tbuckley/cabot-search huggingface dataset:
Association Between Passive and Active Smoking and Incident Type 2 Diabetes in Women
Authors: Luxia Zhang, Gary C. Curhan, Frank B. Hu, Eric B. Rimm, John P. Forman
Journal: Diabetes Care (2011)

Accumulating evidence has identified a positive association between active smoking and the risk of diabetes, but previous studies had limited information on passive smoking or changes in smoking behaviors over time. This analysis examined the association between exposure to passive smoke, active smoking, and the risk of incident type 2 diabetes among women.This is a prospective cohort study of 100,526 women in the Nurses' Health Study who did not have prevalent diabetes in 1982, with follow-up for diabetes for 24 years.We identified 5,392 incident cases of type 2 diabetes during 24 years of follow-up. Compared with nonsmokers with no exposure to passive smoke, there was an increased risk of diabetes among nonsmokers who were occasionally (relative risk [RR] 1.10 [95% CI 0.94-1.23]) or regularly (1.16 [1.00-1.35]) exposed to passive smoke. The risk of incident type 2 diabetes was increased by 28% (12-50) among all past smokers. The risk diminished as time since quitting increased but still was elevated even 20-29 years later (1.15 [1.00-1.32]). Current smokers had the highest risk of incident type 2 diabetes in a dose-dependent manner. Adjusted RRs increased from 1.39 (1.17-1.64) for 1-14 cigarettes per day to 1.98 (1.57-2.36) for ≥25 cigarettes per day compared with nonsmokers with no exposure to passive smoke.Our study suggests that exposure to passive smoke and active smoking are positively and independently associated with the risk of type 2 diabetes.
Genome of the house fly, Musca domestica L., a global vector of diseases with adaptations to a septic environment
Authors: Jeffrey G Scott, Wesley C Warren, Leo W Beukeboom, Daniel Bopp, Andrew G Clark, Sarah D Giers, Monika Hediger, Andrew K Jones, Shinji Kasai, Cheryl A Leichter, Ming Li, Richard P Meisel, Patrick Minx, Terence D Murphy, David R Nelson, William R Reid, Frank D Rinkevich, Hugh M Robertson, Timothy B Sackton, David B Sattelle, Francoise Thibaud-Nissen, Chad Tomlinson, Louis van de Zande, Kimberly KO Walden, Richard K Wilson, Nannan Liu
Journal: Genome biology (2014)

Adult house flies, Musca domestica L., are mechanical vectors of more than 100 devastating diseases that have severe consequences for human and animal health. House fly larvae play a vital role as decomposers of animal wastes, and thus live in intimate association with many animal pathogens. We have sequenced and analyzed the genome of the house fly using DNA from female flies. The sequenced genome is 691 Mb. Compared with Drosophila melanogaster, the genome contains a rich resource of shared and novel protein coding genes, a significantly higher amount of repetitive elements, and substantial increases in copy number and diversity of both the recognition and effector components of the immune system, consistent with life in a pathogen-rich environment. There are 146 P450 genes, plus 11 pseudogenes, in M. domestica, representing a significant increase relative to D. melanogaster and suggesting the presence of enhanced detoxification in house flies. Relative to D. melanogaster, M. domestica has also evolved an expanded repertoire of chemoreceptors and odorant binding proteins, many associated with gustation. This represents the first genome sequence of an insect that lives in intimate association with abundant animal pathogens. The house fly genome provides a rich resource for enabling work on innovative methods of insect control, for understanding the mechanisms of insecticide resistance, genetic adaptation to high pathogen loads, and for exploring the basic biology of this important pest. The genome of this species will also serve as a close out-group to Drosophila in comparative genomic studies.
Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations
Authors: Ponpan Matangkasombut, Muriel Pichavant, Doris E. Saez, Silvia Giliani, Evelina Mazzolari, Andrea Finocchi, Anna Villa, Cristina Sobacchi, Patricia Cortes, Dale T. Umetsu, Luigi D. Notarangelo
Journal: Blood (2007)
Proarrhythmic Aspects of Atrial Fibrillation Surgery
Authors: H. Thomas McElderry, David C. McGiffin, Vance J. Plumb, Kumaraswamy Nanthakumar, Andrew E. Epstein, Takumi Yamada, G. Neal Kay
Journal: Circulation (2007)

Surgery for the treatment of atrial fibrillation may be associated with early or late postoperative atrial arrhythmias. In many cases, the arrhythmias that occur early in the postoperative course may be related to pericardial inflammation or increased catecholamine levels and tend to resolve without further therapy. In contrast, late postoperative arrhythmias often are persistent, highly symptomatic, and refractory to medical therapy. The incidence and mechanisms of these late atrial arrhythmias have not been thoroughly described.In this study, a total of 143 consecutive patients undergoing atrial fibrillation surgery from 1996 to 2005 were prospectively followed up. Sustained atrial tachycardia developed in 22 of 143 patients (15%) >8 weeks after the surgical procedure. These patients underwent electrophysiological study. A total of 25 separate tachycardias were mapped in these 22 patients, including 15 located in right atrium and 10 in the left atrium. Right atrial tachycardias included cavotricuspid isthmus-dependent atrial flutter (n=7), non-isthmus-dependent right atrial reentry (n=7), and 1 focal atrial tachycardia. Left atrial tachycardias included reentry around the mitral valve (n=3) and in the roof of the left atrium (n=7). All tachycardias were successfully treated with radiofrequency catheter ablation with no recurrences in long-term follow-up.Postoperative arrhythmias are not uncommon late after surgery for atrial fibrillation and typically are reentrant and related to surgically created boundaries. Radiofrequency catheter ablation is highly effective in the management of these late arrhythmias.
An Early PEEP/F<scp>i</scp><sub>O<sub>2</sub></sub> Trial Identifies Different Degrees of Lung Injury in Patients with Acute Respiratory Distress Syndrome
Authors: Jesús Villar, Lina Pérez-Méndez, José López, Javier Belda, Jesús Blanco, Iñaki Saralegui, Fernando Suárez-Sipmann, Julia López, Santiago Lubillo, Robert M. Kacmarek
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Current American-European Consensus Conference definitions for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inadequate for inclusion into clinical trials due to the lack of standardization for measuring the oxygenation defect.We questioned whether an early assessment of oxygenation on specific ventilator settings would identify patients with established ARDS (persisting over 24 h).At the time of meeting ARDS criteria (Day 0) and 24 hours later (Day 1), arterial blood gases were obtained on standard ventilator settings, Vt 7 ml/kg predicted body weight plus the following positive end-expiratory pressure (PEEP) and Fi(O(2)) settings in sequence: (1) PEEP >or= 5 cm H(2)O and Fi(O(2)) >or= 0.5, (2) PEEP >or= 5 cm H(2)O and Fi(O(2)) 1.0, (3) PEEP >or= 10 cm H(2)O and Fi(O(2))>or=0.5, and (4) PEEP >or= 10 cm H(2)O and Fi(O(2)) 1.0.One hundred seventy patients meeting ARDS criteria (Pa(O(2))/Fi(O(2)) 128 +/- 33 mm Hg) were enrolled. Overall hospital mortality was 34.1%. The standard ventilator settings that best identified patients with established ARDS and predicted differences in intensive care unit (ICU) mortality were PEEP >or= 10 cm H(2)O and Fi(O(2)) >or= 0.5 at Day 1 (P = 0.0001). Only 99 (58.2%) patients continued to meet ARDS criteria (Pa(O(2))/Fi(O(2)), 155.8 +/- 29.8 mm Hg; ICU mortality, 45.5%), whereas 55 patients were reclassified as having ALI (Pa(O(2))/Fi(O(2)), 246.5 +/- 25.6 mm Hg; ICU mortality, 20%) and 16 patients as having acute respiratory failure (Pa(O(2))/Fi(O(2)), 370 +/- 54 mm Hg; ICU mortality, 6.3%) (P = 0.0001) on these settings.Patients meeting current American-European Consensus Conference ARDS criteria may have highly variable levels of lung injury and outcomes. A systematic method of assessing severity of lung injury is required for enrollment of patients with ARDS into randomized controlled trials. Clinical trial registered with www.clinicaltrials.gov (NCT 00435110).
Prospective inquiry studying of tobacco smoking among high-school students in Plovdiv, Bulgaria (2004-2010)
Authors: Filip Shterev, Rositza Ivancheva, Zlatka Iankova, Stanislav Kartev, Georgi Belev, Nonka Mateva, Ivan Novakov
Journal: European Respiratory Journal (2012)

Introduction: Tobacco smoking is world major cause for premature death and serious health problems. The efforts should be directed towards prevention of smoking, which most often is even in childhood.  Aims: To investigate in dynamics certain aspects of smoking among adolescents.  Methods: It was organized a study in sections method, using a direct anonymous group survey among students from 16 to 18 years in Plovdiv schools. There were interviewed 800 students in 2004 and 460 in 2010. The questionnaire is from translated and adapted version by GYTS, WHO9s program form. The statistical processing of data is completed by descriptive statistics and Student9s t-test. It was used the program pack SPSS v.18.0.  Results: For the six year period, we reported a statistically significant decrease in the number of students who have tried to smoke cigarettes and of those who smoke regularly. In 2004, 84.875% of the adolescents have tried a cigarette, as well as in 2010- 72.39% (t=5.12, p  Conclusions: There is a significant decrease in the number of adolescents who smoke and in the same time there is more to be done in preventing tobacco smoking by children.
Blood, sweat and tears: training and competing in the heat
Authors: BM Pluim, S Racinais, JD Périard
Journal: British Journal of Sports Medicine (2015)

The Consensus Statement by Racinais et al 1 on training and competing in the heat provides practical recommendations for athletes, clinicians and event organisers to optimise performance during sporting activities in the heat. The focus is on three different areas: heat acclimatisation, hydration and cooling strategies, with practical recommendations for event organisers.

Heat acclimatisation is the most important intervention available to reduce physiological strain and optimise exercise capacity in hot ambient conditions. Most adaptations develop within the first week of heat acclimatisation, and more slowly in the subsequent 2 weeks.2 Consequently, athletes benefit from only a few days of acclimatisation, but may require up to 2 weeks for optimal performance. Training sessions should last at least 60 min per day and induce a significant increase in body and skin temperatures, as well as …
<i>ΔDNMT3B</i> Variants Regulate DNA Methylation in a Promoter-Specific Manner
Authors: Jie Wang, Manisha Bhutani, Ashutosh K. Pathak, Wenhua Lang, Hening Ren, Jaroslav Jelinek, Rong He, Lanlan Shen, Jean-Pierre Issa, Li Mao
Journal: Cancer Research (2007)

DNA methyltransferase 3B (DNMT3B) is critical in de novo DNA methylation during development and tumorigenesis. We recently reported the identification of a DNMT3B subfamily, DeltaDNMT3B, which contains at least seven variants, resulting from alternative pre-mRNA splicing. DeltaDNMT3Bs are the predominant expression forms of DNMT3B in human lung cancer. A strong correlation was observed between the promoter methylation of RASSF1A gene but not p16 gene (both frequently inactivated by promoter methylation in lung cancer) and expression of DeltaDNMT3B4 in primary lung cancer, suggesting a role of DeltaDNMT3B in regulating promoter-specific methylation of common tumor suppressor genes in tumorigenesis. In this report, we provide first experimental evidence showing a direct involvement of DeltaDNMT3B4 in regulating RASSF1A promoter methylation in human lung cancer cells. Knockdown of DeltaDNMT3B4 expression by small interfering RNA resulted in a rapid demethylation of RASSF1A promoter and reexpression of RASSF1A mRNA but had no effect on p16 promoter in the lung cancer cells. Conversely, normal bronchial epithelial cells with stably transfected DeltaDNMT3B4 gained an increased DNA methylation in RASSF1A promoter but not p16 promoter. We conclude that promoter DNA methylation can be differentially regulated and DeltaDNMT3Bs are involved in regulation of such promoter-specific de novo DNA methylation.
Secretion of Platelet-Activating Factor Is Mediated by MDR1 P-Glycoprotein in Cultured Human Mesangial Cells
Authors: SYLVAIN ERNEST, ELSA BELLO-REUSS
Journal: Journal of the American Society of Nephrology (1999)

MDR1 P-glycoprotein (Pgp), the product of the MDR1 gene involved in multidrug resistance in cancer cells, is also expressed in normal tissues. In the human kidney, it is localized in the mesangium, the proximal tubule, the thick ascending limb of Henle's loop, and the collecting duct. Pgp actively transports lipophilic xenobiotics, peptides, steroids, and lipids, and perhaps endogenous substrates. It has been shown previously that human mesangial cells in culture express active Pgp and that the expression of Pgp can be down-regulated by exposure to antisense oligonucleotides. Mesangial cells do not express multidrug resistance-related protein (MRP). Experiments were performed to determine whether 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (generically platelet-activating factor, PAF) is a substrate of Pgp in human mesangial cells in culture. This study found: (1) PAF C-16 and analogs inhibited Pgp-mediated efflux of rhodamine 123 by 59 to 88% in multidrug-resistant KBV-1 cells and by 85 to 97% in cultured human mesangial cells. (2) In mesangial cells stimulated with A23187, the secretion of endogenously produced PAF was inhibited by >80% by the Pgp blockers verapamil, cyclosporin A, PSC-833, vinblastine, and adriamycin. (3) Preincubation with MDR1 antisense oligonucleotides also blocked PAF secretion by human mesangial cells. PAF analogs do not modify the transport of MRP substrates in MCF-7/VP cells expressing MRP but not Pgp. These results indicate that PAF is an endogenous substrate of Pgp in human mesangial cells. Inhibition of Pgp transport may be useful in reducing glomerular damage occurring in pathologic conditions where PAF secretion is elevated.
Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations
Authors: J M FitzGerald, A Becker, M R Sears, S Mink, K Chung, J Lee
Journal: Thorax (2004)

<b>Background:</b> Previous guidelines recommend doubling the daily dose of maintenance inhaled corticosteroid to treat or prevent progression of exacerbations of asthma. <b>Methods:</b> Over a 6 month period a cohort of patients were evaluated prospectively and randomised in a double blind controlled trial to treatment with either a continued maintenance dose (MD) of inhaled corticosteroid or doubling the dose (DD) at the time of an exacerbation. <b>Results:</b> A total of 290 patients were randomised (33% male) and 98 (DD, n = 46) experienced evaluable asthma exacerbations during the study period. Mean (SD) baseline characteristics at randomisation (age 33.5 (14.0) years; forced expiratory volume in 1 second (FEV<sub>1</sub>) 2.8 (0.7) l; peak expiratory flow (PEF) 422.9 (110.5) l/min) were similar in both groups. In the DD group 41% of patients were considered treatment failures because they either required systemic steroids (n = 12), had an unscheduled visit to a physician (n = 1), or their asthma did not return to baseline (n = 6). This did not differ from the MD group in which 40% were treatment failures (n = 9, 0, and 12, respectively; p = 0.94). <b>Conclusions:</b> In patients who regularly take an inhaled corticosteroid, doubling the maintenance dose may not affect the pattern of the exacerbation.
Eribulin Mesylate: Mechanism of Action of a Unique Microtubule-Targeting Agent
Authors: Nicholas F. Dybdal-Hargreaves, April L. Risinger, Susan L. Mooberry
Journal: Clinical Cancer Research (2015)

Abstract Eribulin mesylate (eribulin), an analogue of the marine natural product halichondrin B, is a microtubule-depolymerizing drug that has utility in the treatment of patients with breast cancer. Clinical trial results have demonstrated that eribulin treatment provides a survival advantage to patients with metastatic or locally advanced breast cancer previously treated with an anthracycline and a taxane. Furthermore, a pooled analysis of two pivotal phase III trials has demonstrated that eribulin also improves overall survival in several patient subgroups, including in women with HER2-negative disease and triple-negative breast cancer. This review covers the preclinical research that led to the clinical testing and approval of eribulin, as well as subsequent research that was prompted by distinct and unexpected effects of eribulin in the clinic. Initial studies with halichondrin B demonstrated unique effects on tubulin binding that resulted in distinct microtubule-dependent events and antitumor actions. Consistent with the actions of the natural product, eribulin has potent microtubule-depolymerizing activities and properties that distinguish it from other microtubule-targeting agents. Here, we review new results that further differentiate the effects of eribulin from other agents on peripheral nerves, angiogenesis, vascular remodeling, and epithelial-to-mesenchymal transition. Together, these data highlight the distinct properties of eribulin and begin to delineate the mechanisms behind the increased survival benefit provided by eribulin for patients. Clin Cancer Res; 21(11); 2445–52. ©2015 AACR.
Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis
Authors: M Esteve
Journal: Gut (2004)

<b>Background:</b> There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. <b>Patients and methods:</b> Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. <b>Results:</b> Three Crohn's disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. <b>Conclusions:</b> Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.
Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack
Authors: Yukinori Enomoto, Kanami Orihara, Tetsuya Takamasu, Akio Matsuda, Yasuhiro Gon, Hirohisa Saito, Chisei Ra, Yoshimichi Okayama
Journal: Journal of Allergy and Clinical Immunology (2009)
Induction of apoptosis in ischemia-reperfusion model of mouse kidney
Authors: S Nogae, M Miyazaki, N Kobayashi, T Saito, K Abe, H Saito, P K Nakane, Y Nakanishi, T Koji
Journal: Journal of the American Society of Nephrology (1998)

Although ischemia-reperfusion of mouse kidney is known to cause severe renal failure due to tubular cell death, the exact cellular mechanism responsible for this phenomenon is not clear. To investigate the spatial and temporal development of renal cell death and the role of Fas/APO-1/CD95 (Fas) in this process, the left renal vessels were occluded in a group of mice for 30, 60, or 120 min followed by reperfusion for 24 h (n = 4 for each group). Analysis of the isolated DNA in agarose-gel electrophoresis revealed a typical ladder pattern of bands consisting of multiples of 180 to 200 bp, considered the hallmark of apoptosis. The intensity of the bands increased proportionately with the duration of ischemia. Histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling showed the presence of nuclei with DNA double-strand breaks specifically in distal renal tubules of the outer medulla. The presence of apoptosis was also confirmed by electron microscopy. Analysis of total RNA by Northern blotting revealed one appropriate-sized band for Fas mRNA in the normal kidney, which intensified in the ischemia-reperfused kidney. Moreover, nonradioactive in situ hybridization revealed that distal renal tubular epithelial cells were positive for Fas mRNA in the outer medulla. Fas antigen was also localized to the renal tubular epithelial cells of the outer medulla by immunohistochemistry. The number of apoptotic cells in the ischemia-reperfusion kidney of the lpr/lpr mouse was low. These findings strongly indicate that ischemia-reperfusion of the kidney induces apoptosis of a specific area of tubular epithelial cells in the outer medulla through the Fas system.
Reduced tumorigenicity and pathogenicity of cervical carcinoma SiHa cells selected for resistance to cidofovir
Authors: Tim De Schutter, Graciela Andrei, Dimitri Topalis, Sophie Duraffour, Tania Mitera, Joost van den Oord, Patrick Matthys, Robert Snoeck
Journal: Molecular Cancer (2013)

Abstract Background Insights into the mechanisms associated with chemotherapy-resistance are important for implementation of therapeutic strategies and for unraveling the mode of action of chemotherapeutics. Although cidofovir (CDV) has proven efficacious in the treatment of human papillomavirus (HPV)-induced proliferation, no studies concerning the development of resistance to CDV in HPV-positive tumor cells have been performed yet. Methods From the cervical carcinoma SiHa cells (SiHa parental ), which are HPV-16 positive, cidofovir-resistant cells (SiHa CDV ) were selected, and differential gene expression profiles were analyzed by means of microarrays. We examined in vitro phenotyping of resistant cells compared to parental cells as well as tumorigenicity and pathogenicity in a mouse-xenograft model. Results SiHa CDV had a resistant phenotype and a reduced growth both in vitro and in vivo . A markedly diminished inflammatory response (as measured by production of host- and tumor-derived cytokines and number of neutrophils and macrophages in spleen) was induced by SiHa CDV than by SiHa parental in the xenograft model. Gene expression profiling identified several genes with differential expression upon acquisition of CDV-resistance and pointed to a diminished induction of inflammatory response in SiHa CDV compared to SiHa parental . Conclusions Our results indicate that acquisition of resistance to cidofovir in SiHa cells is linked to reduced pathogenicity. The present study contributes to our understanding on the antiproliferative effects of CDV and on the mechanisms involved, the inflammatory response playing a central role.