tbuckley/cabot-search huggingface dataset:
Impaired intravascular triglyceride lipolysis constitutes a marker of clinical outcome in patients with stable angina undergoing secondary prevention treatment
Authors: Andrei C. Sposito, Pedro A. Lemos, Raul D. Santos, Whady Hueb, Carmen G.C. Vinagre, Edgard Quintella, Otavio Carneiro, M.John Chapman, Jose A.F. Ramires, Raul C. Maranhão
Journal: Journal of the American College of Cardiology (2004)
Abstract 2553: Novel Cobalt-Chromium Ultra-Thin Strut Stent: Feasibility, Vascular Compatibility, and Safety Evaluation in Porcine Coronary Arteries
Authors: Refat Jabara, Sarah Geva, Dongming Hou, Jinsheng Li, Nicolas Chronos, Keith Robinson Robinson
Journal: Circulation (2008)

Stent-strut thickness is related to in-stent restenosis. Therefore, modern bare-metal stents (BMS) with lower strut thickness are in development. We sought to evaluate a new ‘third-generation’ BMS comprising an ultra-thin-strut, cobalt-chromium platform with fixed geometry and uniform cell sizes, in a clinically relevant animal model. 36 BMS of two types were implanted in pig coronaries using quantitative coronary angiography (QCA) to optimize stent apposition: a commercially available cobalt alloy thin-strut stent (91μm) as control (n=18), and an ultra-thin-strut (65μm) cobalt-chromium stent (Protea CoCr; n=18). Animals underwent angiographic restudy and termination 1-wk and 1-mo post-implant for coronary artery histology. In addition, 12 overlapping Protea CoCr stents were analyzed at 1-mo. All stents deployed without difficulties. Thin neointima and mild inflammation was seen in both groups at 1-wk. For 1-mo, QCA % diameter stenosis was significantly less for Protea CoCr (2±5% vs. 17±16%, p=0.032). By histomorphometry, intima thickness (0.11±0.05mm vs. 0.23±0.11mm, p=0.003) and % area stenosis (19±1% vs. 32±11%, respectively, p=0.004) were also significantly lower for Protea CoCr. The strut injury score was low and similar between the two groups. QCA % stenosis; intima thickness; and % area stenosis of overlapping Protea CoCr were 3±3%, 0.13±0.02mm, and 22±4%, respectively. Stable fibrocellular neointimal incorporation of all stents including overlapped Protea CoCr, with complete endothelialization and minimal inflammation, was seen at one month. Protea CoCr showed favorable arterial response with significant reduction of neointima formation compared to a commercial cobalt alloy BMS, one month post implant in pig coronary arteries. This ultra-thin-strut stent platform therefore appears to be a suitable and attractive alternative to current BMS. Combining the lower levels of neointima formation, fixed geometry, and uniform cell size, the Protea CoCr may be a preferred platform for next-generation drug-eluting stents.
Adhesion of NFS-60 myeloid leukemia cells to MC3T3-G2/PA6 stromal cells induces granulocyte colony-stimulating factor production
Authors: T Yoshikubo, K Ozawa, K Takahashi, M Nishikawa, N Horiuchi, A Tojo, K Tani, H Kodama, S Asano
Journal: Blood (1994)
Abstract 14214: The Association of Multiple Phenotypic Presentations of Metabolic Syndrome with Subclinical Atherosclerosis in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Todd M Brown, Vera Bittner, Catherine Loria, Monika M Safford, Cora E Lewis
Journal: Circulation (2011)

Background: Significant phenotypic variation exists among individuals classified as having metabolic syndrome (MetSyn). Moreover, not all individuals with MetSyn are obese, and not all obese indivi...
Medical education is brutalising
Authors: R. Haigh, J. Appleford, A. Bond
Journal: BMJ (1995)

EDITOR,—We believe that the dehumanisation of medicine that D J Weatherall describes lies behind much of the miscontent, demoralisation, and mental ill health of doctors, increasing numbers of whom are being referred for help.1 Last year we piloted a preventive intervention, which was not entirely successful. We invite discussion on why this might be so.

We taught psychotherapy to fifth year medical students over eight weeks. We covered subjects such as death and dying, the doctor-patient relationship, difficult patients, …
Altering stem cell fate by deregulated c-Myc influences tumor phenotype.
Authors: Kimberly A. Honeycutt, Rebekah L. Waikel, Dennis R. Roop
Journal: Cancer Research (2004)

2397   c-Myc is an oncoprotein known to induce proliferation, transformation and apoptosis in mammalian cells. We have previously shown that c-myc influences epidermal stem cell fate determination, specifically diverting multipotent stem cells to sebaceous glands. To determine how c-myc affects stem cells  in vivo , we generated an inducible mouse model (Gene-switch c-Myc) in which deregulated expression of c-myc is targeted to the basal layer of the epidermis and multipotent stem cells located within the bulge region of the hair follicle. The expression of c-myc can be regulated by topical application of the anti-progesterone RU486. Gene expression profiling studies using samples from mice treated once with RU486 and taken 12 and 24 hours after treatment indicate that c-myc activates specific target genes to influence epidermal stem cell fate. Target genes include the wnt pathway inhibitor, dickkopf1, and a member of the hedgehog family, Indian Hedgehog. Dickkopf1 has been shown to inhibit hair follicle formation when ectopically expressed in the epidermis. Indian Hedgehog has been shown to be involved in sebaceous gland development. Thus, c-myc diverts stem cells to a sebaceous gland fate at the expense of the hair follicle by activating specific target genes. To determine if c-myc’s ability to divert stem cells into sebaceous glands would influence tumor phenotype, we subjected K14.myc2 mice to a chemical carcinogenesis protocol. K14.myc2 mice developed tumors at an accelerated rate and higher incidence compared to wildtype littermates. Interestingly, K14.myc2 mice developed sebaceous gland tumors at a frequency of 100%, while none developed in wildtype littermates. In addition, we are currently assessing the role of c-Myc in tumor progression using the Gene-switch c-Myc model, since the K14.myc2 mice die prematurely due to severe ulcerated lesions. Gene-switch c-Myc mice exposed to DMBA/TPA, followed by induction of c-Myc exhibited accelerated tumorigenesis. Furthermore, we have now observed progression of tumors that developed in DMBA/TPA treated mice to metastatic lesions in the lung, and determined by an analysis of DNA content that the metastases were aneuploid. A member of the minichromosome maintenance family of proteins, MCM7, has been found to be a direct target of c-Myc and may potentially play a role in inducing genomic instability. Tumors that developed in both the K14.myc2 mice and Gene-switch c-Myc stained positively for MCM7. Interestingly, recent preliminary data demonstrate that induction of c-Myc can also take the place of TPA and function as a tumor promoter. The predisposition of K14.myc2 mice to develop sebaceous adenomas suggests that tumor phenotype can be influenced by deregulated expression of genes that alter stem cell fate and further analysis indicates that c-Myc may induce genomic instability through direct targets as well.
Abstract 299: In vitro compound screening identifies enhancers of adenoviral oncolysis with Delta24-RGD in patient-derived glioblastoma stem cells
Authors: Lotte ME Berghauser Pont, Rutger Balvers, Jenneke Kloezeman, Michal O. Nowicki, Andreas Kremer, E. Antonio Chiocca, Sieger Leenstra, Clemens MF Dirven, Sean Lawler, Martine LM Lamfers
Journal: Cancer Research (2015)

Abstract The tumor targeted oncolytic adenovirus Delta24-RGD is currently under phase I/II investigation for the malignant brain tumor glioblastoma. Despite encouraging results, the efficacy of oncolytic virotherapy still requires improvements due to heterogeneous or poor responses. In this study, we performed a screen of 446 clinically applied drugs to identify those that enhance Delta24-RGD oncolysis in glioblastoma. Cell viability was determined five days post-infection in Delta24-RGD resistant patient-derived glioblastoma stem cell (GSCs) cultures. Potential ‘hits’ were tested for synergistic viral sensitization using the Chou-Talalay method. Effects on viral infection and replication were investigated using Ad-Luc-RGD and Delta24-RGD-GFP viruses, and apoptosis and necrosis were evaluated using caspase-3/7 and lactate dehydrogenase (LDH) assays. Selection based on the efficacy of combination treatment led to the identification of ten drugs as potential Delta24-RGD sensitizers from the initial screen. Further analysis of effects on viral replication, synergistic interactions and ability to penetrate the blood-brain barrier narrowed this down to four remaining compounds, fluphenazine, indirubin, lofepramine and ranolazine. These four agents increased caspase-3/7 activity and fluphenazine also increased LDH levels in combination with Delta24-RGD. Fluphenazine, indirubin, lofepramine and ranolazine sensitized 12/12, 11/12, 9/12 and 11/12 distinct GSC cultures to Delta24-RGD, respectively. In conclusion, a clinical compound screen on glioblastoma stem cells in combination with in vitro mechanistic studies, revealed four highly effective compounds that sensitize GSCs to Delta24-RGD oncolytic therapy. Citation Format: Lotte ME Berghauser Pont, Rutger Balvers, Jenneke Kloezeman, Michal O. Nowicki, Andreas Kremer, E. Antonio Chiocca, Sieger Leenstra, Clemens MF Dirven, Sean Lawler, Martine LM Lamfers. In vitro compound screening identifies enhancers of adenoviral oncolysis with Delta24-RGD in patient-derived glioblastoma stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 299. doi:10.1158/1538-7445.AM2015-299
Angiographic Surrogate End Points in Drug-Eluting Stent Trials
Authors: Stuart J. Pocock, Alexandra J. Lansky, Roxana Mehran, Jeffrey J. Popma, Martin P. Fahy, Yingbo Na, George Dangas, Jeffrey W. Moses, Tereza Pucelikova, David E. Kandzari, Stephen G. Ellis, Martin B. Leon, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2008)
Global Longitudinal Strain Is Not Impaired in Type 1 Diabetes Patients Without Albuminuria
Authors: Magnus Thorsten Jensen, Peter Sogaard, Henrik Ullits Andersen, Jan Bech, Thomas Fritz Hansen, Tor Biering-Sørensen, Peter Godsk Jørgensen, Søren Galatius, Jan Kyst Madsen, Peter Rossing, Jan Skov Jensen
Journal: JACC. Cardiovascular imaging (2015)
Abstract 1443: Systems-Based Analysis of HDL Metabolism in a Mouse Intercross between Strains CAST and C57BL6/J (CxB)
Authors: Margarete Mehrabian, Charles Farber, Peter Langfelder, Anatole Ghazalpour, Zhiqiang Zhou, Jason Aten, Lawrence Castellani, Thomas Drake, Eric Schadt, Aldons Lusis
Journal: Circulation (2008)

A recent meta-analysis of three large genome-wide association studies for HDL cholesterol levels revealed several highly significant associations, but altogether these explained less than 10% of the population variance of HDL. Since HDL levels are highly heritable, with heritability estimated at 50–70% in many studies, there are clearly many additional genes, and probably complex genetic and environmental interactions, involved in HDL metabolism. Thus, if “personalized medicine” is to become a reality, these complex factors must be addressed. Combined genetic-genomic approaches have rejuvenated the analysis of complex traits using mouse models, and here report an integrative genomic study of HDL in a large mouse cross. We previously reported the identification of loci associated with HDL cholesterol concentrations using a CXB F2 intercross. We have now generated a much larger CXB cross, consisting of 438 mice, and have integrated genome wide gene expression analysis of liver and adipose with quantitative trait locus (QTL) mapping and causality modeling. These studies were carried out on mice fed a low fat, chow diet and then switched to a high fat, ’Western’ diet. QTL analysis on the clinical traits using R/QTL (http://cran.r-project.org/) revealed a complex inheritance pattern with significant LOD scores at 9 loci, on chromosomes 1,2,4,5,8,9,10,16,18. Of these loci, 6 (chr: 1,4,5,10,16,18) were seen to be involved in genetic-dietary regulation of HDL cholesterol. Expression QTLs (eQTL) were determined using Agilent microarrays for 23,624 transcripts. Genes expressed within a 1-LOD support interval or correlated with HDL (p&lt;2.7E-11) in both adipose and liver were identified. Using Network Edge Orienting (NEO) methods, causal relationships between the identified genes, related QTL peak markers and HDL levels were accessed. The genes were then ranked based on the NEO scores. In liver the highest ranked genes were associated with mitochondrial, ER and golgi trafficking. In adipose, on the other hand, pathways associated with cell signaling, transcription regulation and protein ubiquitation were predicted to be causal for HDL levels. In conclusion, our results reveal a large number of novel pathways and candidate genes for plasma lipid metabolism. This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada &amp; Utah).
Abstract 54: Ezrin enhances signaling and nuclear translocation of the epidermal growth factor receptor in non-small cell lung cancer cells
Authors: Yasemin Saygideger Kont, Haydar Celik, Hayriye V. Erkizan, Tsion Minas, Jenny Han, Jeffrey Toretsky, Aykut Uren
Journal: Cancer Research (2015)

Abstract The cytoskeletal cross linker protein ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles not only in cell motility, cell adhesion, and apoptosis, but also in various cell-signaling pathways. Ezrin interacts with EGFR in the cell membrane and involves in cell motility events, but little is known about the effects of this interaction on the EGFR signaling pathway. We investigated the role of Ezrin in EGFR signaling and nuclear trafficking in non-small cell lung cancer (NSCLC) cell lines. The ligand induced interaction between Ezrin and EGFR was evaluated by immunoprecipitation (IP) and immunofluorescence (IF) in H292 and A549 cells. Ezrin levels were reduced using siRNA in these two cell lines. Downstream signaling protein phosphorylation and nuclear localization of EGFR were detected after EGF treatment. Expressions of nuclear EGFR target genes were evaluated by qPCR. Endogenous Ezrin was found in a complex with EGFR in IP and IF. When Ezrin protein expression was inhibited, phosphorylation levels of EGFR at Y1068, Y1101 and Y845 were reduced as well as phosphorylation levels of downstream signaling pathway proteins ERK and STAT3. Cell fractionation revealed that EGFR nuclear translocation after EGF treatment significantly reduced in Ezrin-knockdown cells. Further, mRNA levels of EGFR target genes AuroraK-A, COX2, Cyclin D1 and iNOS were decreased in Ezrin-knockdown A549 cells. Small molecule ezrin inhibitors showed strong synergy with EGFR inhibitors in cytotoxicity assays. These results suggest that Ezrin has a role as an enhancer in the EGFR pathway and targeting ezrin may potentiate anti-EGFR based therapies in NSCLC. Citation Format: Yasemin Saygideger Kont, Haydar Celik, Hayriye V. Erkizan, Tsion Minas, Jenny Han, Jeffrey Toretsky, Aykut Uren. Ezrin enhances signaling and nuclear translocation of the epidermal growth factor receptor in non-small cell lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 54. doi:10.1158/1538-7445.AM2015-54
Abstract 17797: The Impact of Ethnicity and Hospital Ethnic Make-up on 30-Day Readmission Rates for Elderly Hispanic Patients With Heart Failure
Authors: Fatima Rodriguez, Karen Joynt, Fidencio Saldana, Lenny Lopez, Ashish Jha
Journal: Circulation (2010)

Hispanics are the fastest growing segment of the US population, and have a higher prevalence of heart failure (HF) than non-Hispanic whites. However, little is known about the care they receive for...
Abstract 17187: Clinical Indications, Appropriateness, and Results of Repeat Myocardial Perfusion Imaging
Authors: Shepard D Weiner, Adam Bernheim, Michal Kulon, Sabahat Bokhari, Lynne L Johnson, Jeffrey W Moses, Stephen Balter, Andrew J Einstein
Journal: Circulation (2010)

Background: There has been a significant increase in myocardial perfusion imaging (MPI) exams performed. Appropriate use criteria (AUC) have been published to provide guidance in the use of MPI tes...
UK advisory body supports chemotherapy drugs for lung cancer.
Authors: Susan Mayor
Journal: BMJ (2001)

The National Institute for Clinical Excellence (NICE), which advises the NHS in England and Wales on the clinical and cost effectiveness of medicines, has issued guidance recommending several new drugs for chemotherapy in non-small cell lung cancer.

Gemcitabine, paclitaxel, and vinorelbine should each be considered as part of firstline chemotherapy for patients with advanced non-small cell lung cancer, the guidance says. The use of any one of these drugs in combination with a platinum based chemotherapy drug is likely to be the most effective form of treatment, the guidelines suggest.

Docetaxel monotherapy should be considered in the treatment of patients with locally advanced or metastatic cancer, but only if …
Abstract 3681: Prophylactic Sodium Nitroprusside Administration in Saphenous Vein Graft Intervention Reduces Post-procedural Cardiac Marker Elevation
Authors: Gilbert J Zoghbi, Munish K Goyal, Fadi G Hage, Brigitta C Brott, Vijay K Misra, Paul R Myers, William B Hillegass
Journal: Circulation (2006)
Abstract 1460: Nox2 Signalling via p21 <sup>Cip1</sup> and p53 in Endothelial Cell Cycle Regulation
Authors: Lampson M Fan, Vinoj George, Gavin Brooks, Jian-Mei Li
Journal: Circulation (2007)

The abilities of endothelial cells to proliferate, to be quiescent in monolayer and to undergo apoptosis during remodeling are important determinants relating to angiogenesis, wound healing and many diseases including atherosclerosis. During ischemia, angioplasty or organ transplantation, endothelial cells experience sustained nutrient deprivation (starvation), which causes cell oxidative stress and apoptosis. Endothelial cells express constitutively an NADPH oxidase, which is a major source of superoxide production. The catalytic subunit of NADPH oxidase has several isoforms (Nox1–5). However, their individual roles in endothelial function remain unknown. In this study, we investigated the role of Nox2 in nutrient deprivation-induced cell cycle arrest and apoptosis. In proliferating human dermal microvascular EC (HMEC1), Nox2 mRNA expression was low relative to Nox4 (Nox2:Nox4~1:13), but was upregulated 24h after starvation and increased to 8±3.5-fold at 36h of starvation as detected by quantitative real-time PCR. Accompanying the upregulation of Nox2, there was a 2.28±0.18-fold increase in O 2 .− production detected by tiron (O 2 −. scavenger)-inhibitable lucigenin (5 μM)-chemiluminescence; a dramatic induction of p21 cip1 and p53 protein expression detected by immunoblotting; cell cycle arrest and the onset of cell apoptosis detected by propidium-iodide FACS analysis (all P&lt;0.05). All these changes were inhibited significantly by adding apocynin (an NADPH oxidase inhibitor), or by in vitro deletion of Nox2 expression using full-length antisense Nox2 cDNA, or in coronary microvascular endothelial cells isolated from Nox2 knockout mice. In Nox2 knockout cells, although there was a 3.8±0.5-fold increase in Nox4 mRNA expression after 36h of starvation (P&lt;0.01), neither O 2 .− production nor the p21 cip1 and p53 expressions were increased significantly and only 0.46% of cells were apoptotic compared to ~12% apoptotic cells found in wild-type control cells cultured under the same condition. In conclusion, Nox2-derived O 2 .− , through the modulation of p21 cip1 and p53 expression, participates in the regulation of endothelial cell cycle control and apoptosis.
Effects of Folic Acid on Phenylalanine Tolerance Test in Phenylketonuria
Authors: B TISCHLER, E G McGEER
Journal: JAMA (1963)

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Abstract 10331: Predictors of Outcomes Following Cardiac Resynchronization Therapy in Diabetics with Heart Failure: A Prospective Cohort Study
Authors: Robert K Altman, Ravi Shah, Jodi Zilinski, Jordan Leyton-Mange, Mary Orencole, Amanda Anderson, E. Kevin Heist, Conor D Barrett, Mi Young Park, Michael H Picard, Ranendra K Das, Jagmeet P Singh, Saumya Das
Journal: Circulation (2011)
Cardioversion should be attempted
Authors: R C Davis
Journal: BMJ (1996)

A random sample of 151 patients (83 female) was given a questionnaire, and the current international normalised ratio was noted in addition.The mean (SD) age was 63-7 (10-7) years (range 24-93).Most of the patients (126) had a cardiac diagnosis (valve replacement, valvular disease, etc), while the rest had deep venous thrombosis and pulmonary embolism.Strength of warfatin tablets-Warfarin tablets are available in three strengths (1, 3, and 5 mg).Only seven patients used the 5 mg tablet.Since only five patients were taking 9 mg or more daily, we suggest that all patients could be simply and perhaps more safely treated with the 1 and 3 mg tablets only.We suggest that the 5 mg tablet be abandoned.Playing safe and computerisation-With increasing numbers of patients being treated, computeri- sation of the dose is being considered.The official target for the international normalised ratio was 2-0-3-0.Our results showed a peak in the lower half of the target zone, presumably because the doctors were playing safe: the ratio was 1-0-1-4 in 11 patients, 1-5-1-9 in 37, 2-0-2-4 in 45, 2-5-2.9 in 38, 3 0-3 4 in 16, 3 5-3 9 in three, and 4-0-4-4 in one.The low incidence of side effects (only one patient required admission to hospital) reflects this caution.A transfer to computerised control, aiming for the middle of the official target zone, would shift the distribution to the right, possibly increasing the rate of complications.Communication with patients-Patients were aware of their dose of warfarin (n-148), knew the reason for taking it (143), and were meticulous in their compliance (149 took it at same time each day, and 138 knew not to take a double dose to compensate for forgetting a dose).Ninety five, however, did not know the desirable international normalised ratio, and only three knew that the abbreviation INR stood for international normalised ratio.With patients being encouraged to have more involvement in their treatment, it is important for them to have a better of under- standing of the goals of treatment and the terms used to monitor it.