tbuckley/cabot-search huggingface dataset:
The impact of anemia of chronic disease on exercise capacity among patients with chronic obstructive pulmonary disease
Authors: Afroditi Boutou, Georgia Pitsiou, Ioannis Stanopoulos, Theodoros Kontakiotis, Kyriazis George, Nikolaos Chavouzis, Chrysanthi Nakou, Lazaros Sichletidis, Paraskevi Argyropoulou
Journal: European Respiratory Journal (2011)

Background:  The presence of anemia has been associated with reduced performance in 6 minute walk test among patients with Chronic Obstructive Pulmonary Disease (COPD).   Aim:  To investigate, for the first time, the impact of Anemia of Chronic Disease (ACD) on exercise capacity among COPD patients, utilising cardiopulmonary exercise testing (CPET).   Methods:  It is a case-control study. Cases (27 stable COPD outpatients who were identified to fulfill clinical and laboratory criteria of ACD) and 27 matched by age, height, sex, FEV 1  and current smoking status non-anemic stable COPD controls underwent maximal CPET. Student9s T-test for independent samples was used for statistical comparisons between the groups; level of p   Results:  Cases (92.6% males; 64.8±8 years old; FEV 1 %predicted=42.3±10) compared to controls (92.6% males; 65.3±7.2 years old; FEV 1 %predicted=42.8±12.8) achieved lower: a) peak%predicted oxygen uptake (59.5±17.2 vs 71.3±11.9; p   Conclusions:  The presence of ACD significantly impairs the exercise capacity of COPD patients.
Abstract 123: Mechanism of oncogenic signal activation by the novel fusion kinase FGFR3-BAIAP2L1
Authors: Yoshito Nakanishi, Nukinori Akiyama, Toshiyuki Tsukaguchi, Toshihiko Fujii, Yasuko Satoh, Hideaki Mizuno, Nobuya Ishii, Masahiro Aoki
Journal: Cancer Research (2015)

Abstract Recent cancer genome profiling studies have identified many novel genetic alterations, including rearrangements of genes encoding fibroblast growth factor receptor (FGFR) family members. However, most fusion genes are not functionally well characterized, and the oncogenicity of some fusions as well as their potential sensitivity to targeted therapy are still unclear. In a previous study, we investigated a recently discovered gene fusion between FGFR3 and BAI1-associated protein 2-like 1 (BAIAP2L1). The FGFR3-BAIAP2L1 fusion gene was identified in 4 bladder cancer patients and 2 lung cancer patients via screens involving PCR and a break-apart fluorescence in situ hybridization assay. The functional analysis of FGFR3-BAIAP2L1 transfectant in Rat-2 fibroblast cells (Rat-2_F3-B) indicated that FGFR3-BAIAP2L1 forms a dimer via the Bin-Amphiphysin-Rvs (BAR) BAIAP2L1 dimerization domain that constitutively activates its FGFR3 kinase activity. CH5183284/Debio 1347*, a selective FGFR inhibitor, effectively inhibits growth of Rat-2_F3-B both in vitro and in vivo, indicating that the FGFR3 kinase activity is critical for tumorigenic activity of this fusion. These results indicate a potential application of FGFR inhibitors to treat FGFR3-BAIAP2L1fusion gene positive patients. In this study, we further elucidate the mechanism of tumorigenic potential of FGFR3-BAIAP2L1A by a comprehensive gene expression analysis of 4 cell lines (Rat-2_mock, Rat-2_FGFR3, Rat-2_F3-B, and Rat-2_BAIAP2L1) using RNA sequencing. We identified 143 up-regulated and 67 down-regulated genes specifically engaged by FGFR3-BAIAP2L1. Our gene signature analysis with this gene set revealed that FGFR3-BAIAP2L1 activates growth signals, such as the mitogen-activated protein kinase pathway, and inhibits tumor-suppressive signals, such as the p53, RB1, and CDKN2A pathways. Analysis by Western blot in xenograft tissues confirmed the activation and inactivation status of those pathways. These data suggest that a concurrent regulation of an oncogenic pathway and a tumor-suppressive pathway results in the tumorigenic potential of FGFR3-BAIAP2L1. *CH5183284/Debio 1347 was discovered by Chugai Pharmaceutical Co., Ltd. and is being developed by Debiopharm International S.A. under an exclusive worldwide license. Citation Format: Yoshito Nakanishi, Nukinori Akiyama, Toshiyuki Tsukaguchi, Toshihiko Fujii, Yasuko Satoh, Hideaki Mizuno, Nobuya Ishii, Masahiro Aoki. Mechanism of oncogenic signal activation by the novel fusion kinase FGFR3-BAIAP2L1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 123. doi:10.1158/1538-7445.AM2015-123
Idiopathic pulmonary fibrosis treatment: Combined pirfenidone + acetylcysteine vs N-acetylcysteine in monotherapy
Authors: Carolina Vitale, Maurizia Lanza, Giovanna Calabrese, Giovanna Caccavo, Maria D'Amato, Anna Agnese Stanziola
Journal: European Respiratory Journal (2014)

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal disease for which there are no currently effective therapies to improve patient outcomes and slow the progression of the disease. Recent clinical trials provided encouraging data on the use of pirfenidone in patients with mild -to-moderate IPF.  Fourteen 14 patients (mean age etc..) with moderate IPF were randomly treated with Pirfenidone + Acetylcysteine (group 1; 7 patients , 4male , mean age 63.3 ± 13 , 2 former-smokers / 5 non-smokers; functional data: FVC 2.14 L ( 59.75 % th ) , DLCO 43% , 6MWT mt 474 ± 115) or with Acetlcysteine alone (group 2; 7 patients, 6 male, mean age 66.1 ± 11 , 3 former-smokers / 4 non-smokers; FVC 1.99 L ( 64.7% th ) , 46% DLCO , 6MWT paths 482 mt ± 138). The patients were followed as outpatients for one year.   Results : After 12 months, respiratory functional data documented reduced FVC (-5 and -3 relative percent respectively in group 1 and 2 , chi2 -test p = 0.8), DLCO (-8 and -7 relative percent difference respectively in group 1 and 2, p = 0.9 chi2 -test ) as well as reduced distance walked in meters. (- 45 and -50 m paths respectively in group 1 and 2, chi2 -test p = 0.9 ).   Conclusions:  Combined therapy with pirfenidone and acetylcysteine in patients with moderate IPF is well tolerated but did not have significant effects on functional outcomes compared with acetylcysteine treatment in monotherapy.
Frequencies and dynamics of peripheral immune cell subsets in idiopathic pulmonary fibrosis: Preliminary results and clinical implications
Authors: Marialuisa Bocchino, Domenico Galati, Marina De Martino, Maria Napolitano, Annamaria Trotta, Anna Stanziola, Alessandro Sanduzzi
Journal: European Respiratory Journal (2012)

Involvement of the immune response in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is not well clarified. Emerging T cell subsets including IL-17 secreting T helper cells (TH17) and regulatory T lymphocytes (Treg) expressing TGF-beta may exert antithetical actions. Distribution and phenotype characteristics of peripheral immune cells along with TH17/Treg dynamics were investigated by multi-parametric flow cytometry in 15 IPF patients (mean age 63 yrs; 13 men) and 10 age- and sex-matched healthy subjects. Proportions of CD4 +  and CD8 +  T cells and of B (CD20 + ) lymphocytes were similar in the two groups. Frequencies of NKT (CD3 + CD56 + ) and NK cells (CD3 - CD56 + CD16 + ) were reduced in IPF (p + CD25 high FoxP3 + ) (0.71±0.4  vs  0.3±0.13; p + ) cells were found. Upon stimulation, Treg expression of TGF-beta was similar in the two groups. Conversely, frequencies of IL-17-espressing CD4 +  cells were significantly lower in IPF (0.92±0.56  vs  0.21±0.11; p vs  0.38±0.2; p=0.001). This study first provides evidence in IPF of a peripheral Treg/TH17 functional imbalance along with a depletion of NK cells which display an inhibitory phenotype. Dynamics of Treg/TH17 cells may represent a non invasive tool for disease severity assessment and treatment monitoring. Efforts are requested to thoroughly delineate these observations at the lung level.
Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response.
Authors: I Tannock, M Gospodarowicz, W Meakin, T Panzarella, L Stewart, W Rider
Journal: Journal of Clinical Oncology (1989)

Thirty-seven men with symptomatic bone metastases from prostate cancer that had progressed following earlier treatment with estrogens and/or orchidectomy were treated with low-dose prednisone (7.5 to 10 mg daily). The rationale for this treatment was that some patients might still have hormone-sensitive disease that was stimulated by weak androgens of adrenal origin, and that these androgens could be suppressed by prednisone through its negative feedback on secretion of adrenocorticotrophic hormone (ACTH). Response to treatment was assessed by requirement for analgesics, by the McGill-Melzack pain questionnaire, and by a series of 17 linear analog self-assessment (LASA) scales relating to pain and to various aspects of quality of life. Fourteen patients (38%) had improvement in indices used to assess pain at 1 month after starting prednisone, and seven patients (19%) maintained this improvement for 3 to 30 months (median, 4 months). Reduction in pain was associated with improvement in other dimensions of quality of life, and in the scale for overall well-being. Prednisone treatment led to a decrease in the concentration of serum testosterone in seven of nine patients where it was not initially suppressed below 2 nmol/L, and caused a decrease in serum levels of androstenedione and dehydroepiandrosterone sulfate in more than 50% of patients. Symptomatic response was associated with a decrease in serum concentration of adrenal androgens. We conclude that (1) low-dose prednisone may cause useful relief of pain in some patients with advanced prostatic cancer; (2) relief of pain was associated with suppression of adrenal androgens; and (3) measures of pain and quality of life can be used to assess possible benefits of systemic therapy in patients with metastatic prostate cancer.
Efficiency of ipratropium bromide and salbutamol deposition in the lung delivered via a soft-spray inhaler or chlorofluorocarbon metered-dose inhaler
Authors: Mo Ghafouri
Journal: European Respiratory Journal (2011)

Purpose: The dose combination of ipratropium bromide (Ip) 42 mcg and albuterol (Alb) 200 mcg, propelled by CFC, is currently marketed in a single canister dosage form. A soft-spray, aqueous solution-based delivery system of this combination was developed. This pharmacokinetic study compared the efficiency of a soft-spray delivery of the combination to the lung compared to CFC delivery.

Methods: A steady state pharmacokinetic substudy comprised of 278 patients was conducted from two trials differing only by doses evaluating Ip and Alb delivered via the soft-spray inhaler or CFC-MDI in 2,578 patients. Ip alone delivered via the soft-spray inhaler and placebos delivered via either delivery system were used as controls. LC/MS/MS assays for analytes were developed for plasma and urine biofluids.

Results: Comparing AUC, Cmax, and Cmin showed that systemic exposure to Alb and Ip delivered via the soft-spray inhaler were proportional to the doses delivered. Comparability was obtained when comparing the soft-spray inhaler-delivered Ip at half the dose of the CFC-MDI. Since Ip is not significantly absorbed from the gastrointestinal tract, the systemic exposure observed is a relevant marker for lung deposition. Ip alone gave equivalent exposure as the combination demonstrating a lack of interaction.

Conclusions: These systemic exposure analyses can be regarded as a marker of lung deposition and therefore demonstrate that the soft-spray inhaler delivers drug more efficiently to the lung than CFC-MDI.
Abstract 9691: Group X Secretory Phospholipase A2 in Neutrophils Plays a Pathogenic Role in Abdominal Aortic Aneurysms in Mice
Authors: Kazuhiro Watanabe, Daisuke Fujioka, Yukio Saito, Takamitsu Nakamura, Jun-ei Obata, Kenichi Kawabata, Yosuke Watanabe, Hideto Mishina, Shun Tamaru, Kiyotaka Kugiyama
Journal: Circulation (2011)

Group X secretory phospholipase A2 (sPLA2-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. Neutrophils have a critical role...
Static and Dynamic Upper Airway Obstruction in Sleep Apnea
Authors: Ramon Farré, Jordi Rigau, Josep M. Montserrat, Lara Buscemi, Eugeni Ballester, Daniel Navajas
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Increased upper airway collapsibility in the sleep apnea/hypopnea syndrome (SAHS) is usually interpreted by a collapsible resistor model characterized by a critical pressure (Pcrit) and an upstream resistance (Rup). To investigate the role played by the upstream segment of the upper airway, we tested the hypothesis that breathing different gases would modify Rup but not Pcrit. The study was performed on 10 patients with severe SAHS (apnea-hypopnea index: 59 +/- 14 events/hour) when breathing air and helium-oxygen (He-O2) during non-REM sleep. The continuous positive airway pressure that normalized flow (CPAPopt) was measured. Rup and Pcrit were determined from the linear relationship between maximal inspiratory flow VImax and nasal pressure (PN):VImax = (PN - Pcrit)/Rup. Changing the breathing gas selectively modified the severity of dynamic (CPAPopt, Rup) and static (Pcrit) obstructions. CPAPopt was significantly (p = 0.0013) lower when breathing He-O2 (8.44 +/- 1.66 cm H2O; mean +/- SD) than air (10.18 +/- 2.34 cm H2O). Rup was markedly lower (p = 0.0001) when breathing He-O2 (9.21 +/- 3.93 cm H2O x s/L) than air (15.92 +/- 6.27 cm H2O x s/L). Pcrit was similar (p = 0.039) when breathing He-O2 (4.89 +/- 2.37 cm H2O) and air (4.19 +/- 2.93 cm H2O). The data demonstrate the role played by the upstream segment of the upper airway and suggest that different mechanisms determine static (Pcrit) and dynamic (Rup) upper airway obstructions in SAHS.
Abstract 15149: Achievement of NCEP-Recommended Lipid Goals in Patients with Dyslipidemia: Insights From the NCDR PINNACLE Registry
Authors: Sarah A Spinler, Mark J Cziraky, Paul S Chan, Feng-ming Tang, Thomas M Maddox, Tyan F Thomas, Gladys G Duenas, Jennifer A Reinhold, Vincent J Willey
Journal: Circulation (2011)

Background: Epidemiologic studies have found that nonHDL cholesterol (nonHDL-C) is a superior marker for coronary heart disease risk (CHD) compared to low-density lipoprotein cholesterol (LDL-C). T...
Asthma control and interest in participation in patient education seminars: Data from the integrated care of asthma in Switzerland (INCAS)-study
Authors: Selina Dürr, Kurt Hersberger, David Miedinger, Prashant Chhajed, Andreas Zeller, Claudia Steurer-Stey, Jörg Daniel Leuppi
Journal: European Respiratory Journal (2014)

Introduction: Achievement of good asthma control is the goal of the Global Initiative for Asthma (GINA) guidelines. Patient education is one of the most important methods for achieving this.  Methods: Health insurance companies, pneumologists and pharmacists invited patients with asthma to complete a survey, which included the Asthma Control Test (ACT) and the Patients Assessment Chronic Illness Care Questionnaire (PACIC 5A). Patients were offered the possibility to take part in a patient education seminar run by the Swiss Lung Leagues or Swiss Allergy Centres (aha). The patients9 overall asthma control and interest in receiving education about their asthma were assessed.  Results: 246 asthma patients participated (mean age 43.5 ± 11.9 yrs; 39% males). Asthma was well-controlled in 162 (66%), not well-controlled in 49 (20%) and very poorly controlled in 33 (13%) patients (2 ACT scores missing). 131 (53%) patients showed interest in taking part in an education seminar. Of these, 75 (57%) patients were well-controlled, 29 (22%) were not well-controlled and 25 (19%) were very poorly controlled. Mean PACIC and 5A summary score was 41.25 ± 13.73 and 31.23 ± 11.50, respectively. Conversely, of patients who were not interested in taking part in a seminar, 87 (76%) were well-controlled, 20 (17%) were not well-controlled and 8 (7%) very poorly controlled. Mean PACIC and 5A summary score was 52.61 ± 17.37 and 48.29 ± 63.62.  Conclusions: Approximately one third of the patients showed uncontrolled asthma. Patients with uncontrolled asthma and worse PACIC and 5A score were more likely to express interest in taking part in a patient education seminar.
Self-reported traffic air pollution and respiratory symptoms among never-smokers and ever-smokers in a general population
Authors: Ane Johannessen, Roberto de Marco, Trude Skorge, Marie Waatevik, Øistein Svanes, Francisco Real, Bertil Forsberg, Jakob Bønløkke, Vivi Schlünssen, Torben Sigsgaard, Thorarinn Gislason, Kjell Torén, Hans Orru, Ernst Omenaas, Cecilie Svanes, Dan Norbäck, Lars Modig, Christer Janson
Journal: European Respiratory Journal (2014)

Background : Traffic air pollution is a known risk factor for respiratory symptoms. If associations between air pollution and respiratory symptoms differ between never-smokers and ever-smokers is so far not known.

Aims : To examine prevalence of respiratory symptoms and associations with self-reported traffic air pollution exposure in never-smokers and ever-smokers in a large general population.

Methods : As part of the Respiratory Health in Northern Europe study (RHINE III), 12860 subjects 38-65 yrs old answered questionnaires on exposures and symptoms in 2010-12. We estimated prevalence of wheeze, chest tightness, productive cough and long term cough, and calculated relative risks (RR) with 95% confidence intervals (CI) for self-reported traffic air pollution exposure (defined as bedroom near busy road). Analyses were stratified by smoking status and adjusted for age, sex, education and study centre.

Results : Overall prevalence of asthmatic symptoms (wheeze and chest tightness) and COPD symptoms (productive cough and longterm cough) were 19%, 11%, 16% and 16%, respectively. In multivariate analyses, traffic air pollution was associated with all four symptoms in never-smokers: RR 1.32 (95%CI 1.1,1.6) for wheeze, RR 1.49 (1.2,1.9) for chest tightness, 1.21 (1.0,1.5) for productive cough and 1.24 (1.0, 1.5) for longterm cough. In ever-smokers, RR were only significant for the asthmatic symptoms wheeze (RR 1.14 (1.0,1.3)) and chest tightness (RR 1.26 (1.1, 1.5)).

Conclusions : Self-reported traffic air pollution exposure is associated with asthmatic symptoms in both never-smokers and ever-smokers, but with COPD symptoms only in never-smokers.
Towards targeting PD-1/PD-L1 axis in breast cancer, pre-clinical data
Authors: Hazem Ghebeh, Dilek Colak, Asma Tulbah, Abdullah Alsuliman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts PD-L1 is a ligand that upon binding to its receptor (PD-1) on T-cells leads to T-cell anergy/and or apoptosis [[1][1], [2][2]]. We have shown that PD-L1 is expressed in breast cancer where its expression correlates with estrogen receptor (ER) negativity [[3][3]]. To understand the
Supersensitivity of Atherosclerotic Rabbit Aorta to Ergonovine
Authors: Philip D. Henry, Mitsuhiro Yokoyama
Journal: Journal of Clinical Investigation (1980)

Patients with coronary vasospasm appear to be supersensitive to the coronary constrictor effects of ergonovine. To determine whether atherosclerosis alters arterial reactivity and sensitizes arteries to ergonovine, contractile responses of isolated aortae from control rabbits and from rabbits fed a high-cholesterol diet were compared. Aortic strips were mounted in a myograph for the monitoring of isometric tension, equilibrated in oxygenated Krebs buffer, and exposed to graded concentrations of agonists and antagonists. The concentration-response relation for ergonovine in atherosclerotic arteries exhibited a markedly depressed constrictor threshold concentration (0.5 pM vs. 0.23 μM in controls), a significantly lowered one-half effective dose (ED50) value, and an augmented maximal response. Furthermore, atherosclerotic arteries showed similar, although less pronounced changes in the concentration-response relation for serotonin. In contrast, responses to 34 mM KCl were virtually identical, and the concentration-response relation for phenylephrine were similar in the two groups. In control arteries, 0.1 μM phentolamine and 0.1 μM prazosin suppressed responses to 1 μM ergonovine by 71 and 90%, respectively. However, in atherosclerotic arteries α-blockers in the same concentration inhibited responses to 0.01 μM ergonovine by less than 10%. On the other hand, 0.1 μM cyproheptadine, a serotonergic antagonist, suppressed these responses by 82%. Thus, the supersensitivity to ergonovine appeared to be mediated predominantly by a serotonergic mechanism. These results indicate that smooth muscle in atherosclerotic arteries may be supersensitive to specific vasoconstricting stimuli, a change that might contribute to arterial dysfunction in vivo.
Somatic mutations of the CHOP gene in gastric cancers
Authors: Yong Gu Cho, Jae Hwi Song, Chang Jae Kim, Won Sang Park
Journal: Clinical Cancer Research (2006)

A28   CHOP (GADD153) is a protein of the C/EBP family of transcriptional regulators, which dimerizes with other C/EBP members and changes their DNA-binding and transactivation properties. It induces growth arrest and apoptosis after endoplasmatic reticulum stress or DNA damage. CHOP is also expressed during early embryogenesis and upregulated in tumor tissues with defective Wnt signals. Gastric cancer showed frequent genetic alterations of the APC gene, and the risk for gastric cancer in familial adenomatous polyposis patients is 10 times higher that that in the general population. The genetic alterations of exon 3 of the β-catenin gene, especially in GSK-3β consensus sequence, have already been described. These findings raise the possibility that genetic analysis of genes of β-catenin degradation may be associated with the development of gastric cancer. Interestingly, recent report showed that CHOP can function as a specific inhibitor of the Wnt/TCF pathway in Xenopus embryos as well as in mammalian embryonic and tumor cells. In order to determine whether genetic alterations of CHOP gene are involved in the development and/or progression of gastric cancer, we searched for mutation of the CHOP gene in 81 gastric cancers by single-strand conformational polymorphism and sequencing. We found five missense mutations (P41T, E69K, S79D, P80S, P80L) of the CHOP gene in the transactivation domain. How these mutations can act in gastric carcinomas and contribute to the pathogenesis of gastric carcinogenesis will be discussed.
Prevalence of obesity hypoventilation syndrome in OSA patients in the UAE
Authors: Ashraf Al Zaabi, Salahudeen Fizal, M.K. Rafeek, Nico Nagelkerke
Journal: European Respiratory Journal (2013)

Study objectives: Obesity causing hypoventilation in OSA patient has been termed Obesity Hypoventilation Syndrome (OHS). A retrospective analysis was done to find the Prevalence of OHS in diagnosed Obstructive Sleep Apnea (OSA) patients. Comorbidities like Diabetes (DM), Hypertension (HT), ischemic Heart disease (IHD), and pulmonary hypertension were also assessed  Design: Descriptive analysis of retrospectively collected clinical data of patients who underwent a sleep study during March 2008 – June 2009.  Setting: Sleep disorder centre of tertiary level military hospital  Results: 215underwent sleep study. 107 (85 males and 22 females) had OSA (AHI > 5/hr).  16.8% of OSA patients (18 /107) were diagnosed to have OHS, 31.8% of females (7/22, p= 0.05) and 13% (11/85, p= .052, Fisher’s exact test) of males. The females tended to be older with a mean age of 60yrs versus 48 for males.  Adjusted for sex, using the Mantel-Haenzel test, OHS was significantly associated with hypertension with an OR of 3.5 (p= 0.030, 95% CI 1.19- 10.33) and DM with an OR of 4.6 (p= 0.017, 95% CI of 1.39 – 15.4), as well as with IHD with an OR of 5.09 (p = 0.036, 95% CI 1.21-21.35).  Pulmonary hypertension and OHS: 6 OHS patients had PHT, (RVSP 25mm Hg at rest by echo). with sex adjusted OR of 16.1 (95%CI of 3.2 – 82.0).  Conclusions: Prevalence of OHS was 16.8% There was a strong association between OHS, cardiovascular comorbidities, diabetes & PHT.  1 Oslone AL, et al OHS Am J Med 2005; 118:948 -56  2 Hida W (2003) Quality of life in OHS Sleep Breath 7:1–2.