tbuckley/cabot-search huggingface dataset:
Opacity over the left hemithorax after abdominal aortic aneurysm repair
Authors: A.P. van der Weerdt, H.A van Dijk, W.G. Boersma
Journal: European Respiratory Journal (2000)

Case historyA 77-yr-old male was admitted for aortic aneurysm repair.His history recorded hypertension, left carotid artery desobstruction, stroke and an anterior invocardial infarction.Aspirin was discontinued 1 day before surgery.For peri-and postoperative haemodynamic surveillance, a Swan-Ganz catheter (7.5 Fr thermodilution catheter; Criticath; Ohmeda, Bilthoven, the Netherlands) was introduced through the venae cubiti of the right arm 1 day before surgery.Initially the catheter was in overwedged position.After withdrawal of the catheter a correct wedge curve was obtained.As a result of congestive heart failure, there were elevated pulmonary artery and wedge pressures.For this reason, the patient was treated with diuretics and nitroglycerin intravenously.The abdominal aortic repair was uncomplicated, with a blood loss of 1,900 mL.After surgery the chest radiograph showed a diffuse opacity over the left hemithorax (fig.1).
RanGTPase: A Candidate for Myc-Mediated Cancer Progression
Authors: Hiu-Fung Yuen, Vignesh-Kumar Gunasekharan, Ka-Kui Chan, Shu-Dong Zhang, Angela Platt-Higgins, Kathy Gately, Ken O’Byrne, Dean A. Fennell, Patrick G. Johnston, Philip S. Rudland, Mohamed El-Tanani
Journal: JNCI Journal of the National Cancer Institute (2013)

Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman’s rank correlation and Kaplan–Meier plots coupled with Wilcoxon–Gehan tests, respectively. All statistical tests were two-sided. Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P < .001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P = .01) cancer cohorts. Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.
Oesophagitis is as important as oesophageal stricture diameter in determining dysphagia.
Authors: M Dakkak, R C Hoare, S C Maslin, J R Bennett
Journal: Gut (1993)

It is a common observation that stricture patients with severe dysphagia may have a wide lumen, while others with a narrow stricture have few swallowing complaints. In 64 patients with benign oesophageal stricture the dysphagia score (determined by questionnaire and by a test meal both based on nine different items of food scored according to their solidity) was compared with the diameter of the stricture measured radiologically by premeasured barium spheres. There was evidence of an association, but the correlation coefficient (r) was 0.544 (p = 0.0001), suggesting that the diameter of the stricture is an important, although not the sole, determinant of dysphagia. Stricture diameter explains 29.6% (r2) of variation in dysphagia score. The patients (mean dysphagia score 71 of a maximum possible 90) were divided into three groups according to the severity of oesophagitis (19 patients had minimal, 22 moderate and 23 severe oesophagitis). Analysis revealed the mean dysphagia score to be 83, 73, 59 in each group respectively. Dysphagia score of each group was significantly different from the others (Kruskal-Wallis test). Relating the dysphagia score to stricture diameter for each group gives correlation coefficient r = 0.379 (p = 0.110) in the minimal oesophagitis group, r = 0.651 (p = 0.001) in the moderate group, r = 0.583 (p = 0.004) in the severe group. If both diameter and severity of oesophagitis are included then 66.0% of the variation can be explained. It is concluded that the degree of oesophagitis is as important as luminal diameter in determining swallowing ability.
Unequal evolutionary conservation of human protein interactions in interologous networks
Authors: Kevin R Brown, Igor Jurisica
Journal: Genome biology (2007)

Protein-protein interaction (PPI) networks have been transferred between organisms using interologs, allowing model organisms to supplement the interactomes of higher eukaryotes. However, the conservation of various network components has not been fully explored. Unequal conservation of certain network components may limit the ability to fully expand the target interactomes using interologs.In this study, we transfer high quality human interactions to lower eukaryotes, and examine the evolutionary conservation of individual network components. When human proteins are mapped to yeast, we find a strong positive correlation (r = 0.50, P = 3.9 x 10(-4)) between evolutionary conservation and the number of interacting proteins, which is also found when mapped to other model organisms. Examining overlapping PPI networks, Gene Ontology (GO) terms, and gene expression data, we are able to demonstrate that protein complexes are conserved preferentially, compared to transient interactions in the network. Despite the preferential conservation of complexes, and the fact that the human interactome comprises an abundance of transient interactions, we demonstrate how transferring human PPIs to yeast augments this well-studied protein interaction network, using the coatomer complex and replisome as examples.Human proteins, like yeast proteins, show a correlation between the number of interacting partners and evolutionary conservation. The preferential conservation of proteins with higher degree leads to enrichment in protein complexes when interactions are transferred between organisms using interologs.
Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma, nasal type: a multicentre, retrospective analysis
Authors: Seok Jin Kim, Joon Young Choi, Seung Hyup Hyun, Chang-Seok Ki, Dongryul Oh, Yong Chan Ahn, Young Hyeh Ko, Sunkyu Choi, Sin-Ho Jung, Pek-Lan Khong, Tiffany Tang, Xuexian Yan, Soon Thye Lim, Yok-Lam Kwong, Won Seog Kim
Journal: The Lancet Haematology (2015)
International models of investigator-initiated trials: implications for Japan
Authors: E.L. Trimble, J. Ledermann, K. Law, T. Miyata, C.K. Imamura, B.-H. Nam, Y.H. Kim, Y.-J. Bang, M. Michaels, D. Ardron, S. Amano, Y. Ando, T. Tominaga, K. Kurokawa, N. Takebe
Journal: Annals of Oncology (2012)
Hormone Replacement Therapy and Colorectal Adenoma Recurrence Among Women in the Polyp Prevention Trial
Authors: K. Woodson, E. Lanza, J. A. Tangrea, P. S. Albert, M. Slattery, J. Pinsky, B. Caan, E. Paskett, F. Iber, J. W. Kikendall, P. Lance, M. Shike, J. Weissfeld, A. Schatzkin
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Epidemiologic studies have suggested that estrogen may protect against the development of colorectal cancers and adenomatous polyps. We conducted a prospective study to evaluate the association between hormone replacement therapy (HRT) and adenoma recurrence among perimenopausal and postmenopausal women participating in the Polyp Prevention Trial, a randomized dietary intervention study of individuals with colorectal adenomas. Methods: We used a questionnaire and interviews to collect detailed information, at baseline and at each of four annual study visits, from 620 women regarding hormone use, menopausal status, diet, alcohol consumption, and other risk factors. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 years. Logistic regression models were used to evaluate the association between hormone use and adenoma recurrence after adjusting for intervention group and for age and body mass index at baseline. All statistical tests were two-sided. Results: Adenomas recurred in 200 women. There was no overall association between adenoma recurrence and either overall hormone use (odds ratio [OR] = 1.01; 95% confidence interval [CI] = 0.70 to 1.45), combined estrogen and progestin use (OR = 0.94; 95% CI = 0.57 to 1.56), or unopposed estrogen use (OR = 1.04; 95% CI = 0.68 to 1.59). HRT use was associated with a reduction in risk for recurrence of distal adenomas (OR = 0.56; 95% CI = 0.32 to 1.00) and a statistically nonsignificant increase in risk for recurrence of proximal adenomas (OR = 1.39; 95% CI = 0.85 to 2.26). We observed a statistically significant interaction between the HRT–adenoma recurrence association and age (P = .02). HRT was associated with a 40% reduced risk of adenoma recurrence among women older than 62 years (OR = 0.58; 95% CI = 0.35 to 0.97) but with an increased risk among women younger than 62 years (OR = 1.99; 95% CI = 1.11 to 3.55). Conclusions: HRT was not associated with a reduced risk for overall adenoma recurrence in this trial cohort, although there was a suggestion of an age interaction. The effect of age on the association needs to be confirmed in other adenoma recurrence trials.
Classic Preconditioning Decreases the Harmful Accumulation of Nitric Oxide During Ischemia and Reperfusion in Rat Hearts
Authors: Csaba Csonka, Zoltán Szilvássy, Ferenc Fülöp, Tibor Páli, Ingolf E. Blasig, Arpad Tosaki, Richard Schulz, Péter Ferdinandy
Journal: Circulation (1999)

Background —The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor. Methods and Results —Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes’ duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 μmol/L N G -nitro- l -arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/reperfusion-induced functional depression and NO accumulation were abolished. When 4.6 μmol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 μmol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts. Conclusions —Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.
Update in Sleep Medicine 2013
Authors: Yüksel Peker, Susan Redline
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Update in Sleep Medicine 2013 Yuksel Peker and Susan Redline Department of Molecular and Clinical Medicine, Institution of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sleep Medicine Unit, Skaraborg Hospital, Skovde, Sweden; Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Leucocyte Migration Inhibition Test and Tuberculin Hypersensitivity
Authors: A. Sabioncello, D. Dekaris
Journal: Allergy (1980)

Tuberculin hypersensitivity was evaluated in 71 Mantoux‐positive and 58 Mantoux‐negative persons by the leucocyte migration inhibition test. The capillary lube technique discriminated these two groups, bill variability of results and overlapping of the groups were considerable. The shorter the incubation period, the better discrimination between the groups. Only after short incubation (2 h) was the correlation between the intensities of Mantoux reactions and migration inhibitions evident. The observed variability in migration areas, similar in the Mantoux‐positives and controls, was the result of technical causes and variations in cells’ ability to migrate. Further, in Mantoux‐positive persons the migration progression (per min) increased during the first 2 h, but slowed down later on, more in controls than in chamber with antigen. Smaller migration areas in controls (early intervals) tended to produce lower migration indices than the larger ones. Finally, it was possible, using the standard score c, to calculate whether each individual result differed significantly from controls. By this procedure the intensity of cell‐mediated immunity in individual patients could be estimated.
Systematic identification of trans eQTLs as putative drivers of known disease associations
Authors: Harm-Jan Westra, Marjolein J Peters, Tõnu Esko, Hanieh Yaghootkar, Claudia Schurmann, Johannes Kettunen, Mark W Christiansen, Benjamin P Fairfax, Katharina Schramm, Joseph E Powell, Alexandra Zhernakova, Daria V Zhernakova, Jan H Veldink, Leonard H Van den Berg, Juha Karjalainen, Sebo Withoff, André G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Peter A C 't Hoen, Eva Reinmaa, Krista Fischer, Mari Nelis, Lili Milani, David Melzer, Luigi Ferrucci, Andrew B Singleton, Dena G Hernandez, Michael A Nalls, Georg Homuth, Matthias Nauck, Dörte Radke, Uwe Völker, Markus Perola, Veikko Salomaa, Jennifer Brody, Astrid Suchy-Dicey, Sina A Gharib, Daniel A Enquobahrie, Thomas Lumley, Grant W Montgomery, Seiko Makino, Holger Prokisch, Christian Herder, Michael Roden, Harald Grallert, Thomas Meitinger, Konstantin Strauch, Yang Li, Ritsert C Jansen, Peter M Visscher, Julian C Knight, Bruce M Psaty, Samuli Ripatti, Alexander Teumer, Timothy M Frayling, Andres Metspalu, Joyce B J van Meurs, Lude Franke
Journal: Nature Genetics (2013)
Autoimmune Polyendocrine Syndrome Type 1 and NALP5, a Parathyroid Autoantigen
Authors: Mohammad Alimohammadi, Peyman Björklund, Åsa Hallgren, Nora Pöntynen, Gabor Szinnai, Noriko Shikama, Marcel P. Keller, Olov Ekwall, Sarah A. Kinkel, Eystein S. Husebye, Jan Gustafsson, Fredrik Rorsman, Leena Peltonen, Corrado Betterle, Jaakko Perheentupa, Göran Åkerström, Gunnar Westin, Hamish S. Scott, Georg A. Holländer, Olle Kämpe
Journal: New England Journal of Medicine (2008)

Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified.We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues.NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells.NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.
SiRNA-mediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogenic thrombospondin-1 and slows tumor vascularization and growth.
Authors: Stéphanie Filleur, Aurélie Courtin, Slimane Ait-Si-Ali, Julien Guglielmi, Carole Merle, Annick Harel-Bellan, Philippe Clézardin, Florence Cabon
Journal: Cancer Research (2003)

In the past few years, several laboratories have developed antiangiogenic molecules that starve tumors by targeting their vasculature and we have shown that, when produced in tumors, the antiangiogenic molecule thrombospondin-1 (TSP1) reduces the vascularization and delays tumor onset. Yet over time, tumor cells producing active TSP1 do eventually form exponentially growing tumors. These tumors are composed of cells secreting unusually high amounts of the angiogenic stimulator vascular endothelial growth factor (VEGF) that are sufficient to overcome the inhibitory TSP1. Here, we use short double-stranded RNA (siRNA) to trigger RNA interference and thereby impair the synthesis of VEGF and ask if this inability to produce VEGF prevents the development of TSP1 resistance. Systemic in vivo administration of crude anti-VEGF siRNA reduced the growth of unaltered fibrosarcoma tumor cells, and when the anti-VEGF siRNA was expressed from tumor cells themselves, such inhibition was synergistic with the inhibitory effects derived from TSP1 secretion by the tumor cells. Anti-VEGF siRNA delayed the emergence of TSP1-resistant tumors and strikingly reduced their subsequent growth rate.
Quantitative Effect of Gender, Age, Liver Function, and Body Size on the Population Pharmacokinetics of Paclitaxel in Patients with Solid Tumors
Authors: Markus Joerger, Alwin D.R. Huitema, Desiree H.J.G. van den Bongard, Jan H.M. Schellens, Jos H. Beijnen
Journal: Clinical Cancer Research (2006)

Abstract Background: The aim of this study was to quantitatively assess the effect of anthropometric and biochemical variables and third-space effusions on paclitaxel pharmacokinetics in solid tumor patients. Materials and Methods: Plasma concentration-time data of paclitaxel were collected in patients with non–small cell lung cancer (n = 84), ovarian cancer (n = 40), and various solid tumors (n = 44), totaling 168 patients. Paclitaxel was given as a 3-hour infusion (n = 163) at doses ranging from 100 to 250 mg/m2, or as a 24-hour infusion (n = 5) at a dose of 135 or 175 mg/m2. Data were analyzed using nonlinear mixed-effect modeling. Results: A three-compartment model with saturable elimination and distribution was used to describe concentration-time data. Male gender and body surface area were positively correlated with maximal elimination capacity of paclitaxel (VMEL); patient age and total bilirubin were negatively correlated with VMEL (P &amp;lt; 0.005 for all correlations). Typically, male patients had a 20% higher VMEL; a 0.2 m2 increase of body surface area led to a 9% increase of VMEL; a 10-year increase of patient age led to a 5% decrease of VMEL; and a 10-μmol increase of total bilirubin led to a 14% decrease of VMEL. Third-space effusions were not correlated with paclitaxel pharmacokinetics. Conclusions: This extended retrospective population analysis showed patient gender to significantly and independently affect paclitaxel distribution and elimination. Body surface area, total bilirubin, and patient age were confirmed to affect paclitaxel elimination. This pharmacokinetic model allowed quantification of the covariate effects on the elimination of paclitaxel and may be used for covariate-adapted paclitaxel dosing.
Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection
Authors: Pierre Guermonprez, Julie Helft, Carla Claser, Stephanie Deroubaix, Henry Karanje, Anna Gazumyan, Guillaume Darasse-Jèze, Stephanie B Telerman, Gaëlle Breton, Heidi A Schreiber, Natalia Frias-Staheli, Eva Billerbeck, Marcus Dorner, Charles M Rice, Alexander Ploss, Florian Klein, Melissa Swiecki, Marco Colonna, Alice O Kamphorst, Matthew Meredith, Rachel Niec, Constantin Takacs, Fadi Mikhail, Aswin Hari, David Bosque, Tom Eisenreich, Miriam Merad, Yan Shi, Florent Ginhoux, Laurent Rénia, Britta C Urban, Michel C Nussenzweig
Journal: Nature Medicine (2013)
Transforming growth factor beta 1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells.
Authors: T M McIntyre, D R Klinman, P Rothman, M Lugo, J R Dasch, J J Mond, C M Snapper
Journal: The Journal of Experimental Medicine (1993)

Bacterial lipopolysaccharide (LPS) has been reported to induce immunoglobulin (Ig)G2b class switching, yet we observed strain differences in IgG2b secretion in response to this mitogen. Specifically, BALB/c B cells, unlike those from DBA/2, synthesized relatively low amounts of IgG2b relative to IgG3, IgG1, or IgM. This report demonstrates that transforming growth factor (TGF) beta 1, previously shown to induce IgA class switching, selectively stimulates IgG2b secretion by BALB/c resting B cells activated with LPS. This activity was specifically reversed with a neutralizing anti-TGF-beta 1 antibody. The ability of TGF-beta 1 to act directly on highly purified membrane (m)IgM+ mIgG2b- cells to stimulate IgG2b production, stimulate an increase in IgG2b-secreting cells, and selectively increase the steady-state levels of germline gamma 2b RNA, suggests that it promotes IgG2b class switching. In this regard, addition of anti-TGF-beta antibody to cultures of DBA/2-derived resting B cells activated by LPS, alone, led to selective reduction in IgG2b secretion, indicating that endogenous TGF-beta 1 accounts for the high IgG2b secretory response observed in that strain. Finally, TGF-beta 1 failed to stimulate IgG2b secretion by B cells activated with dextran-conjugated anti-IgD antibody. We propose that TGF-beta 1 is a switch factor for the murine IgG2b subclass for appropriately activated B cells. In combination with other data, this would show that all six non-IgM, non-IgD isotypes in the mouse can be selectively induced by specific cytokines.