tbuckley/cabot-search huggingface dataset:
Pulmonary Inflammation and Thrombogenicity Caused by Diesel Particles in Hamsters
Authors: Abderrahim Nemmar, Benoit Nemery, Peter H. M. Hoet, Jos Vermylen, Marc F. Hoylaerts
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Short-term increases in particulate air pollution are associated with increased incidence of cardiovascular events. Previously, we showed that intratracheally instilled diesel exhaust particles (DEPs) are prothrombotic. Here, we investigated the time course and the mechanisms. At 1, 6, and 24 hours after instillation of 50 μg DEPs per hamster, the mean size of in vivo-induced and quantified venous thrombosis was increased by 480%, 770%, and 460%, respectively. Platelets activation in blood was confirmed by a shortened closure time in the platelet function analyzer (PFA-100). In bronchoalveolar lavage, neutrophils and histamine levels were increased at all time points. In plasma, histamine was increased at 6 and 24 hours but not at 1 and 3 hours. Pretreatment with a histamine H1-receptor antagonist (diphenhydramine, 30 mg/kg intraperitoneally) abolished the DEP-induced neutrophil influx in bronchoalveolar lavage at all time points. However, diphenhydramine pretreatment did not affect DEP-induced thrombosis or platelet activation at 1 hour, whereas both were markedly reduced at 6 and 24 hours. In conclusion, pulmonary inflammation and peripheral thrombosis are correlated at 6 and 24 hours, but at 1 hour, the prothrombotic effects do not appear to result from pulmonary inflammation but possibly from the blood penetration of DEP-associated components or by DEP particles themselves.
GRANULOCYTE TRANSFUSIONS IN TREATMENT OF INFECTIONS IN PATIENTS WITH ACUTE LEUKÆMIA AND APLASTIC ANÆMIA
Authors: R.M. Lowenthal, J.M. Goldman, N.A. Buskard, B.C. Murphy, L. Grossman, R.A. Storring, D.S. Park, A.S.D. Spiers, D.A.G. Galton
Journal: The Lancet (1975)
Tumor Escape from Endogenous, Extracellular Matrix–Associated Angiogenesis Inhibitors by Up-Regulation of Multiple Proangiogenic Factors
Authors: Namali T. Fernando, Moritz Koch, Courtney Rothrock, Lila K. Gollogly, Patricia A. D'Amore, Sandra Ryeom, Sam S. Yoon
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Thrombospondin-1 (Tsp1), endostatin, and tumstatin are extracellular matrix–associated proteins that inhibit angiogenesis. We examined the mechanisms by which tumor cells may bypass the antiangiogenic effects of these endogenous regulators. Experimental Design: CT26 colon and RenCa renal carcinoma cells were stably transfected with Tsp1, endostatin, or tumstatin cDNA. Subcutaneous and metastatic tumor growth in syngeneic mice was analyzed. Expression of proangiogenic factors in resulting tumors was measured by quantitative real-time PCR. The combination of Tsp1 and vascular endothelial growth factor (VEGF) receptor-2 inhibition was also examined. Results: There was significant suppression of angiogenesis in flank tumors and liver metastases formed from cells overexpressing Tsp1, endostatin, or tumstatin. However, all tumors ultimately escaped angiogenesis inhibition. The combination of all three angiogenesis inhibitors had no additive effect beyond overexpression of a single inhibitor. Using quantitative real-time PCR, we found that VEGF and platelet-derived growth factor (PDGF)-A levels were routinely up-regulated at least 5-fold in all CT26 tumors overexpressing any antiangiogenic protein, and there were variable increases in angiopoietin 2 (Ang2), basic fibroblast growth factor, and PDGF-B. In contrast, RenCa tumors, which have high baseline levels of VEGF and PDGF-B, relied on basic fibroblast growth factor, Ang1, and PDGF-A up-regulation to counteract Tsp1 overexpression. Growth of CT26 cells with Tsp1 overexpression was suppressed when anti–VEGFR-2 treatment was added. Conclusions: Cancer cells with overexpression of three different endogenous angiogenesis inhibitor eventually escape angiogenesis inhibition by up-regulation of various proangiogenic factors. Tsp1, endostatin, and tumstatin may be functionally redundant in this system. These endogenous angiogenesis inhibitors are likely best used in combination with the blockade of proangiogenic pathways or with traditional chemotherapy or radiation therapy.
Airway inflammation in patients with chronic non-asthmatic cough
Authors: Marcin Grabowski, Sven Seys, Ann Decraene, Ahmad Kasran, Ellen Dilissen, Wojciech Barg, Wojciech Medrala, Lieven J Dupont, Bernard Panaszek, Dominique M A Bullens
Journal: Thorax (2012)

<h3>Introduction</h3> Chronic non-asthmatic cough (CC) is a clinical challenge and underlying pathophysiological mechanisms remain still not completely understood. One of the most common comorbidities in CC is gastro-oesophageal reflux disease (GORD). Airway epithelium damage can contribute to airway inflammation in CC. <h3>Aims</h3> We studied airway inflammation in patients with CC compared to healthy controls. Patients with GORD were treated with proton pump inhibitors (PPI) and cough response to PPI was evaluated. <h3>Patients and methods</h3> Sputum was induced in 41 adults with CC and 20 healthy non-smokers who were age and sex matched. We compared sputum differential cell count by cytospin and cytokine and chemokine production at the mRNA and/or protein levels by real-time (RT)-PCR and cytokine bead array (CBA), between patients with CC and healthy subjects. Furthermore we studied airway inflammation in patients with different comorbidities. <h3>Results</h3> No differences in sputum differential cell counts were observed between patients with CC and healthy subjects. Sputum monocyte chemoattractant protein-1 (MCP-1) protein levels were significantly higher in patients when compared to controls. Thymic stromal lymphopoietin (TSLP) mRNA was significantly more often expressed in sputum of patients with CC than from healthy controls. Sputum transforming growth factor (TGF)-β levels did not differ between patients and controls, but were significantly lower in the PPI responders compared to the non-responders; p=0.047. There is no evidence for impaired T helper cell (Th)1/Th2/Th17 balance in CC. Patients with reflux oesophagitis (RO) have significantly more sputum eosinophils than patients without RO. <h3>Conclusions</h3> CC is a condition presenting with different disease phenotypes. High sputum MCP-1 levels are present in a large group of patients with CC and a majority of these patients with CC have increased sputum TSLP levels, most likely produced by damaged airway epithelial cells.
Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer
Authors: Je In Youn, Vinit Kumar, Michelle Collazo, Yulia Nefedova, Thomas Condamine, Pingyan Cheng, Alejandro Villagra, Scott Antonia, Judith C. McCaffrey, Mayer Fishman, Amod Sarnaik, Pedro Horna, Eduardo Sotomayor, Dmitry I. Gabrilovich
Journal: Nature Immunology (2013)
Prevalence of chronic cough and phlegm among male cigar and pipe smokers: results of the Scottish Heart Health Study.
Authors: C A Brown, M Woodward, H Tunstall-Pedoe
Journal: Thorax (1993)

BACKGROUND--Previous studies investigating the effect of cigar or pipe smoking on the occurrence of chronic cough and chronic phlegm have reported prevalences among cigar and pipe smokers lying between those of non-smokers and current cigarette smokers. This study uses data on previous cigarette consumption, current cigar or pipe consumption, and biochemical markers of smoking to provide a detailed analysis of chronic cough and chronic phlegm among cigar and pipe smokers. METHODS--A total of 10,359 men and women aged 40-59 years were sampled for the Scottish Heart Health Study between 1984 and 1986. Prevalence of chronic cough and chronic phlegm among male cigar and pipe smokers (non-cigarette smokers) was compared with those who had never smoked, between ex-smokers of cigarettes and those who had never smoked cigarettes, between cigar-only and pipe-only smokers, and by cigar or pipe consumption levels. RESULTS--In all, 463 ex-smokers of cigarettes and 154 who had never smoked cigarettes were cigar or pipe smokers; 1080 had never smoked any form of tobacco. Ex-cigarette smokers smoked and inhaled more than those who had never smoked cigarettes. Among the ex-cigarette smokers, cigar or pipe smokers had 1.63-1.71 times the prevalence of both chronic cough and chronic phlegm than those who had never smoked (1.31-1.36 among cigar only smokers; 2.23-2.84 among pipe only smokers). A strong positive dose-response effect was found between the prevalence of symptoms and cigar or pipe consumption. CONCLUSIONS--Cigar and pipe smokers have a higher prevalence of chronic cough and phlegm than those who have never smoked, and the difference is more marked in pipe-only smokers than in cigar-only smokers. Both categories show a positive dose-response effect. Among cigar and pipe smokers, ex-cigarette smokers have a higher prevalence of symptoms than those who have never smoked cigarettes, which may be because they inhale more or may be attributable to previous cigarette smoking.
Synonymous Codon Usage in Escherichia coli: Selection for Translational Accuracy
Authors: N. Stoletzki, A. Eyre-Walker
Journal: Molecular Biology and Evolution (2006)

In many organisms, selection acts on synonymous codons to improve translation. However, the precise basis of this selection remains unclear in the majority of species. Selection could be acting to maximize the speed of elongation, to minimize the costs of proofreading, or to maximize the accuracy of translation. Using several data sets, we find evidence that codon use in Escherichia coli is biased to reduce the costs of both missense and nonsense translational errors. Highly conserved sites and genes have higher codon bias than less conserved ones, and codon bias is positively correlated to gene length and production costs, both indicating selection against missense errors. Additionally, codon bias increases along the length of genes, indicating selection against nonsense errors. Doublet mutations or replacement substitutions do not explain our observations. The correlations remain when we control for expression level and for conflicting selection pressures at the start and end of genes. Considering each amino acid by itself confirms our results. We conclude that selection on synonymous codon use in E. coli is largely due to selection for translational accuracy, to reduce the costs of both missense and nonsense errors.
Low-Dose Tamoxifen for Combination Hormone Replacement Therapy Users
Authors: Carol J. Fabian
Journal: Journal of Clinical Oncology (2007)

Despite a dramatic reduction in postmenopausal hormone use after the initial publication of the Women’s Health Initiative results, 1-4 a substantial number of women continue to use some form of hormonal supplementation predominately to control menopausal symptoms. The conjugated equine estrogen Premarin (Wyeth Pharmaceuticals, Madison, NJ) is the 22nd most frequently prescribed brand name drug in the United States with more than 13 million prescriptions issued in 2006. 5 Almost 3 million prescriptions were issued in 2006 for Prempo (Wyeth Pharmaceuticals) a combination of an androgenic progestin with conjugated equine estrogen. 5 As the preponderance of clinical trial data indicating an increased risk of breast cancer and an unfavorable global health index has been for conjugated equine estrogens and progestins, interest in more physiologic types of hormone replacement has soared. These so-called bioidentical forms of hormone replacement include estradiol, estriol, testosterone, and progesterone, given as either single agents or compounded together and administered as pills, troches, transdermal patches, creams, or vaginal gels. More than 4 million brand name estradiol patches are currently sold annually. 5 Change in risk of breast cancer by the use of postmenopausal hormones may be dependent on the type of drug(s) and dose, route of administration, prior oophorectomy, age at initiation, and duration of use. Women using standard dose oral or transdermal estrogen without a progestin might anticipate either no increase or
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells
Authors: Surya M. Nauli, Francis J. Alenghat, Ying Luo, Eric Williams, Peter Vassilev, Xiaogang Li, Andrew E. H. Elia, Weining Lu, Edward M. Brown, Stephen J. Quinn, Donald E. Ingber, Jing Zhou
Journal: Nature Genetics (2003)
CNS Involvement in Primary Mediastinal Large B-Cell Lymphoma
Authors: Philippe C. Bishop, Wyndham H. Wilson, Debra Pearson, John Janik, Elaine S. Jaffe, Patrick C. Elwood
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The risk of CNS involvement by non-Hodgkin's Lymphoma (NHL) has been associated with bone marrow and/or testicular involvement; however, it was recently reported that the number of extranodal sites is a more reliable predictor of CNS disease. Because primary mediastinal thymic large B-cell lymphoma (PMLCL) has a high propensity for involving extranodal sites, we investigated the frequency and pattern of CNS involvement in PMLCL. PATIENTS AND METHODS: The medical records of 219 patients with aggressive NHL, consecutively entered onto protocols at the National Cancer Institute between 1987 and 1998, were retrospectively reviewed. RESULTS: Twenty-three patients (11%) had clinical and pathologic features of PMLCL. These patients were young (median age, 29 years), female (61%), and presented with massive mediastinal adenopathy (70%). Extranodal disease occurred at presentation in 70% and at relapse in 93% of patients and involved contiguous intrathoracic structures and/or distant sites, including the lungs, kidneys, liver, adrenals, ovaries, pancreas, and bone. Six patients (26%) developed CNS involvement, two (9%) at presentation and four (27%) at relapse. All had extranodal disease, but only one had bone marrow involvement. Parenchymal and leptomeningeal CNS disease occurred in four and three patients, respectively. CONCLUSION: CNS involvement in PMLCL is associated with extranodal involvement other than bone marrow and may reflect the unique biology of this disease. The propensity to involve the CNS parenchyma raises the concern that intrathecal prophylaxis may not be effective and suggests that CNS imaging should be considered in patients with extranodal disease.
Sham device <i>v</i> inert pill: randomised controlled trial of two placebo treatments
Authors: Ted J Kaptchuk, William B Stason, Roger B Davis, Anna R T Legedza, Rosa N Schnyer, Catherine E Kerr, David A Stone, Bong Hyun Nam, Irving Kirsch, Rose H Goldman
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To investigate whether a sham device (a validated sham acupuncture needle) has a greater placebo effect than an inert pill in patients with persistent arm pain. <b>Design</b> A single blind randomised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls. Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study. <b>Setting</b> Academic medical centre. <b>Participants</b> 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale. <b>Interventions</b> Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks. <b>Main outcomemeasures</b> Arm pain measured on a 10 point pain scale. Secondary outcomes were symptoms measured by the Levine symptom severity scale, function measured by Pransky9s upper extremity function scale, and grip strength. <b>Results</b> Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups, but changes were not different between the groups (−0.14, 95% confidence interval −0.52 to 0.25, P = 0.49). Changes in severity scores for arm symptoms and grip strength were similar between groups, but arm function improved more in the placebo pill group (2.0, 0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group (−0.33 (−0.40 to −0.26) <i>v</i> −0.15 (−0.21 to −0.09), P = 0.0001) and on the symptom severity scale (−0.07 (−0.09 to −0.05) <i>v</i> −0.05 (−0.06 to −0.03), P = 0.02). Differences were not significant, however, on the function scale or for grip strength. Reported adverse effects were different in the two groups. <b>Conclusions</b> The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in. Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals.
Age related increase in the intra-alveolar macrophage population of non-smokers.
Authors: W A Wallace, M Gillooly, D Lamb
Journal: Thorax (1993)

The alveolar macrophage population is higher in smokers than in non-smokers. An age related increase in the alveolar macrophage number in the lungs of non-smokers has been found, whether expressed per unit lung volume or per unit lung surface area.
Endomyocardial Nitric Oxide Synthase and Left Ventricular Preload Reserve in Dilated Cardiomyopathy
Authors: Christophe Heymes, Marc Vanderheyden, Jean G. F. Bronzwaer, Ajay M. Shah, Walter J. Paulus
Journal: Circulation (1999)

Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy.In patients with dilated, nonischemic cardiomyopathy, invasive measures of LV contractile performance were derived from LV microtip pressure recordings and angiograms and correlated with intensity of gene expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simultaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial expression of NOS2 was linearly correlated with LV stroke volume (P=0.001; r=0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003; r=0.62). In patients with elevated LV end-diastolic pressure (>16 mm Hg), a closer correlation was observed between endomyocardial expression of NOS2 and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression of NOS3 was linearly correlated with LV stroke volume (P=0.01; r=0.53) and LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO) as a mediator of the observed correlations, substance P (which causes endothelial release of NO) was infused intracoronarily (n=12). In patients with elevated LV end-diastolic pressure, an intracoronary infusion of substance P increased LV stroke volume from 72+/-13 to 91+/-16 mL (P=0.06) and LV stroke work from 67+/-11 to 90+/-15 g. m (P=0.03) and shifted the LV end-diastolic pressure-volume relation to the right.In patients with dilated cardiomyopathy, an increase in endomyocardial NOS2 or NOS3 gene expression augments LV stroke volume and LV stroke work because of a NO-mediated rightward shift of the diastolic LV pressure-volume relation and a concomitant increase in LV preload reserve.
Butyrate production from dietary fibre and protection against large bowel cancer in a rat model.
Authors: A McIntyre, P R Gibson, G P Young
Journal: Gut (1993)

Butyrate slows the growth of cancer cells cultured in vitro. To determine the relevance of the fermentative production of butyrate in vivo, colonic butyrate concentrations were manipulated by feeding different dietary fibres and were related to tumour development in the rat dimethylhydrazine model of large bowel cancer. It has previously been shown that guar gum and oat bran, while highly fermentable, are associated with low butyrate levels in the distal colon, while wheat bran causes significantly higher concentrations. Diets containing these fibres (nominally 10% w:w) were administered for 3 weeks before, for 10 weeks during, and for 20 weeks after dimethylhydrazine administration, after which animals were killed and examined for tumours. Significantly fewer tumours were seen in the rats fed wheat bran compared with those fed guar or oat bran, and the total tumour mass was lowest in rats fed wheat bran. Rats on a 'no added fibre diet' had an intermediate tumour mass. Regression analysis, performed regardless of dietary group, showed that the concentration in stools of butyrate but not of acetate or stool volume, correlated significantly (and negatively) with tumour mass. These findings indicate that fibre which is associated with high butyrate concentrations in the distal large bowel is protective against large bowel cancer, while soluble fibres that do not raise distal butyrate concentrations, are not protective. Thus, butyrate production in vivo does bear a significant relationship to suppression of tumour formation.
Identification of Soluble Candidate Biomarkers of Therapeutic Response to Sunitinib in Medullary Thyroid Carcinoma in Preclinical Models
Authors: Sophie Broutin, Nabahet Ameur, Ludovic Lacroix, Thomas Robert, Benoit Petit, Nassima Oumata, Monique Talbot, Bernard Caillou, Martin Schlumberger, Corinne Dupuy, Jean-Michel Bidart
Journal: Clinical Cancer Research (2011)

Medullary thyroid carcinoma (MTC), an aggressive rare tumor due to activating mutations in the proto-oncogene RET, requires new therapeutic strategies. Sunitinib, a potent inhibitor of RET, VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor (PDGFR)α/β, has been reported as clinically effective in some patients with advanced MTC. In this study, we examine molecular mechanisms of action of sunitinib and identify candidate soluble biomarkers of response.Both in vitro and in vivo assays, using the human TT RET(C634W) MTC cell line, were done to assess the activity of sunitinib. Kinetic microarray studies were used to analyze molecular pathways modified by sunitinib and to identify candidate biomarkers that were subsequently investigated in the serum of patients.Sunitinib displayed antiproliferative and antiangiogenic activities and inhibited RET autophosphorylation and activation of downstream signaling pathways. We showed that sunitinib treatment induced major changes in the expression of genes involved in tissue invasion and metastasis including vimentin (VIM), urokinase plasminogen (PLAU), tenascin-C (TN-C), SPARC, and CD44. Analyzing downregulated genes, we identified those encoding secreted proteins and, among them, interleukin (IL)-8 was found to be modulated in the serum of xenografted mice under sunitinib treatment. Furthermore, we demonstrated that metastatic MTC patients presented increased serum levels of IL-8 and TGF-β2.Experimental models confirm the clinical efficacy of sunitinib observed in a few studies. Molecular pathways revealed by genomic signatures underline the impact of sunitinib on tissue invasion. Selected soluble candidate biomarkers could be of value for monitoring sunitinib response in metastatic MTC patients.