, hypertension, metabolic alkalosis, and suppression of the renin-aldosterone system.1 We describe two cases showing that hypokalaemia induced by glycyrrhizinic acid should be considered in patients with hypertension or oedema even if they have not eaten sweets that obviously contain liquorice.

### Case 1

A 21 year old woman presented to her general practitioner with a headache. She ate about 100 g of liquorice daily. She used an oral contraceptive. On earlier occasions her blood pressure had been 110/70 mm Hg. Clinical examination was unremarkable except that her blood pressure was 190/120 mm Hg. She was advised to stop eating liquorice and taking the oral contraceptive. Despite these measures, her blood pressure remained raised even after treatment with a combination of atenolol, lisinopril, hydrochlorothiazide, and amlodipine.

She was referred to our outpatient clinic. Two weeks after the drug treatment had been discontinued her blood pressure was 180/110 mm Hg and plasma concentrations of sodium, potassium, and bicarbonate were 143 mmol/1 (normal 136-146 mmol/1), 2.6 mmol/1 (3.8-5.0), and 35.9 mmol/1 (23-29), respectively. Plasma renin activity was 0.096 ng/(lxs) (normal 0.96-3.61), and plasma aldosterone concentration was 160 pmol/1 (normal …
Abstract 10838: Tyrosine Phosphorylation of Syndecan-1, a Receptor for Remnant Lipoproteins, Triggers its Binding to Cortactin, an Essential Intracellular Mediator of a Novel Endocytic Pathway
Authors: Keyang Chen, Kevin Jon Williams
Journal: Circulation (2011)

BACKGROUND We previously reported that the syndecan-1 heparan sulfate proteoglycan directly mediates cellular uptake of model remnant lipoproteins through a novel endocytic pathway distinct from co...
V2 Carcinoma in the rabbit eye.
Authors: David R. Ginder, William F. Friedewald
Journal: Cancer Research (1952)

Summary  1.V2 carcinoma was successfully grown and carried through seven consecutive passages in the anterior eye chamber of the domestic rabbit. Rapid confluent growth in the iris and ciliary body necessitated the harvest 9–12 days after inoculation to prevent rupture of the cornea.  2.V2 carcinoma from the eyes of domestic rabbits was utilized to initiate six consecutive passages of V2 tumor in the anterior eye chamber of the cottontail rabbit. Rapid growth occurred as single or multiple isolated tumors on the iris and ciliary body in 75 per cent of the inoculated eyes.  3.Confirmatory evidence was obtained that the V2 carcinoma no longer carries a masked papilloma antigen. No papilloma virus nor any papilloma complement-fixing antigen was detected in the eye fluids or the eye tissues of domestic or cottontail rabbits with V2 eye tumors. Complement-fixing antibodies against the papilloma virus were not demonstrable in the sera of rabbits with V2 eye or V2 intramuscular tumors.
Management of Soft Tissue and Bone Sarcomas.
Authors: A. T. van Oosterom, J. A. M. van Unnik
Journal: Annals of Internal Medicine (1986)

This book contains 32 papers. Some of the titles are: Adjuvant Treatment for Osteosarcoma of the Limbs; Trial 20781 of the SIOP and the EORTC Radiotherapy/Chemotherapy; Application of Magnetic Resonance Imaging (MRI) in Diagnosis and Follow-up During Treatment of Bone Tumors; Radiological Assessment of Local Involvement in Bone Sarcomas; and Prevention of Lung Metastases by Irradiation Alone or Combined with Chemotherapy in an Animal Model.
Src-Dependence and Pertussis-Toxin Sensitivity of Urokinase Receptor-Dependent Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells
Authors: Bernard Degryse, Massimo Resnati, Shafaat A. Rabbani, Antonello Villa, Francesca Fazioli, Francesco Blasi
Journal: Blood (1999)
A Handbook on Drug and Alcohol Abuse. The Biomedical Aspects.
Authors: Gail Winger, James H Woods, Frederick G Hofmann
Journal: Annals of Internal Medicine (1975)

This comprehensive text on the pharmacological, medical, and legal aspects of drug abuse has been thoroughly updated for the Fourth Edition, and a new chapter on club drugs added. The chapter on medical effects was completely rewritten to focus on infections that develop in i.v. drug abusers, and information on the international regulation of drug use was added to the chapter on drug abuse and the law. The book is written at a level appropriate for upper level undergraduate students, graduate or medical students, and drug counselors. 

All major drugs of abuse are covered: tobacco, opioids, central stimulants (including cocaine, amphetamine, and caffeine), alcohol and other sedatives, marijuana, club drugs (MDMA, GHB, and ketamine), hallucinogens, and volatile solvents. For each type the authors discuss history and culture, the characteristic patterns of use, subjective and physiological effects, mechanisms of pharmacological action, and toxic effects. Epidemiological aspects are discussed as well as pharmacological treatment possibilities where applicable.
Detection of hepatitis C viral RNA in sporadic acute non-A, non-B hepatitis by polymerase chain reaction
Authors: Naoya Sakamoto, Chifumi Sato, Hideaki Haritani, Shinya Maekawa, Masayuki Kurosaki, Nobuyuki Enomoto, Yuji Hoshino, Jun-ichi Tazawa, Masanobu Nishimura, Fumiaki Marumo
Journal: Journal of Hepatology (1993)
Modern Principles of Athletic Training.
Authors: Daniel D. Klafs Carl E. Arnheim
Journal: JAMA (1963)

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
Alcohol Consumption and Breast Cancer Risk—Reply
Authors: Wendy Y. Chen
Journal: JAMA (2012)

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
Abstract 14717: Endocrine Mechanisms against Ischemic Cardiomyocyte Calcification
Authors: Shu Liu, Brian Zhang, Yu H Wu
Journal: Circulation (2014)

Myocardial infarction causes cardiomyocyte calcification or deposition of hydroxyapatite crystals, structures disrupting cardiomyocytes and intensifying myocardial injury. While cardiomyocyte calcification is well recognized, the underlying mechanisms remain elusive and few treatment strategies have been established. Here, we test the hypotheses that annexins (ANXs), intracellular Ca++ carriers associated with the plasma membrane, contribute to ischemic cardiomyocyte calcification and the endocrine protein trefoil factor 3 (TFF3) is upregulated and released from the liver in ischemic myocardial injury, protecting ischemic cardiomyocytes from annexin-dependent calcification. Myocardial ischemia/reperfusion injury in 129s1/sv Imj mice caused translocation of ANXs A2, A3, A4, A5, and A7 from the cardiomyocyte membrane to α actin filaments in association with hydroxyapatite deposition to α actin filaments prior to cardiomyocyte death from 1 to 10 days. siRNA-mediated silencing of the ANX A2, A3, A4, A5, and A7 genes reduced the fraction of calcified cardiomyocytes at day 5 from 6.3+/-1.8% (control siRNA) to 2.1+/-0.6% in reference to the infarct area (p&lt;0.01), suggesting a pro-calcification role for these ANXs. Myocardial injury caused upregulation and release of TFF3 from the liver. TFF3-/- mice exhibited intensified ischemic cardiomyocyte calcification (17.8+/-5.2%) compared to wildtype mice (5.6+/-2.3%, p&lt;0.001), suggesting an anti-calcification role for TFF3. TFF3 was able to bind to ANXs A2, A3, A4, A5, and A7, demonstrated by TFF3 crosslinking assay and mass spectroscopy. ANX A2, A3, A4, A5, or A7 was able to co-immunoprecipitate with TFF3 in ischemic cardiomyocytes. Computational molecular interaction analyses by using the Autodocking software system showed TFF3 interaction with the ANX C-terminus, a structure binding to actin filaments. Myocardial administration of recombinant TFF3 reduced ANX-dependent cardiomyocyte calcification. These observations suggest that ANXs cause ischemic cardiomyocyte calcification by binding to α actin filaments and TFF3 is upregulated and released from the liver in myocardial ischemia, mitigating cardiomyocyte calcification by blocking ANX binding to actin filaments.
Cancer Detection and Cancer Characteristics in the European Randomized Study of Screening for Prostate Cancer (ERSPC) – Section Rotterdam
Authors: Renske Postma, Fritz H. Schröder, Geert J.L.H. van Leenders, Robert F. Hoedemaeker, Andre N. Vis, Monique J. Roobol, Theodorus H. van der Kwast
Journal: European Urology (2007)
Abstract 3662: Transformation of LVAD Destination Therapy, "Good to Great": Ever Increasing Survival Benefit
Authors: Barry A Boilson, John A Schirger, Lucian A Durham, Margaret M Redfield, Alfredo L Clavell, Naveen L Pereira, Sudhir S Kushwaha, Richard C Daly, Soon J Park
Journal: Circulation (2009)
Adolescents With Depression
Authors: David Antonuccio, David Burns
Journal: JAMA (2004)

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
A Review of: “Timothy F. Murphy. 2004.<i>Case Studies in Biomedical Research Ethics</i>”
Authors: David Rodríguez-Arias, Christian Hervé
Journal: The American Journal of Bioethics (2005)

Cases are, in many ways, the lifeblood of bioethics (Crigger 1998, 15). Moral theory must be checked against the practical experience case studies provide, which experience may engender reasons to ...