tbuckley/cabot-search huggingface dataset:
Abstract 11971: Early Intravenous Beta Blockers Improve In-Hospital and Short-Term Mortality without Increasing the Risk of Cardiogenic Shock in Patients with Acute Coronary Syndrome-A Meta-Analysis
Authors: Saurav Chatterjee, Debanik Chaudhuri, Rajesh Vedanthan, Valentin Fuster, Borja Ibanez, Sripal Bangalore, Debabrata Mukherjee
Journal: Circulation (2011)

Background: Intravenous (IV) beta-blockade is currently only a Class IIa recommendation in the early management of patients with acute coronary syndromes (ACS) even for subjects without obvious contraindications. We performed a systematic review and meta-analysis of the medical literature to determine if early intravenous beta-blockade improves outcomes of patients with ACS. Methods: We searched the PubMed, EMBASE and the Cochrane Register for Controlled Clinical Trials for randomized and controlled clinical trials from 1965 through December, 2010 comparing intravenous beta-blockers administered within 12 hours of presentation of ACS with standard medical therapy and/or placebo. The primary outcome assessed was the risk of short-term (up to short terms) all-cause mortality in the intervention group versus the comparator group. The secondary outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction, cardiogenic shock, and stroke. Pooled treatment effects were estimated using relative ris...
Abstract 12372: Dose-dependent Relationship between Life-long Exercise Training and Central Arterial Stiffness in the Elderly
Authors: Shigeki Shibata, Naoki Fujimoto, Jeffrey L Hastings, Graeme Carrick-Ranson, Nainesh K Gandhi, Paul S Bhella, Benjamin D Levine
Journal: Circulation (2010)

Masters athletes who trained 6–7 sessions per week throughout their adult lives maintain youthful arterial compliance, suggesting that regular and intensive exercise training prevents arterial stif...
Bcl-2 family members are involved in the impaired T cell development in the thymuses of tumor bearing mice
Authors: Roberto Carrio-Jardines, Diana Lopez
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1783 

The thymus is the major site of T cell maturation; extensive proliferation, differentiation, and apoptosis occur in this organ. Thymocyte differentiation progresses through well-defined stages in which apoptosis are central to the selection of a functional TCR repertoire. During mammary tumorigenesis, there is a profound thymus involution associated with a severe depletion of the most abundant subset of thymocytes, CD4+CD8+ double positive (DP) immature cells. The life span of DP thymocytes depends on proper signals mediated first by the pre-TCR and then by the TCR. These signals ultimately regulate the expression of Bcl-2 family prosurvival members, which control susceptibility of DP cells to apoptosis. Previous results from our laboratory have reported that the thymic involution observed in tumor bearing mice is associated with an early block in T cell maturation, changes in the levels of cytokines expressed in the thymus microenvironment, and a minor increase in thymic apoptosis in tumor-bearers. In the present study we have used our well characterized murine D1-DMBA-3 mammary tumor model to better analyze the specific T cell subpopulations present in the thymus of tumor bearing animals. The expression of the different members of the Bcl-2 family was studied in the whole thymus during its involution in mammary tumor bearers. As shown before, flow cytometric analysis revealed a moderate increase in the apoptosis in thymuses of tumor bearing mice. Interestingly, our results show that Bcl-xL, a crucial protein that inhibits apoptosis during thymocyte development, is profoundly down-regulated in total thymuses of tumor hosts as compared to those of normal mice. Also, the protein for A1, another anti-apoptotic Bcl-2 family member that is developmentally regulated in T cells, is down-regulated in thymuses of tumor bearers. Collectively, our data suggest that the presence of the tumor induces changes in the levels of the Bcl-2 family members expressed in the thymus microenvironment contributing to the impaired T cell development in the thymuses of tumor bearers.
Longitudinal Changes of Angle Configuration in Primary Angle-Closure Suspects
Authors: Yuzhen Jiang, Dolly S. Chang, Haogang Zhu, Anthony P. Khawaja, Tin Aung, Shengsong Huang, Qianyun Chen, Beatriz Munoz, Carlota M. Grossi, Mingguang He, David S. Friedman, Paul J. Foster
Journal: Ophthalmology (2014)
Guidelines may affect audit
Authors: A. N Stark
Journal: BMJ (1995)

health care and its evaluation have led to the expectation that studies of use of health services will become prominent.It would be deplorable if unreasonable procedures regarding access to data were to hinder practical applications of health record linkage.Some people will undoubtedly argue that the consent of each subject should be obtained for any procedure that links records.We believe that governments, as custodians of health care data- bases, have a duty to allow scientific investigators access to them in view of the benefits that have resulted from previous studies based on these databases.A requirement for individual consent would lead to the extinction of useful research using health care databases.
Abstract 16815: Cholesterol Efflux Capcity in Genetic Forms of HDL Deficiency
Authors: Sara Alrasheed
Journal: Circulation (2011)

Objective: High-density lipoprotein cholesterol (HDL-C) deficiency is the most frequent lipoprotein abnormality in patients with premature coronary artery disease. In order to determine the functionality of HDL particles in genetically defined HDL deficiency (&lt;5th percentile), we employed a cell-based assay to examine ABCA1-dependent cholesterol efflux capacity in apoB-depleted plasma isolated from 19 probands of French Canadian descent. First degree relatives with normal HDL levels served as controls. Methods and Results: We determined the ability of apoB-depleted plasma to promote cholesterol efflux from [ 3 H] cholesterol-labeled, cAMP-stimulated J774 macrophages. Cases consisted of 16 ABCA1 heterozygotes, and three APOA1 E136X heterozygotes. We obtained evidence that ApoB-depleted plasma isolated from subjects with genetic forms of HDL deficiency had significantly reduced levels of ABCA1-mediated cholesterol efflux as compared to sibling controls (72.33 %). Conversely, when normalized to apoA-I levels, the efflux capacity of apoB-depleted plasma from subjects was attenuated as compared to sibling controls. Linear regression was used to determine which biochemical measurement (apoA-I concentration, HDL-C level and HDL subfractions quantified by 2DPAGGE) best explained the cholesterol efflux results. A strong, positive correlation was found between cholesterol efflux measurements and apoA-I levels, HDL-C levels, alpha-2 HDL levels, and alpha-3 HDL levels (all p&lt; 0.05). However, HDL-C levels only explained approximately 27% of the variability in cellular cholesterol efflux, suggesting that efflux capacity may help better understand HDL functionality. Conclusion: While HDL obtained from subjects with ABCA1 or APOA1 gene defects had decreased cellular cholesterol efflux compared with sibling controls, this difference was markedly attenuated when corrected for apoA-I mass, suggesting that such particles remain functional in cholesterol efflux through ABCA1.
Copy number analysis and allele quantitation by Molecular Inversion Probe (MIP) on GeneChip arrays
Authors: Yuker Wang, Martin Moorhead, Jason Hubbard, Chunnuan Chen, Faroog Siddiqui, Tom Willis, Malek Faham
Journal: Cancer Research (2006)

4210   Copy number change in genomic DNA is a hallmark of cancer cells. These changes include polyploidy, deletions, amplifications. In addition there are changes leading to Loss Of Heterozygosity (LOH) without any copy number change. The identification of these changes may elucidate targets for drug treatment, shed light on the process of tumor progression, and define markers that can predict the patient prognosis and pharmaceutical response. Many chip based technology, including Bacterial Artificial Chromosome (BAC) CGH, cDNA CGH, and oligonucleotide CGH have been developed in recent years to address the issues. We here describe a new approach for copy number analysis based on the Molecular Inversion Probe (MIP) technology. Advantages of this technology include; 1.Sensitivity: Detection of single copy changes. 2.Customization: Ability to focus on the most relevant genomic segments 3.Preservation of allele information: LOH and other disturbances in the allele ratio can be detected 4.Ability to work with FFPE (formalin fixed paraffin embedded) samples: Given the small probe footprint, degraded samples can work successfully with MIP. We have designed a panel about 17,000 probes focusing on SNPs across the genome as well as in 1,200 cancer related genes. In addition to the detection of large genomic abnormalities, small aberrations in the candidate genes can be detected. Using this panel of probes we have identified copy number and allele ratio abnormalities in cell lines from normal individuals. In this presentation we will report high degree amplification and deletions in tumor samples.
Imipramine and seizures
Authors: Theodore Petti, M. Campbell
Journal: American Journal of Psychiatry (1975)

The authors report the case of a psychotic preschool child who manifested a seizure disorder while on imipramine treatment. They note that according to his history and physical exam, the child fell within a group which seems predisposed to this side effect. Although tricyclic antidepressant compounds can be used judiciously with seizure-prone individuals, the authors recommend that alternative modalities be given first consideration.
Identification of OSGPR78 and OSGPR114 as two novel lysophosphatidic acid G-protein coupled receptors
Authors: Graeme Griffin, April Thelemann, Gina Radosinic, Diane Triebe, Alexandra Eyzaguirre, Kathryn Weinslaw, Jianping Song, Graham Craggs, Utsav Bali, Salam Shaaban, Martin McKinney, Neil Gibson, Bert Oehlen, John Haley
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4499 

Lysophosphatidic acid (LPA) is a well characterized growth and survival factor for cancer cells in culture. This study details the identification of two G-protein coupled receptors, OSGPR78 and OSGPR114 as novel lysophosphatidic acid (LPA) receptors. OSGPR78 and OSGPR114, when expressed in a yeast-based reporter assay, are activated by multiple analogs of LPA, including myristoyl, palmitoyl, oleoyl, stearoyl and polyunsaturated LPA analogs. Similarly, when expressed in mammalian cells, the receptors also respond to the same LPA analogs. Pertussis toxin sensitivity of the effects of LPA activation of OSGPR114 expressed in CHO cells suggests a coupling to Gi/o proteins. Amino acid homologies of OSGPR114 and OSGPR78 demonstrate no obvious similarity with the known LPA G-protein coupled receptors LPA1-3. The expression of these novel LPA receptors in normal human tissues, cancer cell lines and in tumor samples has been characterized using fluorogenic real-time PCR. In normal tissues, OSGPR114 was expressed at the highest levels in areas such as the lung, kidney, leukocytes and ovary, whereas OSGPR78 was found to be expressed at high levels in almost every tissue studied. Several cancer cell lines have been identified which express OSGPR78 or OSGPR114 as the predominant LPA receptor and both receptors are widely expressed in human tumor samples. Furthermore, in cell lines shown to express OSGPR114 or OSGPR78, small interfering RNA oligonucleotides (siRNA) designed to specifically knockdown OSGPR114 and OSGPR78 expression induced a growth-inhibitory and pro-apoptotic phenotype in cells maintained in full serum. In summary, we demonstrate that OSGPR78 and OSGPR114 are novel LPA activated G-protein coupled receptors. Initial evidence suggests that OSGPR114 and OSGPR78, like the known LPA receptors (LPA1-3 and gpr23), are involved in mediating the proliferation and survival effects of LPA on cancer cells in culture.
Delivery of siRNA Using CXCR4-targeted Nanoparticles Modulates Tumor Microenvironment and Achieves a Potent Antitumor Response in Liver Cancer
Authors: Jia-Yu Liu, Tsaiyu Chiang, Chun-Hung Liu, Guann-Gen Chern, Ts-Ting Lin, Dong-Yu Gao, Yunching Chen
Journal: Molecular Therapy (2015)

Antiangiogenic therapy has recently emerged as a highly promising therapeutic strategy for treating hepatocellular carcinoma (HCC). However, the only clinically approved systemic antiangiogenic agent for advanced HCC is sorafenib, which exerts considerable toxicity. Moreover, acquired resistance to antiangiogenic therapy often develops and restricts the therapeutic efficacy of this treatment. Hence, in this study, we develop a CXCR4-targeted lipid-based nanoparticle (NP) formulation to specifically deliver vascular endothelial growth factor (VEGF) siRNA as an antiangiogenic substance into HCC. AMD3100, a CXCR4 antagonist, is added into NPs to serve as both a targeting moiety and a sensitizer to antiangiogenic therapy. We demonstrate that AMD-modified NPs (AMD-NPs) can efficiently deliver VEGF siRNAs into HCC and downregulate VEGF expression in vitro and in vivo. Despite the upregulation of the SDF1α/CXCR4 axis upon the induction of hypoxia after antiangiogenic therapy, CXCR4 inhibition by AMD-NPs in combination with either conventional sorafenib treatment or VEGF siRNA prevents the infiltration of tumor-associated macrophages. These dual treatments also induce synergistic antiangiogenic effects and suppress local and distant tumor growth in HCC. In conclusion, the tumor-targeted multifunctional AMD-NPs that co-deliver VEGF siRNA and AMD3100 provide an effective approach for overcoming tumor evasion of antiangiogenic therapy, leading to delayed tumor progression in HCC.
Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR)
Authors: RK Puri, P Leland, NI Obiri, SR Husain, RJ Kreitman, GP Haas, I Pastan, W Debinski
Journal: Blood (1996)
Cell Death Identification in Anticancer Therapy—Letter
Authors: J. Martin Brown, Bradly G. Wouters, David G. Kirsch
Journal: Cancer Research (2015)

In their recent review, Rello-Varona and colleagues (1) emphasize that “The correct evaluation of cell death in every experimental setting related to cancer research is a must.” Accordingly, they discuss the variety of methods to identify dead cells and to distinguish the various forms of cell death from one another. While we agree with their descriptions of the different forms of cell death and appreciate that the mechanism of cell death is often worth characterizing in cancer research, we would emphasize three aspects of cell killing that make the precise characterization of the type of cell death less important than the quantification of cell survival using clonogenic endpoints when evaluating cancer therapies: We believe that the above considerations are succinctly summarized by the Nomenclature Committee on Cell Death 2012 (6): “During the process of functional characterization, great attention should be paid to ensure that genetic and chemical interventions truly modify the incidence of cell death (as assessed by clonogenic cell survival), rather than activate alternative lethal pathways.”See the Response, p. 3682No potential conflicts of interest were disclosed.
Abstract 1845: Automated Assessment of Left Atrial Function from Time-Left Atrial Volume Curve by Velocity Vector Imaging
Authors: Keitaro Ogawa, Takeshi Hozumi, Kenichi Sugioka, Shinichi Iwata, Hiroki Oe, Ryo Otsuka, Yasuhiro Takagi, Hidetoshi Yoshitani, Minoru Yoshiyama, Junichi Yoshikawa
Journal: Circulation (2006)

Background: Velocity vector imaging (VVI) is one such approach that allows measurement of myocardial velocity and deformation in the apical and short-axis views of a cardiac chamber. Using VVI, tim...
Pulmonary embolism
Authors: T. Fennerty
Journal: BMJ (1998)

The management of suspected pulmonary embolism is a subject in which consensus has been difficult to achieve due to the lack of firm evidence.1 Against this background, the British Thoracic Society has suggested a “practical approach to suspected acute pulmonary embolism.”2 After a comprehensive review of current literature, the report makes several recommendations, graded for evidence, and finishes with a series of charts designed for a junior doctor's handbook covering diagnosis and management. While some of the recommendations lack top grade evidence and inevitably will be controversial, the authors achieve what they set out to do and provide a practical approach to a difficult subject using new knowledge “little of which,” as the report bluntly states, “has filtered through to clinical practice.” Certain items in this comprehensive report are worth emphasising.

Pulmonary embolism is both underdiagnosed and overdiagnosed. Ten per cent of all hospital deaths are due to acute pulmonary embolism, most of which are diagnosed only at necroscopy. It is easily missed in patients with cardiorespiratory disease (in whom even small emboli can be fatal), elderly patients, and those …
Abstract 409: Ex-vivo Targeting Of Insulin-like Growth Factor-1 Gene To The Heart Promotes Mobilization And Homing Of Stem Cells Through Paracrine Release Of Stromal Cell Derived Factor-1{alpha}
Authors: Shujia Jiang, Husnain K Haider, Niagara Muhammad Idris, Muhammad Ashraf
Journal: Circulation (2007)

Background:  We hypothesize that genetic modification of mesenchymal stem cells (MSCs) to overexpress IGF-1 enhances their survival and engraftment in the infarcted heart and promotes recruitment of stem cells through paracrine release of SDF-1α   Methods and Results:  MSCs from male rat were either used as non-transduced ( Non-Trans MSCs) or transduced with adenoviral null-vector ( Null MSCs) or vector encoding for IGF-1 ( IGF-1 MSCs). IGF-1 mRNA and protein levels in  IGF-1 MSCs were higher until 12 days as compared with  Null MSCs ( p ). Molecular studies revealed higher levels of phosphorylated (p) p-Akt (2-fold), p-P27 (>20-fold), and p-P21 (>30-fold) together with SDF-1α(>24-fold), all of which increased in parallel with IGF-1 expression (200-fold) in  IGF-1  MSCs as compared with  Null MSCs. For in vivo studies, coronary artery was ligated in female rats and 70μl DMEM without cells (group-1) or containing 3x10 6 Null MSCs (group-2) or  IGF-1 MSCs (group-3) were implanted into infarct and peri-infarct areas. One week later, immunoblot showed elevated myocardial levels of IGF-1, p-Akt, and p-P27 accompanied by higher survival of  IGF-1 MSCs ( p  Null MSCs) as determined by real-time PCR for  sry -gene. Enhanced cell proliferation was observed after immunostaining for Ki67+in group-3 ( p  vs all groups). SDF-1α protein was increased in group-3 animal hearts (20-fold vs group-2), with massive mobilization and homing of ckit + GATA4 +, MDR1 + GATA4−, ckit + GATA4−, and CXCR4 + cells into infarcted heart. Animals harvested at six weeks showed significantly reduced infarction size in groups-2 & 3 as compared with group-1. Confocal imaging after immunostaining for myosin heavy chain, troponin-I, actinin, connexin-43, vonWilbrand factor-VIII and smooth muscle actin showed extensive myogenic regeneration and angiogenesis in the infarcted heart. Indices of left ventricle function including ejection fraction and fractional shortening were significantly improved in group-3 as compared with group-1 ( p ).   Conclusions:  Ex-vivo delivery of IGF-1 activated pro-survival and proliferation signaling. Moreover, paracrine release of SDF-1α subsequent to IGF-1 overexpression caused extensive mobilization and homing of stem cells into infarcted heart.
Are males more likely than females to develop schizophrenia?
Authors: W G Iacono, M Beiser
Journal: American Journal of Psychiatry (1992)

This study was undertaken to determine whether the incidence of schizophrenia is equivalent for males and females.An attempt was made to identify every first-episode case of psychosis in a large Canadian city over a period of 2 1/2 years. A comprehensive referral network was established that included hospital and community settings where psychotic persons might appear. More than 300 potential subjects were identified, 175 of whom underwent a structured psychiatric interview and were assigned diagnoses according to five different diagnostic systems.The incidence of schizophrenia was two to three times higher among males than among females. Even though the use of different diagnostic systems yielded slightly different risk rates, the elevated risk for males remained consistent. There were no differences between the sexes in the incidence of affective psychosis. In comparison with schizophrenia, the incidence rates for mood disorders with psychotic features were sometimes lower and sometimes higher, depending on the diagnostic system used.The findings, coupled with reports in the past 10 years from other investigators, challenge the conventional belief that the incidence of schizophrenia is the same for the two sexes.
Incidence of Vascular Thrombotic Events in 183 Consecutive Patients Treated with Nilotinib: A Single Centre Experience
Authors: James Gilbert, Simona Deplano, Richard Szydlo, Renuka Palanicawandar, Gareth Gerrard, Letizia Foroni, Jane F. Apperley, Dragana Milojkovic
Journal: Blood (2014)
Abstract P144: Determinants of Cardiorespiratory Fitness in an Overweight and Obese High-Risk African-American Population
Authors: Lisa R Yanek, Dhananjay Vaidya, Devon A Dobrosielski, Brian G Kral, Taryn F Moy, Diane M Becker, Kerry J Stewart
Journal: Circulation (2013)

Introduction:  African Americans (AA) often have low levels of cardiorespiratory fitness, explained in prior studies primarily by body mass index (BMI). Given the marked heterogeneity in the ratio of metabolically active lean (muscle) mass versus fat mass, even across ranges of higher BMI, we examined the extent to which higher levels of lean versus fat mass are independently associated with fitness in healthy overweight and obese AA from families with early-onset coronary disease.   Methods:  Subjects were screened for demographics, smoking, blood pressure, levels of blood lipids, hsCRP, glucose, and insulin; body composition was determined by dual energy X-ray absorptiometry; the ratio of lean mass to fat mass was calculated and log-transformed for analysis. Habitual physical activity was assessed with the Stanford 7-Day Physical Activity Recall. Fitness was expressed as VO2peak attained during maximal treadmill testing. Linear regression was used to model VO2peak, adjusted for cardiovascular risk factors and nonindependence of families.   Results:  Participants (n=195; 69% women) were 44.8 ± 11 years old with mean BMI 34 ± 5 kg/m2. In regression analysis, increased lean to fat mass ratio was associated with increased VO2peak (p   Conclusions:  The ratio of lean to fat mass was the key determinant of cardiorespiratory fitness, independent of sex, age, and the magnitude of obesity in this cohort of high-risk overweight and obese AAs. The results suggest that interventions that preserve or increase lean mass may increase cardiorespiratory fitness.