tbuckley/cabot-search huggingface dataset:
Heparanase Gene Silencing, Tumor Invasiveness, Angiogenesis, and Metastasis
Authors: Evgeny Edovitsky, Michael Elkin, Eyal Zcharia, Tamar Peretz, Israel Vlodavsky
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Heparanase is an endoglycosidase that degrades heparan sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. Expression of the heparanase gene is associated with the invasive, angiogenic, and metastatic potential of diverse malignant tumors and cell lines. We used gene-silencing strategies to evaluate the role of heparanase in malignancy and to explore the therapeutic potential of its specific targeting. Methods: We designed plasmid vectors to express hammerhead ribozymes or small interfering RNAs (siRNAs) directed against the human or mouse heparanase mRNAs. Human breast carcinoma (MDA-MB-435) and mouse lymphoma (Eb) and melanoma (B16-BL6) tumor cell lines, which have naturally high levels of endogenous heparanase or have been genetically engineered to overexpress heparanase, were transfected with anti-heparanase ribozyme or siRNA. Semiquantitative reverse transcription–polymerase chain reaction (RT-PCR) and measurements of enzymatic activity were used to confirm the efficient silencing of heparanase gene expression. Cells transfected with the anti-heparanase ribozyme and siRNA vectors were tested for invasiveness in vitro and metastatic dissemination in animal models of experimental and spontaneous metastasis . Results: Compared with cells transfected with control constructs, cells transfected with the anti-heparanase ribozyme or siRNA vectors had profoundly reduced invasion and adhesion in vitro, regardless of cell type, and expressed less heparanase. In vivo, tumors produced by cells transfected with the anti-heparanase ribozyme and siRNA vectors were less vascularized and less metastatic than tumors produced by cells transfected with the control vectors. Mice injected with cells transfected with the anti-heparanase ribozyme and siRNA vectors lived longer than mice injected with control cells. Conclusions: The association of reduced levels of heparanase and altered tumorigenic properties in cells with anti-heparanase ribozyme- or siRNA-mediated gene-silencing vectors suggests that heparanase is important in cancer progression. Heparanase gene silencing has potential use as a target for anticancer drug development.
Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial
Authors: Karen M Edmond, Sam Newton, Caitlin Shannon, Maureen O'Leary, Lisa Hurt, Gyan Thomas, Seeba Amenga-Etego, Charlotte Tawiah-Agyemang, Lu Gram, Chris N Hurt, Rajiv Bahl, Seth Owusu-Agyei, Betty R Kirkwood
Journal: The Lancet (2014)
Effects of neuropeptide Y on cell length and membrane currents in isolated guinea pig ventricular myocytes.
Authors: S M Bryant, K O Ryder, G Hart
Journal: Circulation Research (1991)

Direct effects of neuropeptide Y were studied in left ventricular myocytes isolated from guinea pigs. Contraction was measured as the change in unloaded cell length using a photodiode array. Action potentials were elicited at 1 Hz in current-clamp mode, and membrane currents were measured using a switch-clamp amplifier with 2 M-KCl microelectrodes. At concentrations of 10(-6) M and above, neuropeptide Y reduced contraction in a concentration-dependent fashion. The reduction in contraction by the peptide was proportionately greater in the presence of isoproterenol, and the increase in contraction caused by isoproterenol was completely inhibited by 10(-6) M neuropeptide Y. In response to neuropeptide Y, action potential duration was shortened, and the time course of the shortening was similar to that of the reduction in contraction. Under voltage clamp, 1 x 10(-5) M neuropeptide Y reduced peak L-type calcium current by 32% and shifted the myocyte current-voltage relation during a slow ramp in a manner that suggested a reduction in the background rectifier K+ current. The effects of the peptide on membrane currents were greatly attenuated by preincubation of the cells with pertussis toxin (100 ng/ml). We conclude that neuropeptide Y reduces developed shortening, action potential duration, L-type calcium current, and background rectifier current in single guinea pig ventricular myocytes and that these effects are mediated, at least in part, via membrane G proteins.
<i>FGFR2</i> Gene Amplification in Gastric Cancer Predicts Sensitivity to the Selective FGFR Inhibitor AZD4547
Authors: Liang Xie, Xinying Su, Lin Zhang, Xiaolu Yin, Lili Tang, Xiuhua Zhang, Yanping Xu, Zeren Gao, Kunji Liu, Minhua Zhou, Beirong Gao, Danping Shen, Lianhai Zhang, Jiafu Ji, Paul R. Gavine, Jingchuan Zhang, Elaine Kilgour, Xiaolin Zhang, Qunsheng Ji
Journal: Clinical Cancer Research (2013)

Abstract Purpose: FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer and the therapeutic potential of AZD4547, a potent and selective ATP-competitive receptor tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR)1–3, in patients with FGFR2-amplified gastric cancer. Experimental Design: Array-comparative genomic hybridization and FISH were used to identify FGFR2 amplification in gastric cancer patient tumor samples. The effects of FGFR2 modulation were investigated in gastric cancer cells with FGFR2 amplification and in patient-derived gastric cancer xenograft (PDGCX) models using two approaches: inhibition with AZD4547 and short hairpin RNA (shRNA) knockdown of FGFR2. Results: Amplification of the FGFR2 gene was identified in a subset of Chinese and Caucasian patients with gastric cancer. Gastric cancer cell lines SNU-16 and KATOIII, carrying the amplified FGFR2 gene, were extremely sensitive to AZD4547 in vitro with GI50 values of 3 and 5 nmol/L, respectively. AZD4547 effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules and induced apoptosis in SNU-16 cells. Furthermore, inhibition of FGFR2 signaling by AZD4547 resulted in significant dose-dependent tumor growth inhibition in FGFR2-amplified xenograft (SNU-16) and PDGCX models (SGC083) but not in nonamplified models. shRNA knockdown of FGFR2 similarly inhibited tumor growth in vitro and in vivo. Finally, compared with monotherapy, we showed enhancement of in vivo antitumor efficacy using AZD4547 in combination with chemotherapeutic agents. Conclusion: FGFR2 pathway activation is required for driving growth and survival of gastric cancer carrying FGFR2 gene amplification both in vitro and in vivo. Our data support therapeutic intervention with FGFR inhibitors, such as AZD4547, in patients with gastric cancer carrying FGFR2 gene amplification. Clin Cancer Res; 19(9); 2572–83. ©2013 AACR.
Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone.
Authors: N Mauras, M W Haymond, D Darmaun, N E Vieira, S A Abrams, A L Yergey
Journal: Journal of Clinical Investigation (1994)

We investigated the effects of 4-6-wk administration of testosterone on calcium and protein metabolism in six healthy prepubertal short boys (mean age +/- SE = 12.9 +/- 0.6 yr). At baseline, subjects received a 4-h infusion of L-[1-13C]leucine and L-[2-15N]glutamine, and were given 42Ca intravenously, and 44Ca PO. Testosterone enanthate (approximately 3 mg/kg) was given I.M. 2 wk apart (two doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last injection. After testosterone therapy, there were significant increases in serum testosterone and mean peak and total growth hormone concentrations. Net calcium absorption (Va) and retention (Vbal) also increased (Va 13.3 +/- 2.3 vs 21.5 +/- 2.3; mg.kg-1.d-1, Vbal 8.0 +/- 2.1 vs 16.6 +/- 2.5, mg.kg-1.d-1, P < .05 both), as well as Ca's net forward flow into bone and total exchangeable pool (16 and 20%, respectively). The rate of appearance of leucine (an indicator of proteolysis) increased by 17.6 +/- 5.9%, P = 0.036. Leucine oxidation decreased by 48.6 +/- 8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which estimates protein synthesis, increased significantly by 34.4 +/- 7.7%, P = 0.009. Glutamine's rate of appearance also increased (+32%), mostly through enhanced glutamine de novo synthesis (+42%). In conclusion, short term testosterone administration significantly increases calcium's retention and net forward flow into bone in prepubertal humans, as well as whole body estimates of protein and calcium anabolism. These effects may represent a pure androgen effect, an amplification of growth hormone's action or some combination of these factors.
Airway remodeling-associated mediators in moderate to severe asthma: Effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression
Authors: Jamila Chakir, Joanne Shannon, Sophie Molet, Motonori Fukakusa, Jack Elias, Michel Laviolette, Louis-Philippe Boulet, Qutayba Hamid
Journal: Journal of Allergy and Clinical Immunology (2003)
Nasal mucociliary transport is impaired at altitude
Authors: PW Barry, NP Mason, C O'Callaghan
Journal: European Respiratory Journal (1997)

There have been a number of anecdotal reports of rhinitis and nasal obstruction occurring at altitude. To quantify these reports, we investigated nasal obstruction and mucociliary transport in a group of healthy volunteers trekking to Mount Everest Base Camp, Nepal, altitude 5,300 m. Nasal obstruction was estimated by subjective scoring and mucociliary transport was determined by the saccharin method. Subjective assessment showed that nasal obstruction was increased on arrival at 5,300 m in 23 out of 54 subjects, unchanged in 24, and decreased in seven (McNemar's test: chi 2 = 7.5; p &lt; 0.01). The median saccharin time at sea level was 11 min (95% confidence interval (95% CI) 8-17 min) and increased to 60 min (95% CI 27-60 min) on arrival at 5,300 m. Compared to sea level, the saccharin time was prolonged in 25 out of 33 subjects (McNemar's test: chi 2 = 14.7; p &lt; 0.01), and remained prolonged after 2 weeks at altitude (median 60 min; 95% CI 38-60 min). These results confirm the subjective feelings of nasal obstruction and show that nasal mucociliary transport times are increased at altitude. The mechanisms of these findings are not clear, but nasal obstruction may impede breathing and adversely affect performance at altitude.
Bacteriological analysis of lower respiratory tract in patients with rheumatoid arthritis and other collagen vascular diseases
Authors: Kentarou Akata, Shuya Nagata, Takashi Kido, Kei Yamasaki, Toshinori Kawanami, Hiroshi Ishimoto, Kazuhiro Yatera, Hiroshi Mukae
Journal: European Respiratory Journal (2012)

Background  Lower respiratory tract infections (LRTI, bronchiectasis, bronchitis and bronchiolitis) are common comorbidities in patients with rheumatoid arthritis (RA). According to the recent advances of the treatment modalities of RA and other collagen vascular diseases (CVD) including anti-inflammatory biological agents, an aggressive diagnosis of LRTI including nontuberculous mycobacteriosis (NTM) is becoming more important.  Patients and Methods  From April 2008 to August 2011, patients with RA and other CVD with suspicion of NTM were enrolled. Additionally, patients with non-CVD with suspicion of NTM were also enrolled as controls. Bronchial washing were directly obtained from the pathological lesions, and bacteriological analyses were demonstrated. Chest CT findings were also evaluated.  Results  A total of 106 patients (41 with RA, 22 with CVD other than RA and 43 with non-CVD) were enrolled.  P. aeruginosa  (26.8%) were the most frequently detected in patients with RA, followed by  S. aureus  (19.5%) and NTM (7.3%). In patients with CVD other than RA,  P. aeruginosa  (9.1%),  S. aureus  (13.6%), NTM (4.5%) were detected. Additionally,  P. aeruginosa  (7.0%),  S. aureus  (11.6%) and NTM (25.6%) were detected in non-CVD patients. Chest CT findings of patients with RA complicating  P. aeruginosa  infection demonstrated that these patients showed more widespread of granular opacities and bronchiectasis and tendency of exacerbation of these pathological lesions.  Conclusion   P. aeruginosa  was frequently detected in patients with RA complicating LRTI, and it is speculated that  P. aeruginosa  infection in patients with RA seemed to be an indicative factor of exacerbation of LRTI.
An analysis of injuries resulting from professional horse racing in France during 1991–2001: a comparison with injuries resulting from professional horse racing in Great Britain during 1992–2001
Authors: P McCrory, M Turner, B LeMasson, C Bodere, A Allemandou
Journal: British Journal of Sports Medicine (2006)

It has been previously shown that professional jockeys suffer high rates of fatal and non-fatal injuries in the pursuit of their occupation. Little is known, however, about differences in injury rates between countries.To determine the rate of fatal and non-fatal injuries in flat and jump jockeys in France and to compare the injury rates with those in Great Britain and Ireland Method: Prospectively collected injury data on professional jockeys were used as the basis of the analysis.Limb fractures occur four times more often in both flat and jump racing in France than in Great Britain. Similarly dislocations are diagnosed 20 times more often in flat and three times more often in jump racing. This difference is surprising given that French jockeys have fewer falls per ride than their British counterparts in flat racing, although they do have more falls than the British in jump racing. Similarly concussion rates seem to be higher in French jockeys, although there may be a difference in the diagnostic methods used in the different countries. By contrast, soft tissue injuries account for a far smaller percentage of injuries than in Great Britain.There are striking differences in injury rates between countries which may be explained in part by a difference in track conditions-for example, harder tracks in France-or different styles of racing--for example, larger fields of horses per race in France.
Role of sarcolemmal phospholipid in cardiac excitation-contraction coupling
Authors: G A LANGER
Journal: Cardiovascular Research (1988)

Journal Article Role of sarcolemmal phospholipid in cardiac excitation-contraction coupling Get access G A LANGER G A LANGER From the Cardiovascular Research Laboratory, UCLA School of Medicine, Los Angeles, California 90024-1760, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 8, August 1988, Page 588, https://doi.org/10.1093/cvr/22.8.588 Published: 01 August 1988
Insulin-Like Growth Factor-1 as a Vascular Protective Factor
Authors: Elena Conti, Cinzia Carrozza, Ettore Capoluongo, Massimo Volpe, Filippo Crea, Cecilia Zuppi, Felicita Andreotti
Journal: Circulation (2004)

R ecent advances in cardiology have focused on prolifer- ation and regeneration as potential cardiovascular defense mechanisms.Within this framework, growth factors are acquiring increasing importance; insulin-like growth factor-1 (IGF-1) emerges among them for its versatile pleiotropic actions.This review provides a current perspective on IGF-1 and vascular disease. I. Insulin-Like Growth Factor-1 and VascularDisease: Friend or Foe?The IGF-1 system is dynamic and complex, 1,2 involving at least 6 IGF-1-binding proteins (IGFBP-1 through -6) and several binding protein-related proteases, 1 including pregnancy-associated plasma protein-A (PAPP-A).The latter promotes IGF-1 bioavailability by cleaving IGFBP-4 and -5. 3 Acute coronary syndromes have been associated with raised PAPP-A concentrations in blood, leading to the interpretation that PAPP-A may enhance the risk of coronary artery disease through increased IGF-1 in vascular tissues. 4Recent results, however, suggest a different relation between IGF-1 and ischemic syndromes.
Fibroblast Growth Factor Receptors Control Epithelial–Mesenchymal Interactions Necessary for Alveolar Elastogenesis
Authors: Sorachai Srisuma, Soumyaroop Bhattacharya, Dawn M. Simon, Siva K. Solleti, Shivraj Tyagi, Barry Starcher, Thomas J. Mariani
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The mechanisms contributing to alveolar formation are poorly understood. A better understanding of these processes will improve efforts to ameliorate lung disease of the newborn and promote alveolar repair in the adult. Previous studies have identified impaired alveogenesis in mice bearing compound mutations of fibroblast growth factor (FGF) receptors (FGFRs) 3 and 4, indicating that these receptors cooperatively promote postnatal alveolar formation.To determine the molecular and cellular mechanisms of FGF-mediated alveolar formation.Compound FGFR3/FGFR4-deficient mice were assessed for temporal changes in lung growth, airspace morphometry, and genome-wide expression. Observed gene expression changes were validated using quantitative real-time RT-PCR, tissue biochemistry, histochemistry, and ELISA. Autocrine and paracrine regulatory mechanisms were investigated using isolated lung mesenchymal cells and type II pneumocytes.Quantitative analysis of airspace ontogeny confirmed a failure of secondary crest elongation in compound mutant mice. Genome-wide expression profiling identified molecular alterations in these mice involving aberrant expression of numerous extracellular matrix molecules. Biochemical and histochemical analysis confirmed changes in elastic fiber gene expression resulted in temporal increases in elastin deposition with the loss of typical spatial restriction. No abnormalities in elastic fiber gene expression were observed in isolated mesenchymal cells, indicating that abnormal elastogenesis in compound mutant mice is not cell autonomous. Increased expression of paracrine factors, including insulin-like growth factor-1, in freshly-isolated type II pneumocytes indicated that these cells contribute to the observed pathology.Epithelial/mesenchymal signaling mechanisms appear to contribute to FGFR-dependent alveolar elastogenesis and proper airspace formation.
Ideal Cardiovascular Health
Authors: Earl S. Ford
Journal: Circulation (2012)

andmark developments during the second half of the 20th century established that smoking, hypertension, and hypercholesterolemia constituted cardinal risk factors for cardiovascular morbidity and mortality. 1These insights proved critical in reversing decades of increases in the mortality rate from coronary heart disease in the United States starting in the late 1960s.As knowledge concerning the pathogenesis and pathophysiology of cardiovascular disease evolved rapidly during ensuing decades, research tended to focus on how much risk for adverse cardiovascular events increased in function of levels of risk factors (high-risk emphasis).However, this paradigm has shifted as research increasingly emphasized that low-risk cardiovascular risk factor profiles were associated with large reductions in cardiovascular mortality and improvements in other outcomes (low-risk emphasis). 2Thus, the conceptual framework for preventing cardiovascular disease that had been anchored largely in primary prevention increasingly embraced primordial prevention.
An acidic fibroblast growth factor protein generated by alternate splicing acts like an antagonist.
Authors: Y L Yu, H Kha, J A Golden, A A Migchielsen, E J Goetzl, C W Turck
Journal: The Journal of Experimental Medicine (1992)

Polymerase chain reaction amplification of cDNA for acidic fibroblast growth factor in several lines of cultured human cells revealed two forms of mRNA. The novel smaller mRNA lacks the entire second coding exon of the acidic fibroblast growth factor gene, whereas the previously identified mRNA consists of three coding exons. The truncated variant of acidic fibroblast growth factor (aFGF') is only 60 amino acids long with an apparent molecular mass of 6.7 kD on sodium dodecyl sulfate gels in contrast to 18 kD for the full-length acidic fibroblast growth factor. aFGF' elicits only minimal fibroblast proliferation and antagonizes the effects of acidic fibroblast growth factor when added exogenously to or when coexpressed with aFGF in BALB/c/3T3 fibroblasts. Thus, the truncated variant of acidic fibroblast growth factor may provide fibroblasts with a unique mechanism for endogenous regulation of their responses to acidic fibroblast growth factor.
Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis
Authors: C E Collins, D T La, H-T Yang, F Massin, S Gibot, G Faure, W Stohl
Journal: Annals of the Rheumatic Diseases (2008)

To determine whether synovial expression of triggering receptor expressed on myeloid cells 1 (TREM-1) is upregulated in patients with distinct types of inflammatory or non-inflammatory arthritis.Synovial fluid (SF) samples were analysed for levels of soluble TREM-1 (sTREM; n = 132), tumour necrosis factor alpha (TNFalpha, n = 78) and leucocyte TREM-1 messenger RNA (n = 48). Synovial tissue from four rheumatoid arthritis (RA) patients, two patients with Crohn's-associated arthritis, one patient with ankylosing spondylitis and one patient with osteoarthritis were examined for TREM-1 expression by immunohistology, and three of the RA samples were also analysed by Western blotting.Synovial fluid sTREM-1 levels in septic arthritis and RA were similar to each other and were each greater than those in gouty arthritis, non-septic/non-RA inflammatory arthritis and non-inflammatory arthritis. Synovial fluid TNFalpha and sTREM-1 levels correlated with each other, and sTREM-1 and leucocyte TREM-1 mRNA levels each correlated with SF leucocyte counts. TREM-1 in RA was expressed in situ in synovial tissue by cells of myelomonocytic lineage but was not detectably expressed in control osteoarthritis synovial tissue.Synovial TREM-1 expression is increased in septic arthritis and RA. In patients with acute inflammatory arthritis, elevated SF sTREM-1 levels may point the clinician to a diagnosis of septic arthritis or RA. In RA patients, targeting TREM-1 may have therapeutic benefits by reducing local proinflammatory cytokine and chemokine release.
An Official American Thoracic Society/American Association of Critical-Care Nurses/American College of Chest Physicians/Society of Critical Care Medicine Policy Statement: The Choosing Wisely® Top 5 List in Critical Care Medicine
Authors: Scott D. Halpern, Deborah Becker, J. Randall Curtis, Robert Fowler, Robert Hyzy, Lewis J. Kaplan, Nishi Rawat, Curtis N. Sessler, Hannah Wunsch, Jeremy M. Kahn
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

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Sexual Function After Left Ventricular Assist Device
Authors: Peter M. Eckman, Vinayak Dhungel, Stacy Mandras, Meredith A. Brisco, Sitaramesh Emani, Sue Duval, JoAnn Lindenfeld, Nasir Sulemanjee, George G. Sokos, Jamie Feldman
Journal: Journal of the American College of Cardiology (2013)
THE FREQUENCY OF ANTIGEN-SENSITIVE CELLS IN TISSUE TRANSPLANTATION
Authors: Norman W. Nisbet, Morten Simonsen, Marek Zaleski
Journal: The Journal of Experimental Medicine (1969)

Graft-vs.-host (GVH) reactions were performed in chicken embryos by intravenous injection of adult chicken blood dilutions, and the result was scored by weighing the spleens as well as by karyological identification of host and donor metaphases. From the frequency of detectable signs of GVH reaction when low doses of donor cells were injected into hosts containing one foreign allele of the B locus it is concluded that 1–2% must be a minimum estimate for the frequency of antigen-sensitive cells of a given specificity in this system. It is not found possible to reconcile the findings with the strictest form of clonal selection which postulates a single receptor specificity per clone of antigen-sensitive cells.