tbuckley/cabot-search huggingface dataset:
Abstract 3451: Risk for Coronary Artery Disease at the 9p21.3 Locus Is Abolished by a Protective Locus at 8p21.3 Identified by a Genome-Wide Association Study
Authors: Alexandre F Stewart, Ruth McPherson, Li Chen, Kathryn Williams, Heather Doelle, Robbie Davies, Sonny Dandona, Nihan Kavaslar, Julie Ruthberg, Gwen Ewart, Rosemary LaRose, Lan Vo, Yanquing Wang, Paulina Lau, Marino Labinaz, Benjamin Chow, George A Wells, Robert Roberts
Journal: Circulation (2008)

Background : Coronary artery disease (CAD) is the leading cause of death in the western world. The only common genetic risk locus identified to date by us and others in genome wide association studies (GWAS) resides at 9p21.3. Methods: The Ottawa Heart Genomic Study compared genotypes of 1,542 early onset CAD patients (average 49y) and 1,455 elderly control Caucasians (average 75y). Results: Here, we report two protective haplotypes in the 3′ region of the lipoprotein lipase (LPL) gene at 8p21.3. LPL promotes lipolysis of circulating triglycerides (TG) and increases levels of atheroprotective high density lipoprotein (HDL) cholesterol. Since the 8p21.3 haplotypes are protective, we tested their interaction with the 9p21.3 risk allele. The rs10503669 haplotype associated with elevated TG and HDL levels but did not affect risk from 9p21.3. In contrast, the rs17411031 haplotype was not associated with TG or HDL levels and showed a significant interaction that abolished 9p21.3 risk independent of known risk factors. The interaction was confirmed using data of the Wellcome Trust Case Control Consortium. Excluding carriers of the interacting allele, accuracy of 9p21.3 to predict CAD risk is dramatically improved. Conclusion: Identification of the first modifier gene of the 9p21.3 risk locus for CAD improves CAD risk assessment and provides novel insight into coronary atherosclerosis. This protective 8p21.3 locus may provide a target for novel therapy.
Abstract 290: Low Minute Ventilation Volume During CPR Disturbs the Relationship between End-Tidal CO2 and Coronary Perfusion Pressure
Authors: Simone Ordelman, Paul van Berkom, Paul Aelen, Pierre Woerlee, Gerrit J Noordergraaf
Journal: Circulation (2013)

End-tidal CO 2 (ETCO 2 ) is important for monitoring CPR quality as a surrogate for coronary perfusion pressure (CPP) and flow. We hypothesized that sufficient minute volume ventilation is not only needed to control CO 2 buildup, but also for the exhaled CO 2 to CPP relationship to remain valid. To test our hypothesis, we measured minute volume ventilation together with CPP, arterial PCO 2 (PaCO 2 ), and ETCO 2 in a pig model. Ventricular fibrillation was induced in 24 pigs, after which automated CPR (5 cm, 100 cpm) followed for 20 minutes. Animals were ventilated manually using a bag-mask-valve, either continuously at 10 min -1 (group 1, n=8) or 30:2 mode (group 2, n=16). Correlation coefficients between CPP and ETCO 2 were calculated for each pig during the CPR interval. Minute volume ventilation during CPR was 3.4 ± 1.0 L/min for group 1 and 2.2 ± 0.3 L/min for group 2 pigs. In group 1, PaCO 2 changed little during CPR (41.1 ± 7.6 mmHg initially vs. 38.6 ± 16.5 mmHg at 20 minutes), indicating suitable minute volume ventilation. ETCO 2 decreased concurrently with CPP. The correlation coefficient between CPP and ETCO 2 was 0.52 ± 0.39. Group 2 pigs showed a large increase in PaCO 2 (49.8 ± 6.6 mmHg initially vs. 58.0 ± 13.6 mmHg at 20 minutes), consistent with small minute volume ventilation. This increase in PaCO 2 was accompanied by a progressively increasing ETCO 2 , while the CPP consistently decreased. The CPP to ETCO 2 correlation coefficient showed a low, but negative (-0.18 ± 0.51) relationship, strongly supporting that the indicator function of ETCO 2 was lost. The figure shows an example. In conclusion, insufficient ventilation affects ETCO 2 and can disturb the relationship between ETCO 2 and CPR quality as measured by CPP. This is reminiscent of hyperventilation effects. Ventilation minute volumes should therefore be monitored, and hypoventilation avoided, to prevent clinical misinterpretation of ETCO 2 values.
Abstract 540: A MALDI imaging mass spectrometry approach using tissue microarrays to identify an N-glycan biomarker panel for pancreatic cancers
Authors: Richard R. Drake, Thomas W. Powers, Benjamin A. Neely
Journal: Cancer Research (2015)

Abstract We have recently developed a MALDI imaging mass spectrometry (MALDI-IMS) method to spatially profile N-linked glycans in frozen and formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMAs). Tissues are incubated with peptide N-glycosidase, and released N-glycans are detected directly using MALDI-FTICR, linked directly with tissue histopathology. Other methods to detect the localization of glycans in tissues rely on detection of broader glycan structural motifs (i.e., lectins or carbohydrate antigen antibodies), whereas our method is able to simultaneously identify and distinguish 40 or more components of the N-glycome on a single slide. To demonstrate the ability of MALDI-IMS to generate biomarker panels, pancreatic cancer tissue blocks and six TMAs containing matched tumor and non-tumor regions from over 70 patients were profiled. Aberrant glycosylation, such as elevated CA-19-9, is well documented in pancreatic cancer, making this an ideal sample set. To best analyze this complex data set, we developed an in-house analysis script that can extract spectra from tissue cores, and return non-biased statistics for observed glycan ions. Panels were generated using a training set of data and tested on external validation data set. The most accurate panel of 12 glycans achieved an overall sensitivity of 92.9% and specificity of 86.7%. Structural identification of N-glycans has been confirmed by techniques such as on-tissue CID, ethylation analysis, sequential glycosidase digestions, and comparison to glycan structural databases. Furthermore, imaging of entire FFPE sections matched with histological analysis revealed a vast diversity of N-glycan localizations, which could distinguish not only tumor from normal tissue, but also regions of pancreatitis and pancreatic intraepithelial neoplasia. The generated glycan tissue maps will also be used to determine specific glycoprotein carriers of biomarker candidate glycans in tissue and biofluid samples. Citation Format: Richard R. Drake, Thomas W. Powers, Benjamin A. Neely. A MALDI imaging mass spectrometry approach using tissue microarrays to identify an N-glycan biomarker panel for pancreatic cancers. [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 540. doi:10.1158/1538-7445.AM2015-540
Elavated mammary tumorigenesis in rats exposed to estradiol or leptin during pregnancy
Authors: Sonia De Assis, Mingyue Wang, Aaron Foxworth, Leena Hilakivi-Clarke
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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Obesity and weight gain throughout a woman’s adult life are risk factors for postmenopausal breast cancer. Results from epidemiological studies suggest that excessive weight gain during pregnancy also increases the risk of developing breast cancer, perhaps by increasing pregnancy estrogen levels. Findings obtained in several studies suggest that the higher the estrogen levels are during pregnancy, the higher is mother’s later risk of breast cancer. Another possible mediator of excessive pregnancy weight gain is leptin that is associated with body weight and it increases estrogen levels. In this study, we aimed to determine the effects of an exposure to estradiol or leptin during pregnancy on mother’s mammary tumorigenesis. To initiate mammary tumorigenesis, 50 day-old female Sprague Dawley rats were given 10 mg of 7,12-dimethylbenz(a)anthracene (DMBA). Ten days later, rats were mated. Between days 8 and 19 of pregnancy, dams were treated daily with 10 μg of 17β-estradiol, 15 μg of leptin or vehicle. Involuted mammary glands of dams treated with estradiol during pregnancy contained a higher number of proliferating cells than the other two groups, when determined using PCNA assay (p<0.05). The number of apoptotic cells, determined using ISOL assay, was lower in the leptin and estradiol groups compared to controls (p<0.05). Both pregnancy estradiol and leptin exposures increased the incidence of mammary tumors, when compared to the controls (χ2-test: p<0.001). Tumor latency was longer in the estradiol group than in the controls (ANOVA: p<0.02), but not in the leptin group. Tumor multiplicity was higher in the leptin group than in the controls, although this increase failed to reach statistical significance. These findings indicate that an increase in estradiol or leptin levels during pregnancy increases dams’ breast cancer risk.
Usefulness of urine dipstick tests
Authors: P. Wilson, R. R Cutler, P. Jenks, F. V Clarke, J. Merrett
Journal: BMJ (1996)

EDITOR,—Several studies,1 2 including that by J H Beer and colleagues,3 have highlighted the fact that there is still debate over the diagnostic accuracy of rapid dipstick tests. Beer and colleagues point out that the presence of certain antibiotics in urine samples may cause false positive results. Other workers have pointed out that false negative results may be due to antibiotics, glucose, or oxalic acid. Bonnardeaux et al concluded that results of dipstick tests were an unreliable predictor of results of microscopy and that false negative results can …
Prevalence and Risk Factors for Myopic Retinopathy in a Japanese Population
Authors: Tomoko Asakuma, Miho Yasuda, Toshiharu Ninomiya, Yoshihiro Noda, Satoshi Arakawa, Sawako Hashimoto, Kyoko Ohno-Matsui, Yutaka Kiyohara, Tatsuro Ishibashi
Journal: Ophthalmology (2012)
Abstract 1514: RXP-E: A Connexin43-Binding Peptide that Prevents Action Potential Propagation Block
Authors: Rebecca Lewandowski, Kristina Procida, Ravi Vaidyanathan, José Jalife, Morten S Nielsen, Steven M Taffet, Mario Delmar
Journal: Circulation (2008)

Gap junctions (GJ’s) provide a low resistance pathway for cardiac electrical propagation. The role of GJ regulation in arrhythmias is unclear, partly due to the limited availability of pharmacological tools. Recently, we showed that a peptide called “RXP-E” binds to the carboxyl terminal of connexin43 (Cx43) and prevents chemically-induced uncoupling in Cx43-expressing N2a cells. Here, we used pull-down experiments to show that RXP-E binds to adult cardiac Cx43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes (NRVM’s). Separately, RXP-E was concatenated to a cytoplasmic transduction peptide for translocation into the cytoplasm (construct CTP-RXP-E). The effect of RXP-E on action potential (AP) propagation was assessed by high resolution optical mapping in monolayers of NRVMs, containing approximately 20% of randomly distributed myofibroblasts. Conduction velocity (CV) was 164 ± 8mm/sec (avg±SEM; n=12; pacing frequency 2Hz) in untreated cells, and 158±10mm/sec, (n=6) and 180±7mm/sec (n=10) in monolayers treated with CTP-RXPE or a scrambled version of the peptide (CTP-Scr), respectively (pNS). Exposure of either untreated, or CTP-Scr-treated monolayers to heptanol caused propagation block. However, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, AP propagation was maintained, albeit at a slower velocity (87±5mm/sec;n=4; P&lt;0.001). Similarly, intracellular acidification (pHi=6.2) caused a loss of AP propagation in control or CTP-Scr monolayers; however, propagation was maintained in CTP-RXP-E treated cells, though at a slower rate (CV=93 ± 28mm/sec; n=4). Consistent with these results, patch clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium or calcium currents, nor did it alter the voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to: bind cardiac Cx43; prevent heptanol and acidification-induced uncoupling of cardiac GJ’s and preserve AP propagation among cardiac myocytes. RXP-E can be used to characterize the role of GJ’s in the function of multicellular systems, including the heart. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Adaptation of lung epithelial cells subjected to chronic cyclic strain
Authors: Bettina Weber, Susanne Wodischeck, Andreas Simm, Rolf-Edgar Silber, Babett Bartling
Journal: European Respiratory Journal (2014)

Background:  Breathing movements cause cyclic mechanical strain of the lung tissue, in particular of the alveolar epithelium.Since this is a physiological process, it also suggests a certain capacity of alveolar epithelial cells (AEC) to adapt to this stress situation. Therefore, we studied cell signaling pathways and the gene expression profile in various AEC lines.  Methods:  Adherent human AEC (A549 as principal cell line and four others) were subjected to cyclic strain (16% surface distension at 0.2 Hz) for up to 24 h in a self-constructed strain chamber. Activation of general signaling pathways was estimated by immunoblot (phosphorylation of signaling molecules), electron spin resonance spectroscopy (generation of reactive oxygen species (ROS)), gene microarray and qPCR technique (gene expression).  Results:  Microarray analyses revealed many differences in the gene expression but at very moderate levels. In all, 25 genes were moderately down-regulated (0.86-fold ±0.06) and 26 genes were up-regulated (1.18-fold ±0.10) in A549 and the others. Strain-regulated genes often code for transcription factors, such as E2F4 and SRF, which was confirmed by qPCR analyses. In accordance with this observation, we identified an immediate increase in selected signaling molecules (active p42/p44, active PKB/Akt and ROS but not active JNK/SAPK) but with time their increase normalized relatively fast.  Conclusion:  Fast normalization of cell signaling pathways and moderate changes in the gene expression profile suggests an effective adaptation of lung cells to chronic mechanical stress.
Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients
Authors: B V Siegel, M S Buchsbaum, W E Bunney, L A Gottschalk, R J Haier, J B Lohr, S Lottenberg, A Najafi, K H Nuechterlein, S G Potkin
Journal: American Journal of Psychiatry (1993)

The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms.Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects.Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions.Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.
Abstract 153: Does Telemetry Monitoring Improve Outcomes After In-Hospital Cardiac Arrest?
Authors: Rami Mohammad, Nicholas Hartmann, Sachil Shah, Elie Donath, Ann Rasmussen, Shaun Isaac, Steven Borzak
Journal: Circulation (2013)

Introduction: Telemetry is increasingly used to monitor patients with lower intensities of care, but its effect on in-hospital cardiac arrest (IHCA) outcomes in non-critical care patients is unknow...
Abstract 3793: Nutritional Status is Associated With Cardiac Outcomes and Mortality in Children With Idiopathic Dilated Cardiomyopathy
Authors: Tracie L Miller, E J Orav, James D Wilkinson, Lynn A Sleeper, Jeffrey A Towbin, Steven D Colan, Daphne T Hsu, Charles E Canter, Steven A Webber, Steven Lipshultz
Journal: Circulation (2009)

Objective: Impaired growth and nutrition can have an adverse impact on, or be a consequence of, chronic disease. The nutritional status of children with idiopathic dilated cardiomyopathy (IDCM) and the association of nutritional status on clinical endpoints, including mortality, have been poorly defined. Methods: The Pediatric Cardiomyopathy Registry database was reviewed for children with complete entry data on weight (wt), height (ht), demographics, and echocardiography (echo). Ht and wt z-scores (z) and body mass index (BMI) were calculated. Mortality was determined at 1 y after entry into the registry. IDCM was dichotomized by diagnosis (dx) <1 y or ≥1 y of age. Proportional hazards regression was used to look at the comparative impact of ht, wt, and BMI on time-to-death. All regression models were adjusted for age and echo measures of disease severity. Comparisons were made between children dx <1 y and ≥1 year of age. Results: Complete data were available for 759/1429 children with IDCM (53%); the 47...
Abstract 16772: Quality of Life in Patients After LAD Revascularization by MIDCAB or by PCI
Authors: Breuer Martin, Björn Georgi, Tim Sandhaus, Michael Ferrari, Thorsten Doenst
Journal: Circulation (2011)

Purpose: Outcome comparisons of minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) for LAD-revascularization demonstrated equal survival. We assessed quality of life (QOL) in propensity matched MIDCAB and PCI patients where revascularization of the LAD was required. Methods: We used the SF-36 Health Survey to assess post-treatment health related QOL (HRQOL) in 330 patients (172 MIDCAB, 158 PCI). MIDCAB patients were all patients having undergone surgery between 11/1999 and 12/2006 in our department. The PCI patients were selected by propensity matching out of 1186 patients having undergone PCI of the LAD in this time period. HRQOL analysis consisted of 8 subscales including general health perception, and physical and emotional role functioning. We further subdivided the patients into two groups (less than 80 years of age and 80 years or older) Results: Follow up was up to 84 months, the average follow-up was 38 months. There was no significant difference in survival at latest follow-up ( 94% versus 92% in PCI patients, n.s.). Analyzing all patients, HRQOL was better in MIDCAB patients with significant improvements in general health perception (p&lt;0.05). However, subdividing the groups by age showed continuous improvement of HRQOL by patients younger than 80 years but inferior HRQOL in patients older than 80 years of age. In the older patients specifically physical and emotional role function was improved (p&lt;0.05). Conclusions: MIDCAB revascularization of the LAD results in improved HRQOL compared to PCI only in patients under the age of 80 years. Since survival is equal HRQOL aspects maybe helpful in guiding treatment selection for patients with isolated LAD-stenosis.
Effect of Hypercholesterolemia on Myocardial Necrosis and Apoptosis in Response to Ischemia Reperfusion Injury
Authors: Robert Osipov
Journal: Circulation (2008)

Abstract 1098 Robert M Osipov, Cesario Bianchi, Jun Feng, Yuhong Liu, Richard T Clements, Neel Sodha, Frank W Sellke, Beth Israel Deaconess Medical Ctr, Boston, MA Robert Osipov, 2008 Finalist and Presenting Author
FcγRIIIa polymorphisms in racial disparity and the role of cetuximab mediated antibody dependent cellular cytotoxicity in head and neck squamous cell carcinoma
Authors: Siaw Lin Chan, Wei Lin, Caroline Voskens, Aaron Wood, Jeff Wolf, Andrei Chapoval, Dan Schulze, Scott Strome, Rodney Taylor
Journal: Cancer Research (2008)

2137    Background:  Over-expression of EGFR is a common characteristic of head and neck squamous cell carcinoma (HNSCC). Cetuximab, an IgG 1  chimeric monoclonal antibody that recognizes EGFR, is a novel FDA approved treatment for HNSCC patients that demonstrates a significant improvement in locoregional control and overall survival when combined with radiation therapy. Mechanistically, Cetuximab is thought to stimulate natural killer (NK) cell activity through FcγIII receptor and induces antibody-dependent-cellular-cytotoxicity (ADCC). Individuals with different FcγRIIIa polymorphisms (FcγRIIIa FF, FcγRIIIa FV and FcγRIIIa VV) at codon 158 have been shown to exhibit different binding affinities to other monoclonal antibody treatments. The aim of this study is to show that individuals with the FcγRIIIa V allele will respond better to Cetuximab treatment than those with the FcγRIIIa F allele. It is also our aim to compare the frequency of FcγRIIIa polymorphisms in ethnically diverse patients with SCCHN to better target patients benefiting from Cetuximab treatment. In light of well described racial differences in HNSCC treatment outcomes in the African American population compared to the Caucasian population, we are interested in investigating whether differences in FcγRIIIa polymorphisms contribute to treatment outcomes.   Methods:  Three HNSCC cell lines were used in this study: Tu167, Tu159 and O12SCC. EGFR expression and the binding of Cetuximab to these cell lines were quantified using flow cytometry. NK cells were isolated from PBMC of healthy donors and selected with magnetic beads. FcγRIIIa polymorphisms of the donors were determined by allele-specific polymerase chain reaction. Thymidine assay was used to determine cell lines proliferative activity. Antibody-dependent-cellular-cytotoxicty assay was determined using  51 Cr-release assay.   Results:  In our study, we were able to demonstrate the anti-proliferative activity in all three HNSCC cell lines in the presence of 10 ug/mL Cetuximab. In Cetuximab mediated ADCC, the cumulative percent cytotoxicity for each polymorphism among the cell lines was 58.2% for FcγRIIIa  V/V, 50.6% for FcγRIIIa  V/F, and 26.1% for FcγRIIIa  F/F  (p V  allele at codon 158 induces enhanced ADCC compared to homozygous  F/F .   Conclusion:  In translational research, these data show both prognostic and therapeutic relevance and support the design of a trial aimed at determining whether FcγRIIIa polymorphisms in ethnically diverse HNSCC patients influence the clinical outcome of anti-EGFR mAb Cetuximab treatment.