tbuckley/cabot-search huggingface dataset:
The Potential Health Impacts of Climate Variability and Change for the United States: Executive Summary of the Report of the Health Sector of the U.S. National Assessment
Authors: Jonathan A. Patz, Michael A. McGeehin, Susan M. Bernard, Kristie L. Ebi, Paul R. Epstein, Anne Grambsch, Duane J. Gubler, Paul Reiter, Isabelle Romieu, Joan B. Rose, Jonathan M. Samet, Juli Trtanj
Journal: Environmental Health Perspectives (2000)

We examined the potential impacts of climate variability and change on human health as part of a congressionally mandated study of climate change in the United States. Our author team, comprising experts from academia, government, and the private sector, was selected by the federal interagency U.S. Global Change Research Program, and this report stems from our first 18 months of work. For this assessment we used a set of assumptions and/or projections of future climates developed for all participants in the National Assessment of the Potential Consequences of Climate Variability and Change. We identified five categories of health outcomes that are most likely to be affected by climate change because they are associated with weather and/or climate variables: temperature-related morbidity and mortality; health effects of extreme weather events (storms, tornadoes, hurricanes, and precipitation extremes); air-pollution-related health effects; water- and foodborne diseases; and vector- and rodent-borne diseases. We concluded that the levels of uncertainty preclude any definitive statement on the direction of potential future change for each of these health outcomes, although we developed some hypotheses. Although we mainly addressed adverse health outcomes, we identified some positive health outcomes, notably reduced cold-weather mortality, which has not been extensively examined. We found that at present most of the U.S. population is protected against adverse health outcomes associated with weather and/or climate, although certain demographic and geographic populations are at increased risk. We concluded that vigilance in the maintenance and improvement of public health systems and their responsiveness to changing climate conditions and to identified vulnerable subpopulations should help to protect the U.S. population from any adverse health outcomes of projected climate change.
Endothelin-A Receptor Blockade Prevents Left Ventricular Hypertrophy and Dysfunction in Salt-Sensitive Experimental Hypertension
Authors: LarsRothermund, RolandVetter, MaikeDieterich, PeterKossmehl, ÖzlemGögebakan, ChanaYagil, YoramYagil, ReinholdKreutz
Journal: Circulation (2002)

Background— Salt-sensitive hypertension represents a major cause of left ventricular (LV) dysfunction. We therefore explored the potential effects of the selective endothelin-A (ETA) receptor antagonist darusentan on the development of hypertension, LV hypertrophy (LVH), and dysfunction in a genetic rat model of salt-sensitive hypertension. Methods and Results— Animals from the salt-sensitive Sabra rat strain (SBH/y) and the salt-resistant strain (SBN/y) were treated with either normal diet (SBH/y and SBN/y) or with deoxycorticosterone-acetate (DOCA) and salt (SBN/y-DOCA and SBH/y-DOCA). Additional groups were treated with 50 mg · kg−1 · d−1 of darusentan (SBH/y-DOCA-DA and SBN/y-DOCA-DA). Systolic blood pressure and LV weight increased in response to DOCA only in the SBH/y strain (+75 mm Hg and +30%; P<0.05). LV end-diastolic pressure increased and −dP/dtmax decreased in SBH/y-DOCA compared with SBH/y (P<0.05). This was paralleled by a 5-fold upregulation of LV mRNA expression of atrial natriuretic facto...
Re: Isabel Rauscher, Charlotte Düwel, Bernhard Haller, et al. Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen–ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy. Eur Urol 2018;73:656–61
Authors: Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2018)
Abstract 2921: Co-inhibition of BET and proteasome enhances ER stress and Bim-dependent apoptosis with augmented cancer therapeutic efficacy
Authors: Guoqing Qian, Weilong Yao, Williams D. Hall, Mala Shanmugam, Sagar Lonial, Shi-Yong Sun
Journal: Cancer Research (2018)

Abstract Background: Agents that inhibit bromodomain and extra-terminal domain (BET) protein, a promising cancer therapeutic target which imposes epigenetic modulation of gene expression, have been actively tested in the clinic as potential anticancer drugs. Some proteasome inhibitors such as carfilzomib (CFZ) are FDA-approved drugs for the treatment of patients with advanced multiple myeloma. The current study focuses on studying the combination of a BET inhibitor (e.g., JQ1) and a proteasome inhibitor (e.g., CFZ) as a novel cancer therapeutic strategy. Methods: Diverse solid and hematologic cancer cell lines were used to test the effects of the combinations on cell survival and apoptosis via SRB assay, colony formation assay, flow cytometric analysis, and Western blotting. Bim knockout cell lines were generated using a CRISPR-based method for mechanistic study. Transcriptional regulation of target genes was examined by quantitative RT-PCR. The anti-tumor effects were also examined in a xenograft tumor model. Results: The tested combinations (e.g., JQ1 with CFZ) synergistically decreased cancer cell survival and enhanced apoptosis in vitro and inhibited tumor growth in vivo. The combinations dramatically induced apoptosis accompanying with enhanced elevation of Bim and several ER stress marker proteins. Bim knockout significantly blocked apoptosis induced by the combinations in both HCT116 and L363 cells. Transcriptional upregulation of Bim by the combinations was observed. Conclusions: The enhanced anti-tumor effects of dual inhibition of BET and proteasome is likely due to augmented induction of ER stress and Bim-dependent apoptosis. Our findings warrant further investigation of this combinatorial strategy as an effective regimen against cancer in the clinic. Citation Format: Guoqing Qian, Weilong Yao, Williams D. Hall, Mala Shanmugam, Sagar Lonial, Shi-Yong Sun. Co-inhibition of BET and proteasome enhances ER stress and Bim-dependent apoptosis with augmented cancer therapeutic efficacy [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 2921.
99mTc-MDP Bone Scan and 18F-FDG PET/CT Imaging of Multiple Extraskeletal Osteosarcomas
Authors: Zhen-Kui Sun, Chen-Tian Shen, Zhong-Ling Qiu, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2018)

Extraskeletal osteosarcomas are uncommon entities in clinical practice, which account for 1% to 2% of all soft tissue sarcomas. We here reported a case of multiple extraskeletal osteosarcomas and nuclear medicine imaging findings of this disease in Tc-MDP bone scan as well as F-FDG PET/CT.
Dual-Loop Intra-Atrial Reentry in Humans
Authors: DipenShah, PierreJaïs, AtsushiTakahashi, MelezeHocini, Jing TianPeng, JacquesClementy, MichelHaïssaguerre
Journal: Circulation (2000)

Background—Dual-loop atrial reentrant tachycardias have not been clinically described. Methods and Results—Five patients (3 men, 2 women; mean age, 48±16 years) were studied 24±15 years after surgical closure of an ostium secundum atrial septal defect for drug-resistant atrial tachycardia. Complete tachycardia mapping was performed in the right atrium with multipolar catheters and a 3-dimensional electroanatomic mapping system (Biosense), followed by linear radiofrequency ablation of the narrowest part of each complete loop. Six tachycardias with a typical flutter morphology, a cycle length of 262±40 ms, and a superior f-wave axis (−77±11°) were mapped, 4 with a Biosense map including 106±32 points. Five figure-8 tachycardias had a counterclockwise loop around the tricuspid valve sharing a common anterior channel with a clockwise loop around the lateral atriotomy scar. One tachycardia was thought to have 2 counterclockwise loops around the same obstacles. Radiofrequency delivery in the cavotricuspid isthm...
Abstract 4407: Targeting BMP4 and miR-139-5p in EGFR-mutant non-small cell lung cancer cells
Authors: Duc-Hiep Bach, Thi-Thu-Trang Luu, Dong-Hwa Kim, Yong Jin An, Hyen Joo Park, Sunghyouk Park, Sang Kook Lee
Journal: Cancer Research (2018)

Abstract Non-small cell lung cancer (NSCLC) cells with harboring EGF receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Recent studies suggest that bone morphogenetic proteins (BMPs) and microRNAs (miRNAs) might act as oncogenes or suppressors in tumor microenvironment. We identified the potential roles of BMPs and miRNAs involved in EGFR TKIs resistance by analyzing datasets from a pair of NSCLC-sensitive and NSCLC-resistant cells. BMP4 was found to be significantly over-expressed in EGFR-TKI resistant cells and its underlying mechanism was highly associated with induction of energy metabolism for cancer cells through modulating Acyl-CoA synthetase long-chain family member 4. In addition, miR-139-5p was found to be importantly down-regulated in the resistant NSCLC cells. The combination of miR-139-5p and yuanhuadine, a natural product-derived antitumor agent, synergistically suppressed the BMP4 expression in the resistant cells. We furthermore confirmed that LDN-193189, a small molecule BMP receptor 1 inhibitor inhibited the tumor growth in a xenograft nude mouse model implanted with drug resistant cells. These findings suggest a role of BMP4-mediated tumorigenesis in the progression of acquired drug resistance in EGFR-mutant NSCLC cells. Key words: microRNAs, bone morphogenetic proteins, drug resistance, metabolism, EGFR-TKIs, NSCLC. Acknowledgements This study was funded by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1D1A1A02062012). Citation Format: Duc-Hiep Bach, Thi-Thu-Trang Luu, Dong-Hwa Kim, Yong Jin An, Hyen Joo Park, Sunghyouk Park, Sang Kook Lee. Targeting BMP4 and miR-139-5p in EGFR-mutant non-small cell lung cancer cells [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 4407.
Influence of Amyl Nitrite Inhalation on the Systolic Time Intervals in Normal Subjects and in Patients with Ischemic Heart Disease
Authors: Toshitamisawayama, Masakazuochiai, Susumumarumoto, Tohrumatsuura, Isaoniki
Journal: Circulation (1969)

The systolic time intervals of the left ventricle in 30 patients with ischemic heart disease but without heart failure were compared with those of 30 normal individuals before and after inhalation of amyl nitrite by using polygraphic recordings. In the normal subjects, following amyl nitrite, the ejection-time index was significantly prolonged, and the pre-ejection period and its index were significantly reduced, while the ejection time was not significantly shortened. The ischemic heart disease group, however, exhibited no significant changes in the ejection-time index, pre-ejection period, or its index, whereas the ejection time was significantly shortened. These differences were not related to heart rate or diastolic blood pressure level but may be explained by a postulated lack of increase in stroke volume or in the contractility of the ischemic myocardium, or both, at the maximal effect of amyl nitrite. The responses of the left ventricular systolic intervals to amyl nitrite may prove useful as a cli...
Interaction of Cytotoxic T Lymphocytes and Guinea Pig Ventricular Myocytes
Authors: BellaFelzen, RevitalLavy, MariaGarcia, GideonBerke, PhyllisGardner, OferBinah
Journal: Circulation Research (1996)

Abstract Infiltrating cytotoxic T lymphocytes (CTLs) are important immune effectors that damage the myocardium during heart transplant rejection as well as in cardiomyopathy and Chagas’ heart disease. We have previously shown that in an in vitro model of murine-derived peritoneal exudate CTL (PEL)–guinea pig ventricular myocyte interaction, PEL induced in conjugated myocytes reduction of resting membrane potential and action potential (AP) amplitude, shortening of AP duration, delayed afterdepolarizations (DADs), and myocyte contracture and destruction. Since these findings indicated that cytotoxicity was largely caused by [Ca2+]i overload, in the present study we tested the hypothesis that blocking the L-type Ca2+ current (ICa,L) in the myocyte will eliminate the trigger for Ca2+ release from intracellular stores and will reduce [Ca2+]i overload and subsequent myocyte deterioration. CoCl2 (3 mmol/L) prevented PEL-induced AP changes, induction of DADs, and myocyte destruction. Since verapamil (2 μmol/L) w...
Abstract 14726: Right Ventricular Strain Analysis May Be Useful in Differentiating Takotsubo Cardiomyopathy From Left Anterior Descending Coronary Artery Disease
Authors: LiYingCai, KarimaAddetia, VictorMor-Avi, KirkSpencer
Journal: Circulation (2015)

Background: Takotsubo cardiomyopathy (TTC) is a transient form of left ventricular (LV) dysfunction triggered by significant physiological stress and associated with a distinctive pattern of regional LV dysfunction on echocardiography. This pattern can be similar to and therefore difficult to differentiate from that seen in left anterior descending coronary artery (LAD) occlusion. We hypothesized that right ventricular (RV) involvement as detected by RV free-wall longitudinal strain (FWLS) might help differentiating TCC from LAD infarction. Methods: 44 patients with TTC and 36 with LAD infarct were studied. The RV focused view was used to measure TAPSE (M-mode), S’ (pulsed-wave Doppler), and fractional area change (FAC). RVFWLS was measured offline (Epsilon). Apical 2-, 3- and 4-chamber views were used to measure LV longitudinal strain (LS) (QLAB) and biplane Simpsons was used to assess LV ejection fraction (EF). Results: LVEF was 31±10% in TTC and 41±9% in the LAD group. There was no significant differen...
A protective Langerhans cell–keratinocyte axis that is dysfunctional in photosensitivity
Authors: William D. Shipman, Susan Chyou, Anusha Ramanathan, Peter M. Izmirly, Sneh Sharma, Tania Pannellini, Dragos C. Dasoveanu, Xiaoping Qing, Cynthia M. Magro, Richard D. Granstein, Michelle A. Lowes, Eric G. Pamer, Daniel H. Kaplan, Jane E. Salmon, Babak J. Mehrara, James W. Young, Robert M. Clancy, Carl P. Blobel, Theresa T. Lu
Journal: Science Translational Medicine (2018)

Photosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a feature of lupus erythematosus and other autoimmune and dermatologic conditions, but the mechanistic underpinnings are poorly understood. We identify a Langerhans cell (LC)-keratinocyte axis that limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation. We show that the absence of LCs in Langerin-diphtheria toxin subunit A (DTA) mice leads to photosensitivity and that, in vitro, mouse and human LCs can directly protect keratinocytes from UVR-induced apoptosis. LCs express EGFR ligands and a disintegrin and metalloprotease 17 (ADAM17), the metalloprotease that activates EGFR ligands. Deletion of ADAM17 from LCs leads to photosensitivity, and UVR induces LC ADAM17 activation and generation of soluble active EGFR ligands, suggesting that LCs protect by providing activated EGFR ligands to keratinocytes. Photosensitive systemic lupus erythematosus (SLE) models and human SLE skin show reduced epidermal EGFR phosphorylation and LC defects, and a topical EGFR ligand reduces photosensitivity. Together, our data establish a direct tissue-protective function for LCs, reveal a mechanistic basis for photosensitivity, and suggest EGFR stimulation as a treatment for photosensitivity in lupus erythematosus and potentially other autoimmune and dermatologic conditions.
Abstract SY28-01: Management of MAP kinase and apoptosis signaling thresholds by microRNAs
Authors: W. Brent Derry
Journal: Cancer Research (2018)

Abstract An important problem in cancer biology is concerned with how apoptotic thresholds are established. Defective regulation of apoptosis can cause resistance to chemotherapeutic agents and radiation therapy, which highlights the need to resensitize these tumors to therapy. The apoptosis pathway was first elucidated in the roundworm Caenorhabditis elegans, and studies in this organism continue to uncover regulatory mechanisms that are also conserved in humans. By taking advantage of the powerful genetics, cell biology, and proteomics tools of C. elegans, we seek to understand how apoptotic signaling is fine-tuned in response to ionizing radiation (IR). Our work has uncovered a network of regulatory mechanisms, such as ubiquitin proteolysis and microRNAs, that control the levels of apoptotic proteins. I will discuss our recent efforts to understand how microRNA 35 (mir-35) antagonizes translation of the BH3-only protein EGL-1 and the Ras/MAPK effector NDK-1 in response to IR. EGL-1 is homologous to human PUMA and NDK-1 is the worm orthologue of human NME1 (NME/NM23 nucleoside diphosphate kinase 1), which has been shown to regulate MAPK signaling in both worms and human cells. mir-35 normally functions to buffer IR-induced apoptosis through its combinatorial effects on EGL-1 and NDK-1 translation. Ablation of mir-35, or mutations in the mir-35 binding sites in the 3'-untranslated region (3'UTR) of egl-1 and ndk-1, increase the levels of these proteins and cause hypersensitivity to IR-induced apoptosis. By targeting both the core apoptosis pathway and the MAPK cascade, we propose that mir-35 plays a key role in fine-tuning apoptotic signaling in order to protect healthy cells and ensure a rapid response to DNA-damaging agents. Given the high conservation in the organization of these pathways from C. elegans to human, manipulating microRNAs might help resensitize tumors that have developed resistance to radiation and/or chemotherapy. Citation Format: W. Brent Derry. Management of MAP kinase and apoptosis signaling thresholds by microRNAs [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 SY28-01.
cis Element Decoy Against Nuclear Factor-κB Attenuates Development of Experimental Autoimmune Myocarditis in Rats
Authors: OsamuYokoseki, Jun-ichiSuzuki, HiroshiKitabayashi, NoboruWatanabe, YukoWada, MotokuniAoki, RyuichiMorishita, YasufumiKaneda, ToshioOgihara, HidekiFutamatsu, YasushiKobayashi, MitsuakiIsobe
Journal: Circulation Research (2001)

Nuclear factor-κB (NFκB) plays a significant role in the coordinated transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NFκB in this process remains obscure. We examined the role of NFκB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFκB blockade with a decoy against the cis element of NFκB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFκB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harvested on day 21. Scrambled decoy was infused on day 0 (group SD0), 7 (group SD7), or 14 (group SD14) and served for control groups. The ratios of myocarditis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF0, 33...
Abstract 3540: Ubiquitin code: Accelerating the discovery of poly-ubiquitylated proteins by novel chain-selective affinity matrices
Authors: Apurva Chaturvedi, Peter Foote, Sarah Julius, Essam Abed, Rajesh K. Singh
Journal: Cancer Research (2018)

Abstract Ubiquitin (Ub) is attached via isopeptide bonds to lysine residues in the target protein or to another Ub to form poly-Ub chains. The reversibility, heterogeneity, and diversity of these modifications combined with the lack of suitable tools have made it difficult to properly isolate and characterize poly-ubiquitylated cellular proteins. However, in 2009, a novel technology called TUBEs (Tandem-repeated Ub-Binding Entities) was developed. TUBEs have revolutionized the Ub field by allowing poly-ubiquitylated proteins to be enriched/purified from cellular extracts. Development of TUBEs that selectively bind K48-, K63-, and M1-linked poly-ubiquitylated proteins has helped understand the role of modified proteins in cell physiology. However, the roles of other Ub-linkages remain obscured mainly due to the lack of tools that specifically recognize them. Structure-based approach to engineer unique high affinity Ub binding domains(UBDs) for rare Ub-linkages has been implemented to design highly selective affinity matrices. Biochemical and biophysical experiments demonstrate highly selective interactions of the matrices to distinct lysine-linked poly-Ub chains. Power of these highly selective affinity matrices has made it possible to perform Ub proteomics bypassing SILAC mass spectrometry. Application of these affinity matrices in Far Western detection, pull-down and imaging will be described in the poster. To conclude, we have identified unique binding partners for K6-, K11-, K27-, K29-, K33- and K48-linked poly-Ub chains. Development of chain selective affinity matrices (TUBEs) that selectively bind to poly-ubiquitylated proteins will dramatically accelerate the pace of discovery in this important area of biology. Citation Format: Apurva Chaturvedi, Peter Foote, Sarah Julius, Essam Abed, Rajesh K. Singh. Ubiquitin code: Accelerating the discovery of poly-ubiquitylated proteins by novel chain-selective affinity matrices [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 3540.