tbuckley/cabot-search huggingface dataset:
The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population
Authors: Hubert Marotte, Beatrice Pallot-Prades, Laurent Grange, Jacques Tebib, Philippe Gaudin, Christian Alexandre, JL Blond, MA Cazalis, Bruno Mougin, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis α). <b>Methods:</b> In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by χ<sup>2</sup> testing and calculation of odds ratios (OR). <b>Results:</b> A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 <i>v</i> 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p&lt;0.001; OR 2 <i>v</i> 0 SE copy = 3.92 (2.65 to 5.80), p&lt;0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. <b>Conclusions:</b> This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.
Response to Letter Regarding Article, “Ischemic Preconditioning for Prevention of Contrast Medium–Induced Nephropathy: Randomized Pilot RenPro-Trial (Renal Protection Trial)”
Authors: Fikret Er, Amir M. Nia, Henning Dopp, Kristina M. Dahlem, Evren Caglayan, Erland Erdmann, Natig Gassanov, Martin Hellmich, Volker Burst, Torsten Kubacki, Thomas Benzing
Journal: Circulation (2013)

We thank the authors for their interest in our study on the impact of remote ischemic preconditioning on contrast medium-induced acute kidney injury (CI-AKI). 1he incidence of CI-AKI varies substantially among several studies because of the lack of a uniform definition of CI-AKI. 2 Rates of CI-AKI may be as high as 50% or even higher, depending on the presence of risk factors such as chronic renal insufficiency and diabetes mellitus.Although the definition of CI-AKI varies across the trials, the most commonly used definition includes an absolute increase in serum creatinine of 0.5 mg/dL or a 25% relative increase in serum creatinine from the baseline value at 48 hours after exposure to contrast agent in the absence of alternative causes of acute kidney injury. 2 This definition of CI-AKI was used consistently in our study. 1ndeed, several scores were established to predict adverse renal events after coronary intervention, yet the score developed by Mehran et al 3 remains the best validated to date. 4 According to the Mehran serum creatinine-based risk score development set (Figure 1 in the referred article 3 ), patients with a calculated risk score of 13 have an ≈40% risk of developing CI-AKI.Considering that the RenPro cohort displayed a mean risk score of 13, the CI-AKI rate of 40% in our control arm coincides exactly with the predicted risk for CI-AKI development.Calculation of the incidence of CI-AKI by combining a serum creatinine increase >25% and >0.5 mg/dL over the baseline did not change the reported outcomes significantly (34% in the control group versus 12% in the remote ischemic preconditioning arm; P=0.016).The different rates of CI-AKI in our study and in the trials cited by Drs Mehta-Oza and Raman 5,6 can be explained solely by the differences in the mean Mehran risk score, since our study group included predominantly high-risk patients with a higher-integer risk score.Furthermore, a different definition of CI-AKI (eg, the glomerular filtration rate-based definition in the report by Brar et al 5 ) along with the use of the different types and volumes of contrast media, population size, planned nature of the interventional procedure, and the different length of patient follow-up, may explain the varying CI-AKI rates.Nevertheless, the relevant difference in incidences among studies reveals the need for a uniform definition of CI-AKI to be used in clinical practice.In this respect, serum creatinine, although simple to obtain in clinical routine, is not reliable enough for identification of patients at risk for CI-AKI development.To evaluate renal function accurately, assessment of other renal markers, such as neutrophil gelatinase-associated lipocalin or cystatin C, might be a better choice.
A National Cancer Clinical Trials System for Targeted Therapies
Authors: John Mendelsohn
Journal: Science Translational Medicine (2011)

Today, modern technologies in genomics, biomarker detection, and molecular imaging are providing information that will enable physicians to select appropriate treatments for individual cancer patients from among more than 800 new experimental drugs and antibodies that target the products of the aberrant genes that can cause cancer. At this promising time in cancer research, the U.S. National Cancer Institute-sponsored collaborative clinical trials program needs an overhaul in its operations and an infusion of adequate funding. The process of clinical trial design, review for approval, and implementation must be streamlined to make it more efficient. Multiple stakeholders in the academic, governmental, and commercial sectors must better integrate their efforts. Improvements must be made in the incorporation of new technologies, prioritization, and timely completion of trials, and provision of financial support that covers actual costs. The result will be more rapid translation of recent scientific advances into increased benefits for patients with cancer.
Prospective study of occupational asthma to laboratory animal allergens: Stability of airway responsiveness to methacholine challenge for one year☆☆☆★★★
Authors: Carol A. Newill, Peyton A. Eggleston, Valerie L. Prenger, James E. Fish, Earl L. Diamond, Qingyi Wei, Richard Evans III
Journal: Journal of Allergy and Clinical Immunology (1995)
Definition, epidemiology and natural history of COPD
Authors: G. Viegi, F. Pistelli, D. L. Sherrill, S. Maio, S. Baldacci, L. Carrozzi
Journal: European Respiratory Journal (2007)

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for α 1 -antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.
Epstein-Barr virus-encoded EBNA1 enhances RNA polymerase III-dependent EBER expression through induction of EBER-associated cellular transcription factors
Authors: Thomas J Owen, John D O'Neil, Christopher W Dawson, Chunfang Hu, Xiaoyi Chen, Yunhong Yao, Victoria HJ Wood, Louise E Mitchell, Robert J White, Lawrence S Young, John R Arrand
Journal: Molecular Cancer (2010)

Abstract Background Epstein-Barr Virus (EBV)-encoded RNAs (EBERs) are non-polyadenylated RNA molecules transcribed from the EBV genome by RNA polymerase III (pol III). EBERs are the most abundant viral latent gene products, although the precise mechanisms by which EBV is able to achieve such high levels of EBER expression are not fully understood. Previously EBV has been demonstrated to induce transcription factors associated with EBER expression, including pol III transcription factors and ATF-2. We have recently demonstrated that EBV-encoded nuclear antigen-1 (EBNA1) induces cellular transcription factors, and given these findings, we investigated the role of EBNA1 in induction of EBER-associated transcription factors. Results Our data confirm that in epithelial cells EBNA1 can enhance cellular pol III transcription. Transient expression of EBNA1 in Ad/AH cells stably expressing the EBERs led to induction of both EBER1 and EBER2 and conversely, expression of a dominant negative EBNA1 led to reduced EBER expression in EBV-infected Ad/AH cells. EBNA1 can induce transcription factors used by EBER genes, including TFIIIC, ATF-2 and c-Myc. A variant chromatin precipitation procedure showed that EBNA1 is associated with the promoters of these genes but not with the promoters of pol III-transcribed genes, including the EBERs themselves. Using shRNA knock-down, we confirm the significance of both ATF-2 and c-Myc in EBER expression. Further, functional induction of a c-Myc fusion protein led to increased EBER expression, providing c-Myc binding sites upstream of EBER1 were intact. In vivo studies confirm elevated levels of the 102 kD subunit of TFIIIC in the tumour cells of EBV-positive nasopharyngeal carcinoma biopsies. Conclusions Our findings reveal that EBNA1 is able to enhance EBER expression through induction of cellular transcription factors and add to the repertoire of EBNA1's transcription-regulatory properties.
Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Systematic Review and Meta-Analysis
Authors: Tara M. Friebel, Susan M. Domchek, Timothy R. Rebbeck
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundThere is substantial variability in cancer risk in women who have inherited a BRCA1 or BRCA2 (BRCA1/2) mutation. Numerous factors have been hypothesized to modify these risks, but studies are of variable quality, and it remains unclear which of these may be of value in clinical risk assessment.
Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma
Authors: John K. Wiencke, Shichun Zheng, Nanette Jelluma, Tarik Tihan, Scott Vandenberg, Tanja Tamgüney, Rachel Baumber, Ramon Parsons, Kathleen R. Lamborn, Mitchel S. Berger, Margaret R. Wrensch, Daphne Adele Haas-Kogan, David Stokoe
Journal: Neuro-Oncology (2007)

Glioblastoma multiforme (GBM) can present as either de novo or secondary tumors arising from previously diagnosed low-grade gliomas. Although these tumor types are phenotypically indistinguishable, de novo and secondary GBMs are associated with distinct genetic characteristics. PTEN mutations, which result in activation of the phosphoinositide 3-kinase (PI3K) signal transduction pathway, are frequent in de novo but not in secondary GBMs or their antecedent low-grade tumors. Results we present here show that grade II astrocytomas, oligodendrogliomas, and oligoastrocytomas commonly display methylation of the PTEN promoter, a finding that is absent in nontumor brain specimens and rare in de novo GBMs. Methylation of the PTEN promoter correlates with protein kinase B (PKB/Akt) phosphorylation, reflecting functional activation of the PI3K pathway. Our results also demonstrate frequent methylation of the PTEN promoter in grade III astrocytomas and secondary GBMs, consistent with the hypothesis that these tumors arise from lower grade precursors. PTEN methylation is rare in de novo GBMs and is mutually exclusive with PTEN mutations. We conclude that methylation of the PTEN promoter may represent an alternate mechanism by which PI3K signaling is increased in grade II and III gliomas as well as secondary GBMs, a finding that offers new therapeutic approaches in these patients.
Insulin like growth factor-I, insulin like growth factor binding protein-1, and insulin in childhood Crohn's disease.
Authors: A G Thomas, J M Holly, F Taylor, V Miller
Journal: Gut (1993)

Twenty nine children with Crohn9s disease were studied before and after treatment with steroids or an elemental diet to assess the effect of disease activity and treatment on serum insulin like growth factor I (IGF-I), insulin like growth factor binding protein (IGFBP-1), and insulin concentrations. The median serum IGF-I concentration was lower in patients with active disease than in matched controls, and lower in stunted than well grown patients, but insulin and IGFBP-1 concentrations were not significantly different between any group. After four weeks of either treatment there was an increase in the median serum IGF-I concentration; this was greater in the steroid group than the elemental diet group. The median serum insulin concentration increased and median serum IGFBP-1 concentration decreased in the steroid treated group but not in the elemental diet group. These changes were accompanied by a greater and more sustained increase in energy intake in the steroid group. Despite this the median height velocity SD score was greater in the elemental diet group than in the steroid group.
Abstract 4203: EF24, a novel curcumin analogue inhibits oncogenic activation induced by radiation abscopal effect in distant mice lungs
Authors: Jamunarani Veeraraghavan, Mohan Natarajan, Vibhudutta Awasthi, Terence S. Herman, Natarajan Aravindan
Journal: Cancer Research (2011)

Abstract Ascertaining the ionizing radiation (IR)-induced carcinogenesis through an abscopal effect would raise a paradigm shift in our understanding of the radiobiological effects and radiation carcinogenesis. EF24, a synthetic analog of curcumin with improved physicochemical properties has been shown to possess potent anticancer activity, both in vitro as well as in vivo. In this study, we investigated the oncogenic activation after IR in an organ (lung) distant from the exposure field. C57/BL6 mice either mock irradiated, exposed to single dose IR (SDR: 2 or 10Gy) or fractionated IR (FIR, 2 Gy/day for 5 days) with or without EF24 (i.p. 200μg/Kg, 3h prior to IR) treatment were sacrificed 1h through 2 weeks post-irradiation. All IR exposures were limited to the lower abdomen area (1cm diameter), while the rest of the animal was protected by a specially designed cerrobend shield. DNA binding activity of AP-1, E2F1, cFOS and FRA1 were examined using EMSA analysis. Transcriptional activation of 88 oncogenes was assessed using QPCR profiling. Phosphorylation of CREB and JNK were examined using immunoblotting. Cellular localization of JunB, JunC and JunD were analyzed by immunohisto staining. IR significantly induced AP-1, E2F1, cFOS and FRA1 DNA binding activity in lungs distant from the exposure fields. EF24 completely and persistently (up to 2wks) suppressed IR-induced distant effect on AP-1, E2F1, cFOS and FRA1 DNA binding activity. Second, EF24 completely suppressed all 52, 31 and 64 oncogenes that were significantly upregulated after 2 Gy, 10Gy and 2Gyx5D exposures. We observed a similar inhibitory effect of oncogene transcriptome even after 2wk with EF24 treatment. Third, a profound increase in JunB, JunC and JunD levels observed in distant lung tissue after IR were significantly inhibited by EF24. Fourth, we observed a profound inhibition of IR-induced CREB phosphorylation with EF24 treatment in distant lungs. Taken together, these data clearly demonstrated an induced abscopal carcinogenic response in mice lungs after clinically relevant doses of IR exposure. The findings further imply that systemic administration of EF24 could potentially inhibit DNA binding activity, transactivation and translation of oncogenes and thereby mitigate IR-induced oncogenic activation at distant site. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4203. doi:10.1158/1538-7445.AM2011-4203
Influence of erdosteine, a mucolytic agent, on amoxycillin penetration into sputum in patients with an infective exacerbation of chronic bronchitis.
Authors: G Ricevuti, A Mazzone, E Uccelli, G Gazzani, G B Fregnan
Journal: Thorax (1988)

Twenty four patients with acute infective exacerbations of chronic bronchitis received amoxycillin alone or in combination with erdosteine (a mucolytic agent) for a week in a double blind, placebo controlled study. Clinical assessment scores, body temperature, serum and sputum amoxycillin concentrations, and sputum culture results were recorded in each group. Erdosteine significantly increased antibiotic concentrations in sputum but not in serum. The combined treatment also caused a more rapid decrease in sputum viscosity and in body temperature and faster sterilisation of the sputum. These results show that erdosteine increases amoxycillin concentration in sputum in patients with acute exacerbations of chronic bronchitis. This effect may be due to a reduction in the viscosity of the bronchial secretions produced by erdosteine.
Pulmonary veno-occlusive disease presenting with thrombosis of pulmonary arteries.
Authors: D S Katz, E M Scalzetti, A L Katzenstein, L J Kohman
Journal: Thorax (1995)

Pulmonary veno-occlusive disease is a rare cause of pulmonary hypertension. An unusual case presenting with thrombosis of the right pulmonary artery and serological evidence of autoimmunity is reported.
The Histone Demethylase JMJD2B Is Regulated by Estrogen Receptor α and Hypoxia, and Is a Key Mediator of Estrogen Induced Growth
Authors: Jun Yang, Adrian M. Jubb, Luke Pike, Francesca M. Buffa, Helen Turley, Dilair Baban, Russell Leek, Kevin C. Gatter, Jiannis Ragoussis, Adrian L. Harris
Journal: Cancer Research (2010)

Abstract Estrogen receptor α (ERα) plays an important role in breast cancer. Upregulation of HIF-1α in ERα-positive cancers suggests that HIF-1α may cooperate with ERα to promote breast cancer progression and consequently affect breast cancer treatment. Here, we show the histone demethylase JMJD2B is regulated by both ERα and HIF-1α, drives breast cancer cell proliferation in normoxia and hypoxia, and epigenetically regulates the expression of cell cycle genes such as CCND1, CCNA1, and WEE1. We also show that JMJD2B and the hypoxia marker CA9 together stratify a subclass of breast cancer patients and predict a worse outcome of these breast cancers. Our findings provide a biological rationale to support the therapeutic targeting of histone demethylases in breast cancer patients. Cancer Res; 70(16); 6456–66. ©2010 AACR.
Tissue-Penetrating Delivery of Compounds and Nanoparticles into Tumors
Authors: Kazuki N. Sugahara, Tambet Teesalu, Priya Prakash Karmali, Venkata Ramana Kotamraju, Lilach Agemy, Olivier M. Girard, Douglas Hanahan, Robert F. Mattrey, Erkki Ruoslahti
Journal: Cancer Cell (2009)
Macrophage/monocyte receptor for nonenzymatically glycosylated protein is upregulated by cachectin/tumor necrosis factor.
Authors: H Vlassara, L Moldawer, B Chan
Journal: Journal of Clinical Investigation (1989)

Proteins of extracellular matrix undergo over time multiple reactions with glucose to form advanced glycosylation endproducts (AGEs) which are highly active in protein crosslinking, and have been implicated in tissue damage associated with aging and diabetes. A macrophage/monocyte receptor for AGE moieties mediates the uptake of AGE-modified proteins by a process that also induces cachectin/tumor necrosis factor (TNF) and IL-1 secretion. Reasoning that cytokines might regulate this AGE-receptor system, we have evaluated the effect of cachectin/TNF, IL-1, and IFN-gamma on AGE-protein processing. We report that cachectin/TNF induced a severalfold enhancement of binding, endocytosis, and degradation of AGE-BSA by both murine peritoneal macrophages and human blood monocytes in vitro, and that cachectin/TNF enhanced the rate of disappearance of AGE-modified red blood cells in vivo. IL-1 and IFN-gamma alone did not increase AGE processing, but IFN-gamma consistently enhanced cachectin/TNF-induced changes in AGE-receptor kinetics. Similar effects were induced by AGE-BSA and FFI-BSA, a chemically synthesized AGE, when used as macrophage stimulants, possibly via cachectin/TNF induction. All upregulatory responses were blocked by anticachectin/TNF monoclonal antibody. These data suggest that AGE-induced cachectin/TNF, in addition to influencing tissue regeneration and remodelling, may also normally regulate the disposal of tissue damaging AGE-proteins through an autocrine upregulation.
Aspects of psychology in sports medicine.
Authors: M Greenspan, P Fitzsimmons, S Biddle
Journal: British Journal of Sports Medicine (1991)

Psychology's impact as an ergogenic aid across sports and competitive levels has been well documented. In addition, exercise can play a major role in disease prevention and health enhancement while also enhancing psychological well-being. In addition to its preventive value, exercise is being recognized as a valuable therapeutic tool. Like most therapeutic modalities, however, exercise also has some potentially negative qualities.
Exploring Breast Cancer Estrogen Disposition: The Basis for Endocrine Manipulation
Authors: Per E. Lønning, Ben P. Haynes, Anne H. Straume, Anita Dunbier, Hildegunn Helle, Stian Knappskog, Mitch Dowsett
Journal: Clinical Cancer Research (2011)

Although normal breast tissue and breast cancer estrogens are known to be elevated compared with plasma estrogen levels, the mechanism behind this phenomenon has been an issue of debate for 2 decades. If local estrogen aromatization were to be confirmed as the main estrogen source in breast cancer tissue, tissue-specific inhibition of estrogen production, avoiding systemic side effects, would become a potentially attractive option for breast cancer treatment and prevention. Based on recent results from our groups exploring tissue estrogens, together with estrogen-synthesizing and estrogen-regulated gene expression levels, we propose a new model to explain elevated breast tissue estrogen levels. Although local estrogen production may be important, the local contribution is overruled by rapid plasma-to-tissue equilibration, including active uptake of circulating estrogens or enhanced tissue binding. As for breast cancer tissue levels, elevated levels of estradiol may be explained to a large extent by estrogen receptor binding and local conversion of estrone into estradiol. This model indicates that effective suppression of benign and malignant tissue estrogens as a treatment for ER+ breast cancer requires systemic suppression and will not be markedly affected by local enzyme targeting.