tbuckley/cabot-search huggingface dataset:
Renin expression by vascular endothelial cells in culture.
Authors: L S Lilly, R E Pratt, R W Alexander, D M Larson, K E Ellison, M A Gimbrone, V J Dzau
Journal: Circulation Research (1985)

Cultured bovine aortic endothelial cells were examined for renin activity by biochemical, immunological, and immunohistochemical techniques. When cell sonicates were incubated with renin substrate, linear generation of angiotensin I was observed (1.12 +/- 0.2 ng angiotensin I/10(6) cells per hr). The effect of pH on this activity was similar to that of bovine renal renin, and renin antibodies inhibited a large portion of the enzymatic activity. Furthermore, immunofluorescence microscopy with antirenin antisera confirmed the presence of renin within these cells. Biosynthetic radiolabeling, followed by immunoprecipitation, demonstrated de novo synthesis of a renin precursor in the endothelial cells, which was processed to a more mature protein. Thus, bovine aortic endothelial cells in culture contain and biosynthesize renin, a key component of the renin-angiotensin system. The expression of renin activity by endothelium may contribute to the local regulation of vascular tone.
Endothelial cell spreading on fibrin requires fibrinopeptide B cleavage and amino acid residues 15-42 of the beta chain.
Authors: L A Bunce, L A Sporn, C W Francis
Journal: Journal of Clinical Investigation (1992)

Adhesion and spreading of cultured human umbilical vein endothelial cells on fibrin surfaces of varying structure were characterized to understand better the interactions occurring between endothelium and fibrin at sites of vascular injury. Fibrin prepared with reptilase, which cleaves only fibrinopeptide A from fibrinogen, and fibrin prepared with thrombin, which cleaves both fibrinopeptide A and fibrinopeptide B, equally supported endothelial cell adhesion. In contrast, only fibrin made with thrombin mediated endothelial cell spreading, as assessed by fluorescence microscopy of cells stained with rhodamine phalloidin to identify actin stress fibers or by scanning electron microscopy. Fibrin prepared with reptilase failed to support cell spreading. To further investigate the role of the amino terminus of the fibrin beta chain after fibrinopeptide B cleavage in promoting cell spreading, protease III from Crotalus atrox venom was used to specifically cleave the amino-terminal 42 residues of the fibrinogen B beta chain. After clotting with thrombin, this fibrin derivative lacking B beta 1-42 failed to support significant cell spreading. Spreading on fibrin was unaffected by depletion of Weibel-Palade bodies from endothelial cells, indicating that the spreading was independent of stimulated von Willebrand factor release. We conclude that endothelial cell spreading on fibrin requires fibrinopeptide B cleavage and involves residues 15-42 of the fibrin beta chain.
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary
Authors: Craig T. January, L. Samuel Wann, Joseph S. Alpert, Hugh Calkins, Joaquin E. Cigarroa, Joseph C. Cleveland, Jamie B. Conti, Patrick T. Ellinor, Michael D. Ezekowitz, Michael E. Field, Katherine T. Murray, Ralph L. Sacco, William G. Stevenson, Patrick J. Tchou, Cynthia M. Tracy, Clyde W. Yancy
Journal: Circulation (2014)
Pegylated Kunitz Domain Inhibitor Suppresses Hepsin-Mediated Invasive Tumor Growth and Metastasis
Authors: Wei Li, Bu-Er Wang, Paul Moran, Terry Lipari, Rajkumar Ganesan, Racquel Corpuz, Mary J.C. Ludlam, Alvin Gogineni, Hartmut Koeppen, Stuart Bunting, Wei-Qiang Gao, Daniel Kirchhofer
Journal: Cancer Research (2009)

The transmembrane serine protease hepsin is one of the most highly upregulated genes in prostate cancer. Here, we investigated its tumor-promoting activity by use of a mouse orthotopic prostate cancer model. First, we compared the tumor growth of low hepsin-expressing LnCaP-17 cells with hepsin-overexpressing LnCaP-34 cells. After implantation of cells into the left anterior prostate lobe, LnCaP-34 tumors not only grew faster based on increased serum prostate-specific antigen levels but also metastasized to local lymph nodes and, most remarkably, invaded the contralateral side of the prostate at a rate of 100% compared with only 18% for LnCaP-17 tumors. The increased tumor growth was not due to nonspecific gene expression changes and was not predicted from the unaltered in vitro growth and invasion of LnCaP-34 cells. A likely explanation is that the in vivo effects of hepsin were mediated by specific hepsin substrates present in the tumor stroma. In a second study, mice bearing LnCaP-34 tumors were treated with a PEGylated form of Kunitz domain-1, a potent hepsin active site inhibitor derived from hepatocyte growth factor activator inhibitor-1 (K(i)(app) 0.30 +/- 0.02 nmol/L). Treatment of established tumors with PEGylated Kunitz domain-1 decreased contralateral prostate invasion (46% weight reduction) and lymph node metastasis (50% inhibition). Moreover, serum prostate-specific antigen level remained reduced during the entire treatment period, reaching a maximal reduction of 76% after 5 weeks of dosing. The findings show that hepsin promotes invasive prostate tumor growth and metastasis and suggest that active site-directed hepsin inhibition could be effective in prostate cancer therapy.
Evaluation of Screening Instruments for Cancer-Related Fatigue Syndrome in Breast Cancer Survivors
Authors: Susanna Alexander, Ollie Minton, Patrick C. Stone
Journal: Journal of Clinical Oncology (2009)

Purpose Cases of cancer-related fatigue syndrome (CRFS) can be reliably indentified using a diagnostic interview combined with a structured psychiatric interview. However, these interviews are time consuming to conduct, require specialist training, and are not suitable for routine clinical use. The purpose of this study was to identify whether a screening questionnaire could identify patients at high risk of clinically significant fatigue who should be considered for a suitable intervention. Patients and Methods The diagnostic interview for CRFS and the structured clinical interview for the diagnostic and statistical manual of mental disorders were used in order to identify breast cancer survivors who fulfilled the criteria for CRFS. Two fatigue questionnaires (the Bidimensional Fatigue Scale [BFS] and the Functional Assessment of Cancer Therapy-Fatigue subscale [FACT-F]) were administered in order to determine their screening properties. Results Two hundred women were interviewed and 60 women fulfilled the criteria for CRFS. The BFS cutoff score of 11 had a sensitivity of 92%, a specificity of 53%, a positive predictive value (PPV) of 46%, and a negative predictive value (NPV) of 94%. The FACT-F cutoff score of 36 had a sensitivity of 80%, a specificity of 71%, a PPV of 55%, and a NPV of 89%. Conclusion The BFS and FACT-F cutoff scores can be used to identify breast cancer survivors at higher risk of clinically significant ongoing post treatment fatigue. Neither scale can be used as a diagnostic instrument for CRFS.
Possible Involvement of RUNX3 Silencing in the Peritoneal Metastases of Gastric Cancers
Authors: Chouhei Sakakura, Kazunori Hasegawa, Koji Miyagawa, Susumu Nakashima, Tetsuji Yoshikawa, Shuichi Kin, Yuenn Nakase, Shujiro Yazumi, Hisakazu Yamagishi, Takeshi Okanoue, Tsutomu Chiba, Akeo Hagiwara
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Our previous results suggested that a lack of RUNX3 function contributed to human gastric carcinogenesis, but the role of RUNX3 in progression and metastasis remains unclear. We examined RUNX3 expression in clinical samples of peritoneal metastases in gastric cancers. Changes in metastatic potential were assessed in animal experiments using stable RUNX3 transfectants of gastric cancer cells. Finally, global expression changes were analyzed using a cDNA microarray. Experimental Design and Results: Significant down-regulation of RUNX3 through methylation on the promoter region was observed in primary tumors (75%) as well as in all clinical peritoneal metastases of gastric cancers (100%) compared with normal gastric mucosa. Stable transfection of RUNX3 inhibited cell proliferation slightly, and modest transforming growth factor-β (TGF-β)–induced antiproliferative and apoptotic effects were observed. Interestingly, it strongly inhibited peritoneal metastases of gastric cancers in animal model (P &amp;lt; 0.01). Furthermore, we did globally analyzed expression profiles of ∼21,000 genes in parent cells and stable transfectant of RUNX3 using a cDNA microarray. Microarray analysis identified ∼28 candidate genes under the possible downstream control of RUNX3, some of these genes were considered to be possibly involved in peritoneal metastases, which were related to signal transduction (vav3, TOLL-like receptor, MAPKK, MET, S1 00A1 1, and cathepsin E), apoptosis (caspase 9), immune responses (CD55 and TLR1O), and cell adhesion (sialyltransferase 1 and galectin 4). Some of the genes are involved in the TGF-β signaling pathway. Conclusion: These results indicate that silencing of RUNX3 affects expression of important genes involved in aspects of metastasis including cell adhesion, proliferation, apoptosis, and promoting the peritoneal metastasis of gastric cancer. Identification of such genes could suggest new therapeutic modalities and therapeutic targets.
Airway Inflammation in Childhood Asthma
Authors: Angelo Barbato, Graziella Turato, Simonetta Baraldo, Erica Bazzan, Fiorella Calabrese, Maria Tura, Renzo Zuin, Bianca Beghé, Piero Maestrelli, Leonardo M. Fabbri, Marina Saetta
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Airway pathology has been extensively investigated in adulthood asthma, whereas only few studies examined bronchial biopsies in childhood asthma. To evaluate the airway pathology in children with asthma, we analyzed bronchial biopsies obtained from 23 children undergoing bronchoscopy for clinical indications other than asthma. Nine had mild/moderate asthma. Six had atopy without asthma, and eight had no atopy or asthma. We measured basement membrane thickness and quantified the number of eosinophils, mast cells, neutrophils, macrophages, T lymphocytes, and positive cells for transforming growth factor-beta1 (TGF-beta1) and its receptors I and II (TGFbeta-RI and TGFbeta-RII) in subepithelium. Children with asthma had an increase in basement membrane thickness and in the number of eosinophils compared with control subjects, but not compared with children with atopy. They also had a decreased expression of TGFbeta-RII compared with both those with atopy and control subjects. In children with asthma, the number of eosinophils correlated negatively with TGFbeta-RII and positively with symptom duration. In conclusion, airway eosinophilia and basement membrane thickening, which are the pathologic features that are characteristic of adulthood asthma, are already present in children with mild asthma, and even in children with atopy without asthma. Moreover, in children with asthma but not in children with atopy without asthma, there is a downregulation of TGFbeta-RII.
The Effects of Alignment Error and Alignment Filtering on the Sitewise Detection of Positive Selection
Authors: G. Jordan, N. Goldman
Journal: Molecular Biology and Evolution (2011)

When detecting positive selection in proteins, the prevalence of errors resulting from misalignment and the ability of alignment filters to mitigate such errors are not well understood, but filters are commonly applied to try to avoid false positive results. Focusing on the sitewise detection of positive selection across a wide range of divergence levels and indel rates, we performed simulation experiments to quantify the false positives and false negatives introduced by alignment error and the ability of alignment filters to improve performance. We found that some aligners led to many false positives, whereas others resulted in very few. False negatives were a problem for all aligners, increasing with sequence divergence. Of the aligners tested, PRANK's codon-based alignments consistently performed the best and ClustalW performed the worst. Of the filters tested, GUIDANCE performed the best and Gblocks performed the worst. Although some filters showed good ability to reduce the error rates from ClustalW and MAFFT alignments, none were found to substantially improve the performance of PRANK alignments under most conditions. Our results revealed distinct trends in error rates and power levels for aligners and filters within a biologically plausible parameter space. With the best aligner, a low false positive rate was maintained even with extremely divergent indel-prone sequences. Controls using the true alignment and an optimal filtering method suggested that performance improvements could be gained by improving aligners or filters to reduce the prevalence of false negatives, especially at higher divergence levels and indel rates.
Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease
Authors: GW Chalmers, KJ Macleod, S Sriram, LJ Thomson, C McSharry, BH Stack, NC Thomson
Journal: European Respiratory Journal (1999)

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.
Delivery Strategies to Achieve Therapeutic Myocardial Angiogenesis
Authors: Ran Kornowski, Shmuel Fuchs, Martin B. Leon, Stephen E. Epstein
Journal: Circulation (2000)

Abstract —The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Currently, it is unknown which is the safest and most effective delivery strategy to induce clinically important therapeutic angiogenic responses in ischemic myocardium. Most strategies for transcatheter delivery of angiogenic factors have used an intracoronary route, which may have limitations because of imprecise localization of genes or proteins and systemic delivery to noncardiac tissue. The effect of direct intraoperative intramyocardial injection of angiogenic factors on collateral function has been reported in experimental models, and angiogenesis is being studied after direct intramyocardial injection of angiogenic peptides or plasmid vectors during open heart surgery in patients. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without the need for surgery. Intrapericardial delivery of angiogenic factors may offer a theoretical advantage of prolonged exposure of either coronary or myocardial tissue to the administered drug as result of a reservoir function of the pericardium. In this article, we review the different modes of administration for therapeutic myocardial angiogenesis therapy.
Association Between Endoscopic vs Open Vein-Graft Harvesting and Mortality, Wound Complications, and Cardiovascular Events in Patients Undergoing CABG Surgery
Authors: Judson B. Williams, Eric D. Peterson, J. Matthew Brennan, Art Sedrakyan, Dale Tavris, John H. Alexander, Renato D. Lopes, Rachel S. Dokholyan, Yue Zhao, Sean M. O’Brien, Robert E. Michler, Vinod H. Thourani, Fred H. Edwards, Hesha Duggirala, Thomas Gross, Danica Marinac-Dabic, Peter K. Smith
Journal: JAMA (2012)

The safety and durability of endoscopic vein graft harvest in coronary artery bypass graft (CABG) surgery has recently been called into question.To compare the long-term outcomes of endoscopic vs open vein-graft harvesting for Medicare patients undergoing CABG surgery in the United States.An observational study of 235,394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median 3-year follow-up) through December 31, 2008.All-cause mortality. Secondary outcome measures included wound complications and the composite of death, myocardial infarction, and revascularization.Based on Medicare Part B coding, 52% of patients received endoscopic vein-graft harvesting during CABG surgery. After propensity score adjustment for clinical characteristics, there were no significant differences between long-term mortality rates (13.2% [12,429 events] vs 13.4% [13,096 events]) and the composite of death, myocardial infarction, and revascularization (19.5% [18,419 events] vs 19.7% [19,232 events]). Time-to-event analysis for those patients receiving endoscopic vs open vein-graft harvesting revealed adjusted hazard ratios [HRs] of 1.00 (95% CI, 0.97-1.04) for mortality and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0% [3654/122,899 events] vs 3.6% [4047/112,495 events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001).Among patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting compared with open vein-graft harvesting was not associated with increased mortality.
Specific Contribution of Estrogen Receptors on Mitogen-Activated Protein Kinase Pathways and Vascular Cell Activation
Authors: Pedro Geraldes, Martin G. Sirois, Jean-François Tanguay
Journal: Circulation Research (2003)

Randomized clinical trials have not provided conclusive data that hormone replacement therapy confers cardioprotection against coronary artery disease in postmenopausal women. However, other studies have shown that estrogens can induce beneficial effects on the vasculature. Nevertheless, the specific contribution of estrogen receptors (ERs) alpha and beta on vascular cells is not well characterized. Therefore, we used an antisense gene therapy approach to investigate the contribution of ERalpha and ERbeta on p38 and p42/44 mitogen-activated protein kinase (MAPK) activation and on vascular cell responsiveness. Treatment of porcine smooth muscle cells (PSMCs) with platelet-derived growth factor-BB induced p38 and p42/44 MAPK activation and their migration and proliferation. These effects were prevented by pretreatment with 17beta-estradiol (17betaE). The inhibitory effects of 17betaE on PSMCs were abrogated by the downregulation of ERbeta protein expression with selective ERbeta mRNA antisense oligomers, whereas the downregulation of ERalpha had no effect. However, treatment of porcine aortic endothelial cells with 17betaE promoted p38 and p42/44 MAPK phosphorylation and their migration and proliferation. These effects were ERalpha dependent, as defined by antisense gene therapy. These results suggest that in PSMCs, 17betaE reduces p42/44 and p38 MAPK activity through ERbeta stimulation, whereas in contrast, in porcine aortic endothelial cells, 17betaE induces p42/44 and p38 MAPK through ERalpha activation. 17betaE may contribute to the vascular healing process and to the prevention of restenosis by improving reendothelialization through ERalpha activation and by decreasing smooth muscle cell migration and proliferation through ERbeta stimulation.
Facile Preparation of Doxorubicin‐Loaded Upconversion@Polydopamine Nanoplatforms for Simultaneous In Vivo Multimodality Imaging and Chemophotothermal Synergistic Therapy
Authors: Fuyao Liu, Xiuxia He, Zhen Lei, Liang Liu, Junping Zhang, Hongpeng You, Huimao Zhang, Zhenxin Wang
Journal: Advanced Healthcare Materials (2014)

The development of biosafe nanoplatforms with diagnostic and therapeutic multifunction is extremely demanded for designing cancer theranostic medicines. Here, a facile methodology is developed to construct a multifunctional nanotheranostic that gathers five functions, upconversion luminescence (UCL) imaging, T 1 ‐weighted magnetic resonance imaging (MRI), X‐ray computed tomography (CT) imaging, photothermal therapy (PTT), and chemotherapy, into one single nanoprobe (named as UCNP@PDA 5 ‐PEG‐DOX). For generating the UCNP@PDA 5 ‐PEG‐DOX, a near‐infrared light (NIR)‐absorbing polydopamine (PDA) shell is directly coated on oleic‐acid‐capped β ‐NaGdF 4 :Yb 3+ ,Er 3+ @ β ‐NaGdF 4 upconverting nanoparticle (UCNP) core for the first time to form monodisperse, ultrastable, and noncytotoxic core–shell‐structured nanosphere via water‐in‐oil microemulsion approach. When combined with 808 nm NIR laser irradiation, the UCNP@PDA 5 ‐PEG‐DOX shows great synergistic interaction between PTT and the enhanced chemotherapy, resulting in completely eradicated mouse‐bearing SW620 tumor without regrowth. In addition, leakage study, hemolysis assay, histology analysis, and blood biochemistry assay unambiguously reveal that the UCNP@PDA 5 ‐PEG has inappreciable cytotoxicity and negligible organ toxicity. The results provide explicit strategy for fabricating multifunctional nanoplatforms from the integration of UCNP with NIR‐absorbing polymers, important for developing multi‐mode nanoprobes for biomedical applications.
Cimetidine decreases indomethacin induced duodenal mucosal damage in patients with acute musculoskeletal disorders.
Authors: R Stalnikowicz, D Pollak, A Eliakim, D Wengrower, A Fich, E Goldin, M Ligumsky, D Rachmilewitz
Journal: Gut (1988)

The effect of two doses of cimetidine, 400 mg at night and 400 mg bd, on the protection of indomethacin (50 mg tid) induced mucosal damage was evaluated in a double blind study in patients with acute musculoskeletal disorders. Endoscopic mucosal lesions were scored before and after five to seven days of treatment. One hundred and ninety one patients were endoscoped before the trial, 34 (17.8%) had greater than one erosion and were not recruited. Forty patients were excluded for non-compliance, or lost to follow up. At the second endoscopy, oesophageal, and fundic damage was negligible. Gastric and duodenal lesion score in patients treated with cimetidine 400 mg bd: 2.7 (0.5) (SE); n = 42) was significantly lower (p less than 0.0122) than in placebo treated patients: 6.1 (0.9) (n = 50) or in patients treated with cimetidine 400 mg at night 7.1 (0.8) (n = 21). Cimetidine 400 mg bd provided significant protection for the duodenum, but its protection of antral mucosa did not reach statistical significance. There was no correlation between upper gastrointestinal symptoms and endoscopic findings.