tbuckley/cabot-search huggingface dataset:
Traffic-Related Air Pollution, <i>APOE</i> ε4 Status, and Neurodevelopmental Outcomes among School Children Enrolled in the BREATHE Project (Catalonia, Spain)
Authors: Silvia Alemany, Natàlia Vilor-Tejedor, Raquel García-Esteban, Mariona Bustamante, Payam Dadvand, Mikel Esnaola, Marion Mortamais, Joan Forns, Barend L. van Drooge, Mar Álvarez-Pedrerol, Joan O. Grimalt, Ioar Rivas, Xavier Querol, Jesus Pujol, Jordi Sunyer
Journal: Environmental Health Perspectives (2018)

BACKGROUND: Traffic-related air pollution is emerging as a risk factor for Alzheimer's disease (AD) and impaired brain development.Individual differences in vulnerability to air pollution may involve the e4 allele of Apolipoprotein E (APOE) gene, the primary genetic risk factor for AD.OBJECTIVE: We analyzed whether the association between traffic air pollution and neurodevelopmental outcomes is modified by APOE e4 status in children.METHODS: Data on parent-reported behavior problems (total difficulties scores, Strengths and Difficulties Questionnaire), teacher-reported attentiondeficit hyperactivity disorder (ADHD) symptom scores, cognitive performance trajectories (computerized tests of inattentiveness and working memory repeated 2-4 times during January 2012-March 2013), and APOE genotypes were obtained for 1,667 children age 7-11 y attending 39 schools in or near Barcelona.Basal ganglia volume (putamen, caudate, and globus pallidum) was measured in 163 of the children by MRI (October 2012-April 2014.)Average annual outdoor polycyclic aromatic hydrocarbons (PAHs), elemental carbon (EC), and nitrogen dioxide (NO 2 ) concentrations were estimated based on measurements at each school (two 1-wk campaigns conducted 6 months apart in 2012).RESULTS: APOE e4 allele carriers had significantly higher behavior problem scores than noncarriers, and adverse associations with PAHs and NO 2 were stronger or limited to e4 carriers for behavior problem scores (P-interaction 0.03 and 0.04), caudate volume (P-interaction 0.04 and 0.03), and inattentiveness trajectories (P-interaction 0.15 and 0.08, respectively).Patterns of associations with the same outcomes were similar for EC.CONCLUSION: PAHs, EC, and NO 2 were associated with higher behavior problem scores, smaller reductions in inattentiveness over time, and smaller caudate volume in APOE e4 allele carriers in our study population, and corresponding associations were weak or absent among e4 noncarriers.These findings support a potential role of APOE in biological mechanisms that may contribute to associations between air pollution and neurobehavioral outcomes in children.
Abstract 18513: School-based Rheumatic Heart Disease Education Results in Improved Knowledge - Data From the PROVAR Study
Authors: Bruno R Nascimento, Andrea Z Beaton, Graziela Chequer, Kaciane K Bruno, Cassio O Miri, Eduardo L Lopes, Iara M Castro, Maria do Carmo P Nunes, Julia P Santos, Antonio Luiz P Ribeiro, Craig Sable
Journal: Circulation (2015)

Introduction: Rheumatic Heart Disease (RHD) remains an important cause of morbidity and mortality in Brazil and other low- and middle-income countries (LMIC). Lack of public awareness of the causes and prevention of RHD limit the efficacy of primary and secondary prevention programs. Objectives: To evaluate the efficacy of knowledge transfer that results from a structured public-school educational program on RHD. Methods: A prospective, cohort study was conducted over 7 months (9/2014-3/2015) in 5 randomly selected low-income public schools in Belo Horizonte, Brazil. All enrolled and present students received education. A nurse and an imaging technician utilized two custom structured educational curriculums, targeting children in grades 6 - 11 (aged 11-17). Pre-tests, taken immediately prior to educational curriculum queried students’ knowledge of the causes, prevention, diagnosis, and treatment of RHD. Post-tests, 1-3 weeks following education assessed the efficacy of knowledge transfer and retention. Results: The educational curriculum was delivered to 3200 students. One-third of these (1025) were randomly selected to participate in pre- and post-testing including 403 (39%) in 6th/7th grades (G1), 360 (35%) in 8th/9th (G2), and 261 (26%) of in 10th/11th grades (G3). The mean interval between pre-test and post-test was 10±10 days. Prior to the intervention, general knowledge regarding RHD was universally low (median score 46.7%, 40.0-60.0). Children in higher grades (G3) knew more about RHD than those in lower grades (60% vs. 40.0% G1/46.7% G2), p&lt;0.001. Children showed significant gains in the post-test, raising the median score by 20 percent (60%, 40.0-73.3). Again, children in the higher grades showed higher overall scores (73%, 60.0-80.0 G3; 56.7%, 40.0-73.3 G2; 53.3%, 33.3-66.7 G1), p&lt;0.001. However, the percent increase was similar between groups (6.8% G1, 6.8% G2, 8.5% G3), p=0.47. Conclusions: School-based RHD education resulted in consistent but modest gains in knowledge. Novel educational techniques and use of technology to engage young learners may lead to improved knowledge gains and retention. Further studies are needed to determine if increased knowledge leads to behavioral changes that could decrease the burden of RHD in LMIC.
Independent and Joint Effects of Antibodies to Human Heat-Shock Protein 60 and Chlamydia pneumoniae Infection in the Development of Coronary Atherosclerosis
Authors: KatalinBurian, ZoltanKis, DezsoVirok, ValeriaEndresz, ZoltanProhaszka, JenoDuba, KlaraBerencsi, KrisztinaBoda, LauraHorvath, LaszloRomics, GeorgeFust, EvaGonczol
Journal: Circulation (2001)

Background—Studies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (Cpn), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. Methods and Results—A total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, Cpn, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and Cpn but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and Cpn did not correlate quantitatively; however, the relative risk of disease developmen...
Abstract 18159: Myocyte Turnover in the Mouse Heart
Authors: Giulia Borghetti, Yingnan Bai, Ewa Wybieralska, Barbara Okorek, Kazuya Isobe, Alex Matsuda, Mark Seymour, Todd Pankratz, Eric Guarin, Polina Goichberg, Annarosa Leri, Marcello Rota, Piero Anversa, Jan Kajstura
Journal: Circulation (2013)

Despite the identification of cardiac stem cells and their ability to differentiate in the various cardiac cell lineages, the controversy on the turnover rate of myocytes in the adult heart continues. Two independent but complementary protocols were employed to define myocyte renewal in the mouse heart. Mice 2-3 months of age were injected every 12 hours with BrdU (50mg/kg bw) for 6 days prior to sacrifice. A second group of mice received one injection of 14 C-thymidine (300 pCi) and the animals were sacrificed from 1 to 90 days later. The BrdU method allowed us to measure the number of myocytes formed in 6 days. The 14 C-thymidine strategy provided us with an evaluation of myocyte regeneration as a function of time. In assay 1, BrdU localization in myocytes was determined by immunolabeling and confocal microscopy. After 12 injections of BrdU, 3.1±0.4% or 100,000±13,000 (n=8) left ventricular (LV) myocyte nuclei were labeled, indicating that a significant number of parenchymal cells was added to the LV in 6 days. Given that the number of LV myocytes is constant in the adult mouse heart, myocyte apoptosis and necrosis were measured by hairpin 1 and hairpin 2 in situ ligation, respectively. Myocyte necrosis was also assessed by the incorporation of circulating vitronectin that reflects an irreversible loss of integrity of the plasma-membrane. Apoptosis comprised 186±55 myocyte nuclei/10 6 (n=6) and cell necrosis 316±71/10 6 nuclei. Similarly, vitronectin-positive myocytes were 280±103/10 6 cell profiles (n=4). Since apoptosis last at most 4 hours and necrosis 20 hours, there was a 2.9±0.4% drop out of myocytes in 6 days. In assay 2, LV myocytes were isolated, purified by differential centrifugation, and the DNA extracted for the measurement of the kinetics of 14 C concentration by Accelerator Mass Spectrometry. 14 C concentration in myocyte DNA increased progressively from 1 to 10 days, and remained essentially constant up to 90 days. These findings indicate that a significant number of new myocytes was formed in 10 days. The regenerated myocytes had a lifespan of at least 90 days as demonstrated by the lack of changes in 14 C from 10 to 90 days. This value is consistent with the rate of myocyte formation and death measured above. Thus, myocyte turnover is high in the adult mouse heart.
Abstract 198: Angiotensin II Inhibits Cardiac Angiogenesis via the Cooperation of p53 and Jagged 1
Authors: Aili Guan, Hui Gong, Yong Ye, Jianguo Jia, Guoping Zhang, Aijun Sun, Junbo Ge, Yunzeng Zou
Journal: Circulation Research (2012)

It is well established that angiotension II (Ang II) is an important regulator in vascular homeostasis. Under certain conditions, Ang II could exert anti-angiogenic effects in cardiovascular system. However, the potential mechanism is unclear. P53 has been reported to suppress angiogenesis by promoting hypoxia-inducible factor-1 (Hif-1α) degradation. This study was conducted to determine the contribution of P53 and the underlying mechanism to the anti-angiogenic effect of Ang II. Angiogenesis was determined by tube formation from the cardiac microvascular endothelial cells (ECs). Microvessel density and cardiac function were analyzed in mice subjected to Ang II infusion (200 ng/kg/min ) or vehicle for 2 weeks. Ang II (1μM) greatly inhibited tube formation and stimulated phosphorylation and upregulation of P53 in cultured cardiac ECs. P53 inhibitor, pifithrin-α (PFT-α,3.0mg/kg), significantly reversed the inhibitory effect of Ang II on tube formation. Vascular endothelial growth factor (VEGF ) and Hif-1α has been reported as important pro-angiogenetic factors. The present study indicated that Ang II decreased VEGF concentration in cultured medium and downregulated Hif-1α expression in cultured ECs. Interestingly, Ang II also stimulated the upregulation of Jagged 1, a ligand of Notch, but it didn't affect the Delta-like 4 (Dll 4) , another ligand of Notch, expression in cardiac ECs. However, PFT-α partly abolished these effects of Ang II. These results were consistent with the study in vivo. Further research revealed that siRNA-Jagged 1 transfection in cultured ECs dramatically abolished the phosphorylation of P53 and the downregulation of Hif-1α induced by Ang II. Additionally, Ang II- induced inhibitory effect on capillary formation was blocked by siRNA-Jagged 1 transfection in cultured cardiac ECs. In conclusion, Ang II promoted the phosphorylation and upregulation of P53, and increased Jagged 1 expression, the upregulation of Jagged 1 in turn stimulated the phosphorylation of P53, which resulted in the downregulation of Hif-1α and VEGF, then induced the inhibitory effects of Ang II on capillary formation. The present data suggest that Ang II exerts anti-angiogenesis via the cooperation of P53 and Jagged 1 in vitro and in vivo.
Abstract 2293: Outstanding chromosomal expression patterning in human cancers
Authors: Spencer Barnes, Mingzhou Song
Journal: Cancer Research (2018)

Abstract Cancer transcriptome is an effect of abnormal genetic and/or epigenetic regulation. In the past, transcriptome was studied at the level of individual transcripts for their differential expression. Spatial gene expression patterns along chromosomes were not yet characterized for cancer. We hypothesized that gene expression patterning is not randomly distributed along the chromosomes in cancer versus normal tissues. We analyzed cancer transcriptome from the National Cancer Institute Genomic Data Commons, and identified genomic regions with significant shifts in expression from normal tissues to tumors. We used a novel highly efficient method in the Ckmeans.1d.dp package for clustering genes by chromosomal location and expression level. We identified two chromosomal zones of note that exhibit similar expression patterns across several cancer types. In breast, lung, liver, and esophageal cancers, a zone near 6p22.2 contains genes that are similarly highly upregulated in tumor tissues compared to matched normal tissues. This zone contains a group of histone cluster 1 genes, among which are 14 known cancer genes. In colorectal, lung, liver, and esophageal cancers, a zone on 14q32.33 exhibits either heavy up- or downregulation, dependent on the specific cancer. This zone is rich in immunoglobulin heavy variable genes. Table 1 lists genomic zones of note specific to six cancer types. Our study provides an atlas of outstanding chromosomal expression patterning that can be used as markers for cancer in general and also for specific cancer types. Table 1. Outstanding genomic zones specific to six human cancer types.Cancer type Chr:start-end (Mb) Cytogenetic band # Matched tumor/normal pairsBreastchr2:88-92p11.2112Colorectalchr7:141-146q3541Esophagealchr11:7-12p15.48Kidneychr12:85-91q21.3323Liverchr8:15-22p2250Lungchr8:121-126q24.1357 Citation Format: Spencer Barnes, Mingzhou Song. Outstanding chromosomal expression patterning in human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2293.
Yttrium-90 ibritumomab tiuxetan (zevalin) induces high response rates in previously treated patients with diffuse large B cell lymphoma (DLBCL)
Authors: F. Morschhauser, D. Huglo, G. Martinelli, G. Paganelli, P. Zinzani, D. Hadjiyiannakis, Anna Marina Liberati, T. Illidge, N. Milpied, J. Kalmus, P. Morel, U. Reimann, R. Marcus
Journal: Annals of Oncology (2005)
Abstract 16174: Regions With Low Rates of Bystander CPR Also Have Lower Rates of Residents With CPR Training: A Telephone Survey of Residents in Victoria, Australia
Authors: Janet E Bray, Lahn Straney, Karen Smith, Susie Cartledge, Rosalind Case, Stephen Bernard, Judith Finn
Journal: Circulation (2016)

Introduction: Despite the availability of dispatcher cardiopulmonary resuscitation (CPR) instructions, recent data showed variation in bystander CPR rates across the Australian state of Victoria (population 5.79 million). This study aims to determine if there is an associated regional variation in Victorian’s CPR training rates, knowledge and attitudes. Methods: In April 2015, we conducted a telephone survey of 404 adult Victorians. Using adult bystander witnessed data from the Victorian Cardiac Arrest Registry (VACAR) for the period 2008 to 2015, we calculated smoothed bystander CPR rates for each Victorian postcode (adjusting for temporal trends). The residential postcodes of those surveyed were then categorised as either high or low bystander CPR regions using the smoothed median bystander CPR rate (75.8%). Respondents residing in postcodes with no OHCAs in the study period (n=18), were categorised using the average rates of surrounding postcodes. The telephone survey data was then compared between reg...
Angiogenesis by Implantation of Peripheral Blood Mononuclear Cells and Platelets Into Ischemic Limbs
Authors: OsamuIba, HiroakiMatsubara, YoshihisaNozawa, SoichiroFujiyama, KatsuyaAmano, YasukiyoMori, HiroyukiKojima, ToshijiIwasaka
Journal: Circulation (2002)

Background— Peripheral blood mononuclear cells (PBMNCs), platelets, and polymorphonuclear leukocytes (PMNs) contain various angiogenic factors and cytokines. Methods and Results— Unilateral hindlimb ischemia was surgically induced in athymic nude rats, and fluorescence-labeled human blood cells (PBMNCs [107 cells]+platelets [109] or PBMNCs [107]+platelets [109]+PMNs [107]) were intramuscularly implanted into the ischemic limbs. Laser Doppler imaging revealed markedly increased blood perfusion in PBMNC+platelet-implanted limbs (44% increase, P<0.001) compared with control implantation of human umbilical vein vascular endothelial cells. The addition of PMNs to PBMNCs+platelets attenuated blood perfusion (27% decrease, P<0.01). Neocapillary densities were increased by implantation of PBMNCs+platelets or platelets alone (3.5-fold and 2.4-fold, respectively; P<0.001), whereas PMNs inhibited (32%, P<0.05) PBMNC+ platelet-mediated capillary formation. There was no incorporation of implanted PBMNCs into neocapill...
Maladaptive Aortic Properties in Children After Palliation of Hypoplastic Left Heart Syndrome Assessed by Cardiovascular Magnetic Resonance Imaging
Authors: IngaVoges, MichaelJerosch-Herold, JürgenHedderich, CharlotteWestphal, ChristopherHart, MichaelHelle, JensScheewe, EileenPardun, Hans-HeinerKramer, CarstenRickers
Journal: Circulation (2010)

Background—The status of the reconstructed aorta in hypoplastic left heart syndrome is considered an important determinant of long-term prognosis. Therefore, we assessed the anatomy, elastic properties, and viability of the aorta and right ventricular function in patients with hypoplastic left heart syndrome by cardiovascular magnetic resonance imaging. Methods and Results—Cardiovascular magnetic resonance imaging was performed in 40 patients with hypoplastic left heart syndrome (age, 6.0±2.2 years) and 13 control subjects (age, 6.6±2.2 years). Aortic dimensions and distensibility were calculated at different locations of the aorta using gradient-echo cine imaging at 3.0 T. Additionally, pulse-wave velocity, right ventricular ejection fraction, and aortic late gadolinium enhancement for viability assessment were measured. Compared with control subjects, patients with hypoplastic left heart syndrome had increased axial diameters of the aortic root (36.0±5.5 versus 24.1±2.7 mm/m2; P<0.01), ascending aorta (...
Abstract 14928: Significance of Slow Potential Recorded at the Slow Conduction Zone in Verapamil-sensitive Atrial Reentrant Tachycardia Originating From the Atrioventricular Annulus
Authors: Hiroshige Yamabe, Hisanori Kanazawa, Miwa Ito, Shozo Kaneko, Yusuke Kanemaru, Takuya Kiyama, Hisao Ogawa
Journal: Circulation (2016)

Background: Calcium-channel dependent tissue (Ca-DT) forms the slow conduction zone (SCZ) of the reentry circuit in verapamil-sensitive atrial tachycardia originating from the atrioventricular annulus (AVA-AT). This suggest the presence of specific electrogram which reflects the Ca-DT at the SCZ in AVA-AT, as slow potential is recorded at the slow pathway area in AV nodal reentrant tachycardia. Objective: The purpose of this study was to elucidate whether there is a specific electrogram which represents the Ca-DT of the SCZ in AVA-AT. Methods: In 21 AVA-AT, the proximity of SCZ was identified by the rapid atrial pacing from which manifest entrainment and orthodromic capture of the earliest atrial activation site (EAAS) were observed. To define the entrance site of SCZ, radiofrequency energy was delivered starting at a site 2 cm proximal to the EAAS and then gradually advanced toward EAAS until termination of AVA-AT. The electrogram morphology at successful site (i.e., entrance site of SCZ) was compared wi...
Abstract 51: The eukaryotic translation initiation factor 4H regulates proliferation, migration, and invasion in cancer cells
Authors: Manohar Singh, Rachana Trivedi, Durga Prasad Mishra
Journal: Clinical Cancer Research (2017)

Abstract Background: Dysregulated translation during protein synthesis is a hallmark of multiple human cancers. However, the precise mechanisms remain to be understood. Protein translation of oncogenic mRNAs is highly upregulated in cancer cells and these cells are very sensitive to therapeutic strategies/agents targeting translation inhibition. In this study we investigated the role of translation initiation factor eIF4H in proliferation and survival of cancer cells. Methods: We selected the breast cancer cell line MDA-MB 231 and the CML cell line K562 for our study. We silenced eIF4H by shRNA and cell proliferation were analyzed by MTT assay and flowcytometry. Expression of antiapoptotic and proproliferative proteins were analyzed by Western blotting and for analysis of mRNA expression real-time PCR was used. Effect of eIF4H silencing on cell migration and invasion was analyzed by migration and invasion assays, respectively. Results: Using 2D Gel based proteomics we targeted the translational machinery in chronic myeloid leukemia cell line K562 and identified eIF4H as a critical regulator of carcinogenesis. The eIF4H expression was found to be overexpressed in a variety of cancer cell line vis-à-vis the normal nontransformed cells. Similarly, the real-time PCR analysis showed eIF4H overexpression in chronic myeloid leukemia clinical samples compared to that of the healthy controls. The pharmacologic inhibition of eIF4H induced downregulation of its regulatory proteins cMYC, cyclin D1, and antiapoptotic proteins in breast cancer cell line MDAMB-231 and CML cell line K562 cells. The genomic inhibition of eIF4H decreased cell migration and invasion in vitro in MDA-MB 231 cell line and it also inhibits proliferation of both cell lines. Furthermore, the p65-dependent transcriptional activation of eIF4H was observed to be associated with this process. Conclusion: Our results demonstrate that eIF4H plays an important role in the proliferation, migration, and invasion of cancer cells. Silencing of eIF4H markedly decreased expression of antiapoptotic and proproliferative proteins. Collectively, our findings suggest that eIF4H may have translational relevance as a therapeutic target in cancer therapy. Citation Format: Manohar Singh, Rachana Trivedi, Durga Prasad Mishra. The eukaryotic translation initiation factor 4H regulates proliferation, migration, and invasion in cancer cells [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 51.