tbuckley/cabot-search huggingface dataset:
The association of NQO1 C609T polymorphism and the susceptibility of bronchopulmonary dysplasia in preterm neonates
Authors: Aggeliki Daraki, Sophia Zachaki, Elena Polycarpou, Christos Costalos, Stavroula Gavrili
Journal: European Respiratory Journal (2012)

Introduction:  The development of bronchopulmonary dysplasia (BPD) involves genetic and environmental factors. Supplemental oxygen can damage the pulmonary epithelium through the generation of reactive oxygen species (ROS). The NAD(P)H:quinone oxidoreductase (NQO1) enzyme is involved in ROS detoxification. The encoding gene is subjected to the inactivating sense polymorphism (C 609 T). Individuals homozygous for the mutant allele (T/T) completely lack NQO1 activity, whereas heterozygotes (C/T) have low enzyme activity. We conducted a case-control study to investigate the potential role of NQO1 inborn polymorphism in BPD susceptibility.   Patients/Methods:  The study enrolled 119 Greek premature neonates with gestational age ≤32 weeks; 42 developed BPD (case group) and 77 did not develop BPD (control group). Genomic DNA was extracted from peripheral blood of all neonates. NQO1 genotyping was performed by real-time PCR. The NQO1 gene status was also evaluated in respect to gender.   Results:  A different distribution of NQO1 genotypes was found between BPD neonates and controls, with a higher frequency of variant genotypes (heterozygotes C/T and homozygotes T/T) in BPD population (50% in BPD  vs  28.6% in no BPD neonates,  p =0.046). Thus, a significantly higher frequency of the mutant T allele was observed in BPD neonates as compared to controls (0.27  vs  0.17,  p =0.058). According to gender, we observed no genotypic differences.   Conclusion : The higher incidence of the C/T and T/T variant genotypes among neonates who developed BPD suggests that the NQO1 C 609 T inborn polymorphism probably constitutes an early biomarker of BPD development.
Abstract 3636: The Effects of Arginase II Overexpression on Endothelial Function in Transgenic Mouse Model
Authors: Boris L Vaisman, Katherine C Wood, Stephen J Demosky, Catherine L Knapper, Jaye Chin-Dusting, Sidney M Morris, Mark T Gladwin, Alan T Remaley
Journal: Circulation (2008)

Endothelium is a major regulator of local vascular homeostasis. Its normal function is crucial for prevention of the development of atherosclerosis, hypertension and other cardiovascular disorders. Reduced nitric oxide (NO) bioavailability is one of the earliest and most important markers of endothelial dysfunction. L-arginine is the substrate for nitric oxide synthases (NOS). Arginase (Arg) can compete with eNOS for L-arginine and thus may play a role in endothelial dysfunction. To further investigate the role of ArgII in endothelial function and in atherosclerosis we generated transgenic mice with human ArgII (hArgII) gene under control of endothelial-specific Tie2 promoter. Expression of hArgII was measured by RT-PCR in eight tissues of transgenic males and compared with the level of mouse ArgII (mArgII) expression in kidneys of normal C57Bl mice, which was taken as 100%. hArgII was expressed at very high levels in all tissues, especially in aorta (2700%), heart (3500%), kidney (1600%), lung (9860%) and muscle (2000%). Arginase activity was elevated 4.6 – 62 fold in all tissues except liver. Lung endothelial cells isolated from hArgII transgenic mice had 4.4-fold greater of arginase activity than whole lung. Resident peritoneal macrophages from hArgII transgenic and normal mice had similar levels of arginase activity, confirming endothelial specificity of the Tie2 promoter. Overexpression of hArgII neither led to significant changes in plasma level of arginine, citrulline, NOHA, ADMA, SDMA and ornithine, nor to changes in plasma lipid levels. However, ArgII overexpression on apoE-knockout background was accompanied by a 10% increase in plasma total cholesterol (p&lt;0.05). hArgII transgenic mice also had blood pressure (mean arterial and diastolic) that averaged 17% higher than controls. Aortic ring segments from hArgII transgenic mice, precontracted with phenylephrine (10 −6 M), exhibited decreased endothelium-dependent relaxation to increasing concentrations of acetylcholine (10 −9 to 10 −3.5 M), indicating endothelial dysfunction secondary to NO insufficiency. These results show that the Tie2hArgII transgenic mouse is a new model for investigating the role of ArgII in endothelial function and in atherosclerosis.
Evolution in Cardiovascular Care for Elderly Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Karen P. Alexander, Matthew T. Roe, Anita Y. Chen, Barbara L. Lytle, Charles V. Pollack, Joanne M. Foody, William E. Boden, Sidney C. Smith, W. Brian Gibler, E. Magnus Ohman, Eric D. Peterson
Journal: Journal of the American College of Cardiology (2005)
Objectively identified comorbidities in COPD: impact on pulmonary rehabilitation outcomes
Authors: Rafael Mesquita, Lowie E.G.W. Vanfleteren, Frits M.E. Franssen, Janeli Sarv, Ziad Taib, Miriam T.J. Groenen, Swetlana Gaffron, Piet L.B. Bruijnzeel, Fabio Pitta, Emiel F.M. Wouters, Martijn A. Spruit
Journal: European Respiratory Journal (2015)

Pulmonary rehabilitation (PR) is a comprehensive intervention recognised as a core component in the treatment of patients with chronic obstructive pulmonary disease (COPD) [1]. Comorbidities are highly prevalent in patients with COPD entering PR [2–4], which may be associated with the change in exercise performance and health status after PR [3–5]. Nonetheless, previous studies used self-reported and/or chart-based comorbidities, and only the impact of individual comorbidities or arbitrarily grouped comorbidities were studied [3, 4]. Patients with COPD and multiple comorbidities can still benefit from pulmonary rehabilitation <http://ow.ly/LXAWc>
Effect of pulmonary hypertension on gas exchange
Authors: A G Agustí, R Rodriguez-Roisin
Journal: European Respiratory Journal (1993)

This paper reviews the effects of pulmonary artery hypertension on gas exchange by exploring three different issues, namely: 1) how does gas exchange behave in diseases characterized by increased vascular tone (primary pulmonary hypertension (PPH), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF)) or decreased vascular tone ("hepatopulmonary syndrome"); 2) how does exercise, as a non-pharmacological tool of increasing pulmonary blood flow, modify gas exchange in these diseases; and 3) how do several drugs that lower (vasodilators) or increase (almitrine) the active component of pulmonary hypertension interact with gas exchange. Available data show that: 1) in PPH a high pulmonary vascular tone enhances gas exchange and when it is lowered, either by oxygen or vasodilators, ventilation perfusion (VA/Q) distributions deteriorate; 2) in COPD a lowered (vasodilators) or augmented (almitrine) active vascular tone is almost invariably paralleled by a deterioration or enhancement of ventilation-perfusion matching, respectively; 3) in IPF an adequate active response of the pulmonary vasculature is essential to maintain gas exchange, both at rest and during exercise; and 4) in patients with liver cirrhosis a low pulmonary vascular tone induces an abnormal VA/Q distribution. In summary, these data show that any situation and/or therapeutic intervention that lowers the active vascular tone deteriorates VA/Q relationships and vice versa. The final effect of pulmonary vascular tone on arterial oxygen tension (PaO2) is less predictable. The reason for this uncertainty is that the actual PaO2 value depends on the interplay of the intra- and extrapulmonary factors that control gas exchange in humans, and not only on the degree of VA/Q mismatching.
Oral contraceptives or NSAIDs before surgery for a fracture distal to the knee were linked to postdischarge VTE
Authors: Charalambos Dokos
Journal: Annals of Internal Medicine (2015)

Source Citation Wahlsten LR, Eckardt H, Lyngbaek S, et al.Symptomatic venous thromboembolism following fractures distal to the knee: a nationwide Danish cohort study. J Bone Joint Surg Am. 2015;97:470-7. 25788303
Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression.
Authors: M Adachi, T Taki, T Konishi, C I Huang, M Higashiyama, M Miyake
Journal: Journal of Clinical Oncology (1998)

PURPOSE The transmembrane-4 superfamily (TM4SF) is a recently discovered family of genes. Of the TM4SF members, MRP-1/CD9, KAI1/CD82, and ME491/CD63 have been reported to modulate tumor progression or metastasis. In this study, we investigated the relationships between these three genes, MRP-1, KAI1, and ME491, in patients with non-small-cell lung cancers (NSCLCs). Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs. PATIENTS AND METHODS One hundred seventy-two patients up to stage IIIB NSCLC underwent radical surgery during the period of January 1991 through June 1994. Using a quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we studied the expression of MRP-1, KAI1, and ME491 genes in these patients. RESULTS We found that 109 patients (63.4%) had MRP-1-positive tumors and 42 patients (24.4%) had KAl1-positive tumors. Conversely, all 172 patients expressed ME491. No relationship was found between MRP-1 expression and KAI1 expression. We classified these patients into three groups. The 36 patients who were positive for both MRP-1 and KAI1 were defined as group A; the 79 patients with reduced expression of either MRP-1 or KAI1 were defined as group B, and the remaining 57 patients with reduced expression of both MRP-1 and KAI1 were defined as group C. This new classification was correlated with nodal status, tumor status, and pathologic stage (P = .0056, P = .0003, and P &lt; .0001, respectively). In NSCLC patients, the 5-year survival rate of group A patients was significantly better than that of group B patients and much better than that of group C patients (86.8%, 53.9%, and 31.5%, respectively; P &lt; .0001). Cox multivariate regression analysis showed that this new classification in NSCLCs was a significant prognostic factor, as was the nodal status (P &lt; .0001). CONCLUSION Our results suggest that a low MRP-1 and KAI1 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that the evaluation for MRP-1 and KAI1 expression may identify node-negative lung cancer patients who are at high risk for early disease recurrence, and thus need intensive adjuvant therapy.
Bariatric–metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial
Authors: Geltrude Mingrone, Simona Panunzi, Andrea De Gaetano, Caterina Guidone, Amerigo Iaconelli, Giuseppe Nanni, Marco Castagneto, Stefan Bornstein, Francesco Rubino
Journal: The Lancet (2015)
Erratum to: gespeR: a statistical model for deconvoluting off-target-confounded RNA interference screens
Authors: Fabian Schmich, Ewa Szczurek, Saskia Kreibich, Sabrina Dilling, Daniel Andritschke, Alain Casanova, Shyan Huey Low, Simone Eicher, Simone Muntwiler, Mario Emmenlauer, Pauli Rämo, Raquel Conde-Alvarez, Christian von Mering, Wolf-Dietrich Hardt, Christoph Dehio, Niko Beerenwinkel
Journal: Genome biology (2015)

After the publication of this work [1], some content was missing from the Acknowledgements section. The corrected Acknowledgements section is given below:
Acute exacerbation of idiopathic pulmonary fibrosis: Analysis in a post-marketing surveillance of pirfenidone
Authors: Hiroyuki Taniguchi, Arata Azuma, Takashi Ogura, Yoshikazu Inoue, Kingo Chida, Masashi Bando, Shinichi Kakutani, Shuichiro Inagaki, Moritaka Suga, Yukihiko Sugiyama, Shoji Kudoh, Toshihiro Nukiwa
Journal: European Respiratory Journal (2014)

Background:  Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is recognized as a common and critical event in the clinical course of IPF. However, the risk factors and association of AE with disease severity of IPF remains unclear.   Aims and objectives:  The aim of this study was to evaluate the risk factors and impact of disease severity on the frequency of AE.   Methods:  We analyzed 1342 patients with IPF who had been consecutively enrolled in a post-marketing surveillance of pirfenidone between Dec 2008 and Oct 2009 in Japan. In the population, the mean age was 69.5 ± 8.5 years with 76.4% males. Average baseline %VC was 66.1%, and 40% of patients were diagnosed as grade IV of disease severity according to Japanese Respiratory Society (JRS) criteria. AE-IPF was diagnosed by physicians according to the criteria in Japan (Taniguchi H. et al. Eur Respir J 2010; 35: 821-9). A Cox proportional hazards regression analysis was used to identify risk factors for AE-IPF.   Results:  Occurrence of AE-IPF was reported in total of 170 patients within 1 year of the observation, and 65% of AE-IPF cases died within 6 months after AE (median survival time after AE, 31 days). Multivariate analysis with Cox proportional hazards regression models showed that sex (male) [HR, 2.621; p=0.0031], %VC [HR, 0.976; p=0.0002] and high disease severity grade according to JRS criteria [HR, 1.341; p=0.0069] were risk factors for AE-IPF.   Conclusions:  This study suggests that sex (male), low %VC and high disease severity grade according to JRS criteria are risk factors for AE-IPF. Further analysis on the risk factors and the impact of disease severity will be presented.
European Treatment and Outcome Study (Eutos) Score Predicts Early Molecular Response to Imatinib Therapy in Chronic Phase Chronic Myeloid Leukemia Patients (Cp-Cml)
Authors: K. Sudheer Reddy, M. Manickavasagam, V. Venkata Sampath, D. Barghavi, A. Vindhyavasini, A. Pai, R.G. Balambika
Journal: Annals of Oncology (2014)
Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer.
Authors: M A Poon, M J O'Connell, H S Wieand, J E Krook, J B Gerstner, L K Tschetter, R Levitt, C G Kardinal, J A Mailliard
Journal: Journal of Clinical Oncology (1991)

In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results.
Six minute step test reproducibility in COPD patients: Cross-sectional study
Authors: Juliano Ferreira Arcuri, Joyce Nogueira Ferreira da Costa, Ivana Gonçalves Labadessa, Bruna Varanda Pessoa, Maurício Jamami, Valéria Amorim Pires Di Lorenzo
Journal: European Respiratory Journal (2013)

Introduction: Functional tests, like six minute walk test (6MWT) are very useful in determining exercise capacity in COPD patients. However, to perform 6MWT, it is necessary a 30m corridor that could be difficult in small facilities. Six minute step test (6MST) could be an alternative, but its reproducibility hasn’t been tested in those patients. Aims: The aim of this study is to analyze 6MST reproducibility in COPD patients. Methods: In this study, 31 patients with clinical and spirometrical diagnosis of COPD were enrolled to participate. They performed three 6MST (Dal Corso, S. et al, Europ Respir J 2007; 29: 330–6), the first and second were executed by the same evaluator with a 30min interval, and the last by a different evaluator a week later. Exercise capacity was determinated by the number of steps. Intraclass correlation coefficient (ICC) and Bland-Altmann plots were used. Results: Intra and inter-rater relative reproducibility was excellent (ICC>0,8). Bland-Altman plots (Figure 1) revealed acceptable error in the intra-rater analysis and higher errors in the inter-rater analysis.

![Figure][1] 



Figure 1: Reproducibility A: Intra-rater; B: Inter-rater.

6MST: Six minute step test.

Conclusion: 6MST could be used as an alternative test to verify exercise capacity in COPD patients, especially in large samples and in small facilities, since it doesn’t require a learning test like 6MWT and can be done in a room.

 [1]: pending:yes
Abstract 3680: Transfusion-Induced Tissue Hypoxia is Ameliorated by <i>S</i> -nitrosohemoglobin Repletion of Stored Red Blood Cells
Authors: Diana L Diesen, Jonathan S Stamler
Journal: Circulation (2008)

Transfusion of stored red blood cells (RBCs) is associated with a decrease in tissue oxygenation in animal models and with increased mortality and morbidity in patients. Recent studies have demonstrated that stored RBCs are deficient in vasodilatory ability and depleted of S -nitrosohemoglobin (SNO-Hb), and that renitrosylation ex vivo can increase SNO-Hb levels and restore vasoactivity. We have examined in a mouse model the extent to which transfusion impairs tissue oxygenation and whether SNO-Hb repletion can ameliorate that impairment. We report here that transfusion of (mouse) RBCs stored for 1 day or 1 week results in tissue hypoxia that is largely prevented by SNO-Hb repletion prior to transfusion ( 1 day stored blood : % decrease in oxygenation 58+/−10% untreated vs. 92+/−0.7% SNO-Hb repleted, p&lt;0.05, n=3– 6; 1 week stored blood : % decrease in oxygenation 66+/−10% untreated vs. 91+/−2.8% SNO-Hb repleted, p&lt;0.05, n=3– 6). Storage of mouse blood beyond human expiration-equivalents (1 month) resulted in substantial lysis and the death of all mice transfused (native and SNO-Hb repleted blood, n=5). In conclusion, repletion of SNO-Hb ameliorates the decrease in tissue oxygenation that results from transfusion of untreated stored blood. Therefore, SNO-Hb repletion may provide a simple and efficacious method to reduce transfusion-related mortality and morbidity.
Bronchial antiproteases activation as a tolerance factor to COPD development in healthy long term smokers
Authors: Sergey Fedosenko, Georgiy Chernogoryuk
Journal: European Respiratory Journal (2011)

Not all smokers suffer from COPD. It is possible that tolerance to COPD emergence among healthy long term smokers is supported by supressing the excessive proteolytic activity.   Aim:  To investigate the factors of tolerance to COPD development among healthy long term smokers according to content of proteases and antiproteases in induced sputum.   Methods:  There are 145 stable COPD pftients and 48 long term smoking men (>30 pack/year), without symptoms of COPD have been enrolled in our research. The control group consisted of 48 healthy nonsmokers volunteers. All patients were men of identical age of 59.2±4.07 years. Induced sputum was studied on elastase, protease9s inhibitor α 1 , macroglobulin α 2 .   Results:  An activity of protease9s inhibitor α 1  and macroglobulin α 2  in induced sputum of long term smokers is higher than among healthy non-smokers and patients with COPD.   Conclusion:  The tolerance to development COPD among long term smokers is supported high activity of antiproteases in bronchial region.
Molecular Chaperones: Biology and Prospects for Pharmacological Intervention
Authors: David F. Smith, Luke Whitesell, Emmanuel Katsanis
Journal: Pharmacological Reviews (1998)

Successful expression of polypeptide gene products requires transcription machinery to generate messenger ribonucleic acids and translation machinery to synthesize polypeptide chains but the protein product is functional, and thus the gene is effectively expressed, only when the polypeptide chain is
Lentiviral gene transfer into primary and secondary NOD/SCID repopulating cells
Authors: Niels-Bjarne Woods, Cecilia Fahlman, Hanna Mikkola, Isao Hamaguchi, Karin Olsson, Romain Zufferey, Sten Eirik Jacobsen, Didier Trono, Stefan Karlsson
Journal: Blood (2000)
The application of bi-level positive airway pressure in patients with severe pneumonia and acute respiratory failure caused by influenza A (H1N1) virus
Authors: Liu Wei, Liping Peng
Journal: European Respiratory Journal (2011)

Objective:  To evaluate the effect of noninvasive Bi-level Positive Airway Pressure (BiPAP) ventilation on the severe influenza A virus associated with pneumonia and acute respiratory failure (ARF).   Methods:  Based on conventional therapy via face mask using BiPAP ventilator positive airway pressure ventilation in the treatment of severe pneumonia caused by influenza A (H1N1) virus with acute respiratory failure (ARF) in 18 cases, we observed and evaluated the therapeutic effects.   Results:  PaO 2  and SaO 2  before and after treatment were (48.85±12.15)mmHg, (68.56±16.25) mmHg and (80±6)%, (92±5)%, respectively. The results were significantly different (P    Conclusion:  BiPAP ventilator airway pressure by face mask ventilation can reduce the rate of endotracheal intubation in the treatment of severe pneumonia caused by influenza A (H1N1) virus in acute respiratory failure. It could be an effective approach in the emergency treatment with clinical value.