tbuckley/cabot-search huggingface dataset:
Nicotine, IFN-γ and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades
Authors: Sateesh Kunigal, Moorthy P Ponnusamy, Navneet Momi, Surinder K Batra, Srikumar P Chellappan
Journal: Molecular Cancer (2012)

Abstract Background The membrane-bound mucins are thought to play an important biological role in cell–cell and cell–matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce the expression of MUC4 in pancreatic cancer cell lines CD18, CAPAN2, AsPC1 and BxPC3. Results Chromatin immunoprecipitation assays and real-time PCR showed that transcription factors E2F1 and STAT1 can positively regulate MUC4 expression at the transcriptional level. IFN-γ and RA could collaborate with nicotine in elevating the expression of MUC4, utilizing E2F1 and STAT1 transcription factors. Depletion of STAT1 or E2F1 abrogated the induction of MUC4; nicotine-mediated induction of MUC4 appeared to require α7-nicotinic acetylcholine receptor subunit. Further, Src and ERK family kinases also mediated the induction of MUC4, since inhibiting these signaling molecules prevented the induction of MUC4. MUC4 was also found to be necessary for the nicotine-mediated invasion of pancreatic cancer cells, suggesting that induction of MUC4 by nicotine and other agents might contribute to the genesis and progression of pancreatic cancer. Conclusions Our studies show that agents that can promote the growth and invasion of pancreatic cancer cells induce the MUC4 gene through multiple pathways and this induction requires the transcriptional activity of E2F1 and STAT1. Further, the Src as well as ERK signaling pathways appear to be involved in the induction of this gene. It appears that targeting these signaling pathways might inhibit the expression of MUC4 and prevent the proliferation and invasion of pancreatic cancer cells.
Implications of LINE1 Methylation for Bladder Cancer Risk in Women
Authors: Charlotte S. Wilhelm, Karl T. Kelsey, Rondi Butler, Silvia Plaza, Luc Gagne, M. Scot Zens, Angeline S. Andrew, Steven Morris, Heather H. Nelson, Alan R. Schned, Margaret R. Karagas, Carmen J. Marsit
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Epigenetic alterations including changes to cellular DNA methylation levels contribute to carcinogenesis and may serve as powerful biomarkers of the disease. This investigation sought to determine whether hypomethylation at the long interspersed nuclear elements (LINE1), reflective of the level of global DNA methylation, in peripheral blood–derived DNA is associated with increased risk of bladder cancer. Experimental Design: LINE1 methylation was measured from blood-derived DNA obtained from participants of a population-based incident case-control study of bladder cancer in New Hampshire. Bisulfite-modified DNA was pyrosequenced to determine LINE1 methylation status; a total of 285 cases and 465 controls were evaluated for methylation. Results: Being in the lowest LINE1 methylation decile was associated with a 1.8-fold increased risk of bladder cancer [95% confidence interval (95% CI), 1.12-2.90] in models controlling for gender, age, and smoking, and the association was stronger in women than in men (odds ratio, 2.48; 95% CI, 1.19-5.17 in women; and odds ratio, 1.47; 95% CI, 0.79-2.74 in men). Among controls, women were more likely to have lower LINE1 methylation than men (P = 0.04), and levels of arsenic in the 90th percentile were associated with reduced LINE1 methylation (P = 0.04). Conclusions: LINE1 hypomethylation may be an important biomarker of bladder cancer risk, especially among women. Clin Cancer Res; 16(5); 1682–9
Indwelling pleural catheters for non-malignant effusions: a multicentre review of practice: Table 1
Authors: Rahul Bhatnagar, Elaine D Reid, John P Corcoran, Jessamy D Bagenal, Sandra Pope, Amelia O Clive, Natalie Zahan-Evans, Peter O Froeschle, Douglas West, Najib M Rahman, Sumit Chatterji, Pasupathy R Sivasothy, Nick A Maskell
Journal: Thorax (2013)

Indwelling pleural catheters (IPCs) are commonly used in the management of malignant pleural effusion (MPE). There is little data on their use in non-malignant conditions. All IPC insertions for non-malignant cases from five large UK centres were found using prospectively maintained databases. Data were collected on 57 IPC insertions. The commonest indications were hepatic hydrothorax (33%) and inflammatory pleuritis (26%). The mean weekly fluid output was 2.8 L (SD 2.52). 48/57 (84%) patients had no complications. Suspected pleural infection was documented in 2 (3.5%) cases. 33% (19/57) of patients underwent ‘spontaneous’ pleurodesis at a median time of 71 days. Patients with hepatic disease achieved pleurodesis significantly less often than those with non-hepatic disease (p=0.03). These data support the use of IPCs in select cases of non-malignant disease when maximal medical therapy has failed.
Asthma control index in European countries: The LIAISON (InternationaL cross-sectIonAl and longitudinal assessment on aSthma cONtrol) study cross-sectional results
Authors: Fulvio Braido, Daniele Guastalla, Eleonora Ingrassia, Gabriele Nicolini, David Price, Nicolas Roche, Joan B. Soriano, Heinrich Worth
Journal: European Respiratory Journal (2014)

RATIONALE: Monitoring asthma control is required to help building management strategies and assessing their effectiveness.  OBJECTIVES: To describe the prevalence of asthma control in each of the 12 European countries included in the LIAISON study.  METHODS: LIAISON is a large, multicentre, prospective, observational study with a cross-sectional phase (completed) and a 12-month longitudinal phase (ongoing). Adult patients with a diagnosis of asthma since at least 6 months and receiving the same asthma treatment in the 4 weeks before enrolment were included. Asthma Control Index (ACI) was computed as the ratio of patients with controlled asthma to patients with not well-controlled asthma (partly controlled and uncontrolled asthma) according to the 6-item Asthma Control Questionnaire scores.  RESULTS: The ACI of the overall population is 0.77. Among countries, patients in Italy and Spain had greater levels of asthma control, whereas the lowest rates of control were in Hungary, The Netherlands and France.  CONCLUSIONS: Although the overall percentage of patients with controlled asthma in Europe is about 43%, there are important differences among countries in terms of asthma control level. Further analyses are required to explain these variations.
Rugby football injuries, 1980-1983.
Authors: J P Sparks
Journal: British Journal of Sports Medicine (1985)

The injuries sustained by the boys at one English public school have been recorded and analysed by age, experience, position, phase, duration of the game and of the season. Few injuries have been serious. Detailed reference is made to concussion, injuries from collapsed scrums and injuries of the cervical spine. The paper emphasises that the tackle leads to most injuries. This paper presents the Rugby football injuries sustained by the boarders of Rugby School in the four seasons 1980-1983. The injury rate was 194 per 10,000 player hours, compared with the rate of 198 per 10,000 player hours for the thirty seasons 1950-1979 (Sparks, 1981). Tables I-VI list the injuries by different criteria. Table VII lists the sites of injury; Table VIII the time off Rugby football after injury; Table IX lists some of the more important injuries; Table XI summarises the playing results of the various school teams; Table XIII compares some of the Rugby School figures with those recorded in the Accident and Emergency Department of Christchurch Hospital during the 1979 New Zealand Rugby football season (Inglis and Stewart, 1981); Table XIV records information on three aspects of Rugby football that have occasioned much recent concern, viz:--Time off playing after concussion, injuries caused by collapsed scrums and neck injuries.
Tobacco false attributions in smokers and not smokers teenagers
Authors: Khalil Abu Shams, Maria Hernandez, Mercedes De Carlos, Amaia Iridoy, Susana Clemos, Amaya Villanueva
Journal: European Respiratory Journal (2012)

Introduction: The tobacco is now a widespread habit among the teenagers where thy begin early to smoke. The false attribution have an important role to push the adolescents to take the decision to begin early to smoke.i.e. to think that they are more attractive, modern, adult and more independent.  Methods: a representative sample of teenagers of our community offering a questionaire that include the false attributions with two answers: true or not true.The sample was of 350 students, 180 girls and 170 boys between12-18 years. The values of the correct answers is between 0 and 10 points analyzing the results with Kruskal Wallis test.  Results: 193 students (55.14%) smoke and 157 (44.86%) not smoke. We found significant differences of false attributions between smokers and not smokers.The smokers have most of false attributions about smoke habit having less scoring in the questionary (H:6.45, gl:1, p: 0.011).  Conclusions: The smoke teenagers have more false attributions than not smokers.
THE EFFECT OF X-RAY ON THE SKIN OF VITALLY STAINED WHITE MICE
Authors: Gerty T. Cori
Journal: The Journal of Experimental Medicine (1924)

1. The time interval between radiation and the occurrence of epilation is shorter in mice injected with trypan blue than in normal animals. 2. An x-ray unit defined as that causing total spontaneous epilation on the skin of the mouse is suggested. It corresponds to four to five human erythema doses.
Health-related quality-of-life of people with HIV in the era of combination antiretroviral treatment: a cross-sectional comparison with the general population
Authors: Alec Miners, Andrew Phillips, Noemi Kreif, Alison Rodger, Andrew Speakman, Martin Fisher, Jane Anderson, Simon Collins, Graham Hart, Lorraine Sherr, Fiona C Lampe
Journal: The Lancet HIV (2014)

Combination antiretroviral therapy has substantially increased life-expectancy in people living with HIV, but the effects of chronic infection on health-related quality of life (HRQoL) are unclear. We aimed to compare HRQoL in people with HIV and the general population.We merged two UK cross-sectional surveys: the ASTRA study, which recruited participants aged 18 years or older with HIV from eight outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012; and the Health Survey for England (HSE) 2011, which measures health and health-related behaviours in individuals living in a random sample of private households in England. The ASTRA study has data for 3258 people (response rate 64%) and HSE for 8503 people aged 18 years or older (response rate 66%). HRQoL was assessed with the Euroqol 5D questionnaire 3 level (EQ-5D-3L) instrument that measures health on five domains, each with three levels. The responses are scored on a scale where a value of 1 represents perfect health and a value of 0 represents death, known as the utility score. We used multivariable models to compare utility scores between the HIV and general population samples with adjustment for several sociodemographic factors.3151 (97%) of 3258 of participants in ASTRA and 7424 (87%) of 8503 participants in HSE had complete EQ-5D-3L data. The EQ-5D-3L utility score was lower for people with HIV compared with that in the general population (marginal effect in utility score adjusted for age, and sex/sexuality -0·11; 95% CI -0·13 to -0·10; p < 0·0001). HRQoL was lower for people with HIV for all EQ-5D-3L domains, particularly for anxiety/depression. The difference in utility score was significant after adjustment for several additional sociodemographic variables (ethnic origin, education, having children, and smoking status) and was apparent across all CD4 cell count, antiretroviral therapy, and viral load strata, but was greatest for those people diagnosed with HIV in earlier calendar periods. Reduction in HRQoL with age was not greater in people with HIV than in the general population (pinteraction > 0·05).People living with HIV have significantly lower HRQoL than do the general population, despite most HIV positive individuals in this study being virologically and immunologically stable. Although this difference could in part be due to factors other than HIV, this study provides additional evidence of the loss of health that can be avoided through prevention of further HIV infections.UK National Institute for Health Research.
Expression of T cell receptor genes in human B cells.
Authors: A F Calman, B M Peterlin
Journal: The Journal of Experimental Medicine (1986)

We analyzed the transcription and rearrangement of the T cell antigen receptor (Ti) genes Ti alpha and Ti beta in human B cell, T cell, and myeloid cell lines, as well as in purified tonsillar B and T cells. All four B cell lines examined, as well as one of two myeloid cell lines, expressed low levels of truncated Ti beta transcripts, as did freshly purified tonsillar B cells. Two of the B cell lines and one of the myeloid lines also expressed truncated Ti alpha transcripts, while tonsillar B cells did not. Sequence analysis of cDNA clones from a B cell line demonstrated that these truncated Ti alpha and Ti beta transcripts were composed of unrearranged J and C gene segments. Comparison of cDNA clones from T and B cells suggests that D alpha genes or N regions contribute to the formation of Ti alpha transcripts in T cells but not in B cells. None of the B cell or myeloid cell lines in this study showed evidence of Ti beta gene rearrangements by Southern blotting. Our data, and other studies of gene rearrangements in human tumors, demonstrate that the level of Ti beta transcriptional activity and the frequency of Ti beta gene rearrangements are correlated in all cell types examined. Thus, our data support the accessibility model of antigen receptor gene rearrangement, whereby the susceptibility of gene segments to recombination enzymes is correlated with their transcriptional activity.
Assessment of 1,3-butadiene epidemiology studies.
Authors: M G Ott
Journal: Environmental Health Perspectives (1990)

Positive carcinogenicity studies in mice and rats have led to concerns that 1,3-butadiene may be carcinogenic in humans under exposure conditions that have existed in occupational settings and perhaps exist today. The principal settings of interest are the styrene-butadiene rubber (SBR) manufacturing industry, which uses large quantities of 1,3-butadiene, and the 1,3-butadiene monomer industry. The potential for 1,3-butadiene exposure is highest during monomer transfer operations and is lowest in finishing areas of polymerization plants where the polymer products are processed. Three large cohort mortality studies have been conducted in the SBR and monomer producing industries since 1980. These studies, which examined the mortality experience of over 17,000 men employed in one monomer and 10 SBR facilities, are the subject of this review. All but one of the facilities began operations during the early 1940s. The mortality experience observed within these employee cohorts is comparable to that seen in other long-term studies of men employed in the petroleum, chemical, and rubber industries for all causes of death, total malignant neoplasms, and for the specific cancers seen in excess in the toxicologic studies. This paper discusses discrepant findings observed in more detailed analyses within individual cohorts and among employment subgroups, as well as selected limitations of the particular studies. Additional efforts to refine 1,3-butadiene exposure categories are needed. Within the context of sample size limitations inherent in these studies, there is currently inadequate evidence to establish a relationship between cancer mortality outcomes and 1.3-butadiene exposure in humans.
Tyrosine Phosphorylation Profiling Reveals the Signaling Network Characteristics of Basal Breast Cancer Cells
Authors: Falko Hochgräfe, Luxi Zhang, Sandra A. O'Toole, Brigid C. Browne, Mark Pinese, Ana Porta Cubas, Gillian M. Lehrbach, David R. Croucher, Danny Rickwood, Alice Boulghourjian, Robert Shearer, Radhika Nair, Alexander Swarbrick, Dana Faratian, Peter Mullen, David J. Harrison, Andrew V. Biankin, Robert L. Sutherland, Mark J. Raftery, Roger J. Daly
Journal: Cancer Research (2010)

To identify therapeutic targets and prognostic markers for basal breast cancers, breast cancer cell lines were subjected to mass spectrometry-based profiling of protein tyrosine phosphorylation events. This revealed that luminal and basal breast cancer cells exhibit distinct tyrosine phosphorylation signatures that depend on pathway activation as well as protein expression. Basal breast cancer cells are characterized by elevated tyrosine phosphorylation of Met, Lyn, EphA2, epidermal growth factor receptor (EGFR), and FAK, and Src family kinase (SFK) substrates such as p130Cas. SFKs exert a prominent role in these cells, phosphorylating key regulators of adhesion and migration and promoting tyrosine phosphorylation of the receptor tyrosine kinases EGFR and Met. Consistent with these observations, SFK inhibition attenuated cellular proliferation, survival, and motility. Basal breast cancer cell lines exhibited differential responsiveness to small molecule inhibitors of EGFR and Met that correlated with the degree of target phosphorylation, and reflecting kinase coactivation, inhibiting two types of activated network kinase (e.g., EGFR and SFKs) was more effective than single agent approaches. FAK signaling enhanced both proliferation and invasion, and Lyn was identified as a proinvasive component of the network that is associated with a basal phenotype and poor prognosis in patients with breast cancer. These studies highlight multiple kinases and substrates for further evaluation as therapeutic targets and biomarkers. However, they also indicate that patient stratification based on expression/activation of drug targets, coupled with use of multi-kinase inhibitors or combination therapies, may be required for effective treatment of this breast cancer subgroup.
PWE-047 Full thickness small bowel biopsy in gut dysmotility. Case series of eight patients illustrating the benefits as a diagnostic tool
Authors: E Harrison, J E Martin, S C Cooper
Journal: Gut (2012)

<h3>Introduction</h3> Full thickness small bowel biopsies offer the opportunity to make a definitive diagnosis in patients with gastrointestinal dysmotility. However, our experience suggests that standard histological reporting may fail to achieve this diagnosis. This study compares local diagnoses to those of a national expert. <h3>Methods</h3> We retrospectively reviewed eight sequential patients with symptomatic gastrointestinal dysmotility who were reviewed at a tertiary centre having had locally reported full thickness small bowel biopsies. Local histological reports were compared to those of a national expert. Patient notes were reviewed to determine the clinical impact of achieving a definitive diagnosis. Some patients were questioned regarding the impact of their definitive diagnosis. <h3>Results</h3> The biopsies of the eight sequential patients had been reported by one of four centres within the West Midlands. All, except one, of these local reports were normal. However, subsequent review of all eight biopsies by the national expert identified pathological changes in all. Diagnoses established included two cases of polyglucosan body myopathy, confirmation of NSAID enteropathy and differing forms of inflammation (eg, lymphocytic plexitis). Establishing these diagnoses enabled accurate prognoses and implementation of subsequent management, including continuation of home parenteral nutrition (HPN, n=6) and consideration for small intestinal transplantation (SIT, n=3). Patients questioned reported additional benefits. <h3>Conclusion</h3> Gut dysmotility can be highly symptomatic and debilitating leading to intestinal failure (IF), HPN and SIT. Clinical decisions for consideration for HPN and SIT are complex. Decisions must consider the potential for morbidity and mortality against the potential for improvement in nutritional status, quality of life and survival. A full thickness small bowel biopsy, while invasive, offers opportunity for a definitive diagnosis, and thus a prognosis. Published series report an 81% diagnostic yield for small bowel biopsies in patients with suspected gastrointestinal neuromuscular disorders, when using routine and immunohisto-chemical techniques.<sup>1</sup> However, standard histopathological reporting, which is often based on H&amp;E staining alone, has less potential for achieving a diagnosis. This is shown by our study in which a diagnosis was achieved in only 13%. Thus, our study highlights the importance of expert review and demonstrates the importance of achieving a diagnosis for patient and clinician. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Knowles CH</b>, Veress B, Tornblom H, <i>et al.</i> Safety and diagnostic yield of laparoscopically assisted full-thickness bowel biopsy. <i>Neurogastroenterol Motil</i> 2008;<b>20</b>:774–9.
Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension
Authors: Alice Huertas, Ly Tu, Natalia Gambaryan, Barbara Girerd, Frédéric Perros, David Montani, Dominique Fabre, Elie Fadel, Saadia Eddahibi, Sylvia Cohen-Kaminsky, Christophe Guignabert, Marc Humbert
Journal: European Respiratory Journal (2012)

Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the pathophysiology is still unclear. Recent evidence has demonstrated a detrimental involvement of leptin in promoting various autoimmune diseases by controlling regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is currently unknown. We hypothesised that leptin, synthesised by dysfunctional pulmonary endothelium, might play a role in the immunopathogenesis of IPAH by regulating circulating regulatory T-lymphocytes function. First, we collected serum and regulatory T-lymphocytes from controls, and IPAH and scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients; secondly, we recovered tissue samples and cultured endothelial cells after either surgery or transplantation in controls and IPAH patients, respectively. Our findings indicate that serum leptin was higher in IPAH and SSc-PAH patients than controls. Circulating regulatory T-lymphocyte numbers were comparable in all groups, and the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared with controls, whereas their function was reduced in IPAH and SSc-PAH patients compared with controls, in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesised more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH.