tbuckley/cabot-search huggingface dataset:
Does measurement of yield pressure at the cardia during endoscopy provide information on the function of the lower oesophageal sphincter mechanism?
Authors: R C McGouran, J M Galloway, D S Spence, C P Morton, D Marchant
Journal: Gut (1988)

We describe a technique for measuring the yield pressure at the cardia during upper gastrointestinal endoscopy. The test was applied to 47 patients with macroscopic oesophagitis and nine patients with achalasia. Controls were 123 patients from the routine endoscopy list in whom no abnormality was found and 21 healthy volunteers. Yield pressure was similar in both control groups, but was significantly higher in achalasia (p less than 0.001) and lower in oesophagitis (p less than 0.001). Yield pressures fell dramatically after pneumatic dilatation in the achalasia patients. The test was reproducible and yield pressure was not affected by age, sex, weight, or sedation. Measurement of yield pressure during endoscopy provides information which may reflect the function of the whole antireflux mechanism, and not just the lower oesophageal sphincter.
Venous thromboembolism in people with idiopathic pulmonary fibrosis: a population-based study
Authors: William Dalleywater, Helen A Powell, Andrew W Fogarty, Richard B Hubbard, Vidya Navaratnam
Journal: European Respiratory Journal (2014)

To the Editor: 

Laboratory studies and animal models have suggested that the activation of the clotting cascade may be important in the pathogenesis of idiopathic pulmonary fibrosis (IPF) [1–3]. Epidemiological studies have also suggested a strong association between IPF and venous thromboembolism (VTE) [4–6]. We estimated the incidence of pulmonary embolus and deep vein thrombosis (DVT) in people with IPF and the general population, and compared these with the prevalence of a warfarin prescription.

We used data from THIN (The Health Improvement Network; www.thin-uk.com), a UK longitudinal database of electronic primary care records containing information recorded in routine clinical care, from face-to-face consultations, and following communication from secondary care. Medical and diagnostic data are entered using medical Read codes, a comprehensive list of medical terms …
Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial
Authors: J P Mohr, Michael K Parides, Christian Stapf, Ellen Moquete, Claudia S Moy, Jessica R Overbey, Rustam Al-Shahi Salman, Eric Vicaut, William L Young, Emmanuel Houdart, Charlotte Cordonnier, Marco A Stefani, Andreas Hartmann, Rüdiger von Kummer, Alessandra Biondi, Joachim Berkefeld, Catharina J M Klijn, Kirsty Harkness, Richard Libman, Xavier Barreau, Alan J Moskowitz
Journal: The Lancet (2013)
Significance of deep T-wave inversions in asymptomatic athletes with normal cardiovascular examinations: practical solutions for managing the diagnostic conundrum
Authors: M G Wilson, S Sharma, F Carré, P Charron, P Richard, R O'Hanlon, S K Prasad, H Heidbuchel, J Brugada, O Salah, M Sheppard, K P George, G Whyte, B Hamilton, H Chalabi
Journal: British Journal of Sports Medicine (2012)

Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts.
Toll-like receptor 9–dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
Authors: Jane Tian, Ana Maria Avalos, Su-Yau Mao, Bo Chen, Kannaki Senthil, Herren Wu, Peggy Parroche, Stacey Drabic, Douglas Golenbock, Cherilyn Sirois, Jing Hua, Ling Ling An, Laurent Audoly, Greg La Rosa, Angelika Bierhaus, Peter Naworth, Ann Marshak-Rothstein, Mary K Crow, Katherine A Fitzgerald, Eicke Latz, Peter A Kiener, Anthony J Coyle
Journal: Nature Immunology (2007)
Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis
Authors: Florentien D O de Steenwinkel, Anita C S Hokken-Koelega, Yaël A de Man, Y B de Rijke, Maria A J de Ridder, Johanna M W Hazes, Radboud J E M Dolhain
Journal: Annals of the Rheumatic Diseases (2012)

Background High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. Objectives To assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy. Methods This study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied. Results During the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p&lt;0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs. Conclusions Maternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.
Doppler assessment of pulmonary haemodynamics in chronic hypoxic lung disease.
Authors: O. C. Burghuber
Journal: Thorax (1996)

Various methods of Doppler echocardiography are useful in the analysis of flow dynamics within the heart and the pulmonary circulation in patients with COPD. In addition, to distinguish patients with increased pulmonary artery pressures from those with normal pressures, Doppler techniques provide quantitative methods for estimating pulmonary artery pressures non-invasively. Doppler echocardiography can be performed repeatedly and can thus be used to assess serial changes in the clinical state of a patient or in the response to certain pharmaceutical interventions in the pulmonary vascular bed. The most useful and accurate method of estimating pulmonary artery pressures in patients with chronic hypoxic lung disease is the systolic trans-tricuspid gradient, calculated from tricuspid regurgitation detected by continuous wave Doppler echocardiography with estimation of the right ventricular pressure, followed by the acceleration time from pulmonary flow analysis using pulsed Doppler techniques. New contrast materials to enhance the continuous wave Doppler signal and transoesophageal echocardiography may provide even more satisfactory results in the future.
Synergistic anti-tumor effect of combined inhibition of EGFR and JAK/STAT3 pathways in human ovarian cancer
Authors: Wei Wen, Jun Wu, Lucy Liu, Yan Tian, Ralf Buettner, Meng-Yin Hsieh, David Horne, Thanh H Dellinger, Ernest S Han, Richard Jove, John H Yim
Journal: Molecular Cancer (2015)

The EGFR signaling pathway is frequently activated in human ovarian cancer and associated with poor prognosis. However, inhibition of EGFR signaling in patients with recurrent ovarian cancer has been disappointing. It remains to be addressed whether ovarian cancer patients could benefit from targeting EGFR signaling. Here we investigated the mechanisms underlying the resistance to EGFR inhibition in ovarian cancer and developed a strategy to overcome it.We found that treatment of human ovarian cancer cells with an EGFR inhibitor, gefitinib, resulted in increased STAT3 phosphorylation in a dose- and time-dependent manner. Inhibiting STAT3 activation with a small molecule inhibitor of JAK, an upstream kinase that phosphorylates and activates STAT3, synergistically increased the anti-tumor activity of gefitinib in vitro. Similar results were obtained when STAT3 or JAK1 expression was knocked down. In contrast, inhibiting other signaling pathways, such as AKT/mTOR, MEK or SRC, was relatively less effective. The combined treatment resulted in simultaneous attenuation of multiple survival pathways and increased inhibition of ERK pathway. In addition, the dual inhibition showed a stronger suppression of xenograft tumor growth than either single inhibition.Our findings demonstrate that feedback activation of STAT3 pathway might contribute to the resistance to EGFR inhibition. Combined blockade of both pathways appears to be more effective against human ovarian cancer than inhibition of each pathway alone both in vitro and in vivo. This study may provide a strategy to improve clinical benefit of targeting EGFR pathway in ovarian cancer patients.
Signal Transducers and Activators of Transcription-3/Pim1 Axis Plays a Critical Role in the Pathogenesis of Human Pulmonary Arterial Hypertension
Authors: Roxane Paulin, Audrey Courboulin, Jolyane Meloche, Vincent Mainguy, Eric Dumas de la Roque, Nehmé Saksouk, Jacques Côté, Steeve Provencher, Mark A. Sussman, Sébastien Bonnet
Journal: Circulation (2011)

Pulmonary artery hypertension (PAH) is a proliferative disorder associated with enhanced pulmonary artery smooth muscle cell proliferation and suppressed apoptosis. The sustainability of this phenotype required the activation of a prosurvival transcription factor like signal transducers and activators of transcription-3 (STAT3) and nuclear factor of activated T cell (NFAT). Because these factors are implicated in several physiological processes, their inhibition in PAH patients could be associated with detrimental effects. Therefore, a better understanding of the mechanism accounting for their expression/activation in PAH pulmonary artery smooth muscle cells is of great therapeutic interest.Using multidisciplinary and translational approaches, we demonstrated that STAT3 activation in both human and experimental models of PAH accounts for the expression of both NFATc2 and the oncoprotein kinase Pim1, which trigger NFATc2 activation. Because Pim1 expression correlates with the severity of PAH in humans and is confined to the PAH pulmonary artery smooth muscle cell, Pim1 was identified as an attractive therapeutic target for PAH. Indeed, specific Pim1 inhibition in vitro decreases pulmonary artery smooth muscle cell proliferation and promotes apoptosis, all of which are sustained by NFATc2 inhibition. In vivo, tissue-specific inhibition of Pim1 by nebulized siRNA reverses monocrotaline-induced PAH in rats, whereas Pim1 knockout mice are resistant to PAH development.We demonstrated for the first time that inhibition of the inappropriate activation of STAT3/Pim1 axis is a novel, specific, and attractive therapeutic strategy to reverse PAH.
A Novel Molecular Signature for Elevated Tricuspid Regurgitation Velocity in Sickle Cell Disease
Authors: Ankit A. Desai, Tong Zhou, Homaa Ahmad, Wei Zhang, Wenbo Mu, Sharon Trevino, Michael S. Wade, Nalini Raghavachari, Gregory J. Kato, Marlene H. Peters-Lawrence, Tejas Thiruvoipati, Kristin Turner, Nicole Artz, Yong Huang, Amit R. Patel, Jason X.-J. Yuan, Victor R. Gordeuk, Roberto M. Lang, Joe G. N. Garcia, Roberto F. Machado
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD).We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD.Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms.Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10(-7)) and one cis-acting (P = 0.6 × 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B).These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.
Exon skipping with morpholino oligomers: new treatment option for cardiomyopathy in Duchenne muscular dystrophy?
Authors: R. Bauer, H. A. Katus, O. J. Muller
Journal: Cardiovascular Research (2009)

The dystrophin gene encodes an essential component of the transmembrane dystrophin–glycoprotein complex (DGC), which plays a critical role in maintaining membrane stability in cardiac and skeletal muscles.1 Defects in dystrophin destabilize the entire complex, which results in an abnormal susceptibility to sarcolemmal injury in response to contractile stress.2 Mutations that cause slight sequence alterations or loss of internal exons but conserve the reading frame result in Becker muscular dystrophy with a mild phenotype. Complete absence of dystrophin causes Duchenne muscular dystrophy (DMD), a X-chromosomal, fatal, and inherited muscle disease. Affected boys show progressive muscle weakness, leading to early immobility, respiratory failure, and markedly reduced life expectancy. Cardiomyopathy is an almost invariable complication and a frequent cause of death in these patients.3 As a consequence of improvements in overall management for DMD patients, survival has steadily improved. In older patients, however, there is an increasing proportion of patients experiencing premature death due to ventricular dysfunction. Therefore, appropriate treatment strategies to target the cardiomyopathy become more and more crucial to reduce mortality.

Thus far, there is no established curative approach to DMD. However, there now seems to be hope since the identification of the molecular basis of this inherited disease has translated into recent therapeutic principles to … 

*Corresponding author. Tel: +49 6221 5639401; fax: +49 6221 564866. E-mail address : oliver.mueller{at}med.uni-heidelberg.de
Erratum to: Induction of MAPK phosphatase-1 by hypothermia inhibits TNF- -induced endothelial barrier dysfunction and apoptosis
Authors: D. Yang, P. Xie, S. Guo, H. Li
Journal: Cardiovascular Research (2010)

Aims Hypothermia therapy has been shown to confer robust protection against brain injury and cardiac arrest. However, the mechanisms underlying endothelial cell protection of hypothermia have not yet been completely elucidated. Here, we investigated molecular effects of hypothermia on tumour necrosis factor-α (TNF-α)-induced endothelial barrier dysfunction and apoptosis.

Methods and results Human umbilical vein endothelial cells (HUVECs) treated with TNF-α were incubated under normothermia (37°C) or hypothermia (3°C). Endothelial permeability, actin alterations, and apoptosis were examined. The protein levels were determined by immunoblot analysis. Treatment of HUVECs with TNF-α resulted in a significant increase of permeability, actin reorganization, and apoptosis. Hypothermia markedly attenuated TNF-α-induced effects. The inhibitory action of hypothermia on stress fibre formation was mediated via inactivation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein 27 (HSP27), and the decrease in TNF-α-induced apoptosis by hypothermia was associated with inhibition of p38 MAPK and c-Jun N-terminal kinase (JNK) activity. Hypothermia had no action on p38 MAPK and JNK upstream kinases MAPK kinase 3/6 (MKK3/6) and MAPK kinase 7 (MKK7), but it markedly induced the expression of MAPK phosphatase-1 (MKP-1). Furthermore, siRNA experiments showed that MKP-1 was an important mediator of hypothermia in reducing TNF-α-induced inflammatory responses and activation of p38 MAPK and JNK in HUVECs.

Conclusion These results for the first time demonstrate that hypothermia protects against TNF-α-induced endothelial barrier dysfunction and apoptosis through an MKP-1-dependent mechanism.
The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins.
Authors: A Aruffo, M B Melnick, P S Linsley, B Seed
Journal: The Journal of Experimental Medicine (1991)

The isolation, characterization, and expression of a full-length cDNA encoding the human T cell glycoprotein CD6 is described. COS cells transfected with the CD6 clone express a 90-kD protein that reacts with all available anti-CD6 monoclonal antibodies. RNA blot hybridization analysis indicates that CD6 transcripts are predominantly restricted to cells in the T lineage. The predicted CD6 sequence is 468 amino acids long, with the typical features of a type I integral membrane protein. The cytoplasmic domain of CD6 contains two serine residues, one or both of which are substrates for phosphorylation during T cell activation. The extracellular domain of CD6 is significantly related to the extracellular domain of the human and mouse T cell antigen CD5, the cysteine-rich domain of the bovine and mouse type I macrophage scavenger receptor, the extracellular domain of the sea urchin spermatozoa protein that crosslinks the egg peptide speract, the mammalian complement factor 1, and the human lung tumor antigen L3. These molecules, therefore, constitute a new gene superfamily that is well conserved across species boundaries.
A COMPARISON OF ERYTHROCYTE SEDIMENTATION RATES AND ELECTROPHORETIC PATTERNS OF NORMAL AND PATHOLOGICAL HUMAN BLOOD
Authors: Theodore Shedlovsky, John Scudder
Journal: The Journal of Experimental Medicine (1942)

Electrophoretic studies and erythrocyte sedimentation rate measurements were carried out on normal and pathological human blood. An increase in alpha globulin levels appears to take place, as well as an increase in sedimentation rates, when there is present any considerable inflammation or tissue destruction, irrespective of its cause. A graphic correlation is presented between sedimentation rates and alpha globulin levels, which is at least as good as a similar correlation involving fibrinogen levels.
Usefulness of peak expiratory flow measurements: is it just a matter of instrument accuracy?
Authors: V Brusasco
Journal: Thorax (2003)

A method for improving the accuracy of peak flow meters will be valuable if the recommendation to measure PEF is to be maintained in asthma management plans. With the currently available peak flow meters, no evidence has been provided that PEF measurements are of clinical usefulness. A large number of new randomised controlled studies using optimally validated peak flow meters would therefore be necessary. However, by that time these instruments may have become obsolete.

In this issue of Thorax Miller et al 1 present a new method for validation of peak flow meters. They show that applying a computer driven explosive decompression can detect inaccuracies in the dynamic response of commercially available peak flow meters that would be missed using the ATS recommended 26 waveforms for spirometer validation. This work is justified by the compelling recommendations to use peak expiratory flow (PEF) as a main or sole measure of lung function, incorporated in the current guidelines for diagnosis and management of asthma.2–5 In particular, PEF is recommended for daily home monitoring and also as a criterion for admission and discharge from the emergency room. For either application, accuracy of measurement is an obvious prerequisite. Indeed, previous works have shown that commercially available peak flow meters may not be accurate enough to allow correct management of …
New criteria for management of catheter infections in peritoneal dialysis patients using ultrasonography.
Authors: A Vychytil, M Lorenz, B Schneider, W H Hörl, M Haag-Weber
Journal: Journal of the American Society of Nephrology (1998)

Catheter-related infection is one of the most important causes of technical dropout in peritoneal dialysis patients. Both the type of cultured organism and the extent of inflammation are well known prognostic factors for the outcome of these infections. From December 1994 to November 1996, 96 catheter-related infections without simultaneous peritonitis occurred in 49 of 86 peritoneal dialysis patients treated in this study. During the observation period, only single-cuff catheters were used. Staphylococcus aureus was the most common organism cultured (51%). Involvement of the tunnel was diagnosed by sonography in 57.1% of all Staphylococcus aureus cases, but only in 26.1% of Staphylococcus epidermidis-related exit-site infections. Ten of the 96 catheter-related infections (10.4%) resulted in catheter loss. Catheter removal was necessary only in cases of deep tunnel infection caused by Staphylococcus aureus. The number of gram-negative catheter infections was too small to allow conclusive analysis. Although sonography of the catheter tunnel is now well established in the early diagnosis of tunnel infections, no clear guidelines exist for management of these infections. In this study, patients with deep tunnel infection who did not require catheter removal showed a significant decline of the hypoechogenic area around the cuff (from 7.02 +/- 0.70 to 3.75 +/- 1.04 mm, P < 0.002) 2 wk after initiation of therapy. No significant decline was observed in patients who later lost their catheters. On the basis of these data, it is concluded that in cases of exit-site and superficial tunnel infection, conservative treatment should be performed. In cases of deep tunnel infection without peritonitis caused by Staphylococcus aureus, antibiotic treatment should be started and sonographic examination should be performed every second week. If the hypoechogenic area around the cuff decreases (> 30%), conservative treatment should be prolonged. In cases without sonographic improvement (< 30%) 2 wk after therapy, catheter removal is recommended.