tbuckley/cabot-search huggingface dataset:
Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis
Authors: F DENIGRIS, S WILLIAMSIGNARRO, V SICA, L LERMAN, F DARMIENTO, R BYRNS, A CASAMASSIMI, D CARPENTIERO, C SCHIANO, D SUMI
Journal: Cardiovascular Research (2006)

Background: Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress. Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo. Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of l-arginine to l-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC25 values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls. Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.
Antihypertension and Colorectal Cancer Prevention: Getting Two Birds With One Stone?
Authors: M. Song, E. L. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2014)

risk factors for CRC, long-term use of aspirin and nonsteroidal anti-inflammatory drugs can substantially reduce CRC risk. Given the complex lifestyle and medication pattern, it is difficult to determine the direction of aggregate confounding. Although the investigators considered several potential confounders, according to the criterion of “including only factors leading to change of at least 10% in the association,” only the average number of physician contacts after the incident diagnosis of hypertension was adjusted in addition to the matching factors (ie, sex, age, calendar period and duration of follow-up after diagnosis of hypertension before the index date). Although physician visits might reflect disease severity to a certain extent, many factors can influence patients’ contacts with doctors, and thus adjustment for this single composite factor may not address the complicated confounding pattern in this study. On the other hand, adjustment for physician visits could induce selection bias because both drug use and subclinical symptoms or important risk factors (eg, family history) for CRC can lead to more frequent physician visits (10). This is more notable when a statistically significant association with 3 or more years of ACEI/ARB therapy emerges only after such adjustment (crude relative risk [RR] = 0.92, 95% confidence interval [CI] = 0.79 to 1.08; adjusted RR = 0.84, 95% CI = 0.72 to 0.98), whereas statistically significant associations with some other agents disappear after the adjustment (for ≥5 years of diuretics use: crude RR = 0.80, 95% CI = 0.65 to 0.98; adjusted RR = 0.85, 95% CI = 0.70 to 1.05; for ≥5 years of beta-blocker use: crude RR = 0.80, 95% CI = 0.67 to 0.95; adjusted RR = 0.85, 95% CI = 0.71 to 1.01). Again, aggregation of small biases can induce a spuriously moderate association. Given the findings by Makar et al. (9), an obvious question arises: What is the mechanism if ACEI/ARB therapy really reduces CRC risk among hypertension patients? Accumulating data indicate that the renin-angiotensin system (RAS), the target of ACEI and ARB action, is frequently dysregulated in malignancy. Abnormalities in the RAS signaling influence proliferation and apoptosis of cancer cells and promote angiogenesis and formation of cancer inflammatory microenvironment (11). Some experimental data suggest an anticarcinogenic role of RAS inhibitors in colorectal tumors, although the exact mechanisms remain largely unclear. Recent in vivo evidence demonstrates that ACEI or ARB administration substantially reduces the total number of colonic premalignant lesions and decreases oxidative stress and expression of inflammatory cytokines in metabolically disordered mice, suggesting that suppression of inflammation might mediate the effect
PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidation
Authors: Ni-Huiping Son, Shuiqing Yu, Joseph Tuinei, Kotaro Arai, Hiroko Hamai, Shunichi Homma, Gerald I. Shulman, E. Dale Abel, Ira J. Goldberg
Journal: Journal of Clinical Investigation (2010)

Excess lipid accumulation in the heart is associated with decreased cardiac function in humans and in animal models. The reasons are unclear, but this is generally believed to result from either toxic effects of intracellular lipids or excessive fatty acid oxidation (FAO). PPARγ expression is increased in the hearts of humans with metabolic syndrome, and use of PPARγ agonists is associated with heart failure. Here, mice with dilated cardiomyopathy due to cardiomyocyte PPARγ overexpression were crossed with PPARα-deficient mice. Surprisingly, this cross led to enhanced expression of several PPAR-regulated genes that mediate fatty acid (FA) uptake/oxidation and triacylglycerol (TAG) synthesis. Although FA oxidation and TAG droplet size were increased, heart function was preserved and survival improved. There was no marked decrease in cardiac levels of triglyceride or the potentially toxic lipids diacylglycerol (DAG) and ceramide. However, long-chain FA coenzyme A (LCCoA) levels were increased, and acylcarnitine content was decreased. Activation of PKCα and PKCδ, apoptosis, ROS levels, and evidence of endoplasmic reticulum stress were also reduced. Thus, partitioning of lipid to storage and oxidation can reverse cardiolipotoxicity despite increased DAG and ceramide levels, suggesting a role for other toxic intermediates such as acylcarnitines in the toxic effects of lipid accumulation in the heart.
Azygos blood flow: Phase contrast quantitation in volunteers and patients with portal hypertension pre- and postintrahepatic shunt placement
Authors: J F Debatin, B Zahner, C Meyenberger, B Romanowski, W Schopke, B Marincek, W A Fuchs
Journal: Hepatology (1996)

Flow volume in the azygos venous system was quantitated with Cine-phase contrast (PC) velocity mapping in volunteers and compared with patients with known portal hypertension, who were referred for transjugular intrahepatic portosystemic shunt (TIPS) placement. Subsequently, the TIPS-induced hemodynamic effects on portal and azygos flow were analyzed. To assess intra- and intersubject variability, flow in the azygos veins was measured in each of 10 normal subjects at three different times. Subsequently, portal and azygos flow was quantitated in 20 patients with portal hypertension, before and after TIPS placement. All imaging was performed on a 1.5-tesla magnetic resonance imaging (MRI) system. Azygos flow was measured transaxially at the midthoracic level. Cine-PC flow measurements of the main portal vein followed morphological evaluation of the portal venous system with axial and coronal breath-held magnet resonance angiogram. Azygos flow in normal subjects was characterized by high inter- and low intrasubject variability. Azygos flow in patients with portal hypertension was significantly higher (P < .001). Following successful TIPS placement in 18 patients, Cine-PC revealed a mean decrease in azygos flow of 46.3% (P < .001) and a 134% (P < .001) increase of portal flow. Reflecting the complexity of portal hemodynamics, there was no correlation between the changes in the portal and azygos systems. In 2 patients with early occlusion of TIPS, documented invasively, portal and azygos flow values remained largely unchanged. Cine-PC enables the noninvasive, quantitative assessment of flow within the azygos venous system. Azygos flow was found to be markedly elevated in patients with portal hypertension. Combined portal and azygos PC flow measurements quantitate the therapeutic effect of TIPS placement.
Unrecognised obstructive sleep apnoea is common in severe peripheral arterial disease
Authors: Karri T. Utriainen, Juhani K. Airaksinen, Olli Polo, Olli T. Raitakari, Mikko J. Pietilä, Harry Scheinin, Hans Y. Helenius, Kari A. Leino, Erkki S. Kentala, Jouko R. Jalonen, Harri Hakovirta, Tiina M. Salo, Timo T. Laitio
Journal: European Respiratory Journal (2012)

Patients needing surgery for peripheral arterial disease (PAD) represent a severe form of atherosclerosis with an overall 5-yr mortality of 30% after revascularisation. The aetiology for poor post-operative clinical outcome in these high-risk patients is not fully established. Obstructive sleep apnoea (OSA) is associated with atherosclerosis and is an independent risk factor for fatal and nonfatal cardiac events. Here, we determine the prevalence of undiagnosed OSA in a homogenous group of PAD patients undergoing subinguinal surgical revascularisation. 82 consecutive patients (mean age 67±9 yrs, 52 males) with sinus rhythm and without congestive heart failure or previously diagnosed OSA were enrolled for pre-operative polysomnography and echocardiography. OSA was present in 70 (85%) patients (95% CI 75–93%), of whom 24 (34%) had severe OSA. OSA was mostly asymptomatic, and age- and sex-adjusted multivariate regression analysis showed no relation to obesity, metabolic syndrome or any manifestation of atherosclerosis, other than PAD. Left ventricular ejection fraction (p = 0.002) and high-density lipoprotein/total cholesterol ratio (p = 0.03) were the only independent predictors for the severity of OSA. Thus, prevalence of OSA is unexpectedly high in patients with PAD and is not related to classical risk factors of sleep apnoea.
SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas
Authors: Adam J Bass, Hideo Watanabe, Craig H Mermel, Soyoung Yu, Sven Perner, Roel G Verhaak, So Young Kim, Leslie Wardwell, Pablo Tamayo, Irit Gat-Viks, Alex H Ramos, Michele S Woo, Barbara A Weir, Gad Getz, Rameen Beroukhim, Michael O'Kelly, Amit Dutt, Orit Rozenblatt-Rosen, Piotr Dziunycz, Justin Komisarof, Lucian R Chirieac, Christopher J LaFargue, Veit Scheble, Theresia Wilbertz, Changqing Ma, Shilpa Rao, Hiroshi Nakagawa, Douglas B Stairs, Lin Lin, Thomas J Giordano, Patrick Wagner, John D Minna, Adi F Gazdar, Chang Qi Zhu, Marcia S Brose, Ivan Cecconello, Ulysses Ribeiro Jr, Suely K Marie, Olav Dahl, Ramesh A Shivdasani, Ming-Sound Tsao, Mark A Rubin, Kwok K Wong, Aviv Regev, William C Hahn, David G Beer, Anil K Rustgi, Matthew Meyerson
Journal: Nature Genetics (2009)
Role of activin-A in cigarette smoke-induced inflammation and COPD
Authors: F. M. Verhamme, K. R. Bracke, G. D. Amatngalim, G. M. Verleden, G. R. Van Pottelberge, P. S. Hiemstra, G. F. Joos, G. G. Brusselle
Journal: European Respiratory Journal (2013)

Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-β superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown. We first quantified activin-A and follistatin in the lungs of air- or cigarette smoke-exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cells in vitro. Next, activin-A signalling was antagonised in vivo by administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks. Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never-smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke-exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice. These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD.
Calcineurin/Nfat signaling is required for perinatal lung maturation and function
Authors: Vrushank Davé, Tawanna Childs, Yan Xu, Machiko Ikegami, Valérie Besnard, Yutaka Maeda, Susan E Wert, Joel R Neilson, Gerald R Crabtree, Jeffrey A Whitsett
Journal: Journal of Clinical Investigation (2006)

Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1 caused respiratory failure after birth and inhibited the structural maturation of the peripheral lung. Synthesis of surfactant and a lamellar body-associated protein, ABC transporter A3 (ABCA3), was decreased prior to birth. Nuclear factor of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription factor modulated by calcineurin, was identified as a direct activator of Sftpa, Sftpb, Sftpc, Abca3, Foxa1, and Foxa2 genes. The calcineurin/Nfat pathway controls the morphologic maturation of lungs prior to birth and regulates expression of genes involved in surfactant homeostasis that are critical for adaptation to air breathing.
Predictive accuracy of patient-reported exacerbation frequency in COPD
Authors: J.K. Quint, G.C. Donaldson, J.R. Hurst, J.J.P. Goldring, T.R. Seemungal, J.A. Wedzicha
Journal: European Respiratory Journal (2010)

Chronic obstructive pulmonary disease (COPD) exacerbation frequency is important for clinical risk assessment and trial recruitment. In order to accurately establish exacerbation frequency, patients need to be followed for 1 yr, although this is not always practical. 1) Patient recall of exacerbation number during the year prior to recruitment to the London COPD cohort was compared with the number of exacerbations recorded on diary cards during the subsequent year; and 2) patient recall of their exacerbation number after 1 yr of follow-up was compared with documented exacerbations over the same year. A total of 267 patients (forced expiratory volume in 1 s 1.14 L) recorded worsening of respiratory symptoms on daily diary cards for 1 yr. Exacerbations were defined according to previously validated criteria. There was no difference between the exacerbation number recalled by patients prior to recruitment and the number detected during the first year (median 2.0 (interquartile range 1.0–4.0) and 2.0 (1.0–4.0); expected agreement 76.4%; agreement 84.6%; κ = 0.3469). There was no difference between the number of exacerbations remembered by patients and the number recorded on diary cards over the same 1-yr period (2.0 (1.0–4.0) for both groups; expected agreement 74.9%; actual agreement 93.3%; κ = 0.6146). Patients remember the number of exacerbations they have in a year. Accuracy is increased when comparing the same 1-yr period. Patient recall is sufficiently robust for stratification into frequent and infrequent exacerbator groups for subsequent years.
Does human pancreas contain salivary-type isoamylase?
Authors: J Shimamura, L Fridhandler, J E Berk
Journal: Gut (1975)

Amylase isoenzyme analysis was made of extracts of normal human pancreatic tissue by first conducting ion exchange chromatography of the purified material. This gave evidence of only pancreatic type (P-type) isoamylase for all purposes. However, when effluent fractions in which salivary type isoamylase would ordinarily be expected to be present were harvested, pooled, concentrated, and rechromatographed, the pancreatic extracts were found to contain some salivary type (S-type) isoamylase. The latter accounted for approximately 0-8 to 1-7% of the total recovered amylase activity. This finding of S-type isoamylase in normal human pancreas potentially has important bearing on the interpretation of isamylase analysis.
The effects on asthmatics of exposure to a conventional water-based and a volatile organic compound-free paint
Authors: None Beach, J Raven, C Ingram, M Bailey, D Johns, EH Walters, M Abramson
Journal: European Respiratory Journal (1997)

The water-based paints now frequently used for house painting still contain small amounts of volatile organic compounds (VOCs), with the potential to exacerbate symptoms of asthma. Because of these potential problems and environmental concerns, some manufacturers have produced paints with no VOC content. We wished to compare the effects on asthmatics of conventional water-based paint and the new VOC-free paint. Seventeen asthmatics were recruited on the basis of having previously reported exacerbation of symptoms by paint or other odours. Each undertook a standard painting task with identically coloured conventional acrylic and VOC-free paints in a double-blind, crossover study. Respiratory symptoms, lung function, and airway responsiveness were measured at each visit. A significant increase in reported "wheeze" was detected during use of conventional paint (p<0.01), but not with the new paint. There was also a significantly greater increase in reported "breathlessness" whilst using conventional paint than with the new paint (p<0.05). In contrast, lung function measurements showed a small but significant increase during the use of both paints (p<0.05). There was no significant change in airway responsiveness after use of either paint. The new paint appears to be less likely to cause a worsening of respiratory symptoms than conventional acrylic paint, although this difference is not reflected in measurements of lung function or airway responsiveness. Although the benefit conferred in the majority of asthmatics is probably modest, there may be some patients with an increased sensitivity to paint odour, who would derive a useful symptomatic benefit from using the VOC-free paint.
Automated Symptom Alerts Reduce Postoperative Symptom Severity After Cancer Surgery: A Randomized Controlled Clinical Trial
Authors: Charles S. Cleeland, Xin Shelley Wang, Qiuling Shi, Tito R. Mendoza, Sherry L. Wright, Madonna D. Berry, Donna Malveaux, Pankil K. Shah, Ibrahima Gning, Wayne L. Hofstetter, Joe B. Putnam, Ara A. Vaporciyan
Journal: Journal of Clinical Oncology (2011)

Purpose Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery. This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control. Patients and Methods We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm randomized controlled trial; 79 patients completed the study. After hospital discharge, patients rated symptoms twice weekly for 4 weeks via automated telephone calls. For intervention group patients, an e-mail alert was forwarded to the patient's clinical team for response if any of a subset of symptoms (pain, disturbed sleep, distress, shortness of breath, or constipation) reached a predetermined severity threshold. No alerts were generated for controls. Group differences in symptom threshold events were examined by generalized estimating equation modeling. Results The intervention group experienced greater reduction in symptom threshold events than did controls (19% v 8%, respectively) and a more rapid decline in symptom threshold events. The difference in average reduction in symptom interference between groups was −0.36 (SE, 0.078; P = .02). Clinicians responded to 84% of e-mail alerts. Both groups reported equally high satisfaction with the automated system and with postoperative symptom control. Conclusion Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery. Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery. These results should be confirmed in a larger study.
Gender verification in sports by PCR amplification of SRY and DYZ1 Y chromosome specific sequences: presence of DYZ1 repeat in female athletes.
Authors: A Serrat, A García de Herreros
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To perform genetic sex typing during the Barcelona Olympic Games using polymerase chain reaction (PCR) amplification of Y chromosome specific sequences. METHODS: The assay consisted of the amplification of a specific sequence corresponding to the repeat DYZ1 element from buccal smears samples of 2406 female competitors. Positive samples were reanalysed for the presence of another Y chromosome specific gene, SRY. RESULTS: The expression of these two elements did not always correlate; six samples were found where the presence of DYZ1 but not SRY was detected. This presence of DYZ1 sequence in female athletes is higher than in unselected females, where no DYZ1 amplification was observed in any of the 1629 samples analysed. CONCLUSIONS: Amplification of DYZ1 repeat should not be used as the only index for determining genetic sex, at least in sporting events.
Weight Gain in Early-Stage Breast Cancer: Where Do We Go From Here?
Authors: Pamela J. Goodwin
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.9.2367 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11331314 Weight Gain in Early-Stage Breast Cancer: Where Do We Go From Here? Pamela J. GoodwinxPamela J. GoodwinSearch for articles by this author Show More Samuel Lunenfeld Research Institute at Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada https://doi.org/10.1200/JCO.2001.19.9.2367 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology