tbuckley/cabot-search huggingface dataset:
Genetic interaction in the susceptibility of rheumatoid arthritis
Authors: N. A. Daha, A. Willemze, D. B. Robinson, K. G. Oen, I. Smolik, D. Hart, W. Ghidey, J. J. Houwing-Duistermaat, K. Siminovitch, T. W. Huizinga, H. S. El-Gabalawy, R. E. Toes
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Introduction</h3> Recent advances have revolutionised the identification of genes underlying common diseases. For rheumatoid arthritis (RA), over 20 genes have been identified to associate to disease susceptibility. The strongest of these genetic associations is with particular genes within the human leucocyte antigen (HLA) region. To date, however, little is known about underlying relations between genes on a genetic level, which provides more insight into biological pathways involved. In the current study the authors investigated this for the strongly associated HLA region in a North American Native population. This population has a high RA prevalence rate with multicase families and, most importantly, a high prevalence of shared epitope alleles in the background population. <h3>Methods</h3> RA gene polymorphisms, identified previously,1 were genotyped in 333 North American Native RA patients, 295 first degree relatives and 490 unrelated controls. HLA-DRB1 alleles were tested by sequencing. Allele distribution was analysed using a χ<sup>2</sup> test with one degree of freedom and as interaction criteria departure from multiplicative effects was used. Significant associations were tested for replication in a Dutch RA population (n=918) and controls (n=1309). <h3>Results</h3> A significant association was detected for MMEL1-TNFRSF14 in the Native American population (OR 1.45, 95% CI 1.09 to 1.94, p=0.009), with a significant association in the shared epitope positive group and not in the shared epitope negative group (OR 1.66, 95% CI 1.20 to 2.30, p=0.002 and OR 0.85, 95% CI 0.47 to 1.55, p=0.60, respectively). Analysis in the Dutch population demonstrated a similar trend in RA association (shared epitope positive group: OR1.31, 95% CI 1.0 to 1.70, p=0.04; shared epitope negative group: OR 1.11, 95% CI 0.81 to 1.53, p=0.51), but significant statistical evidence for interaction could not be established. <h3>Conclusion</h3> In the current study the authors demonstrate a novel interaction between the HLA region and MMEL1-TNFRSF14 in a Native American population, with a similar trend in a Dutch population of RA patients. This interaction is particularly important since shared epitope alleles are highly present in the Native American population, yet most individuals stay disease free. This finding might give more insight into biological pathways involved in disease and therefore give rise to future therapeutic targets.
Influenza season in Réunion dominated by influenza B virus circulation associated with numerous cases of severe disease, France, 2014
Authors: E Brottet, D Vandroux, B A Gauzere, E Antok, M C Jaffar-Bandjee, A Michault, L Filleul
Journal: Eurosurveillance (2014)

Binary file ES_Abstracts_Final_ECDC.txt matches
Celecoxib and Mucosal Protection: Translation from an Animal Model to a Phase I Clinical Trial of Celecoxib, Irinotecan, and 5-Fluorouracil
Authors: Milind M. Javle, Shousong Cao, Farukh A. Durrani, Lakshmi Pendyala, David D. Lawrence, Patrick F. Smith, Patrick J. Creaven, Diane C. Noel, Renuka V. Iyer, Youcef M. Rustum
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Chemotherapy-induced diarrhea occurs secondary to mucosal inflammation and may be cyclooxygenase-2 mediated. Cyclooxygenase-2 inhibitors may ameliorate chemotherapy-induced mucosal toxicity and enhance its antitumor effect. We investigated this hypothesis in the Ward colorectal cancer rat model and in a phase I clinical study. Experimental Design: In the Ward rat model, irinotecan was given daily × 3 or weekly × 4 with or without celecoxib. In the phase I clinical study, we planned to escalate the dose of irinotecan in the FOLFIRI regimen (irinotecan, 5-fluorouracil, and leucovorin) with a fixed dose of celecoxib. Irinotecan was escalated in four dose levels: 180, 200, 220, and 260 mg/m2. Celecoxib was administered as 400 mg, twice daily starting on day 2 of cycle 1. Pharmacokinetics of irinotecan, SN-38, and SN-38G were obtained on days 1 and 14. A standard 3 + 3 dose escalation scheme was used. Plasma concentrations of irinotecan, SN-38, and SN-38G were measured using high-pressure liquid chromatography. Results: Celecoxib ameliorated diarrhea, weight loss, and lethality and resulted in synergistic antitumor effect in the rat model. Twelve patients with advanced cancers were enrolled and evaluable for dose-limiting toxicity (DLT). Diarrhea was the cause for discontinuation in one. Grade 2 and 3 diarrhea occurred in three and two patients, respectively. One patient had DLT at dose level 2 (grade 3 diarrhea). Two had a DLT at DL3 (G3 emesis and myocardial infarct). Celecoxib had limited influence on the pharmacokinetics of irinotecan in this data set. Conclusions: Maximum tolerated dose of irinotecan in FOLFIRI schedule with celecoxib is 200 mg/m2.
High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT
Authors: Katayoun Rezvani, Stephan Mielke, Mojgan Ahmadzadeh, Yasemin Kilical, Bipin N. Savani, Josette Zeilah, Keyvan Keyvanfar, Aldemar Montero, Nancy Hensel, Roger Kurlander, A. John Barrett
Journal: Blood (2006)
Overexpression of Stefin A in Human Esophageal Squamous Cell Carcinoma Cells Inhibits Tumor Cell Growth, Angiogenesis, Invasion, and Metastasis
Authors: Wendong Li, Fang Ding, Liyong Zhang, Zhongmin Liu, Yu Wu, Aiping Luo, Min Wu, Mingrong Wang, Qimin Zhan, Zhihua Liu
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Evidence is accumulating that an inverse correlation exists between stefin A level and malignant progression. The aim of this study is to investigate the role of stefin A in human esophageal squamous cell carcinoma cells and to evaluate the possibility of stefin A for cancer therapy. Experimental Design: We stably transfected stefin A cDNA into human EC9706 or KYSE150 esophageal squamous cell carcinoma cells. Subsequently, we evaluated the effect of stefin A overexpression on cell growth, cathepsin B activity, cell motility and invasion, tumor growth, and metastasis. Immunoanalysis was done to assess the expression of factor VIII and to support the localization of stefin A and cathepsin B. We also evaluated the effect of CA074Me, a selective membrane-permeant cathepsin B inhibitor. Results: Both transfection of stefin A and treatment with 10 μmol/L CA074Me significantly reduced cathepsin B activity and inhibited the Matrigel invasion. Combination of both further reduced cathepsin B activity and inhibited the Matrigel invasion. Overexpression of stefin A delayed the in vitro and in vivo growth of cells and significantly inhibited lung metastasis compared with 50% of lung metastasis in xenograft mice from EC9706 or empty vector cells. Transfection with stefin A showed a dramatic reduction of factor VIII staining in the tumors of xenograft mice. Conclusions: Our data strongly indicate that stefin A plays an important role in the growth, angiogenesis, invasion, and metastasis of human esophageal squamous cell carcinoma cells and suggest that stefin A may be useful in cancer therapy.
CNS or Bone Marrow Involvement As Risk Factors for Poor Survival in Post-Transplantation Lymphoproliferative Disorders in Children After Solid Organ Transplantation
Authors: Britta Maecker, Thomas Jack, Martin Zimmermann, Hashim Abdul-Khaliq, Martin Burdelski, Alexandra Fuchs, Peter Hoyer, Sabine Koepf, Ulrike Kraemer, Guido F. Laube, Dirk E. Müller-Wiefel, Heinrich Netz, Martin Pohl, Burkhard Toenshoff, Hans-Joachim Wagner, Michael Wallot, Karl Welte, Michael Melter, Gisela Offner, Christoph Klein
Journal: Journal of Clinical Oncology (2007)

Purpose To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. Patients and Methods A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. Results PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (&lt; 1 year). Conclusion Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.
Effective Prostate Cancer Chemopreventive Intervention with Green Tea Polyphenols in the TRAMP Model Depends on the Stage of the Disease
Authors: Vaqar Mustafa Adhami, Imtiaz Ahmad Siddiqui, Sami Sarfaraz, Sabih Islam Khwaja, Bilal Bin Hafeez, Nihal Ahmad, Hasan Mukhtar
Journal: Clinical Cancer Research (2009)

We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP.GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF)-I/IGF binding protein-3 and IGF signaling.Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common.Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.
Macrolide antibiotics in diffuse panbronchiolitis and in cystic fibrosis
Authors: D Spencer
Journal: European Respiratory Journal (1998)

Macrolide antibiotics in diffuse panbronchiolitis and in cystic fibrosisTo the Editor:I share the interest shown by EVERARD et al. [1] in the use of macrolide antibiotics in cystic fibrosis (CF).Some patients with chronic Pseudomonas colonization do appear to improve when given prolonged courses of azithromycin, and the possibility that this is due to an anti-inflammatory rather than an antibacterial effect is supported by the findings of MOLINARI et al.[2] that subinhibitory concentrations of this antibiotic inhibit pseudomonal virulence factors in vitro.Unfortunately, Everard's preliminary findings of a fall in sputum interleukin (IL)-8 levels with erythromycin treatment would appear to be nonsignificant given that a large study has demonstrated that sputum IL-8 levels in CF patients are log-normally distributed [3] rather than normally distributed as suggested by the figure in Everard's letter.
A nontumorigenic variant of FGF19 treats cholestatic liver diseases
Authors: Jian Luo, Brian Ko, Michael Elliott, Mei Zhou, Darrin A. Lindhout, Van Phung, Carmen To, R. Marc Learned, Hui Tian, Alex M. DePaoli, Lei Ling
Journal: Science Translational Medicine (2014)

Nontumorigenic FGF19 variants represent an effective approach for the prevention and treatment of cholestatic liver diseases.
A SYNTHETIC ACYL POLYSACCHARIDE AND THE HEMAGGLUTINATION ACTIVITY
Authors: Toru Tsumita, Masako Ohashi
Journal: The Journal of Experimental Medicine (1964)

From Mycobacterium tuberculosis, a serologically specific polysaccharide was purified. It contained mannose, arabinose, and a trace of glucose. It was not active in hemagglutination (HA) reaction. Partial acylation of the polysaccharide was carried out with palmitoylchloride, and the synthetic lipopolysaccharide contained 15.1 per cent of esterified palmitic acid. The synthetic lipopolysaccharide had hemagglutination activity and 0.5 microg was able to sensitize 1 ml of 2 per cent erythrocyte suspension; it had the same activity as the natural antigenic lipopolysaccharide. The same antibody in the antiserum was involved in the hemagglutination reaction with both the synthetic and natural lipopolysaccharides. The sensitizing activity of the synthetic lipopolysaccharide was completely neutralized by cholesterol. Model experiments showed that the lipid moiety of hemagglutination antigen was essential for the sensitization of erythrocytes. The mechanism of the hemagglutination reaction is discussed.
Oesophageal diverticula: principles of management and appraisal of classification.
Authors: J Borrie, R L Wilson
Journal: Thorax (1980)

In this paper we review a consecutive series of 50 oesophageal diverticula, appraise clinical features and methods of management, and suggest an improvement on the World Health Organization classification. The link between oesophageal diverticula and motor disorders as assessed by oesophageal manometry is stressed. It is necessary to correct the functional disorder as well as the diverticulum if it is causing symptoms. A revised classification could be as follows: congenital--single or multiple; acquired--single (cricopharyngeal, mid-oesophageal, epiphrenic other) or multiple (for example, when cricopharyngeal and mid-oesophageal present together, or when there is intramural diverticulosis.
Effects of Weight Loss and Long-Term Weight Maintenance With Diets Varying in Protein and Glycemic Index on Cardiovascular Risk Factors
Authors: Özlem Gögebakan, Angela Kohl, Martin A. Osterhoff, Marleen A. van Baak, Susan A. Jebb, Angeliki Papadaki, J. Alfredo Martinez, Teodora Handjieva-Darlenska, Petr Hlavaty, Martin O. Weickert, Claus Holst, Wim H.M. Saris, Arne Astrup, Andreas F.H. Pfeiffer
Journal: Circulation (2011)

We sought to separately examine the effects of either weight loss or diets varying in protein content and glycemic index without further changes in body weight on cardiovascular risk factors within the Diet, Obesity, and Genes study (DiOGenes).DiOGenes is a pan-European controlled dietary intervention study in 932 overweight adults who first lost body weight on an 8-week low-calorie diet and were then randomized to 1 of 5 ad libitum diets for 26 weeks. The diets were either high or low protein or high or low glycemic index in 4 combinations or control. Weight loss (-11.23 kg; 95% confidence interval, -11.54 to -10.92; P<0.001) reduced high-sensitivity C-reactive protein (-1.15 mg/L; 95% confidence interval, -1.30 to -0.41; P<0.001), low- and high-density lipoprotein cholesterol, triglycerides, and blood pressure. During the 26-week weight maintenance period in the intention-to-treat analysis, the further decrease of high-sensitivity C-reactive protein blood levels was -0.46 mg/L greater (95% confidence interval, -0.79 to -0.13) in the groups assigned to low-glycemic-index diets than in those on high-glycemic-index diets (P<0.001). Groups on low-protein diets achieved a -0.25 mg/L greater reduction in high-sensitivity C-reactive protein (95% confidence interval, -0.59 to -0.17) than those on high-protein diets (P<0.001), whereas lipid profiles and blood pressure were not differently affected.This large-scale intervention study clearly separates weight loss from dietary composition-related effects. Low-glycemic-index carbohydrates and, to a lesser extent, low-protein intake may specifically reduce low-grade inflammation and associated comorbidities in overweight/obese adults.http://www.clinicaltrials.gov. Unique identifier: NCT00390637.
Rehabilitation and acute exacerbations
Authors: C. Burtin, M. Decramer, R. Gosselink, W. Janssens, T. Troosters
Journal: European Respiratory Journal (2011)

Recent evidence indicates that acute exacerbations of chronic obstructive pulmonary disease aggravate the extrapulmonary consequences of the disease. Skeletal muscle dysfunction, a sustained decrease in exercise tolerance, enhanced symptoms of depression and fatigue are reported. Avoidance of physical activities is likely to be a key underlying mechanism and increases the risk of new exacerbations. Pulmonary rehabilitation is an intervention targeting these systemic consequences. Exercise strategies need to be adapted to the increased feelings of dyspnoea and fatigue. This review aims to describe the systemic consequences of acute exacerbations and compiles evidence for the feasibility and effectiveness of different rehabilitation strategies to counteract these consequences during and/or immediately after the acute phase of the exacerbation. Resistance training and neuromuscular electrical stimulation have been applied safely in frail, hospitalised patients and have the potential to prevent muscle atrophy. Comprehensive pulmonary rehabilitation, including general exercise training, can be implemented immediately after the exacerbation, leading to a reduction in hospital admissions and an increase in exercise tolerance and quality of life. Self-management strategies play a crucial role in changing disease-related health behaviour and preventing hospital admissions.
Assessment of the Potential Cross-Allergenicity between Hen's Egg Lysozyme and Recombinant Human Lysozyme
Authors: D.A. Moneret-Vautrin, C.M.N. Astier, P. Franck, M. Morisset, F. Codreanu, O. Roitel, S.L. Taylor, D.R. Bethell
Journal: Journal of Allergy and Clinical Immunology (2007)
Human Kallikrein 8 Protease Confers a Favorable Clinical Outcome in Non–Small Cell Lung Cancer by Suppressing Tumor Cell Invasiveness
Authors: Yuh-Pyng Sher, Cheng-Chung Chou, Ruey-Hwang Chou, Han-Ming Wu, Wun-Shaing Wayne Chang, Chun-Houh Chen, Pan-Chyr Yang, Cheng-Wen Wu, Chia-Li Yu, Konan Peck
Journal: Cancer Research (2006)

Abstract The human kallikrein 8 (KLK8) gene, a member of the human tissue kallikrein gene family, encodes a serine protease. The KLK8 protein (hK8) is known to be a favorable prognostic marker in ovarian cancer, but the biological basis of this is not understood. We found that overexpressing the KLK8 gene in highly invasive lung cancer cell lines suppresses their invasiveness. This role in invasiveness was further confirmed by the fact that inhibition of endogenous KLK8 expression with a specific short hairpin RNA reduced cancer cell invasiveness. In situ degradation and cell adhesion assays showed that proteins produced from KLK8 splice variants modify the extracellular microenvironment by cleaving fibronectin. DNA microarray experiments and staining of cells for actin filaments revealed that the degradation of fibronectin by hK8 suppresses integrin signaling and retards cancer cell motility by inhibiting actin polymerization. In addition, studies in a mouse model coupled with the detection of circulating tumor cells by quantitative PCR for the human Alu sequence showed that KLK8 suppresses tumor growth and invasion in vivo. Finally, studies of clinical specimens from patients with non–small cell lung cancer showed that the time to postoperative recurrence was longer for early-stage patients (stages I and II) with high KLK8 expression (mean, 49.9 months) than for patients with low KLK8 expression (mean, 22.9 months). Collectively, these findings show that KLK8 expression confers a favorable clinical outcome in non–small cell lung cancer by suppressing tumor cell invasiveness. (Cancer Res 2006; 66(24): 11763-70)
COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness
Authors: Saskia F. Heeringa, Gil Chernin, Moumita Chaki, Weibin Zhou, Alexis J. Sloan, Ziming Ji, Letian X. Xie, Leonardo Salviati, Toby W. Hurd, Virginia Vega-Warner, Paul D. Killen, Yehoash Raphael, Shazia Ashraf, Bugsu Ovunc, Dominik S. Schoeb, Heather M. McLaughlin, Rannar Airik, Christopher N. Vlangos, Rasheed Gbadegesin, Bernward Hinkes, Pawaree Saisawat, Eva Trevisson, Mara Doimo, Alberto Casarin, Vanessa Pertegato, Gianpietro Giorgi, Holger Prokisch, Agnès Rötig, Gudrun Nürnberg, Christian Becker, Su Wang, Fatih Ozaltin, Rezan Topaloglu, Aysin Bakkaloglu, Sevcan A. Bakkaloglu, Dominik Müller, Antje Beissert, Sevgi Mir, Afig Berdeli, Seza ϖzen, Martin Zenker, Verena Matejas, Carlos Santos-Ocaña, Placido Navas, Takehiro Kusakabe, Andreas Kispert, Sema Akman, Neveen A. Soliman, Stefanie Krick, Peter Mundel, Jochen Reiser, Peter Nürnberg, Catherine F. Clarke, Roger C. Wiggins, Christian Faul, Friedhelm Hildebrandt
Journal: Journal of Clinical Investigation (2011)

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease mechanisms remain obscure, and SRNS continues to be treatment refractory. Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping. Each mutation was linked to early-onset SRNS with sensorineural deafness. The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast. Furthermore, knockdown of Coq6 in podocyte cell lines and coq6 in zebrafish embryos caused apoptosis that was partially reversed by coenzyme Q10 treatment. In rats, COQ6 was located within cell processes and the Golgi apparatus of renal glomerular podocytes and in stria vascularis cells of the inner ear, consistent with an oto-renal disease phenotype. These data suggest that coenzyme Q10–related forms of SRNS and hearing loss can be molecularly identified and potentially treated.