tbuckley/cabot-search huggingface dataset:
Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation
Authors: Toru Nyunoya, Martha M. Monick, Aloysius L. Klingelhutz, Heather Glaser, Jeffrey R. Cagley, Charles O. Brown, Eiyu Matsumoto, Nukhet Aykin-Burns, Douglas R. Spitz, Junko Oshima, Gary W. Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Werner's syndrome is a genetic disorder that causes premature aging due to loss-of-function mutations in a gene encoding a member of the RecQ helicase family. Both Werner's syndrome and cigarette smoking accelerate aging. No studies have examined the effect of cigarette smoke on Werner's syndrome protein.To investigate the role of Werner's syndrome protein in cigarette smoke-induced cellular senescence.Cellular senescence and amounts of Werner's syndrome protein were measured in fibroblasts isolated from patients with emphysema and compared with age-matched nonsmokers. The in vitro effects of cigarette smoke on amounts of Werner's syndrome protein, function, and senescence were also evaluated in primary human lung fibroblasts and epithelial cells.Cultured lung fibroblasts isolated from patients with emphysema exhibited a senescent phenotype accompanied by a decrease in Werner's syndrome protein. Cigarette smoke extract decreased Werner's syndrome protein in cultured fibroblasts and epithelial cells. Werner's syndrome protein-deficient fibroblasts were more susceptible to cigarette smoke-induced cellular senescence and cell migration impairment. In contrast, exogenous overexpression of Werner's syndrome protein attenuated the cigarette smoke effects.Cigarette smoke induces cellular senescence and cell migration impairment via Werner's syndrome protein down-regulation. Rescue of Werner's syndrome protein down-regulation may represent a potential therapeutic target for smoking-related diseases.
A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes.
Authors: H Tsubota, C I Lord, D I Watkins, C Morimoto, N L Letvin
Journal: The Journal of Experimental Medicine (1989)

CD8+ (suppressor/cytotoxic) lymphocytes block replication of HIV-1 or the simian immunodeficiency virus of macaques (SIVmac) in PBL of infected individuals. We now show that these CD8+ lymphocytes undergo clonal expansion in vivo after AIDS virus infection of the individual, suggesting they may be antigen-specific T cells. These CD8+ cells block replication of virus in autologous but not MHC class I-mismatched PBL. The inhibitory lymphocytes express the integrin family molecule 4B4 and the CTL-associated S6F1 epitope of LFA-1. Finally, physical contact is required for the CD8+ lymphocyte-mediated inhibition of AIDS virus replication, since this inhibitory function is blocked by anti-LFA-1 and anti-CD8 mAbs. These studies suggest that the cell that inhibits AIDS virus replication in PBL of infected individuals is a CTL.
Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.
Authors: R B Effros, P C Doherty, W Gerhard, J Bennink
Journal: The Journal of Experimental Medicine (1977)

Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.
DEVELOPMENT AND VALIDATION OF AN OBESITY RISK SCORE TO PREDICT MORTALITY IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Kashish Goel, Thais Coutinho, Daniel Correa de Sa, Charlotte Kragelund, Alka Kanaya, Marianne Zeller, Jong-Seon Park, Lars Kober, Christian Torp-Pedersen, Yves Cottin, Luc Lorgis, Sang-Hee Lee, Young-Jo Kim, Randal Thomas, Veronique Roger, Virend Somers, Francisco Lopez-Jimenez
Journal: Journal of the American College of Cardiology (2012)
Anti-type II collagen-immune complex-induced production of interleukin 1 and tumour necrosis factor stimulate production of matrix metalloproteinases from monocyte/rheumatoid arthritis synovial fibroblast co-cultures
Authors: M Mullazehi, L Mathsson, O Feldt, K Schubert, M Korotkova, V Malmstrom, J Ronnelid
Journal: Annals of the Rheumatic Diseases (2010)

We have previously reported that anti-CII-containing immune complexes (anti-CII IC) induced production of tumour necrosis factor (TNF) β, interleukin (IL)1α and IL8 from monocytes via FcγRIIa.1 We have also shown that high levels of anti-CII were associated with IC-induced production of pro-inflammatory cytokines in vitro and increased laboratory signs of inflammation 2 and increased radiological erosions at the time of diagnosis. 3 The objective of this study was to establish an in vitro …
The haemodynamic response to exercise in chronic obstructive pulmonary disease: assessment by impedance cardiography
Authors: HJ Bogaard, BM Dekker, BW Arntzen, HH Woltjer, AR van Keimpema, PE Postmus, PM de Vries
Journal: European Respiratory Journal (1998)

This study aimed to determine the differences in haemodynamic responses to a standard incremental exercise test between outpatients with chronic obstructive pulmonary disease (COPD) and age-matched controls and to discover the relationship between severity of airflow obstruction and exercise haemodynamics in COPD. Twenty-two male patients with COPD (forced expiratory volume in one second (FEV1)/vital capacity (VC))&lt;80% predicted) and 20 age-matched male controls performed an incremental exercise test (10 W x min(-1)) with ventilatory function and changes in stroke volume (deltaSV) and cardiac output (deltaCO) measured by means of electrical impedance cardiography (EIC). Submaximal deltaSV and deltaCO were lower in COPD patients. Peak exercise deltaSV were equal in patients and controls (128+/-33 versus 129+/-29%, p=0.98), whereas peak deltaCO was lower in patients (COPD versus controls: 232+/-71 versus 289+/-54%, p&lt;0.005). In COPD patients, FEV1 (% pred) was significantly correlated to deltaSV at all submaximal exercise intensities, to peak exercise deltaSV and to peak exercise deltaCO. FEV1/VC (% pred) was significantly correlated to deltaSV at 30 and 60 W. In conclusion, in chronic obstructive pulmonary disease an aberrant haemodynamic response to exercise was found, especially in patients with severe airflow obstruction. This aberrant response is related to the degree of airflow obstruction and may limit exercise performance in patients with severe chronic obstructive pulmonary disease.
Comment on Wong et al. Real-Time Continuous Glucose Monitoring Among Participants in the T1D Exchange Clinic Registry. Diabetes Care 2014;37:2702–2709
Authors: David Price, Tomas Walker, Claudia Graham
Journal: Diabetes Care (2015)

We appreciate the efforts of Wong et al. (1) in analyzing continuous glucose monitoring (CGM) use and benefits in the T1D Exchange Clinic Network registry database. Unfortunately, the data reported are reflective of experiences with prior CGM devices, not CGM as it exists today. This disparity may cause readers to draw incorrect conclusions based on the article. …
Fish Oil–Derived Fatty Acids, Docosahexaenoic Acid and Docosapentaenoic Acid, and the Risk of Acute Coronary Events
Authors: Tiina Rissanen, Sari Voutilainen, Kristiina Nyyssönen, Timo A. Lakka, Jukka T. Salonen
Journal: Circulation (2000)

Background —Previous findings concerning the serum levels of fish-derived (n-3) fatty acids and coronary heart disease are inconsistent. The purpose of this study was to investigate the association between the serum n-3 end-product fatty acids docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid and the risk of acute coronary events in middle-aged men. Methods and Results —We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards’ model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk ( P =0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (≤2.0 μg/g) had a 67% reduced risk ( P =0.016) of acute coronary events compared with men in the lowest fifth who had a high hair content of mercury (&gt;2.0 μg/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. Conclusions —Our data provide further confirmation for the concept that fish oil–derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.
Safety and efficacy of desmoteplase given 3–9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial
Authors: Gregory W Albers, Rüdiger von Kummer, Thomas Truelsen, Jens-Kristian S Jensen, Gabriela M Ravn, Bjørn A Grønning, Hugues Chabriat, Ku-Chou Chang, Antonio E Davalos, Gary A Ford, James Grotta, Markku Kaste, Lee H Schwamm, Ashfaq Shuaib
Journal: The Lancet Neurology (2015)
Renal Dendritic Cells Ameliorate Nephrotoxic Acute Kidney Injury
Authors: Raghu K. Tadagavadi, W. Brian Reeves
Journal: Journal of the American Society of Nephrology (2009)

Inflammation contributes to the pathogenesis of acute kidney injury. Dendritic cells (DCs) are immune sentinels with the ability to induce immunity or tolerance, but whether they mediate acute kidney injury is unknown. Here, we studied the distribution of DCs within the kidney and the role of DCs in cisplatin-induced acute kidney injury using a mouse model in which DCs express both green fluorescence protein and the diphtheria toxin receptor. DCs were present throughout the tubulointerstitium but not in glomeruli. We used diphtheria toxin to deplete DCs to study their functional significance in cisplatin nephrotoxicity. Mice depleted of DCs before or coincident with cisplatin treatment but not at later stages experienced more severe renal dysfunction, tubular injury, neutrophil infiltration and greater mortality than nondepleted mice. We used bone marrow chimeric mice to confirm that the depletion of CD11c-expressing hematopoietic cells was responsible for the enhanced renal injury. Finally, mixed bone marrow chimeras demonstrated that the worsening of cisplatin nephrotoxicity in DC-depleted mice was not a result of the dying or dead DCs themselves. After cisplatin treatment, expression of MHC class II decreased and expression of inducible co-stimulator ligand increased on renal DCs. These data demonstrate that resident DCs reduce cisplatin nephrotoxicity and its associated inflammation.
Societal and health care benefits of early use of inhaled steroids
Authors: T. HAAHTELA, T. KLAUKKA
Journal: Thorax (1998)

In this issue of Thorax Blais et al 1 report results from a population based register study which show that first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce by up to 80% the risk of a hospital admission for asthma compared with regular treatment with theophylline. It is a dramatic result, albeit not so surprising. Regular use of inhaled steroids prevents exacerbations of asthma,2 fatal and near fatal episodes of asthma,3 and accelerated loss of lung function.4 From 1985 to 1993 anti-inflammatory treatment with inhaled steroids decreased the number of hospital days per year in Swedish children to less than a third.5 In a large community sample in eastern Massachusetts inhaled steroids halved the risk of admission to hospital in each severity group.6 The data strongly supported the early prescription of inhaled steroids. In contrast, overconfidence in β2 agonists combined with suboptimal use of inhaled steroids increased the risk of admission to hospital fivefold in Belgium.7 

Hospital admission for asthma is a marker of severe and uncontrolled disease and indicates an increased risk of a subsequent fatal attack.8 The cost of hospital admissions represents 25–50% of the total costs for asthma, depending on whether the calculations include only direct …
Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial
Authors: Karim Asehnoune, Philippe Seguin, Jeremy Allary, Fanny Feuillet, Sigismond Lasocki, Fabrice Cook, Hervé Floch, Russell Chabanne, Thomas Geeraerts, Claire Roger, Pierre F Perrigault, Jean L Hanouz, Anne C Lukaszewicz, Matthieu Biais, Perrine Boucheix, Claire Dahyot-Fizelier, Xavier Capdevila, Pierre J Mahe, Pascale Le Maguet, Catherine Paugam-Burtz, Soizic Gergaud, Benoit Plaud, Jean M Constantin, Yannick Malledant, Laurent Flet, Véronique Sebille, Antoine Roquilly
Journal: The Lancet Respiratory Medicine (2014)
Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells
Authors: Liqun Chen, Lilly Y W Bourguignon
Journal: Molecular Cancer (2014)

MicroRNA-21 (miR-21) is associated with the development of solid tumors progression including breast cancer. In this study we investigated matrix hyaluronan (HA)-CD44 (a primary HA receptor) interaction with c-Jun N-Terminal Kinase (JNK)/c-Jun signaling in MDA-MB-468 breast cancer cells [a triple-negative (estrogen receptor-negative/progesterone receptor-negative/HER2-negative) breast cancer cell line]. Our results indicated that HA binding to CD44 promotes c-Jun nuclear translocation and transcriptional activation. Further analyses revealed that miR-21 is regulated by an upstream promoter containing AP1 binding site(s), and chromatin immunoprecipitation (CHIP) assays demonstrated that stimulation of miR-21 expression by HA/CD44 interaction is c-Jun-dependent in these breast cancer cells. This process results in an increase of the anti-apoptosis protein Bcl-2 and upregulation of inhibitors of the apoptosis family of proteins (IAPs) as well as chemoresistance in MDA-MB-468 cells. Treatment with c-Jun specific small interfering RNAs effectively blocks HA-mediated c-Jun signaling and abrogates miR-21 production as well as causes downregulation of survival proteins (Bcl-2 and IAPs) and enhancement of chemosensitivity. In addition, our results demonstrated that anti-miR-21 inhibitor not only downregulates Bcl-2/IAP expression but also increases chemosensitivity in HA-treated breast cancer cells. Together, these findings suggest that the HA/CD44-induced c-Jun signaling plays a pivotal role in miR-21 production leading to survival protein (Bcl-2/IAP) upregulation and chemoresistance in triple negative breast cancer cells such as MDA-MB-468 cell line. This novel HA/CD44-mediated c-Jun signaling pathway and miR-21 production provide a new drug target for the future intervention strategies to treat breast cancer.
NHS regulator is ineffective and has conflicts of interest, say MPs
Authors: A. O'Dowd
Journal: BMJ (2014)

One of the main regulators of the NHS in England, Monitor, is too slow to take action over struggling trusts, is not always effective, and has potential conflicts of interest over its new roles, MPs say.

The parliamentary Public Accounts Committee published a critical report on 4 July about the performance of Monitor, which regulates NHS foundation trusts and which took on new responsibilities as the sector regulator for health services in April.1

MPs said that the number of NHS foundation trusts in difficulty was growing, casting doubt on Monitor’s effectiveness as their regulator. At the time of the committee’s inquiry, it was estimated that more than a quarter of foundation trusts (39 of 147) would be in deficit by the end of 2013-14. By the end of last December 25 trusts were in breach of the conditions set when they were awarded …
Cellular Effects of Guanylin and Uroguanylin
Authors: Aleksandra Sinđic[Combining Acute Accent], Eberhard Schlatter
Journal: Journal of the American Society of Nephrology (2005)

Ingestion of a salty meal induces secretion of guanylin (GN) and uroguanylin (UGN) into the intestinal lumen, where they inhibit Na+ absorption and induce Cl-, HCO3-, and water secretion. Simultaneously, these hormones stimulate renal electrolyte excretion by inducing natriuresis, kaliuresis, and diuresis. GN and UGN therefore participate in the prevention of hypernatremia and hypervolemia after salty meals. The signaling pathway of GN and UGN in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C), which leads to cGMP-dependent inhibition of Na+/H+ exchange and activation of the cystic fibrosis transmembrane regulator. In GC-C-deficient mice, GN and UGN still produce renal natriuresis, kaliuresis, and diuresis, suggesting different signaling pathways in the kidney compared with the intestine. Signaling pathways for GN and UGN in the kidney differ along the various nephron segments. In proximal tubule cells, a cGMP- and GC-C-dependent signaling was demonstrated for both peptides. In addition, UGN activates a pertussis toxin-sensitive G-protein-coupled receptor. A similar dual signaling pathway is also known for atrial natriuretic peptide. Recently, a cGMP-independent signaling pathway for GN and UGN was also shown in principal cells of the human and mouse cortical collecting duct. Because GN and UGN activate different signaling pathways in specific organs and even within the kidney, this review focuses on more recent findings on cellular effects and signaling mechanisms of these peptides and their pathophysiologic implications in the intestine and the kidney.
A sports setting matrix for understanding the implementation context for community sport
Authors: C F Finch, A Donaldson
Journal: British Journal of Sports Medicine (2009)

There has been increasing recognition of the need for effectiveness research within the real-world intervention context of community sport. This is important because, even if interventions have been shown to be efficacious in controlled trials, if they are not also widely adopted and sustained, then it is unlikely that they will have a public health impact. There is very little information about how to best conduct such studies, but application of health promotion frameworks, such as the RE-AIM framework, to evaluate the public health impact of interventions could potentially help to understand the implementation context. Care needs to be taken when directly applying the RE-AIM framework, however, because the definitions for each of its dimensions will depend on the level/s the intervention is targeted at. This paper provides a novel extension to the RE-AIM framework (the RE-AIM Sports Setting Matrix (RE-AIM SSM)), which accounts for the fact that many sports injury interventions need to be targeted at multiple levels of sports delivery. Accordingly, the RE-AIM components also need to be measured across all tiers of possible influence on the rate of uptake and effectiveness. Specific examples are given for coachdelivered exercise training interventions. The RE-AIM SSM is specific to the community sports setting implementation context and could be used to guide the delivery of future sports safety, and other health promotion, interventions in this area.
Airway Alveolar Attachment Points and Exposure to Cigarette Smoke <i>In Utero</i>
Authors: John G. Elliot, Neil G. Carroll, Alan L. James, Philip J. Robinson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The harmful effects of in utero cigarette smoke exposure include increased asthma symptoms and reduced lung function during the neonatal period, increased airway responsiveness to inhaled stimuli, and an increased risk of sudden infant death syndrome. Altered lung function may result from altered airway/lung structure. Airway dimensions, alveolar attachment points, and parenchymal elastin content were measured in 32 infants who died from sudden infant death syndrome and were grouped according to their perinatal cigarette smoke exposure. Compared with those without any exposure to cigarette smoke, the distance between alveolar attachments on airways was greater (p < 0.001) in infants exposed to cigarette smoke only in utero or both in utero and during the postnatal period but not different in those with only postnatal exposure. The percentage of elastin within the alveolar walls was similar in all the exposure groups. These findings suggest that in utero cigarette smoke exposure may result in abnormal airway function due to a reduction of the forces opposing airway narrowing.
Sphingosine-1-phosphate signals the way for Cx43-mediated cardioprotection
Authors: R. D. Veenstra
Journal: Cardiovascular Research (2011)

This editorial refers to ‘The natural cardioprotective particle HDL modulates connexin43 gap junction channels’ by S. Morel et al., doi:10.1093/cvr/cvr257. 
The onset of coronary occlusion caused by vasospasm, thrombosis, or atherosclerotic plaque rupture produces myocardial ischaemia, and acute myocardial infarction (AMI) can result within minutes. Reperfusion with minimal time lapse is the treatment of choice for AMI, but coronary reperfusion can also enhance myocardial injury and the induction of life-threatening cardiac arrhythmias. In 1986, it was fortuitously discovered that brief bouts of myocardial ischaemia prior to the onset of prolonged ischaemia and infarction could protect the myocardium and reduce infarct size.1 Cardioprotection—the promotion of cell survival, myocardial function, and reduction of infarct size—is conferred by brief episodes of ischaemia prior to prolonged occlusion, a phenomenon called ‘ischaemic preconditioning’ (IPC).1,2 High-density lipoproteins (HDL), containing the so-called ‘good cholesterol’, are known to induce IPC independent of their lipid-lowering effects.3 Connexin43 (Cx43), the major myocardial gap junction protein responsible for rapid, synchronous transmission of the cardiac action potential, was also obligatorily linked to IPC when it was observed that the heterozygous deletion of the Gja1 gene in (Cx43+/−) mice eliminated the response.4 This requirement for the presence of Cx43 for IPC to occur was subsequently linked to the preservation of Cx43 phosphorylation during prolonged ischaemia.5 However, a link between the cardioprotective effects of HDL and Cx43 has not previously been established.

An original study by Morel et al. 6 establishes a causal link …