tbuckley/cabot-search huggingface dataset:
Circulating Retinol-Binding Protein 4 and Subclinical Cardiovascular Disease in the Elderly
Authors: Erik Ingelsson, Lars Lind
Journal: Diabetes Care (2008)

OBJECTIVE We evaluated associations of serum retinol-binding protein 4 (RBP4) with subclinical cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS Subclinical CVD was measured with echocardiography, carotid artery ultrasound, brachial artery ultrasound, and invasive forearm endothelial vasoreactivity in 1,008 70-year-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. RESULTS In analyses adjusted for multiple CVD risk factors, we observed inverse associations of RBP4 with carotid artery intima-media (β −0.39, 95% CI −0.55 to −0.22) and plaque (β −0.33, 95% CI −0.60 to −0.05) echogenicity (gray scale median). CONCLUSIONS Circulating RBP4 concentrations were inversely associated with intima-media and plaque echogenicity in carotid arteries. These findings imply that RBP4 could be involved in the development of atherosclerosis.
Peroxisome Proliferator-Activated Receptor δ and γ Agonists Differentially Alter Tumor Differentiation and Progression during Mammary Carcinogenesis
Authors: Yuzhi Yin, Robert G. Russell, Luis E. Dettin, Renkui Bai, Zhi-Liang Wei, Alan P. Kozikowski, Levy Kopleovich, Robert I. Glazer
Journal: Cancer Research (2005)

Abstract Peroxisome proliferator-activated receptor (PPAR) represents a ligand-dependent nuclear receptor family that regulates multiple metabolic processes associated with fatty acid β-oxidation, glucose utilization, and cholesterol transport. These and other receptor-mediated actions pertain to their role in hypolipidemic and antidiabetic therapies and as potential targets for cancer chemopreventive agents. The present study evaluated the chemopreventive activity of two highly potent and selective PPARγ and PPARδ agonists in a progestin- and carcinogen-induced mouse mammary tumorigenesis model. Animals treated with the PPARγ agonist GW7845 exhibited a moderate delay in tumor formation. In contrast, animals treated with the PPARδ agonist GW501516 showed accelerated tumor formation. Significantly, tumors from GW7845-treated mice were predominantly ductal adenocarcinomas, whereas tumors from GW501516-treated animals were adenosquamous and squamous cell carcinomas. Gene expression analysis of tumors arising from GW7845- and GW501516-treated mice identified expression profiles that were distinct from each other and from untreated control tumors of the same histopathology. Only tumors from mice treated with the PPARγ agonist expressed estrogen receptor-α in luminal transit cells, suggesting increased ductal progenitor cell expansion. Tumors from mice treated with the PPARδ agonist exhibited increased PPARδ levels and activated 3-phosphoinositide–dependent protein kinase-1 (PDK1), which co-associated, suggesting a link between the known oncogenic activity of PDK1 in mammary epithelium and PPARδ activation. These results indicate that PPARδ and PPARγ agonists produce diverse, yet profound effects on mammary tumorigenesis that give rise to distinctive histopathologic patterns of tumor differentiation and tumor development.
ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS): how to classify the impact of AS on functioning and health
Authors: A Boonen, J Braun, I E van der Horst Bruinsma, F Huang, W Maksymowych, N Kostanjsek, A Cieza, G Stucki, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2009)

Objective: To report on the results of a standardised consensus process agreeing on concepts typical and/or relevant when classifying functioning and health in patients with ankylosing spondylitis (AS) based on the International Classification of Functioning and Health (ICF). Methods: Experts in AS from different professional and geographical backgrounds attended a consensus conference and were divided into three working groups. Rheumatologists were selected from members of the Assessment of SpondyloArthritis international Society (ASAS). Other health professionals were recommended by ASAS members. The aim was to compose three working groups with five to seven participants to allow everybody’s contribution in the discussions. Experts selected ICF categories that were considered typical and/or relevant for AS during a standardised consensus process by integrating evidence from preceding studies in alternating working group and plenary discussions. A Comprehensive ICF Core Set was selected for the comprehensive classification of functioning and a Brief ICF Core Set for application in trials. Results: The conference was attended by 19 experts from 12 countries. Eighty categories were included in the Comprehensive Core Set, which included 23 Body functions , 19 Body structures , 24 Activities and participation and 14 Environmental factors . Nineteen categories were selected for the Brief Core Set, which included 6 Body functions , 4 Body structures , 7 Activities and participation and 2 Environmental factors . Conclusion: The Comprehensive and Brief ICF Core Sets for AS are now available and aim to represent the external reference to define consequences of AS on functioning.
Trastuzumab-Induced HER Reprogramming in “Resistant” Breast Carcinoma Cells
Authors: Murli Narayan, Jason A. Wilken, Lyndsay N. Harris, Andre T. Baron, Kimberly D. Kimbler, Nita J. Maihle
Journal: Cancer Research (2009)

Although trastuzumab (Herceptin) is an important advance in the treatment of breast cancer, a significant proportion of patients do not respond to trastuzumab either alone or in combination with chemotherapy. In this study, we observe that epidermal growth factor receptor (EGFR) and HER3 expression is substantially increased after long-term trastuzumab exposure of HER2-positive breast carcinoma-derived cell lines that show primary resistance to trastuzumab. Furthermore, long-term trastuzumab exposure of trastuzumab-resistant cell lines induces de novo sensitivity to the EGFR-targeted agents gefitinib or cetuximab in two of three cell lines accompanied by increased EGFR expression. Together, these results indicate that primary trastuzumab resistance is not synonymous with lack of responsiveness to trastuzumab and, importantly, suggest that trastuzumab priming may sensitize trastuzumab-resistant tumors to other HER family-directed therapeutics.
Disorder of colour consciousness: The view from neuropsychology
Authors: Glyn W. Humphreys, M. Jane Riddoch
Journal: Behavioral and Brain Sciences (1999)

We discuss the difficulty of measuring the perceptual experience of colour, supporting Palmer's assertion that neuropsychological disorders of colour processing can be informative in this respect. We point out that some disorders seem to affect the perceptual experience of colour over and above the perceptual processing of colour, providing direct insights into the neural mechanisms supporting perceptual experience.
Queuing for Coronary Angiography During Severe Supply-Demand Mismatch in a US Public Hospital
Authors: S Rosanio, M Tocchi, D Cutler, B F Uretsky, G A Stouffer, C R deFilippi, E J MacInerney, S R Runge, J Aaron, J Otero, S Garg, M S Runge
Journal: JAMA (1999)

<h3>Context</h3> Adverse cardiac events have been reported in patients waiting for either coronary surgery or angioplasty. However, data on the risk of adverse events while awaiting coronary angiography are limited, and none are available from a US population. <h3>Objective</h3> To quantify cardiac outcomes in patients waiting for elective coronary angiography. <h3>Design, Setting, and Participants</h3> Observational cohort study of 381 adult outpatients (mean [SD] age, 55 [12] years; 64% male; 61% white) on a waiting list for coronary angiography at a US tertiary care public teaching hospital during 1993-1994. <h3>Main Outcome Measures</h3> Rates of cardiac death, nonfatal myocardial infarction, and hospitalizations for unstable angina or heart failure as a function of amount of time spent on a waiting list. <h3>Results</h3> Sixty-six patients were dropped from the waiting list but were included in the study analysis. During a mean (SD) follow-up of 8.4 (6.5) months, cardiac death, myocardial infarction, and hospitalization occurred in 6 (1.6%), 4 (1.0%), and 26 (6.8%) patients, respectively. The probability of events was minimal in the first 2 weeks and increased steadily between 3 and 13 weeks. By Cox multivariate analysis, 2 variables independently identified an increased risk of adverse events: a strongly positive treadmill exercise electrocardiogram or positive stress imaging result at referral (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.22-4.16; P=.01) and the use of 2 to 3 anti-ischemic medications (OR, 1.98; 95% CI, 1.19-3.96; P=.04). Among 311 patients who ultimately underwent angiography, those with adverse events had a higher prevalence of coronary disease (96% vs 60%; P&lt;.001), more frequently required revascularization (93% vs 53%; P&lt;.001), and had longer hospital stays (mean [SD], 6.2 [4.3] vs 1.3 [0.7] days; P=.001). <h3>Conclusion</h3> Our data suggest that in a cohort referred for coronary angiography, delaying the procedure places some patients at risk for death, myocardial infarction, unplanned hospitalization, a longer hospital stay, and, potentially, a poorer prognosis. Waits longer than 2 weeks should be avoided, and patients with strongly positive stress test results and those who require 2 to 3 anti-ischemic medications should be prioritized for early intervention.
P156 Outcome and Experience of Laproscopic Nissens Fundoplication in Adult Patients with Severe Asthma and Cough Who Have Gastroesophageal Reflux: Abstract P156 Table 1
Authors: S Ejiofor, J Brebner, B Barker, A Mansur
Journal: Thorax (2012)

<h3>Introduction</h3> Gastroesophageal reflux (GORD) is an important co-morbidity in patients with asthma.<sup>1</sup> It has a detrimental impact on symptoms with many patients being on oral corticosteroids despite maximal proton pump inhibitor (ppi) therapy.<sup>1</sup> Fundoplication in selected patients with severe asthma has been reported to improve asthma symptoms especially in children.<sup>2</sup> Birmingham Heartlands Hospital (BHH) is part of Heart of England NHS trust, one of the largest foundation trusts in UK. The Severe and Brittle Asthma Unit which operates from BHH has a policy of referring selected patients for Fundoplication. <h3>Method</h3> In this prospective study all patients undergoing laparoscopic fundoplication were followed up for 12 months. All patients had GORD symptoms refractory to ppi therapy and proven reflux on oesophageal manometry. Prior to surgery and at 3 months patients symptoms were assessed with a) Mini asthma quality of life questionnaire (mAQLQ) b) Reflux Cough Questionnaire (RCQ)and c) Cough symptom Score (CSS). Lung function and medication were documented at follow up visits. Wilcoxon signed rank test was used in statistical analyses. <h3>Results</h3> Between December 2009 and June 2012 13 patients underwent fundoplication. Patient characteristics are shown below. Fundoplication significantly improved CSS and RCQ at 3 months from baseline, p=0.002 and p=0.008 respectively. No significant change was seen in mAQLQ or lung function in asthmatic patients. <h3>Conclusions</h3> Patients with severe cough and asthmatics with debilitating cough benefit from fundoplication. Asthmatics however have no significant improvement in quality of life scores or pulmonary function in the short term following fundoplication. <h3>References</h3> Sontag et al A Am J Gastroenterol. 2003 May; 98(5):987–99. Rothenburg S et al J Pediatric Surg 2012 Jun; 47(6):1101–4.
Reply: Objective Measurement of the Therapeutic Effectiveness of Continuous Positive Airway Pressure versus Oral Appliance Therapy for the Treatment of Obstructive Sleep Apnea
Authors: David P. White
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

From the Editorialist:

The letter by Dr. Vanderveken and colleagues in response to the article by Dr. Phillips and colleagues (1) and my accompanying editorial (2) nicely addresses both the problems encountered in predicting which patients are likely to respond to an oral appliance in the treatment of their obstructive sleep apnea (OSA) and the assessment of compliance with the device once it has been fabricated. I have only two comments in response to this letter.


First, several of the approaches proposed by Vanderveken and colleagues are not broadly available at this time:

• The embedded microsensor thermometer to measure oral appliance use is, to the best of my knowledge, not currently available in the United States, nor is the associated software to assess compliance. In addition, the device is certainly not provided on the commercially available oral appliances. Vanderveken and colleagues (3) have convincingly demonstrated the accuracy of this device in the clinical trial setting in Belgium and it is being used in several other current clinical trials. However, it needs to be more widely available before its true effectiveness can be determined.
• The “remotely controlled mandibular positioner” for oral appliance titration in the sleep laboratory developed by Remmers and colleagues (4) also has credible data supporting the accuracy of the device in determining who will ultimately respond to an oral appliance. However, few sleep laboratories currently have this technology available. It is also unclear whether such titrations would be readily reimbursed by payers.



Second, the use of drug-induced sleep endoscopy to assess the ability of an oral appliance to treat OSA in a given patient is arguably not sufficiently sensitive and specific to completely rule in or out the use of an oral appliance in that patient (5). It addition, the procedure itself may be more expensive (particularly in the United States) than fabricating the device and determining its efficacy with a home sleep test.

That being said, several of the approaches proposed by Vanderveken and colleagues need to become both more broadly available and more commonly used as oral appliances are a viable method of treating OSA. Despite their being available for decades, use of oral appliances remains modest, and this needs to change.
Extrinsic Notch Ligand Delta-Like 1 Regulates Tip Cell Selection and Vascular Branching Morphogenesis
Authors: L.C. Napp, M. Augustynik, F. Paesler, K. Krishnasamy, J. Woiterski, A. Limbourg, J. Bauersachs, H. Drexler, F. Le Noble, F.P. Limbourg
Journal: Circulation Research (2012)

In developing blood vessels, single endothelial cells (ECs) specialize into tip cells that sense vascular endothelial growth factor (VEGF) and contribute to vessel sprouting and branch formation. Tip cell differentiation is inhibited through lateral Notch signaling between ECs, which is controlled by Notch ligands expressed in vessel sprouts. The contribution of the Notch ligand Delta-like (Dll) 1 herein is unknown.To investigate the role of Dll1 in vascular morphogenesis and tip cell formation in the mouse retina.Mice with heterozygous deletion of Dll1 had fewer tip cells during angiogenic sprouting of the superficial vascular plexus but also showed impaired vessel branching into deeper retinal layers and impaired deep plexus angiogenesis. Interestingly, the formation of vertical branches was also guided by filopodia-extending ECs located at the tip of branches, consistent with tip cells, which emerged from established vessels to form a secondary plexus within the deeper neuronal cell layers. During both phases of vascular patterning, Dll1 was not expressed in ECs but in the superficial neuronal layer in close contact with expanding vessels, where Dll1 expression coincided with tip cell formation in a spatiotemporal manner. In vitro, culture of ECs on DLL1 induced essential tip cell genes, including Dll4, VEGF receptor 3, and ephrin-B2, and stimulated VEGF responsiveness and vascular network formation.Dll1 acts as an extrinsic cue involved in tip cell selection, which directs vessel sprouting and branch formation.
Regulation of Endothelial Constitutive Nitric Oxide Synthase Gene Expression in Endothelial Cells and In Vivo
Authors: Koji Kuboki, Zhen Y. Jiang, Noriko Takahara, Sung Woo Ha, Masahiko Igarashi, Teruaki Yamauchi, Edward P. Feener, Terrance P. Herbert, Christopher J. Rhodes, George L. King
Journal: Circulation (2000)

Background —The vasodilatory effect of insulin can be acute or increase with time from 1 to 7 hours, suggesting that insulin may enhance the expression of endothelial nitric oxide synthase (eNOS) in endothelial cells. The objective of the present study was to characterize the extent and signaling pathways by which insulin regulates the expression of eNOS in endothelial cells and vascular tissues. Methods and Results —Physiological concentrations of insulin (10 −10 to 10 −7 mmol/L) increased the levels of eNOS mRNA, protein, and activity by 2-fold after 2 to 8 hours of incubation in cultured bovine aortic endothelial cells. Insulin enhanced eNOS gene expression in microvessels isolated from Zucker lean rats but not from insulin-resistant Zucker fatty rats. Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase) decreased the effect of insulin on eNOS gene expression, but a general protein kinase C (PKC) inhibitor, GF109203X or PKCβ isoform inhibitor, LY333531 enhanced eNOS expression. In contrast, PKC activators inhibited both the activation by insulin of PI-3 kinase and eNOS mRNA levels. Overexpression of PKCβ isoform in endothelial cells inhibited the stimulation by insulin of eNOS expression and PI-3 kinase activities in parallel. Conclusions —Insulin can regulate the expression of eNOS gene, mediated by the activation of PI-3 kinase, in endothelial cells and microvessels. Thus, insulin may chronically modulate vascular tone. The activation of PKC in the vascular tissues as in insulin resistance and diabetes may inhibit PI-3 kinase activity and eNOS expression and may lead to endothelial dysfunctions in these pathological states.
FusionSeq: a modular framework for finding gene fusions by analyzing paired-end RNA-sequencing data
Authors: Andrea Sboner, Lukas Habegger, Dorothee Pflueger, Stephane Terry, David Z Chen, Joel S Rozowsky, Ashutosh K Tewari, Naoki Kitabayashi, Benjamin J Moss, Mark S Chee, Francesca Demichelis, Mark A Rubin, Mark B Gerstein
Journal: Genome biology (2010)

We have developed FusionSeq to identify fusion transcripts from paired-end RNA-sequencing. FusionSeq includes filters to remove spurious candidate fusions with artifacts, such as misalignment or random pairing of transcript fragments, and it ranks candidates according to several statistics. It also has a module to identify exact sequences at breakpoint junctions. FusionSeq detected known and novel fusions in a specially sequenced calibration data set, including eight cancers with and without known rearrangements.
Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLTspecific probes
Authors: Judith Dierlamm, Mathijs Baens, Margarita Stefanova-Ouzounova, Kristina Hinz, Iwona Wlodarska, Brigitte Maes, Anja Steyls, Ann Driessen, Gregor Verhoef, Philippe Gaulard, Anne Hagemeijer, Dieter Kurt Hossfeld, Christiane De Wolf-Peeters, Peter Marynen
Journal: Blood (2000)
Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension
Authors: Naoto Fujiwara, Tomohiro Osanai, Takaatsu Kamada, Takeshi Katoh, Koki Takahashi, Ken Okumura
Journal: Circulation (2000)

Background —High salt intake suppresses the effect of nitric oxide (NO) in the peripheral resistance vessels in animal models. We tested the hypothesis that the modulation of endogenous NO is related to salt sensitivity in human hypertension. Methods and Results —Inpatients with essential hypertension (n=24) were maintained on a normal-salt diet (12 g/d NaCl) for 3 days, a low-salt diet (2 g), a high-salt diet (20 to 23 g), and a low-salt diet for 7 days. Normotensive subjects (n=16) were maintained on the first 2 salt diets. The hypertensive patients whose average 24-hour blood pressure was increased by &gt;5% by salt loading were assigned to group 1 (n=8) and the others to group 2 (n=16). Nitrate plus nitrite (NO x ) was measured by the Griess method, and asymmetrical dimethylarginine (ADMA) by high-performance liquid chromatography. The plasma NO x level during the normal-salt diet was lower in group 1 than in group 2 and the normotensive group. After salt loading, the plasma NO x level was decreased and reversed after the second salt restriction. Plasma ADMA level was increased after salt loading and decreased after salt restriction. The change in plasma NO x level was correlated inversely with those in blood pressure ( r =−0.59, P =0.0007) and plasma ADMA level ( r =−0.64, P =0.003) after salt loading and restriction. Conclusions —Modulation of NO synthesis by salt intake may be involved in a mechanism for salt sensitivity in human hypertension, presumably via the change in ADMA.
Pharmacodynamic Studies of the Epidermal Growth Factor Receptor Inhibitor ZD1839 in Skin From Cancer Patients: Histopathologic and Molecular Consequences of Receptor Inhibition
Authors: J. Albanell
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom) is under development as an anticancer agent. We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin, an EGFR-dependent tissue, in cancer patients participating in ZD1839 phase I clinical trials. PATIENTS AND METHODS: We studied 104 pre– and/or on–ZD1839 therapy (≈ at day 28 of therapy) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839. We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated (phosphorylated) EGFR. Effects on receptor signaling (activated mitogen-activated protein kinase [MAPK]), proliferation, p27KIP1, and maturation were also assessed. RESULTS: Histopathologically, the stratum corneum of the epidermis was thinner during therapy (P < .001). In hair follicles, prominent keratin plugs and microorganisms were found in dilated infundibula. ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells (P < .001). In addition, ZD1839 inhibited MAPK activation (P < .001) and reduced keratinocyte proliferation index (P < .001). Concomitantly, ZD1839 increased the expression of p27KIP1 (P < .001) and maturation markers (P < .001) and increased apoptosis (P < .001). These effects were observed at all dose levels, before reaching dose-limiting toxicities. CONCLUSION: ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo. These effects were profound at doses well below the one producing unacceptable toxicity, a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials.
Domiciliary care for the elderly sick--economy or neglect?
Authors: L J Opit
Journal: BMJ (1977)

This paper reports an investigation of the costs of domiciliary care for 139 elderly sick patients under the care of the home nursing service. The data suggest that there may be little economic advantage in home care for seriously disabled elderly people. The revenue cost of domiciliary care was equal to or greater than the average associated with residential or hospital custodial care in such patients. Even so, the cost of services received at home did not disclose the real need for domiciliary care, since at present this is obscured by compulsory rationing and the separation of responsibility between health and social services. It is suggested that the supposed economic advantage of domiciliary care will depend increasingly on restricting such services, thus increasing the degree of neglect to some patients.