tbuckley/cabot-search huggingface dataset:
PTH-060 An assessment of quality of, and factors affecting, oesophagogastroduodenoscopy (OGD)
Authors: David Tai, Gloria SZ Tun, Mustafa Jalal, Stefania Chetcuti Zammit, Mark McAlindon
Journal: Endoscopy (2018)

<h3>Introduction</h3> Oesophagogastroduodenoscopy (OGD) is the accepted gold standard investigation for upper GI symptoms although quality has rarely been assessed. In this study, quality of OGD and the effects of sedation, procedural tolerance and duration of examination were investigated. <h3>Methods</h3> Consecutive out-patients undergoing OGD were recruited. Patients scored (none-severe: 0–10) procedural distress, abdominal discomfort (AD) and pain (AP). Video recordings of the OGDs were reviewed, scoring the views (score 1–5:&lt;25%, 25%–50%, 50%–75%,&gt;75% and 100% of mucosa seen) of eight upper GI stations and time spent in retroflexion and in the duodenum. Scores and times are reported as mean (±SEM). <h3>Results</h3> OGD was performed on forty patients (58±3 years old, 62.5% male, 25% sedated) by one of three endoscopists. There was a significant difference between visualisation scores (oesophagus, 4.5 (±0.1); gastro-oesophageal junction, 4.5 (±0.1); cardia, 4.0 (±0.2); fundus, 3.7 (±0.2); upper body, 3.8 (±0.1); distal body, 4.1 (±0.1); incisura, 4.0 (±0.2) and antrum, 4.9 (±0.1); Kruskal-Wallis H Test: H(7)=60.2; p&lt;0.001). Post-hoc analysis shows that the antrum was better visualised compared to all other gastric stations (p&lt;0.001). When composite scores of fundus, antrum and upper body are compared to the distal body, incisura and antrum, views in the distal half of the stomach are significantly better visualised (χ<sup>2</sup>=520, p=0.006). Procedural distress, AD and AP were 4.9 (±0.5), 2.8 (±0.5) and 1.3 (±0.3) respectively: none correlated with views in any station apart from those with more procedural AD who had poorer views of the distal gastric body (r=-0.36 p=0.017). Sedation had no effect on distress, discomfort or pain or views of any station. Procedure time was 5 m 41 s (±18) with 55 s (±5) spent in retroflexion and 58 s (±9) in the duodenum, none of which correlated with any visualisation scores. Time spent in the duodenum correlated with increasing procedural AP (r=0.415, p=0.009). Patients (25%) who said they would decline repeat OGD reported significantly greater AP (3.0±0.9 vs 0.7±0.3) and procedural distress (7.7±0.5 vs 4.0±0.6), but their visualisation scores, procedural times or use of sedation did not differ from those who would have a repeat test. <h3>Conclusion</h3> Visualisation at OGD is variable, with excellent antral but comparatively poorer proximal gastric and incisura views. OGD is the cause of significant distress to patients, rather than discomfort or pain, although duodenal examination may be painful in some. There was little correlation of quality of views with sedation, tolerance or duration of examination.
Graft-versus-host disease, but not graft-versus-leukemia immunity, is mediated by GM-CSF–licensed myeloid cells
Authors: Sonia Tugues, Ana Amorim, Sabine Spath, Guillaume Martin-Blondel, Bettina Schreiner, Donatella De Feo, Mirjam Lutz, Franco Guscetti, Petya Apostolova, Claudia Haftmann, Peter Hasselblatt, Nicolas G. Núñez, Michael O. Hottiger, Maries van den Broek, Markus G. Manz, Robert Zeiser, Burkhard Becher
Journal: Science Translational Medicine (2018)

Allogeneic hematopoietic cell transplantation (allo-HCT) not only is an effective treatment for several hematologic malignancies but can also result in potentially life-threatening graft-versus-host disease (GvHD). GvHD is caused by T cells within the allograft attacking nonmalignant host tissues; however, these same T cells mediate the therapeutic graft-versus-leukemia (GvL) response. Thus, there is an urgent need to understand how to mechanistically uncouple GvL from GvHD. Using preclinical models of full and partial MHC-mismatched HCT, we here show that the granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by allogeneic T cells distinguishes between the two processes. GM-CSF drives GvHD pathology by licensing donor-derived phagocytes to produce inflammatory mediators such as interleukin-1β and reactive oxygen species. In contrast, GM-CSF did not affect allogeneic T cells or their capacity to eliminate leukemic cells, retaining undiminished GvL responses. Last, tissue biopsies and peripheral blood mononuclear cells from patients with grade IV GvHD showed an elevation of GM-CSF-producing T cells, suggesting that GM-CSF neutralization has translational potential in allo-HCT.
A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers
Authors: Tonći Šuštić, Sake van Wageningen, Evert Bosdriesz, Robert J. D. Reid, John Dittmar, Cor Lieftink, Roderick L. Beijersbergen, Lodewyk F. A. Wessels, Rodney Rothstein, René Bernards
Journal: Genome Medicine (2018)

Abstract Background Mutations in KRAS are frequent in human cancer, yet effective targeted therapeutics for these cancers are still lacking. Attempts to drug the MEK kinases downstream of KRAS have had limited success in clinical trials. Understanding the specific genomic vulnerabilities of KRAS -driven cancers may uncover novel patient-tailored treatment options. Methods We first searched for synthetic lethal (SL) genetic interactions with mutant RAS in yeast with the ultimate aim to identify novel cancer-specific targets for therapy. Our method used selective ploidy ablation, which enables replication of cancer-specific gene expression changes in the yeast gene disruption library. Second, we used a genome-wide CRISPR/Cas9-based genetic screen in KRAS mutant human colon cancer cells to understand the mechanistic connection between the synthetic lethal interaction discovered in yeast and downstream RAS signaling in human cells. Results We identify loss of the endoplasmic reticulum (ER) stress sensor IRE1 as synthetic lethal with activated RAS mutants in yeast. In KRAS mutant colorectal cancer cell lines, genetic ablation of the human ortholog of IRE1 , ERN1 , does not affect growth but sensitizes to MEK inhibition. However, an ERN1 kinase inhibitor failed to show synergy with MEK inhibition, suggesting that a non-kinase function of ERN1 confers MEK inhibitor resistance. To investigate how ERN1 modulates MEK inhibitor responses, we performed genetic screens in ERN1 knockout KRAS mutant colon cancer cells to identify genes whose inactivation confers resistance to MEK inhibition. This genetic screen identified multiple negative regulators of JUN N-terminal kinase (JNK) /JUN signaling. Consistently, compounds targeting JNK/MAPK8 or TAK1/MAP3K7, which relay signals from ERN1 to JUN, display synergy with MEK inhibition. Conclusions We identify the ERN1-JNK-JUN pathway as a novel regulator of MEK inhibitor response in KRAS mutant colon cancer. The notion that multiple signaling pathways can activate JUN may explain why KRAS mutant tumor cells are traditionally seen as highly refractory to MEK inhibitor therapy. Our findings emphasize the need for the development of new therapeutics targeting JUN activating kinases, TAK1 and JNK, to sensitize KRAS mutant cancer cells to MEK inhibitors.
Adaptive cellular defense against inflammatory stress induced by Helicobacter pylori: Role of Nrf2
Authors: Jeong-Sang Lee, Ki-Baik Hahm, Jeffrey Johnson, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2008)

4921  Accumulating evidence from preclinical and clinical studies suggest that chronic infection and inflammation contribute the carcinogenesis. Helicobacter pylori infection has been implicated in gastritis and peptic ulcer, which can eventually progress to gastric cancer. However, in a long-term study conducted in a wild-type mouse model, H. pylori infection itself did not induce gastric cancer. To elucidate the mechanisms underlying this discrepancy, we investigated the molecular mechanisms responsible for H. pylori-induced inflammatory responsein human gastric cancer (AGS) cells and genetically engineered animal models. Infection of AGS cells with H. pylori up-regulated the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase, enhanced secretion of interleukin-8, and increased phosphorylation of ERK. The nuclear translocation and subsequent DNA binding of NF-kappaB, which is known to regulate pro-inflammatory gene expression, were augmented after H. pylori treatment. The DNA binding of AP-1 and the expression of c-Jun and phospho-c-Jun were also induced by H. pylori infection. A wide array of phase II detoxifying or antioxidant enzymes constitutes a fundamental cellular defense system against oxidative and proinflammatory insults. Treatment of AGS cells with H. pylori resulted in elevated expression of heme oxygenase-1 (HO-1) mRNA and protein, which is one of the major cellular antioxidant enzymes. The immunofluorescence staining, using an FITC-conjugated HO-1 antibody, verified the elevated localization of HO-1 protein in the cytoplasm after H. pylori treatment. The H. pylori treatment enhanced antioxidant response element (ARE) binding of Nrf2, a redox-sensitive transcription factor responsible for regulating expression of many antioxidant and detoxifying genes, including ho-1. Chromatin-immunoprecipitation and ARE-luciferase reporter gene assays revealed that H. pylori treatment induced Nrf2 binding to the ARE site and that the binding site is located at -0.5 kB of human ho-1 promoter region. After repeated H. pylori inoculation (x 3), mouse stomach tissues were collected at 16 weeks. Following inoculation at 1, 4, 8 and 16th week of H. pylori inflammation was evident in gastric mucosa, and there was the ARE activation in mouse stomach as monitored by utilizing ARE transgenic reporter mice. Analysis of stomach tissues collected from Nrf-2-/-, Nrf-2+/- and Nrf-2+/+ mice infected with H. pylori for 16 weeks revealed that H. pylori-induced inflammation was aggravated in Nrf2 knock-out mice than in hetero and wild-type mice. Taken together, H. pylori infection can trigger the proinflammatory response through up-regulation of COX-2, which provokes adaptive cellular defense response through Nrf2-mediated upregulation of antioxidant enzyme, such as HO-1, thereby protecting cells and tissues against subsequent prooxidative and proinflammatory insults.
Abstract 18461: Myocardial Infarction With Normal Coronary Angiography and Computed Tomography Angiography
Authors: Georgios Panayi, Wouter G Wieringa, Gabija Pundziute, Joakim Alfredsson, Jan Engvall, Anders Persson, Eva Swahn
Journal: Circulation (2013)

Background: Three to five percent of patients, who fulfil the criteria for AMI, have angiographically normal coronary arteries. The mechanisms that cause AMI in the patient with no visible coronary atherosclerosis on the invasive coronary angiography (ICA) are still debatable. The aim of this study was to assess the presence and characteristics of atherosclerotic plaques on computed tomography coronary angiography (CTCA) in patients with AMI who have no visible coronary plaques on ICA. Methods and Results: Patients with AMI without visible coronary plaques on ICA underwent CTCA within three days after ICA. 30 patients were enrolled in the study. According to local routine, echocardiography was performed in the majority (26/30) of patients. Twenty-eight patients presented with NSTEMI and two with STEMI. Mean age of the study population was 60.2 years and 23/30 were women. A total number of 452 coronary segments were analysed. A total of 24/30 (80%) patients had normal coronary arteries and 6 patients had coronary atherosclerosis on CTCA. In case of atherosclerosis, the median number of segments with plaque per patient was one. 12/26 patients had completely normal echocardiography results, 11/26 patients had only wall motion abnormalities (WMA), 2/26 patients had WMA with minimal pericardial effusion and 1 patient had only minimal pericardial effusion. Conclusions: Despite a diagnosis of AMI, the majority of patients (80%) with a completely normal ICA showed no coronary plaques on CTCA. The remaining 20% of patients had only minimal non-obstructive atherosclerosis. The previously proposed mechanism of AMI due to rupture of a non-obstructive-, invisible on ICA-, plaque could only account for a minority (20%) of this study population. Our data suggest that most patients either had AMI caused by a mechanism not involving plaque rupture or did not have an infarction at all. Having in mind what consequences a diagnosis of AMI confers to the patient it is reasonable to extend the diagnostic evaluation of these patients to cardiac MRI for excluding myocarditis and/or intravascular imaging (optical coherence tomography or intravascular ultrasound) to provide information about some mechanisms of coronary damage (i.e. dissection).
Maternal history of miscarriages and measures of fertility in relation to childhood asthma
Authors: Maria Christine Magnus, Øystein Karlstad, Christine Louise Parr, Christian M Page, Per Nafstad, Per Magnus, Stephanie J London, Allen J Wilcox, Wenche Nystad, Siri Eldevik Håberg
Journal: Thorax (2018)

Background It remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (ART). Objective Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between ART and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. Methods We used data from national Norwegian health registries (n=474 402) and the Norwegian Mother and Child Cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. Results ART offspring had greater asthma risk, the adjusted relative risk (aRR) was 1.20 (95% CI 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% CI 1.14 to 1.76) in MoBa. The sibling analysis yielded similar associations, although the CI included the null value. The elevated asthma risk among ART offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception &gt;12 months, aRR 1.22 (95% CI 0.95 to 1.57). Asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an aRR of 1.07 (95% CI 1.03 to 1.11) for one, aRR 1.18 (95% CI 1.10 to 1.26) for two and aRR 1.24 (95% CI 1.12 to 1.37) for three or more. Conclusion Our findings indicate that both parental subfertility and characteristics related to the ART procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis.
Mice Lacking Monoacylglycerol Lipase Are Protected from Hepatic Inflammation and Biliary Fibrosis in Ddc-Induced Sclerosing Cholangitis.
Authors: Matteo Tardelli, Francesca Virginia Bruschi, Thierry Claudel, Claudia Daniela Fuchs, Nicole Auer, Victoria Kunczer, Tatjana Stojakovic, Onne A. H. O. Ronda, Henkjan J. Verkade, Sophie Lotersztajn, Michael H. Trauner
Journal: Hepatology (2018)
Lung function and oral health in adolescents
Authors: Joachim Heinrich, Elisabeth Thiering, Rudolf A. Jörres, Holger Schulz, Jan Kühnisch, Marie Standl
Journal: European Respiratory Journal (2018)

Only a few studies have investigated the association between periodontal diseases (PD), such as gingivitis or periodontitis, and lung health. The latest systematic review identified 14 observational studies and reported a pooled OR of 2.08 (95% CI 1.48–2.91) for chronic obstructive pulmonary disease (COPD) [1]. More recent studies have confirmed the adverse effects of oral inflammation on lung disease [2], but not all [3]. Three interventional trials in adults showed the positive effects of periodontal therapy on lung function in patients with COPD. Poor oral health is associated with poor lung function in adolescents <http://ow.ly/h2Yw30n4B9A> We thank all participants and their families for taking part in the study, the obstetric units for allowing recruitment and the GINIplus and LISA study team for its excellent work. The GINIplus 15 Study Group was made up of the following: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany (J. Heinrich, I. Brüske, H. Schulz, M. Standl, M. Schnappinger, M. Ferland, E. Thiering, C. Tiesler, C. Flexeder and C. Zeller); Dept of Pediatrics, Marien Hospital Wesel, Research Institute, Wesel, Germany (D. Berdel, A. von Berg and B. Filipiak-Pittroff); Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (S. Koletzko and K. Werkstetter); Dept of Pediatrics, Technical University of Munich, Munich, Germany, and Deutsche Rentenversicherung Bayern Süd (C.P. Bauer and U. Hoffmann); and IUF – Leibniz Research Institute for Environmental Medicine, Dusseldorf, Germany (T. Schikowski, E. Link, C. Klümper, U. Krämer and D. Sugiri). The LISA 15 Study Group was made up of the following: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany (J. Heinrich, I. Brüske, H. Schulz, M. Standl, M. Schnappinger, M. Ferland, E. Thiering, C. Tiesler, C. Flexeder and C. Zeller); Dept of Pediatrics, Research Institute, Marien Hospital Wesel, Wesel, Germany (A. von Berg); Pediatric Practice, Bad Honnef, Germany (G. Schaaf); Dept of Pediatrics, Technical University Munich, Munich, Germany (U. Hoffmann); Dept of Environmental Immunology/Core Facility Studies, Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany (I. Lehmann, M. Bauer, G. Herberth, J. Müller, S. Röder and M. Schilde); Dept of Pediatrics, Municipal Hospital "St. Georg", Leipzig, Germany (M. Borte, U. Diez, C. Dorn and E. Braun); and ZAUM – Center for Allergy and Environment, Technical University of Munich, Munich, Germany (M. Ollert and J. Grosch).
Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin
Authors: Sanaz Javanmardi, Ali Mohammad Tamaddon, Mahmoud Reza Aghamaali, Ladan Ghahramani, Samira Sadat Abolmaali
Journal: Asian Journal of Pharmaceutical Sciences (2018)

A series of branched polyethylenimine (PEI) modifications including PEGylation (PEG2k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2k-PEI-ss nanogels and subsequent carboxymethylation (PEG2k-CMPEI-ss) for modulation of the polymer pk
Artificial Pancreas Improves Glycemic Control
Authors: Anita Slomski
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Functional genetic variations in CTLA-4 and susceptibility to multiple types of cancer
Authors: Dongxin Lin, Tong Sun, Yifeng Zhou, Ming Yang, Yingli Guo, Xiaohong Han, Yuankai Shi, Jiarui Yao, Wen Tan, Dianke Yu, Dan Zhao, Junniao Liu
Journal: Cancer Research (2008)

4687  Anti-tumor T lymphocytes play a pivotal role in immune surveillance of cancer cells. The cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a vital negative regulator of T lymphocyte activation and proliferation, which may influence immune surveillance of malignancies. We tested whether genetic variantsin the CTLA-4 gene are associated with cancer susceptibility. Using a haplotype-tagging SNP approach, we found that the 49G>A polymorphism in the CTLA-4leading sequence causing Ala17 to Thr17 amino acid substitution, is associated with increased risk of lung cancer. Biochemical analyses showed thatCTLA-4-Thr17 had higher affinity to bind B7.1 molecule and had stronger inhibitory effect on T lymphocyte activation compared with CTLA-4-Ala17. T lymphocytes carrying the 49AA genotype had significantly lower activation and proliferation rates compared with T lymphocytes carrying the 49GG genotype upon stimulated with PHA ex vivo. Case-control analyses of 4,446 individuals with cancer and 4,433 controls in a Chinese population showed that this genetic variant is associated with increased susceptibility to multiple types of cancer, including lung, esophageal, gastric cardia, pancreatic, breast, and cervical cancers, acting in an allele dose-dependent manner. The odds ratios of overall cancer were 1.92 (95% CI = 1.64-2.25) for the 49AA genotype and 1.26 (95% CI = 1.15-1.37) for the 49GA genotype. These results support the hypothesis that genetic variants influencing T lymphocyte activation and proliferation modify cancer susceptibility.
A Focus on Patient-Centered Care Required to Address the Trauma of Hospitalization
Authors: Cynthia J. Brown
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal