tbuckley/cabot-search huggingface dataset:
No Increased Risk of Second Cancer After Radiotherapy in Patients Treated for Rectal or Endometrial Cancer in the Randomized TME, PORTEC-1, and PORTEC-2 Trials
Authors: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Ina M. Jürgenliemk-Schulz, Jan J. Jobsen, Iris D. Nagtegaal, Harm J.T. Rutten, Cornelis J.H. van de Velde, Carien L. Creutzberg, Corrie A.M. Marijnen
Journal: Journal of Clinical Oncology (2014)

This study investigated the long-term probability of developing a second cancer in a large pooled cohort of patients treated with surgery with or without radiotherapy (RT).All second cancers diagnosed in patients included in the TME, PORTEC-1, and PORTEC-2 trials were analyzed. In the TME trial, patients with rectal cancer (n = 1,530) were randomly allocated to preoperative external-beam RT (EBRT; 25 Gy in five fractions) or no RT. In the PORTEC trials, patients with endometrial cancer were randomly assigned to postoperative EBRT (46 Gy in 2-Gy fractions) versus no RT (PORTEC-1; n = 714) or EBRT versus vaginal brachytherapy (VBT; PORTEC-2; n = 427).A total of 2,554 patients were analyzed (median follow-up, 13.0 years; range 1.8 to 21.2 years). No differences were found in second cancer probability between patients who were treated without RT (10- and 15-year rates, 15.8% and 26.5%, respectively) and those treated with EBRT (10- and 15-year rates, 15.4% and 25.6%, respectively) or VBT (10-year rate, 14.9%). In the individual trials, no significant differences were found between treatment arms. All cancer survivors had a higher risk of developing a second cancer compared with an age- and sex-matched general population. The standardized incidence ratio for any second cancer was 2.98 (95% CI, 2.82 to 3.14).In this pooled trial cohort of > 2,500 patients with pelvic cancers, those who underwent EBRT or VBT had no higher probability of developing a second cancer than patients who were treated with surgery alone. However, patients with rectal or endometrial cancer had an increased probability of developing a second cancer compared with the general population.
Discovery of novel plasma protein biomarkers to predict imminent cystic fibrosis pulmonary exacerbations using multiple reaction monitoring mass spectrometry
Authors: Bradley S Quon, Darlene L Y Dai, Zsuzsanna Hollander, Raymond T Ng, Scott J Tebbutt, S F Paul Man, Pearce G Wilcox, Don D Sin
Journal: Thorax (2015)

<h3>Background</h3> Despite the significant morbidity and mortality related to pulmonary exacerbations in cystic fibrosis (CF), there remains no reliable predictor of imminent exacerbation. <h3>Objective</h3> To identify blood-based biomarkers to predict imminent (&lt;4 months from stable blood draw) CF pulmonary exacerbations using targeted proteomics. <h3>Methods</h3> 104 subjects provided plasma samples when clinically stable and were randomly split into discovery (n=70) and replication (n=34) cohorts. Multiple reaction monitoring mass spectrometry (MRM-MS) was used to measure 117 peptides (79 proteins) from plasma. Plasma proteins with differential abundance between subjects who did versus did not develop an imminent exacerbation were analysed and proteins with fold difference &gt;1.5 between the groups were included in an MRM-MS classifier model to predict imminent exacerbations. Performance characteristics were compared with clinical predictors and candidate plasma protein biomarkers. <h3>Results</h3> Six proteins were included in the final MRM-MS protein panel. The area under the curve (AUC) for the prediction of imminent exacerbations was highest for the MRM-MS protein panel (AUC 0.74) in comparison to FEV<sub>1</sub>% predicted (AUC 0.55) and the top candidate plasma protein biomarkers, including C-reactive protein (AUC 0.61) and interleukin-6 (AUC 0.60). The MRM-MS protein panel performed similarly in the replication cohort (AUC 0.73). <h3>Conclusions</h3> Using MRM-MS, a six-protein panel measured from plasma can distinguish individuals with versus without an imminent exacerbation. With further replication and assay development, this biomarker panel may be clinically applicable for prediction of exacerbations in individuals with CF.
Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine
Authors: K. Y. Tsang, S. Zaremba, C. A. Nieroda, M. Z. Zhu, J. M. Hamilton, J. Schlom
Journal: JNCI Journal of the National Cancer Institute (1995)

The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates.Our objective was to determine if rVCEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs.Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs.While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed.This study demonstrates for the first time (a) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (c) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis.These findings have implications in the development of specific second-generation cancer immunotherapy protocols.
Antigen Presentation in the Lung
Authors: PATRICK G. HOLT
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Studies from our laboratory and elsewhere have implicated populations of dendritic cells in lung and airway tissues as key regulators of both qualitative and quantitative aspects of T cell responses to local antigenic challenge. Under steady state conditions, they are specialized for uptake of antigen, and require additional maturation signals for full expression of their T cell-stimulating activity. Their functional phenotype appears to be controlled via a complex series of interactions with both bone marrow-derived, mesenchymal, and possibly neuroendocrine cells; failure(s) in one or more of these regulatory interactions may be important etiologic and/or pathogenic factors in a variety of respiratory immunoinflammatory disease.
Thymidylate Synthase But Not Excision Repair Cross-Complementation Group 1 Tumor Expression Predicts Outcome in Patients With Malignant Pleural Mesothelioma Treated With Pemetrexed-Based Chemotherapy
Authors: Luisella Righi, Mauro G. Papotti, Paolo Ceppi, Andrea Billè, Elisa Bacillo, Luca Molinaro, Enrico Ruffini, Giorgio V. Scagliotti, Giovanni Selvaggi
Journal: Journal of Clinical Oncology (2010)

Purpose The relationship between thymidylate synthase (TS) expression and outcome in patients with malignant pleural mesothelioma (MPM) treated with pemetrexed (P) was retrospectively evaluated. Patients and Methods Sixty histologically confirmed patients with MPM previously treated with P and platinum (45 of 60) or as single agent (15 of 60) were retrospectively considered. Eighty-one control patients with MPM not P-treated were also evaluated. TS and excision repair cross-complementation group 1 (ERCC1) gene expression levels were evaluated by real-time polymerase chain reaction and by immunohistochemistry using the H-score. Results Median TS H-score value was 90 (range, 5 to 240). A significant correlation between low TS protein expression and longer time to progression (TTP; 17.9 v 7.9 months; hazard ratio [HR], 2.05, 95% CI, 1.19 to 3.77; P = .02) or overall survival (OS; 30 v 16.7 months; HR, 2.38; 95% CI, 1.15 to 4.91; P = .019) was found when patients were divided according to median H-score. Conversely, TS mRNA levels were not significantly correlated with outcome. In platinum-treated patients (n = 45), no correlation was found with survival according to ERCC1 median H-score, but patients in the lower tertile had a significantly shorter survival (HR, 3.06; 95% CI, 1.08 to 8.69; P = .035). In control MPMs, TS had no prognostic role. At multivariate analysis, TS protein levels were the only independent prognostic factor for both TTP (HR, 2.71; 95% CI, 1.13 to 6.49; P = .02) and OS (HR, 6.91; 95% CI, 1.90 to 25.07; P = .003). Conclusion In patients with MPM treated with P-based chemotherapy, low TS protein levels are predictive of improved TTP and OS. The role of TS assessment is worth of prospective validation in future studies on MPM.
Rotavirus Vaccine — A Powerful Tool to Combat Deaths from Diarrhea
Authors: Mathuram Santosham
Journal: New England Journal of Medicine (2010)

Rotavirus infection, the leading cause of severe childhood diarrhea in both developed and developing countries, results in over half a million deaths each year.1 Currently, two rotavirus vaccines (Rotarix [GlaxoSmithKline Biologicals] and RotaTeq [Merck]) are licensed in many countries and used routinely in several. Until recently, available efficacy data were from developed and developing countries with relatively low mortality rates among children younger than 5 years of age. In this issue of the Journal, efficacy trials conducted in Africa by Madhi and colleagues2 and a postmarketing study conducted in Mexico by Richardson and colleagues3 are described. The data support the . . .
Quality of Life and Functional Outcomes 12 Months After Out-of-Hospital Cardiac Arrest
Authors: Karen Smith, Emily Andrew, Marijana Lijovic, Ziad Nehme, Stephen Bernard
Journal: Circulation (2014)

Background— Out-of-hospital cardiac arrest (OHCA) is a significant global health problem. There has been considerable investment in improving the emergency medical response to OHCA, with associated improvements in survival. However, concern remains that survivors have a poor quality of life. This study describes the quality of life of OHCA survivors at 1-year postarrest in Victoria, Australia. Methods and Results— Adult OHCA patients who arrested between 2010 and 2012 were identified from the Victorian Ambulance Cardiac Arrest Registry. Paramedics attended 15 113 OHCA patients of which 46.3% received an attempted resuscitation. Nine hundred and twenty-seven (13.2%) survived to hospital discharge of which 76 (8.2%) died within 12 months. Interviews were conducted with 697 (80.7%) patients or proxies, who were followed-up via telephone interview, including the Glasgow Outcome Scale–Extended, the 12-item short form health survey, and the EuroQol. The majority (55.6%) of respondents had a good recovery via the Glasgow Outcome Scale–Extended≥7 (41.1% if patients who died postdischarge were included and nonrespondents were assumed to have poor recovery). The mean EuroQol index score for respondents was 0.82 (standard deviation, 0.19), which compared favorably with an adjusted population norm of 0.81 (standard deviation, 0.34). The mean 12-item short form Mental Component Summary score for patients was 53.0 (standard deviation, 10.2), whereas the mean Physical Component Summary score was 46.1 (standard deviation, 11.2). Conclusions— This is the largest published study assessing the quality of life of OHCA survivors. It provides good evidence that many survivors have an acceptable quality of life 12 months postarrest, particularly in comparison with population norms.
Connexin Expression and Turnover
Authors: Jeffrey E. Saffitz, James G. Laing, Kathryn A. Yamada
Journal: Circulation Research (2000)

Abstract —Electrical activation of the heart requires current transfer from one cell to another via gap junctions, arrays of densely packed intercellular channels. The extent to which cardiac myocytes are coupled is determined by multiple mechanisms, including tissue-specific patterns of expression of diverse gap junction channel proteins (connexins), and regulatory pathways that control connexin synthesis, intracellular trafficking, assembly into channels, and degradation. Many connexins, including those expressed in the heart, have been found to turn over rapidly. Recent studies in the intact adult heart suggest that connexin43, the principal cardiac connexin, is surprisingly short-lived (half-life ≈1.3 hours). Both the proteasome and the lysosome participate in connexin43 degradation. Other ion channel proteins, such as those forming selected voltage-gated K + channels, may also exhibit rapid turnover kinetics. Regulation of connexin degradation may be an important mechanism for adjusting intercellular coupling in the heart under normal and pathophysiological conditions.
An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial
Authors: N. J. Greening, J. E. A. Williams, S. F. Hussain, T. C. Harvey-Dunstan, M. J. Bankart, E. J. Chaplin, E. E. Vincent, R. Chimera, M. D. Morgan, S. J. Singh, M. C. Steiner
Journal: BMJ (2014)

<b>Objective</b> To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status. <b>Design</b> Prospective, randomised controlled trial. <b>Setting</b> An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom. <b>Participants</b> 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193). <b>Main outcome measures</b> The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome. <b>Interventions</b> Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package. <b>Results</b> Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year. <b>Conclusion</b> Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months. Mortality at 12 months was higher in the intervention group. The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness. <b>Trial registration</b> Current Controlled Trials ISRCTN05557928.
Genetic and functional characterization of human pemphigus vulgaris monoclonal autoantibodies isolated by phage display
Authors: Aimee S. Payne, Ken Ishii, Stephen Kacir, Chenyan Lin, Hong Li, Yasushi Hanakawa, Kazuyuki Tsunoda, Masayuki Amagai, John R. Stanley, Don L. Siegel
Journal: Journal of Clinical Investigation (2005)

Pemphigus is a life-threatening blistering disorder of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein 3 (Dsg3) and Dsg1. Mechanisms of antibody pathogenicity are difficult to characterize using polyclonal patient sera. Using antibody phage display, we have isolated repertoires of human anti-Dsg mAbs as single-chain variable-region fragments (scFvs) from a patient with active mucocutaneous pemphigus vulgaris. ScFv mAbs demonstrated binding to Dsg3 or Dsg1 alone, or both Dsg3 and Dsg1. Inhibition ELISA showed that the epitopes defined by these scFvs are blocked by autoantibodies from multiple pemphigus patients. Injection of scFvs into neonatal mice identified 2 pathogenic scFvs that caused blisters histologically similar to those observed in pemphigus patients. Similarly, these 2 scFvs, but not others, induced cell sheet dissociation of cultured human keratinocytes, indicating that both pathogenic and nonpathogenic antibodies were isolated. Genetic analysis of these mAbs showed restricted patterns of heavy and light chain gene usage, which were distinct for scFvs with different desmoglein-binding specificities. Detailed characterization of these pemphigus mAbs should lead to a better understanding of the immunopathogenesis of disease and to more specifically targeted therapeutic approaches.
Estimating Pesticide Exposure from Dietary Intake and Organic Food Choices: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Cynthia L. Curl, Shirley A.A. Beresford, Richard A. Fenske, Annette L. Fitzpatrick, Chensheng Lu, Jennifer A. Nettleton, Joel D. Kaufman
Journal: Environmental Health Perspectives (2015)

Organophosphate pesticide (OP) exposure to the U.S. population is dominated by dietary intake. The magnitude of exposure from diet depends partly on personal decisions such as which foods to eat and whether to choose organic food. Most studies of OP exposure rely on urinary biomarkers, which are limited by short half-lives and often lack specificity to parent compounds. A reliable means of estimating long-term dietary exposure to individual OPs is needed to assess the potential relationship with adverse health effects.We assessed long-term dietary exposure to 14 OPs among 4,466 participants in the Multi-Ethnic Study of Atherosclerosis, and examined the influence of organic produce consumption on this exposure.Individual-level exposure was estimated by combining information on typical intake of specific food items with average OP residue levels on those items. In an analysis restricted to a subset of participants who reported rarely or never eating organic produce ("conventional consumers"), we assessed urinary dialkylphosphate (DAP) levels across tertiles of estimated exposure (n = 480). In a second analysis, we compared DAP levels across subgroups with differing self-reported organic produce consumption habits (n = 240).Among conventional consumers, increasing tertile of estimated dietary OP exposure was associated with higher DAP concentrations (p < 0.05). DAP concentrations were also significantly lower in groups reporting more frequent consumption of organic produce (p < 0.02).Long-term dietary exposure to OPs was estimated from dietary intake data, and estimates were consistent with DAP measurements. More frequent consumption of organic produce was associated with lower DAPs.
A Patient with Carminic Acid-Induced Anaphylaxis; Usefulness of the Basophil Activation Test
Authors: Naoya Sugimoto, Masao Yamaguchi, Yuko Nakase, Yusuke Tanaka, Hiroyuki Tashimo, Hidenori Arai, Hiroshi Akiyama, Hiroyuki Nagase, Ken Ohta
Journal: Journal of Allergy and Clinical Immunology (2013)
Update in Cardiology
Authors: Joseph S. Alpert
Journal: Annals of Internal Medicine (1996)

Updates from the Annual Session1 July 1996Update in CardiologyJoseph S. Alpert, MD and Melvin D. Cheitlin, MDJoseph S. Alpert, MDFrom Arizona Health Science Center, Tucson, Arizona, and San Francisco General Hospital, San Francisco, California. and Melvin D. Cheitlin, MDFrom Arizona Health Science Center, Tucson, Arizona, and San Francisco General Hospital, San Francisco, California.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-1-199607010-00007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Much of the recent research in cardiology has focused on the pathophysiology of coronary artery disease and the clinical implications that result from an understanding of that physiology, especially the implications surrounding the reduction of cholesterol levels. In addition, studies published in the past year have shown good evidence for the effectiveness of afterload reduction in patients with asymptomatic aortic regurgitation and of carefully monitored anticoagulation in patients with atrial fibrillation. Finally, a previously common practice in patients with myocarditis has been shown to have no effect on outcome.Acute Coronary Artery SyndromesDespite advances in both the prevention and ...References1. Guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. American College of Physicians. Part 1. Ann Intern Med. 1996; 124:515-7. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Arizona Health Science Center, Tucson, Arizona, and San Francisco General Hospital, San Francisco, California.Current Author Addresses: Dr. Alpert: Arizona Health Science Center, 1501 North Campbell Avenue, Room 6334, Tucson, AZ 85724. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCardiovascular Magnetic Resonance: Evaluation of Myocardial Function, Perfusion, and ViabilityIschemic heart diseaseContrast Media–Enhanced Magnetic Resonance Imaging Visualizes Myocardial Changes in the Course of Viral Myocarditis 1 July 1996Volume 125, Issue 1Page: 40-46KeywordsAtrial fibrillationCholesterolCoronary arteriesEjection fractionLow density lipoproteinMyocardial infarctionMyocarditisStable coronary artery diseaseThrombosisValve replacement Issue Published: 1 July 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Acute fulminating intrapulmonary haemorrhage in Wegener's granulomatosis.
Authors: T C Stokes, B G McCann, R T Rees, E H Sims, B D Harrison
Journal: Thorax (1982)

Diffuse pulmonary capillaritis is a rarely described feature of Wegener's granulomatosis.We report a case in which this appears to have been the cause of the acute fulminating course of the disease.Case report