tbuckley/cabot-search huggingface dataset:
Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma
Authors: M. Silvestri, D. Spallarossa, V. Frangova Yourukova, E. Battistini, B. Fregonese, G.a. Rossi
Journal: European Respiratory Journal (1999)

Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p&lt;0.01). Interestingly, 14 out of 22 asthmatic children had NO levels &gt;8.8 ppb (i.e. &gt;2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p&lt;0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p&gt;0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established.
OC-019 Optimising The Performance Of Magnetic Assisted Capsule Endoscopy (mace) Of The Upper Gi Tract Using Ct Modelling
Authors: I Rahman, M Kay, T Bryant, S Pelitari, BD Dimitrov, P Patel
Journal: Gut (2014)

<h3>Introduction</h3> Capsule endoscopy, employed to investigate the small bowel, is now being further developed to visualise the upper GI tract. In a pig model, using a hand held magnet, we have demonstrated that magnetic assisted capsule endoscopy (MACE) in the stomach is feasible. However, it is unclear what the best methodology is to achieve complete gastric luminal views in humans. Our aim was to utilise CT modelling of the abdomen to determine the optimal placements of a capsule endoscope in the stomach to allow complete mucosal visualisation and to determine the optimal placement of the hand held magnet to aid pyloric traversing. <h3>Methods</h3> Using multiplanar reformatting, 100 good quality contrast abdominal CT scans were analysed to assess luminal visualisation by a magnetic capsule endoscope from 5 fixed stations throughout the stomach. From each station, we assessed the ability of a capsule endoscope to visualise 6 anatomical landmarks (cardia, fundus, body, incisura, antrum and pylorus). Success of visualisation of an anatomical area was only accepted when &gt;90% mucosal visualisation was achieved from a particular station. The pyloric canal angles were calculated to create a vector. We mapped the position of this vector on the patient’s skin (pyloric canal vector surface point) to determine the optimal placement of the magnet that would allow traversing of the capsule endoscope through the pylorus. <h3>Results</h3> There were 65 female and 35 male patients. Mean age of patients was 53 years (s.d+/-18 years). Best mucosal visualisation of the stomach landmarks was achieved from 3 stations; fundal dependant, antral dependent and opposite the antral dependent points. Maximal visualisation of the whole of the stomach, required combining 2 stations as shown in Table 1. The box in the figure shows the placement of the magnet in the upper back towards the right loin would allow pyloric traversing of the capsule endoscope in 83% of cases. Increasing age (p = 0.03) and inability to view the pylorus (p = 0.04) were predictors of being outside the box. <h3>Conclusion</h3> CT modelling has provided important data regarding the optimal stations in the stomach to position a magnetic capsule endoscope to allow maximal luminal mucosal visualisation and traversing the pylorus. Although there is some extreme variation in the upper GI anatomy, the majority of cases will allow the use of a single standard method in performing MACE which may be very useful for screening purposes. <h3>Disclosure of Interest</h3> None Declared.
Electrophysiological Basis of Arrhythmogenicity of QT/T Alternans in the Long-QT Syndrome
Authors: Masaomi Chinushi, Mark Restivo, Edward B. Caref, Nabil El-Sherif
Journal: Circulation Research (1998)

Abstract —Tachycardia-dependent QT/T alternans occurs in patients with the congenital or idiopathic form of long-QT syndrome (LQTS) and may presage the onset of polymorphic ventricular tachyarrhythmias. To examine the electrophysiological basis of arrhythmogenicity of QT/T alternans in LQTS, the tridimensional repolarization pattern of QT/T alternans was studied in the anthopleurin-A model of LQTS, a surrogate for LQT3. In 11 anesthetized mongrel puppies, tridimensional repolarization and activation patterns were analyzed from 256 to 384 unipolar electrograms. Cardiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. To induce QT/T alternans, the pacing cycle length (CL) was abruptly shortened in steps of 50 ms from a basic drive of 1000 ms. ARIs were calculated at epicardial (Epi), midmyocardial (Mid), and endocardial (End) sites. ARI restitution at each site was assessed by using a single premature stimulation delivered after the basic drive. ARI alternans occurred at longer CLs at Mid sites compared with End and Epi sites, and the magnitude of alternans at Mid sites was greater. Two factors contributed to the modulation of ARI during QT/T alternans: (1) differences in restitution kinetics at Mid sites, characterized by larger ΔARI and a slower time constant (τ), and (2) differences in diastolic intervals resulting in different input to restitution at the same constant CL. These 2 factors could explain not only the onset of alternans at Mid sites at longer CLs but also the critical observation that ARI dispersion between Epi and Mid sites during alternans was greater than during the slower basic CL. Marked ARI alternans could be present in local electrograms without manifest alternation of the QT/T segment in the surface ECG. The latter was seen at critically short CLs associated with reversal of the gradient of ARI between Epi and Mid sites, with a consequent reversal of polarity of the intramyocardial QT wave in alternate cycles. The arrhythmogenicity of QT/T alternans was primarily due to the greater degree of spatial dispersion of repolarization during alternans than during slower rates not associated with alternans. This could result in functional conduction block and reentrant ventricular tachyarrhythmias during the fixed drive associated with alternans.
Cardiac toxicity in association with chemotherapy and radiation therapy in a large cohort of older patients with non-small-cell lung cancer
Authors: D. Hardy, C.-C. Liu, J.N. Cormier, R. Xia, X.L. Du
Journal: Annals of Oncology (2010)

The study's objective was to investigate the risks of developing cardiac disorders following the administration of chemotherapy and radiation therapy in patients with non-small-cell lung cancer (NSCLC).The study consisted of 34 209 patients aged > or =65 years with American Joint Committee on Cancer stages I-IV NSCLC identified from the Surveillance, Epidemiology, and End Result-Medicare linked database (1991-2002) who were free of cardiac disorders at NSCLC diagnosis.There were significant associations between the use of chemotherapy/radiation and the risks of developing ischemic heart disease, conduction disorders, cardiac dysfunction, and heart failure. The absolute risks for cardiac dysfunction increased with the administration of chemotherapy-only and radiation-only, and incrementally with chemoradiation. Men, blacks, older patients, those with higher comorbidity scores, and advanced disease were at higher risk. The risk for ischemic heart disease increased when radiation/chemoradiation were rendered to the left lung and both lungs and for cardiac dysfunction, radiation administered to the left lung.There were significant associations especially for cardiac dysfunction with use of chemotherapy/radiation therapy and risks of developing cardiac toxicity in NSCLC patients. The risks of treatment-associated cardiac toxicity, specifically ischemic heart disease and cardiac dysfunction, were greatest among those with left-sided lung tumors.
Transepicardial or transendocardial injury: controversies regarding angiogenic potential and mechanism of action
Authors: S Fuchs
Journal: Cardiovascular Research (2001)

Time for primary review 20 days. 

Over the past decade, surgical and now catheter-based approaches using various mechanical devices and energy sources aimed to enhance tissue perfusion are being explored as new adjunctive therapies in patients with refractory ischemic coronary disease [1,2]. It has been suggested that the likely mechanism associated with the initiation of angiogenesis is the induction of local inflammatory processes, and that tissue changes trigger endogenous expression of variety of angiogenic cytokines acting in concert to initiate and maintain microvessel formation (i.e. angiogenesis) [3]. The improved collateral pathways may change the local ischemic milieu in a way that may culminate in a long-standing therapeutic effect in selected patients. Since angiogenesis was assumed to be a primary mechanism associated with ‘direct’ myocardial revascularization (DMR) procedures, it has been termed ‘the mechanical approach for myocardial angiogenesis’. Nevertheless, the evidence for a therapeutically significant angiogenesis following mechanical myocardial injury is inconclusive.

In the current paper we attempt to review the myocardial response to various mechanical channeling and ablative energy sources being used in practice and/or clinical investigations. Data indicative for angiogenesis in response to direct myocardial injury or to a combination of energy sources with pro-angiogenic pharmacotherapy (i.e. ‘hybrid’ approaches) are also provided and critically assessed.

### 1.1 Myocardial tissue responses to mechanical injury

#### 1.1.1 Laser energy

Laser energy has specific tissue interactions that are fundamental to our ability to achieve a desirable tissue response and avoid unwarranted excessive myocardial damage. For example, unlike CO2 laser, which provides more precise ‘ablative’ characteristics with some collateral damage [4], the holmium (Ho):YAG laser (currently used in most catheter-based and several surgical DMR protocols) has profound photoacoustic effects and hence a marked thermal and photochemical impact on myocardial tissue [5,6]. Minimizing the energy being directly delivered to the myocardium may predominantly trigger natural tissue processes that may cause local … 

* Corresponding author. Tel.: +1-202-877-3321; fax: +1-202-877-2715 rxk3{at}mhg.edu
Spore germination in Saccharomyces cerevisiae: global gene expression patterns and cell cycle landmarks
Authors: Daphna Joseph-Strauss, Drora Zenvirth, Giora Simchen, Naama Barkai
Journal: Genome biology (2007)

Abstract Background Spore germination in the yeast Saccharomyces cerevisiae is a process in which non-dividing haploid spores re-enter the mitotic cell cycle and resume vegetative growth. To study the signals and pathways underlying spore germination we examined the global changes in gene expression and followed cell-cycle and germination markers during this process. Results We find that the germination process can be divided into two distinct stages. During the first stage, the induced spores respond only to glucose. The transcription program during this stage recapitulates the general transcription response of yeast cells to glucose. Only during the second phase are the cells able to sense and respond to other nutritional components in the environment. Components of the mitotic machinery are involved in spore germination but in a distinct pattern. In contrast to the mitotic cell cycle, growth-related events during germination are not coordinated with nuclear events and are separately regulated. Thus, genes that are co-induced during G1/S of the mitotic cell cycle, the dynamics of the septin Cdc10 and the kinetics of accumulation of the cyclin Clb2 all exhibit distinct patterns of regulation during spore germination, which allow the separation of cell growth from nuclear events. Conclusion Taken together, genome-wide expression profiling enables us to follow the progression of spore germination, thus dividing this process into two major stages, and to identify germination-specific regulation of components of the mitotic cell cycle machinery.
Pituitary adenylate cyclase-activating peptide 38 a potent endogenously produced dilator of human airways
Authors: J. Kinhult, J.A. Andersson, R. Uddman, P. Stjärne, L-O. Cardell
Journal: European Respiratory Journal (2000)

Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities relevant to obstructive airway disease. In this study, the occurrence of PACAP 38 in human small bronchi and corresponding pulmonary arteries was analysed immunocytochemically. The dilatory effects of this peptide on the same structures were also studied in vitro. A moderate number of PACAP-like immunoreactive nerve fibres was seen in association with bronchial and vascular smooth muscle and around seromucous glands. PACAP 38 caused a concentration-dependent relaxation of precontracted bronchial and pulmonary arterial segments. The maximal relaxation was more pronounced in the airways than in the arteries, whereas the potency in both was identical. PACAP 38 caused relaxation of all segments tested (nine patients), whereas vasoactive intestinal polypeptide (VIP) failed to cause relaxation of bronchial segments from six of nine patients. Both PACAP and VIP dilated all pulmonary arterial segments tested. In conclusion, pituitary adenylate cyclase-activating peptide 38 is a potent dilator of human bronchi and is present in the human lung. Pituitary adenylate cyclase-activating peptide 38 may, therefore, play a role in the endogenous regulation of airway tone. The inhibitory effects of pituitary adenylate cyclase-activating peptide 38 are more consistent than those of the related neuropeptide vasoactive intestinal polypeptide, perhaps reflecting a difference in susceptibility to degrading enzymes.
Electronic cigarettes: reasons to be cautious
Authors: A. Furber
Journal: Thorax (2015)

Tobacco remains the leading cause of preventable mortality, morbidity and of health inequalities in many countries, including the UK. Eighty thousand people die every year in England from smoking.1 Many more suffer terrible disability. Tobacco control remains a public health priority.2 Smoking still kills.

In this context anything which could reduce this toll deserves serious consideration, just as any risks of undermining recent tobacco control successes need to be properly understood.

It is disappointing then that the debate on electronic cigarettes (also known as electronic nicotine delivery systems (ENDS) or nicotine vapourisers) has become characterised more by heat than light. There has been so much focus on these devices that we risk losing our focus on what we know works—a comprehensive strategy to reduce smoking prevalence.3 We must not lose, through neglect, the debate on standardised tobacco packaging or the need to further increase the price of tobacco. We need to move away from fixed positions to some key principles against which we can debate the evidence.

The first principle must be to ask whether electronic cigarettes are safe. First do no harm. Compared with smoking tobacco it is very clear that electronic cigarettes are much safer. Even though it is not difficult to be safer than a product which will kill half of its regular users, this message must not be lost. However, it is equally true to say that electronic cigarettes are not without harm.4 The vapour from some of these devices has been shown to contain ultrafine particles and carcinogens. There is little doubt that there is a risk of harm to …
Functional GATA-3 binding sites within murine CD8 alpha upstream regulatory sequences.
Authors: D B Landry, J D Engel, R Sen
Journal: The Journal of Experimental Medicine (1993)

Genes encoding the accessory molecules CD8 and CD4 are activated early in thymocyte development, generating CD4+8+ double positive intermediates, which give rise to two functionally distinct mature T cell subsets that express either CD4 or CD8. The mechanisms that govern the activation or suppression of the CD8 gene are likely to be central to the T cell development program. To identify the key regulatory factors, we have initiated an analysis of the transcriptional regulation of the murine CD8 alpha gene. We have identified three CD8+ cell-specific DNAase I hypersensitive sites (HSS) located upstream of the murine CD8 alpha gene. In vitro mobility shift analysis of the -4.0-kb HSS region has revealed multiple binding sites for the T cell-restricted transcription factor GATA-3. In vitro translated murine GATA-3 binds specifically to both CD8 GATA sites, and coexpression of this factor in transient transfection assays transactivates a reporter construct containing these sequences. These results provide the first evidence for the role of a T cell-restricted factor in the regulation of either CD8 or CD4 genes.
Interleukin-17A induces glucocorticoid insensitivity in human bronchial epithelial cells
Authors: G.J. Zijlstra, N.H.T. ten Hacken, R.F. Hoffmann, A.J.M. van Oosterhout, I.H. Heijink
Journal: European Respiratory Journal (2011)

A subset of asthma patients suffer from glucocorticoid (GC) insensitivity. T-helper cell type 17 cells have an emerging role in GC insensitivity, although the mechanisms are still poorly understood. We investigated whether interleukin (IL)-17A induces GC insensitivity in airway epithelium by studying its effects on responsiveness of tumour necrosis factor (TNF)-α-induced IL-8 production to budesonide in human bronchial epithelial 16HBE cells. We unravelled the underlying mechanism by the use of specific pathway inhibitors, reporter and overexpression constructs and a histone deacetylase (HDAC) activity assay. We demonstrated that IL-17A-induced IL-8 production is normally sensitive to GCs, while IL-17A pre-treatment significantly reduced the sensitivity of TNF-α-induced IL-8 production to budesonide. IL-17A activated the p38, extracellular signal-related kinase (ERK) and phosphoinositide-3-kinase (PI3K) pathways, and the latter appeared to be involved in IL-17A-induced GC insensitivity. Furthermore, IL-17A reduced HDAC activity, and overexpression of HDAC2 reversed IL-17A-induced GC insensitivity. In contrast, IL-17A did not affect budesonide-induced transcriptional activity of the GC receptor, suggesting that IL-17A does not impair the actions of the ligated GC receptor. In conclusion, we have shown for the first time that IL-17A induces GC insensitivity in airway epithelium, which is probably mediated by PI3K activation and subsequent reduction of HDAC2 activity. Thus, blockade of IL-17A or downstream signalling molecule PI3K may offer new strategies for therapeutic intervention in GC-insensitive asthma.
No Apparent Local Effect of Insulin on Microdialysis Continuous Glucose- Monitoring Measurements
Authors: Jeroen Hermanides, Iris M. Wentholt, Augustinus A. Hart, Joost B. Hoekstra, J. Hans DeVries
Journal: Diabetes Care (2008)

Data investigating the possible disturbing influence of insulin in the vicinity of continuous glucose monitoring (CGM) is lacking. We investigated the hypothesis that high local insulin concentrations would interfere with sensor readings.Two microdialysis sensors were inserted in the periumbilical region of 10 continuous subcutaneous insulin infusion (CSII)-treated type 1 patients. A test sensor was inserted as close as possible to the insulin catheter and compared with a control sensor. Glucose peak and nadir were induced. Horizontal and vertical shifts were assessed using curve fitting, and mean absolute difference (MAD) between paired blood and sensor values were calculated.Curve fitting showed no significant differences between the two sensors. MAD +/- SD was 8.50 +/- 3.47% for the test sensor and 9.21 +/- 3.17% for the control sensor, P = 0.72.Microdialysis CGM can be accurately performed in the proximity of CSII systems.
Improving the Magnetic Resonance Imaging Contrast and Detection Methods with Engineered Magnetic Nanoparticles
Authors: Jing Huang, Xiaodong Zhong, Liya Wang, Lily Yang, Hui Mao
Journal: Theranostics (2012)

Engineering and functionalizing magnetic nanoparticles have been an area of the extensive research and development in the biomedical and nanomedicine fields. Because their biocompatibility and toxicity are well investigated and better understood, magnetic nanoparticles, especially iron oxide nanoparticles, are better suited materials as contrast agents for magnetic resonance imaging (MRI) and for image-directed delivery of therapeutics. Given tunable magnetic properties and various surface chemistries from the coating materials, most applications of engineered magnetic nanoparticles take advantages of their superb MRI contrast enhancing capability as well as surface functionalities. It has been found that MRI contrast enhancement by magnetic nanoparticles is highly dependent on the composition, size and surface properties as well as the degree of aggregation of the nanoparticles. Therefore, understanding the relationships between these intrinsic parameters and the relaxivities that contribute to MRI contrast can lead to establishing essential guidance that may direct the design of engineered magnetic nanoparticles for theranostics applications. On the other hand, new contrast mechanism and imaging strategy can be developed based on the novel properties of engineered magnetic nanoparticles. This review will focus on discussing the recent findings on some chemical and physical properties of engineered magnetic nanoparticles affecting the relaxivities as well as the impact on MRI contrast. Furthermore, MRI methods for imaging magnetic nanoparticles including several newly developed MRI approaches aiming at improving the detection and quantification of the engineered magnetic nanoparticles are described.