tbuckley/cabot-search huggingface dataset:
SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction
Authors: Michiel Alexander de Raaf, Ingrid Schalij, Jose Gomez-Arroyo, Nina Rol, Chris Happé, Frances S. de Man, Anton Vonk-Noordegraaf, Nico Westerhof, Norbert F. Voelkel, Harm Jan Bogaard
Journal: European Respiratory Journal (2014)

The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported. We used telemetry to characterise haemodynamic responses in SuHx rats and associated these with serial histology. Right ventricular systolic pressure (RVSP) increased to a mean± sd of 106±7 mmHg in response to SuHx and decreased but remained elevated at 72±8 mmHg upon return to normoxia. Hypoxia-only exposed rats showed a similar initial increase in RVSP, a lower maximum RVSP and near-normalisation of RVSP during subsequent normoxia. Progressive vascular remodelling consisted of a four-fold increase in intima thickness, while only minimal changes in media thickness were found. The circadian range in RVSP provided an accurate longitudinal estimate of vascular remodelling. In conclusion, in SuHx rats, re-exposure to normoxia leads to a partial decrease in pulmonary artery pressure, with persisting hypertension and pulmonary vascular remodelling characterised by progressive intima obstruction.
Improved characterization of medically relevant fungi in the human respiratory tract using next-generation sequencing
Authors: Kyle Bittinger, Emily S Charlson, Elizabeth Loy, David J Shirley, Andrew R Haas, Alice Laughlin, Yanjie Yi, Gary D Wu, James D Lewis, Ian Frank, Edward Cantu, Joshua M Diamond, Jason D Christie, Ronald G Collman, Frederic D Bushman
Journal: Genome biology (2014)

Abstract Background Fungi are important pathogens but challenging to enumerate using next-generation sequencing because of low absolute abundance in many samples and high levels of fungal DNA from contaminating sources. Results Here, we analyze fungal lineages present in the human airway using an improved method for contamination filtering. We use DNA quantification data, which are routinely acquired during DNA library preparation, to annotate output sequence data, and improve the identification and filtering of contaminants. We compare fungal communities and bacterial communities from healthy subjects, HIV+ subjects, and lung transplant recipients, providing a gradient of increasing lung impairment for comparison. We use deep sequencing to characterize ribosomal rRNA gene segments from fungi and bacteria in DNA extracted from bronchiolar lavage samples and oropharyngeal wash. Comparison to clinical culture data documents improved detection after applying the filtering procedure. Conclusions We find increased representation of medically relevant organisms, including Candida , Cryptococcus , and Aspergillus , in subjects with increasingly severe pulmonary and immunologic deficits. We analyze covariation of fungal and bacterial taxa, and find that oropharyngeal communities rich in Candida are also rich in mitis group Streptococci , a community pattern associated with pathogenic polymicrobial biofilms. Thus, using this approach, it is possible to characterize fungal communities in the human respiratory tract more accurately and explore their interactions with bacterial communities in health and disease.
Full-Dose Peginterferon Alfa-2a and Low-Dose Ribavirin Treatment of Genotypes 1 and 4 Chronic Hepatitis CPatients With End-Stage Renal Disease
Authors: Mamdouh M. Abdulhadi–Ali, Dib Alsaudi, Adnan Agha, Nasser Ibraheem–Alqahtani, Manuele Furnari, Vincenzo Savarino, Edoardo G. Giannini
Journal: Clinical Gastroenterology and Hepatology (2011)
Reduction in First and Recurrent Cardiovascular Events With Ticagrelor Compared With Clopidogrel in the PLATO Study
Authors: Payal Kohli, Lars Wallentin, Eric Reyes, Jay Horrow, Steen Husted, Dominick J. Angiolillo, Diego Ardissino, Gerald Maurer, Joao Morais, José C. Nicolau, Ali Oto, Robert F. Storey, Stefan K. James, Christopher P. Cannon
Journal: Circulation (2013)

We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (e.g., cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events.In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79-0.93; P=0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P=0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70-0.90; P<0.001) and a number needed to treat of 54. For cardiovascular death/myocardial infarction/stroke/(severe) recurrent ischemia/transient ischemic attack/arterial thrombotic events, total events were fewer with ticagrelor (2030 versus 2290; rate ratio, 0.88; 95% confidence interval, 0.82-0.95; P<0.001), with fewer recurrent events with ticagrelor (740 versus 834; P=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75-0.91; P<0.001). Recurrent PLATO major or Thrombolysis in Myocardial Infarction (TIMI) major non-coronary artery bypass graft bleeding events were infrequent and not different between the two therapies (P=0.96 and 0.38, respectively).In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported.URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00391872.
CC chemokine ligand 1 is released into the airways of atopic asthmatics
Authors: R. Montes-Vizuet, A. Vega-Miranda, E. Valencia-Maqueda, M. C. Negrete-García, J. R. Velásquez, L. M. Teran
Journal: European Respiratory Journal (2006)

CC chemokine ligand (CCL)1/I-309 is a potent attractant for T-helper cell type 2 lymphocytes. The present study investigates whether this cytokine is released in the bronchoalveolar fluid (BALF) of asthmatic patients. Measurements of CCL1 using ELISA showed that levels of this cytokine were significantly elevated in BALF from asthmatics compared with normals (median (range) 193 (120–449) pg·mL −1 versus 30 (21–55) pg·mL −1 ). Differential cell counts in BALF showed that either lymphocyte or eosinophil numbers were elevated in asthmatic compared with normal subjects (10.8×10 3 ·mL −1 versus 1.0×10 3 ·mL −1 and 1.7×10 3 ·mL −1 versus 0.2×10 3 ·mL −1 , respectively). There was a trend towards a significant correlation between CCL1 levels and lymphocyte numbers in BALF. Separation of BALF using sequential CCL1 affinity column and reverse-phase high-performance liquid chromatography allowed detection of biologically active CCL1. Using immunohistochemistry, CCL1 immunoreactivity was localised predominantly to the airway epithelium. Interestingly, there was a significant correlation between CC chemokine ligand 1 levels and epithelial cell numbers in bronchoalveolar lavage fluid and between these cells and lymphocyte numbers. Moreover, interleukin-4, interleukin-13 and interferon-γ stimulated primary bronchial airway epithelial cells to release CC chemokine ligand 1. These findings suggest that CC chemokine ligand 1 may play a role in lymphocyte recruitment in bronchial asthma.
Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial
Authors: Peter A Calabresi, Ernst-Wilhelm Radue, Douglas Goodin, Douglas Jeffery, Kottil W Rammohan, Anthony T Reder, Timothy Vollmer, Mark A Agius, Ludwig Kappos, Tracy Stites, Bingbing Li, Linda Cappiello, Philipp von Rosenstiel, Fred D Lublin
Journal: The Lancet Neurology (2014)
Environmental factors predicting nephritis in systemic lupus erythematosus.
Authors: T McAlindon, L Giannotta, N Taub, D D'Cruz, G Hughes
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To evaluate social class, ethnic origin, and various endocrine variables as potential risk factors in the development of nephritis in patients with systemic lupus erythematosus (SLE). METHODS--A cross-sectional survey was carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's Hospital from March to October 1992 using retrospective survival data. The main outcome measure was the duration of SLE before the onset of nephritis. RESULTS--Two hundred and ninety six women and 11 men were studied; the male patients were excluded from the analysis. Univariate analysis showed an increased risk of nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis at five years, in patients of lower social class, in patients who did not drink alcohol, and in those with a history of fetal loss after the onset of lupus. No significant effect of the age of onset of SLE, use of oral contraceptives, normal pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin did not influence the risk of nephritis independently of social class. CONCLUSIONS--Factors associated with socioeconomic deprivation may increase disease severity in patients with SLE.
Anti-apolipoprotein A-1 autoantibodies as an independent cardiovascular prognostic marker affecting basal heart rate in myocardial infarction
Authors: N Vuilleumier, M F Rossier, S Pagano, M Python, E Charbonney, R Nkoulou, R James, G Reber, F Mach, P Roux-Lombard
Journal: Annals of the Rheumatic Diseases (2010)

Background Apolipoprotein A-1 (Apo A-1) is the major protein fraction of high-density lipoproteins whose protective role in the cardiovascular system has been established.Anti-Apo A-1 IgG autoantibodies were described in autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome and might be involved in the genesis of arterial and venous thrombotic events.Anti-Apo A-1 on August 17,
Enhanced Endothelin-Mediated Coronary Vasoconstriction and Attenuated Basal Nitric Oxide Activity in Experimental Hypercholesterolemia
Authors: Verghese Mathew, Charles R. Cannan, Virginia M. Miller, Dustan A. Barber, David Hasdai, Robert S. Schwartz, David R. Holmes, Amir Lerman
Journal: Circulation (1997)

Background Experimental hypercholesterolemia is associated with coronary vasomotor dysfunction. This study was designed to test the hypothesis that experimental hypercholesterolemia is characterized by altered coronary vasomotor responses to endothelin and inhibition of the endogenous NO pathway. Methods and Results Endothelin-1 (ET-1) at 5 ng · kg −1 · min −1 or N G -monomethyl- l -arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase (NOS), at 50 μg · kg −1 · min −1 was infused into the left anterior descending coronary artery in pigs before and after 10 weeks of cholesterol diet. There was a significant increase in serum cholesterol. At 10 weeks, ET-1 resulted in an accentuated decrease in coronary blood flow (CBF) and coronary artery diameter (CAD) compared with baseline (−88±6% versus −45±9%, P &lt;.05, and −77±14% versus −18±8%, P &lt;.05, respectively) and an increase in coronary vascular resistance (CVR) (242±18% versus 110±17%, P &lt;.05); ET receptor density and binding affinity in epicardial coronary arteries were unchanged. The effect of L-NMMA on CBF, CAD, and CVR was attenuated at 10 weeks (−7±8% versus −48±4%, −2±3% versus −17±5%, and 16±10% versus 125±32%; each P &lt;.05). Immunohistochemistry staining for constitutive NOS revealed a decrease in immunoreactivity in the coronary arteries of hypercholesterolemic pigs. Conclusions The present study demonstrates an enhanced coronary vasoconstrictive response to pathophysiological doses of endothelin and an attenuated response to the inhibition of endogenous NO activity, suggesting an alteration in coronary vascular reactivity in experimental hypercholesterolemia.
Connective Tissue Growth Factor Induces Extracellular Matrix in Asthmatic Airway Smooth Muscle
Authors: Peter R. A. Johnson, Janette K. Burgess, Qi Ge, Maree Poniris, Sarah Boustany, Stephen M. Twigg, Judith L. Black
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in airway smooth muscle cells isolated from patients with asthma. In this study, we examined fibronectin and collagen production and signal transduction pathways after stimulation with TGF-beta and connective tissue growth factor. In both asthmatic and nonasthmatic airway smooth muscle cells, TGF-beta and connective tissue growth factor led to the production of fibronectin and collagen I. Fibronectin and collagen expression was extracellular regulated kinase-dependent in both cell types but phosphoinositide-3 kinase-dependent only in asthmatic airway smooth muscle cells. p38 was implicated in fibronectin but not collagen expression in both cell types. TGF-beta induction of fibronectin and collagen was in part mediated by an autocrine action of connective tissue growth factor. Phosphorylation of SMAD-2 may represent an additional pathway because this was increased in asthmatic cells. Our results suggest that these two cytokines may be important in the deposition of extracellular matrix proteins and that the signal transduction pathways may be different in asthmatic and nonasthmatic cells.
Effect of house dust mite avoidance measures on adult atopic asthma.
Authors: A J Dorward, M J Colloff, N S MacKay, C McSharry, N C Thomson
Journal: Thorax (1988)

Twenty one adult patients with asthma, with positive skin test responses to the European house dust mite, Dermatophagoides pteronyssinus, were randomly allocated to a control group or to a group applying house dust mite avoidance measures. These included an initial application of liquid nitrogen to mattresses and bedroom carpets to kill the live house dust mite population. Histamine airway responsiveness, symptom scores, peak expiratory flow rates (PEF), and house dust mite numbers were determined during the two week pretrial and eight week trial periods. Nine patients in each group completed the study. By the end of the study there was a significant reduction in live mites in the "avoidance" group but not in the control group. The avoidance group showed a significant improvement in symptom scores measured on a linear analogue scale, in the number of hours each day spent wheezing (mean reduced from 8.6 to 4.5 hours), and in PEF (l/min) both in the morning (from 364 to 388) and in the evening (from 368 to 392). These changes were not found in the control group. The provocative concentration (PC) of histamine causing a 20% fall in FEV1 (PC20FEV1) had increased significantly in the avoidance group at eight weeks (from 0.58 to 2.3 mg/ml), whereas no change was seen in the control group (from 0.93 to 1.21 mg/ml). These results show that house dust mite avoidance, combined with initial killing of the mite by liquid nitrogen, diminishes airway responsiveness and improves asthma symptom control over an eight week period in adult asthmatic patients with house dust mite allergy.
Qualitative analysis of satisfaction of patients with chronic obstructive pulmonary disease (COPD) submitted to exercise training in water and on land
Authors: Débora R. Carvalho, Laís S. Vidotto, Myriam F. Merli, Josiane M. Felcar, Fabio Pitta, Dirce S. Fujisawa, Vanessa S. Probst
Journal: European Respiratory Journal (2014)

Introduction : Patients9 satisfaction has been associated with greater adherence in rehabilitation programmes. Since patients with COPD often present high dropout rates when taking part in these programmes, the role of satisfaction is critical.  Objective : To analyse the satisfaction of COPD patients submitted to exercise training in water and on land.  Methodology : Qualitative and exploratory study with 22 patients who completed six months of exercise training. Patients were randomized at baseline either to the exercise training group in water (WT) or on land (LT). All patients underwent high intensity endurance and strength training, three times a week, for six months. Patients who completed the programme (13 in the WT and 9 in the LT) were individually interviewed by a physiotherapist and a semi-structured guide was applied. The interviews were recorded, transcribed and analysed according to the criteria of thematic analysis.  Results : Patients9 reports revealed factors related to satisfaction in both exercise training regimens. Benefits for physical activity, muscle strength, respiratory symptoms and patient and therapist relationship were also related to both training regimens. However, patients from the WT reported more prominent benefits regarding respiratory symptoms, leisure, sensation of pain and sleep.  Conclusion : The satisfaction of COPD patients submitted to exercise training in water and on land can be characterized as multifactorial. Patient and therapist relationship was an important factor for success. Furthermore, exercising in water promoted additional benefits in comparison to the land environment.
Ageism in the Undertreatment of High-Risk Prostate Cancer: How Long Will Clinical Practice Patterns Resist the Weight of Evidence?
Authors: Dean A. Shumway, Daniel A. Hamstra
Journal: Journal of Clinical Oncology (2015)

The Conquer Cancer Foundation (CCF) was created by the world's foremost cancer physicians of the American Society of Clinical Oncology to seek dramatic advances in the prevention, treatment, and cures of all types of cancer.Working toward the vision of a world free from the fear of cancer, CCF strives to conquer this disease
Transforming growth factor beta 1 gene expression in human airways.
Authors: J D Aubert, B I Dalal, T R Bai, C R Roberts, S Hayashi, J C Hogg
Journal: Thorax (1994)

BACKGROUND--Asthmatic airways have a characteristic deposition of connective tissue under the epithelial basement membrane, but the mediators involved in this alteration are unknown. Several authors have postulated that transforming growth factor beta 1 (TGF-beta 1) could be overexpressed in asthmatic airways. METHODS--Lung samples from 16 asthmatic patients, six patients with chronic obstructive pulmonary disease (COPD), and six non-obstructed smokers were analysed. RNA was extracted from these tissues to measure expression of TGF-beta 1 by Northern blot analysis using a cDNA probe for TGF-beta 1. The level of expression was quantitated by densitometry using glyceraldehyde 3-phosphate dehydrogenase mRNA as a control. TGF-beta 1 was localised to specific cell types in these lungs by immunohistochemical analysis using polyclonal antibodies specific for intracellular and extracellular TGF-beta 1. RESULTS--The 2.5 kb TGF-beta 1 mRNA was seen in all 18 samples analysed by Northern blotting and densitometric analysis showed no difference between the asthmatic group (mean (SD) 108% (43%)), the group with COPD (122% (33%)), and the non-obstructed group (100% (49%)). The TGF-beta 1 precursor was immunolocalised throughout the airway wall including the epithelium and in alveolar macrophages. The mature TGF-beta 1 was localised primarily within the connective tissue of the airway wall. These patterns of expression of both forms of TGF-beta 1 were similar in lungs from asthmatic patients, those with COPD, and controls. CONCLUSIONS--While TGF-beta 1 mRNA and protein are abundantly expressed in human lungs, there is no clear difference in expression between the airways of asthmatic subjects and those of smokers with and without COPD.
Impact of E2F-1 Expression on Clinical Outcome of Gastric Adenocarcinoma Patients with Adjuvant Chemoradiation Therapy
Authors: Jeeyun Lee, Cheol Keun Park, Joon Oh Park, Taekyu Lim, Young Suk Park, Ho Yeong Lim, Inkyoung Lee, Tae Sung Sohn, Jae Hyung Noh, Jin Seok Heo, Sung Kim, Do Hoon Lim, Kyoung-Mee Kim, Won Ki Kang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: There are no reliable prognostic markers that identify gastric cancer patients who may benefit from adjuvant chemoradiation therapy. E2F-1 was shown to be associated with radiosensitivity and chemosensitivity in certain tumor types. Therefore, we analyzed expression and prognostic significance of E2F-1 along with thymidylate synthase (TS) in R0-resected gastric adenocarcinoma patients, who underwent adjuvant chemoradiation therapy with 5-fluorouracil (5-FU) and leucovorin. Experimental Design: The chemosensitivity to 5-FU and radiosensitivity were tested in three E2F-1–overexpressed gastric cancer cell lines in vitro. The expressions of TS and E2F-1 were analyzed in 467 R0-resected primary gastric cancer patients, who received adjuvant chemoradiation therapy with 5-FU and leucovorin using tissue microarray. Results: The E2F-1 immunopositivity rate was 22.2% (103 of 465 samples) with a cutoff value of 5% immunoreactivity, whereas the TS-positive expression occurred in 19.0% of the 463 tumors tested. Using stepwise Cox proportional hazards regression modeling, multivariate analyses showed that the E2F-1 immunopositivity predicted more favorable survival as compared with the E2F-1 immunonegativity with borderline statistical significance [P = 0.050, hazard ratio (HR) = 0.702, 95% confidence interval, 0.487, 1.013]. However, the E2F-1 immunopositivity did not retain its statistical significance at multivariate analysis for predicting disease-free survival (data not shown, P = 0.270), but stage was the only influential factor for disease-free survival in stages IB to IV (M0) patients (P &amp;lt; 0.001). TS immunopositivity did not influence survival (P = 0.459) or disease-free survival (P = 0.447). Conclusion: E2F-1 is a potentially novel independent prognostic factor that may identify gastric cancer patients who will likely benefit from adjuvant chemoradiation therapy following curative resection.