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Find video protocols related to scientific articles indexed in Pubmed.
IL-33-dependent Type 2 Inflammation During Rhinovirus-induced Asthma Exacerbations In Vivo.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-29-2014
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Rationale: Rhinoviruses are the major cause of asthma exacerbations, however mechanisms are poorly understood. We hypothesised that the epithelial-derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. Objectives: To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway. Methods: We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airway during a rhinovirus infection. Additionally we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus-infected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. Measurements and Main Results: IL-4, IL-5, IL-13 and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with virus load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33 and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33. Conclusions: IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus induced IL-33 and IL-33 responsive T cells and ILC2s are key mechanistic links between virus infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbations.
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IL-25: the missing link between allergy, viral infection, and asthma?
Sci Transl Med
PUBLISHED: 10-03-2014
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Interleukin 25 boosts proinflammatory and proasthmatic responses in the allergic lung and emerges as a key determinant of virally induced asthma exacerbations and as a therapeutic target for asthma (Beale et al., this issue).
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A complete corticotropin releasing factor system localized in human fetal lung.
Hormones (Athens)
PUBLISHED: 04-30-2014
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The Corticotropin Releasing Factor (CRF) system (neuropeptides CRF, Ucn I, II, III and binding sites CRFR1, CRFR2, CRF-BP) is responsible for stress regulation and the homeostasis of an organism. Herein we study the CRF system in human normal and pathological fetal lungs.
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Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma.
J Allergy Clin Immunol Pract
PUBLISHED: 04-21-2014
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Children who begin wheezing during early childhood are frequently seen by health care providers in primary care, in hospitals, and in emergency departments, and by allergists and pulmonologists. When a young child, such as the 2 year-old patient presented here, is evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors that influence prognosis are not mutually exclusive, are interrelated (ie, cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed.
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Microsatellite and Wolbachia analysis in Rhagoletis cerasi natural populations: population structuring and multiple infections.
Ecol Evol
PUBLISHED: 04-21-2014
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Rhagoletis cerasi (Diptera: Tephritidae) is a major pest of sweet and sour cherries in Europe and parts of Asia. Despite its economic significance, there is a lack of studies on the genetic structure of R. cerasi populations. Elucidating the genetic structure of insects of economic importance is crucial for developing phenological-predictive models and environmental friendly control methods. All natural populations of R. cerasi have been found to harbor the endosymbiont Wolbachia pipientis, which widely affects multiple biological traits contributing to the evolution of its hosts, and has been suggested as a tool for the biological control of insect pests and disease vectors. In the current study, the analysis of 18 R. cerasi populations collected in Greece, Germany, and Russia using 13 microsatellite markers revealed structuring of R. cerasi natural populations, even at close geographic range. We also analyzed the Wolbachia infection status of these populations using 16S rRNA-, MLST- and wsp-based approaches. All 244 individuals screened were positive for Wolbachia. Our results suggest the fixation of the wCer1 strain in Greece while wCer2, wCer4, wCer5, and probably other uncharacterized strains were also detected in multiply infected individuals. The role of Wolbachia and its potential extended phenotypes needs a thorough investigation in R. cerasi. Our data suggest an involvement of this symbiont in the observed restriction in the gene flow in addition to a number of different ecological factors.
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Complementing the randomized controlled trial evidence base. Evolution not revolution.
Ann Am Thorac Soc
PUBLISHED: 02-25-2014
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Observational studies and pragmatic trials can complement classical randomized controlled trials (RCTs) by providing data more relevant to the circumstances under which medicine is routinely practiced, thereby providing practical guidance for clinicians. The bearing of RCT findings on day-to-day practice can be weighted and the data more meaningfully interpreted by practicing clinicians if evidence is integrated from a variety of different study designs and methodologies. The advent of observational studies and pragmatic trials, often referred to as "real-life studies," has met with a degree of cynicism, but their role and value is gaining widespread recognition and support among clinicians. This article discusses where observational studies and pragmatic trials have utility, namely: in addressing clinical questions that are unanswered and/or unanswerable by RCTs; in testing new hypotheses and possible license extensions; and in helping to differentiate between available therapies for a given indication. Moreover, it seeks to highlight how the different approaches fit within a conceptual framework of evidence relevant to clinical practice, a step-change in the traditional view of medical evidence.
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The common cold: potential for future prevention or cure.
Curr Allergy Asthma Rep
PUBLISHED: 01-14-2014
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The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.
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Biochemical, Biophysical and IgE-Epitope Characterization of the Wheat Food Allergen, Tri a 37.
PLoS ONE
PUBLISHED: 01-01-2014
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Wheat is an important staple food and potent allergen source. Recently, we isolated a cDNA coding for wheat alpha-purothionin which is recognized by wheat food allergic patients at risk for severe wheat-induced allergy. The purpose of the present study was the biochemical, biophysical and IgE epitope characterization of recombinant alpha-purothionin. Synthetic genes coding for alpha-purothionin were expressed in a prokaryotic system using Escherichia coli and in a eukaryotic expression system based on baculovirus-infected Sf9-insect cells. Recombinant proteins were purified and characterized by SDS-PAGE, mass spectrometry, circular dichroism, chemical cross-linking and size exclusion chromatography. Five overlapping peptid were synthesized for epitope mapping. Alpha-purothionin-specific rabbit antibodies were raised to perform IgE-inhibition experiments and to study the resistance to digestion. The IgE reactivity of the proteins and peptides from ten wheat food allergic patients was studied in non-denaturing RAST-based binding assays. Alpha-purothionin was expressed in the prokaryotic (EcTri a 37) and in the eukaryotic system (BvTri a 37) as a soluble and monomeric protein. However, circular dichroism analysis revealed that EcTri a 37 was unfolded whereas BvTri a 37 was a folded protein. Both proteins showed comparable IgE-reactivity and the epitope mapping revealed the presence of sequential IgE epitopes in the N-terminal basic thionin domain (peptide1:KSCCRSTLGRNCYNLCRARGAQKLCAGVCR) and in the C-terminal acidic extension domain (peptide3:KGFPKLALESNSDEPDTIEYCNLGCRSSVC, peptide4:CNLGCRSSVCDYMVNAAADDEEMKLYVEN). Natural Tri a 37 was digested under gastric conditions but resistant to duodenal digestion. Immunization with EcTri a 37 induced IgG antibodies which recognized similar epitopes as IgE antibodies from allergic patients and inhibited allergic patients' IgE binding. Reactivity to Tri a 37 does not require a folded protein and the presence of sequential IgE epitopes indicates that sensitization to alpha-purothionin occurs via the gut. Both allergens can be used for in-vitro diagnosis of wheat food allergy. The induction of blocking IgG antibodies suggests the usefulness for immunotherapy.
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Use of wild bird surveillance, human case data and GIS spatial analysis for predicting spatial distributions of West Nile virus in Greece.
PLoS ONE
PUBLISHED: 01-01-2014
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West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723-1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841-6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence.
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Physical exercise increases nasal patency in asthmatic and atopic preschool children.
Am J Rhinol Allergy
PUBLISHED: 11-27-2013
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Physical exercise causes a decrease in nasal mucosal congestion and hence an increase in nasal patency. This nasal response has been studied only in adults. A correlation between nasal obstruction and asthma or allergic rhinitis has been previously found. This study evaluates the influences of atopy and asthma on nasal patency and the changes in nasal patency induced by physical exercise in preschool children.
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Foodborne and orofecal pathogens and allergic sensitization: EuroPrevall-International Cooperation study.
Pediatr Allergy Immunol
PUBLISHED: 10-27-2013
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An inverse association between markers of exposure to foodborne and orofecal pathogens and allergic sensitization has been reported. However, the findings of epidemiological studies have not been consistent. This study investigated the relationship between antibodies to hepatitis A, Toxoplasma gondii and salmonella and allergic sensitization to food and aeroallergens in children from different geographical areas.
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Breastfeeding and wheeze prevalence in pre-schoolers and pre-adolescents: the Genesis and Healthy Growth studies.
Pediatr Allergy Immunol
PUBLISHED: 10-22-2013
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To date, extensive research has been undertaken on a potential link of breastfeeding (BF) to wheezing illnesses. Nevertheless, an association remains to be established, partly due to age-dependent discrepancies and different definitions of exposures/outcomes across studies. We thus investigated the relation of diverse infantile feeding patterns with wheeze/asthma prevalence in two cohorts of children of different ages (preschool and preadolescent).
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Conference Scene: novelties in immunotherapy.
Immunotherapy
PUBLISHED: 10-04-2013
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The only method aiming to permanently cure allergic disorders is allergen immunotherapy. Over the last 20 years there has been great progress in understanding the mechanisms that govern allergen immunotherapy in order to meet three basic prerequisites: safety, effectiveness and compliance. In the present summary report from the European Academy of Allergology and Clinical Immunology-World Allergy Organization Congress held last June in Milan, we review key points concerning the main axes as diagnosis, novel modalities, routes and protocols, as well as two important immunotherapy fields: food and insect venom allergy.
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Platelet Activation in Essential Hypertension During Exercise: Pre- and Post-Treatment Changes With an Angiotensin II Receptor Blocker.
Am. J. Hypertens.
PUBLISHED: 08-23-2013
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Acute exercise may exert deleterious effects on the cardiovascular system through a variety of pathophysiological mechanisms, including increased platelet activation. However, the degree of exercise-induced platelet activation in untreated hypertensive (UH) individuals as compared with normotensive (NT) individuals has yet to be established. Furthermore, the effect of antihypertensive treatment on exercise-induced platelet activation in essential hypertension (EH) remains unknown.
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Pediatric Allergic Rhinitis and Asthma: Can the March be Halted?
Paediatr Drugs
PUBLISHED: 08-20-2013
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The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of united airways disease or respiratory allergy, implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the atopic march. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.
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The influence of early feeding practices on fruit and vegetable intake among preschool children in 4 European birth cohorts.
Am. J. Clin. Nutr.
PUBLISHED: 07-17-2013
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Fruit and vegetable intake in children remains below recommendations in many countries. The long-term effects of early parental feeding practices on fruit and vegetable intake are not clearly established.
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Key regulators of sensitization and tolerance: GM-CSF, IL-10, TGF-? and the Notch signaling pathway in adjuvant-free experimental models of respiratory allergy.
Int. Rev. Immunol.
PUBLISHED: 06-18-2013
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Conventional experimental models of respiratory allergy have contributed greatly to our current knowledge of the pathophysiology of allergic airway diseases; nevertheless, they are contingent upon unnatural sensitization techniques, entailing adjuvant-aided intraperitoneal (i.p) administration of antigen. Currently, there is a growing appreciation of the impact of tolerance mechanics in the pathophysiology of respiratory allergy. Thus, inasmuch as adjuvants exert a robust tolerance-modifying action, a transition from the conventional method of experimental sensitization to one that is more naturally and clinically relevant becomes important. We therefore opted to survey the literature and identify agents that could interfere with sensitization mechanics following non-adjuvant-aided airway exposure of laboratory rodents to aeroallergen. GM-CSF was found to exert robust Th2-polarizing action in this setting. Conversely, IL-10 fulfilled an important, albeit not so clear-cut, tolerance-favoring role; TGF-? was also identified as a likely instigator of tolerogenesis. The role of Notch signaling in the sensitization versus tolerance dilemma appeared to be important but diverse. Collectively, these factors appeared to profoundly and diversely modulate the balance between tolerance and sensitization in naturally relevant experimental models of allergic airway disease.
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Clinical characteristics, spontaneous clearance and treatment outcome of acute hepatitis C: a single tertiary center experience.
Saudi J Gastroenterol
PUBLISHED: 03-14-2013
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Acute hepatitis C is rarely diagnosed due to its predominantly asymptomatic course. However, early treatment results in viral eradication in a high number of patients thus, preventing chronicity. The aim of our study was to describe our experience with patients with acute hepatitis C virus (HCV) infection who presented and followed-up in our liver unit, pointing on treatment strategy, and outcome.
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Increasing frequency of gram-positive cocci and gram-negative multidrug-resistant bacteria in spontaneous bacterial peritonitis.
Liver Int.
PUBLISHED: 02-22-2013
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Spontaneous bacterial peritonitis (SBP) is historically caused by Gram-negative bacteria (GNB) almost exclusively Enterobacteriaceae. Recently, an increasing rate of infections with Gram-positive cocci (GPC) and multidrug-resistant (MDR) microorganisms was demonstrated.
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Frequency and predictors of no treatment in anti-hepatitis C virus-positive patients at tertiary liver centers in Greece.
Eur J Gastroenterol Hepatol
PUBLISHED: 02-22-2013
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Despite the improving efficacy of antiviral therapy, a significant proportion of chronic hepatitis C patients never start treatment. We determined the magnitude and reasons for no treatment in anti-hepatitis C virus (HCV)-positive patients visiting tertiary liver centers in Greece.
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A molecular diagnostic algorithm to guide pollen immunotherapy in southern Europe: towards component-resolved management of allergic diseases.
Int. Arch. Allergy Immunol.
PUBLISHED: 02-20-2013
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Correct identification of the culprit allergen is an essential part of diagnosis and treatment in immunoglobulin E (IgE)-mediated allergic diseases. In recent years, molecular biology has made important advances facilitating such identification and overcoming some of the drawbacks of natural allergen extracts, which consist of mixtures of various proteins that may be allergenic or not, specific for the allergen source or widely distributed (panallergens). New technologies offer the opportunity for a more accurate component-resolved diagnosis, of benefit especially to polysensitized allergic patients. The basic elements of molecular diagnostics with potential relevance to immunotherapy prescription are reviewed here, with a focus on Southern European sensitization patterns to pollen allergens. We propose a basic algorithm regarding component-resolved diagnostic work-up for pollen allergen-specific immunotherapy candidates in Southern Europe; this and similar algorithms can form the basis of improved patient management, conceptually a Component-Resolved Allergy Management.
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Experimental and first-principles characterization of functionalized magnetic nanoparticles.
Chemphyschem
PUBLISHED: 02-13-2013
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Magnetic iron oxide nanoparticles synthesized by coprecipitation and thermal decomposition yield largely monodisperse size distributions. The diameters of the coprecipitated particles measured by X-ray diffraction and transmission electron microscopy are between approximately 9 and 15 nm, whereas the diameters of thermally decomposed particles are in the range of 8 to 10 nm. Coprecipitated particles are indexed as magnetite-rich and thermally decomposed particles as maghemite-rich; however, both methods produce a mixture of magnetite and maghemite. Fourier transform IR spectra reveal that the nanoparticles are coated with at least two layers of oleic acid (OA) surfactant. The inner layer is postulated to be chemically adsorbed on the nanoparticle surface whereas the rest of the OA is physically adsorbed, as indicated by carboxyl O-H stretching modes above 3400 cm(-1). Differential thermal analysis (DTA) results indicate a double-stepped weight loss process, the lower-temperature step of which is assigned to condensation due to physically adsorbed or low-energy bonded OA moieties. Density functional calculations of Fe-O clusters, the inverse spinel cell, and isolated OA, as well as OA in bidentate linkage with ferrous and ferric atoms, suggest that the higher-temperature DTA stage could be further broken down into two regions: one in which condensation is due ferrous/ferrous- and/or ferrous/ferric-OA and the other due to condensation from ferrous/ferric- and ferric/ferric-OA complexes. The latter appear to form bonds with the OA carbonyl group of energy up to fivefold that of the bond formed by the ferrous/ferrous pairs. Molecular orbital populations indicate that such increased stability of the ferric/ferric pair is due to the contribution of the low-lying Fe(3+) t(2g) states into four bonding orbitals between -0.623 and -0.410 a.u.
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Misdirected antibody responses against an N-terminal epitope on human rhinovirus VP1 as explanation for recurrent RV infections.
FASEB J.
PUBLISHED: 11-25-2011
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Rhinoviruses (RVs) are the primary cause of upper respiratory tract infections, generally known as the common cold. Moreover, RV infections can trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). We expressed the 4 major RV capsid proteins, VP1-VP4, in Escherichia coli and used these proteins as well as recombinant and synthetic VP1 fragments to study and map antibody responses in RV-infected humans. VP1, which on infection binds to ICAM 1, was identified as a major target for the memory immune response, residing in the IgG1 subclass and IgA class. Interestingly, this response was mainly directed against an N-terminal 20 mer peptide in VP1, P1a, which becomes exposed on intact RV only when it docks to its receptor ICAM 1. Molecular modeling using the 3-dimensional RV capsid structures revealed that P1a was localized inside the capsid and outside the areas involved in receptor binding or RV neutralization. Our results suggest misdirection of antibody responses against a nonprotective epitope as a mechanism how RV escapes immunity and causes recurrent infections. Based on these findings, it may be possible to design vaccines against RV infections and RV-induced respiratory diseases.
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Genetic and cytogenetic analysis of the American cherry fruit fly, Rhagoletis cingulata (Diptera: Tephritidae).
Genetica
PUBLISHED: 10-17-2011
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The American eastern cherry fruit fly, Rhagoletis cingulata, a pest of cherries in the western hemisphere, invaded Europe in 1983, and since then dispersed to several European countries. Information on the genetics and cytogenetics of this pest is very scarce. The mitotic karyotype and detailed photographic maps of the salivary gland polytene chromosomes of R. cingulata are presented here. The mitotic metaphase complement consists of six pairs of chromosomes with the sex chromosomes being very small and similar in size. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes (10 polytene arms), which correspond to the five autosomes of the mitotic nuclei and an extrachromosomal heterochromatic mass, which corresponds to the sex chromosomes. The banding patterns and the most characteristic features and prominent landmarks of each polytene chromosome are presented and discussed. Chromosomal homologies between R. cingulata, R. completa and R. cerasi are also proposed, based on the comparison of chromosome banding patterns. Furthermore, the detection and characterization of Wolbachia pipientis in the R. cingulata population studied is presented and the potential correlation with the asynaptic phenomena found in its polytene complement is discussed. In addition, 10 out of 24 microsatellite markers developed for other Rhagoletis species are cross-amplified, evaluated and proposed as useful markers for population and genetic studies in R. cingulata.
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Aortic root replacement in case of isolated aortitis and previous coronary artery bypass.
Hellenic J Cardiol
PUBLISHED: 09-24-2011
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The surgical management of aortic regurgitation in a patient with aortitis is potentially of high risk, especially if it is a reoperation. We present the case of a 59-year-old man for whom coronary artery bypass surgery was not feasible due to structural abnormalities of the aorta and hybrid management was applied. The histopathological examination showed aortitis. One year later, the same patient developed severe aortic regurgitation. In order to minimize the surgical risk of the reoperation we considered all the surgical options. The modified Bentall procedure still seems to be the gold standard in these cases.
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Molecular and immunological characterization of Mus a 5 allergen from banana fruit.
Mol Nutr Food Res
PUBLISHED: 08-03-2011
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Banana fruit has become an important cause of fruit allergy in the recent years. Among the five registered IUIS allergens, Mus a 1 and Mus a 2 have been characterized in detail. In this study, molecular characterization and evaluation of the allergenic properties of ?-1,3-glucanase from banana (Musa acuminata), denoted as Mus a 5, were performed.
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Risk of allergic reactions to wine, in milk, egg and fish-allergic patients.
Clin Transl Allergy
PUBLISHED: 06-07-2011
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European legislators and wine producers still debate on the requirement for labeling of wines fined with potentially allergenic food proteins (casein, egg white or fish-derived isinglass). We investigated whether wines fined with known concentrations of these proteins have the potential to provoke clinical allergic reactions in relevant patients.
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Effect of simulated gastro-duodenal digestion on the allergenic reactivity of beta-lactoglobulin.
Clin Transl Allergy
PUBLISHED: 05-31-2011
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Cows milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of ?-lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children.
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An insight into the early mechanisms of allergen-specific immunotherapy.
Immunotherapy
PUBLISHED: 03-15-2011
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The mechanisms governing the induction of peripheral tolerance as a result of specific immunotherapy are far from being clearly characterized. In the last 15 years, a number of studies have highlighted the tolerogenic role of regulatory T cells, blocking antibodies and anti-inflammatory cytokines such as IL-10 and TGF-?; however, the best part of our knowledge is mostly limited to mechanisms underlying the maintenance phase. By contrast, little is known regarding the very early effects seen in rush and ultrarush immunotherapy protocols. In this article, Bussmann et al. provide evidence on the possible role, first, of inhibitory receptors of the leukocyte immunoglobulin-like receptor family and, second, of the upregulation of indoleamine 2,3-dioxygenase and subsequent tryptophan starvation on the induction of specific tolerance within a few hours after the initial doses. They also suggest that the observed changes reflect the activation of protective mechanisms, which we are just beginning to understand.
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Pringle maneuver exacerbates systemic inflammatory response and multiple-organ injury induced by extended liver radiofrequency ablation.
Hum Exp Toxicol
PUBLISHED: 03-07-2011
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To assess the systemic inflammatory response (SIR) and the multi-organ damage after large-volume liver radiofrequency ablation (RFA) with or without concurrent Pringle maneuver.
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The management of post-intubation tracheal stenoses with self-expandable stents: early and long-term results in 11 cases.
Eur J Cardiothorac Surg
PUBLISHED: 02-12-2011
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The optimal management of post-intubation tracheal stenoses is surgical reconstruction of the airway. Stenting of the trachea using silastic T-tubes or one of the various types of tracheal stents are the alternative ways to surgical reconstruction for the management of post-intubation tracheal stenoses. The early and long-term results of 11 patients with post-intubation tracheal stenosis, who underwent tracheal stenting with self-expandable metallic stents (SEMSs), are presented.
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Childhood acute urticaria in northern and southern Europe shows a similar epidemiological pattern and significant meteorological influences.
Pediatr Allergy Immunol
PUBLISHED: 01-26-2011
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Acute urticaria (AU) is a common condition that often presents in childhood. Although there is a general perception of cyclic annual trends in AU, no one has tried to identify any seasonal variation on its prevalence and incidence, associate environmental influences and impute geographic, ethnic, or even genetic features that may contribute to its onset. We aimed to analyze the influence of climate and geographic parameters on annual fluctuation of AU cases referred to the Emergency Departments (EDs) of Norwich (UK) and Heraklion (Crete, Greece), compare all identifiable potential triggers and severity, and calculate the prevalence and incidence of AU. Record-based data of all children up to 14 yr of age referred to both EDs between June 2005 and May 2007 were examined retrospectively. Demographic characteristics and any potential identifiable triggers of AU were recorded and compared. Poissons regression was utilized to examine any influence of meteorological parameters on AU incidence. Edwards test for seasonality was applied to identify any significant seasonal trend of the AU incidence within each city. Seven hundred and twenty-nine AU cases were identified (324 in Norwich and 405 in Heraklion), among 56,624 total referrals (28,931 and 27,693 cases, respectively). Respiratory infections were found to be the most commonly associated potential triggers of AU and food allergens the least. AU cases and incidence rates in both cities were equally distributed during the study period. A non-significant seasonal trend in AU incidence (October, April-May) was observed in Norwich, in contrast to a significant seasonal pattern (December, February-May) of AU in Heraklion. Temperature was inversely associated with AU incidence, while the statistically significant effect of relative humidity varied. Acute childhood urticaria shows a similar epidemiological pattern in northern and southern Europe regardless of the expected differences in genetic, geographic, and environmental background. Temperature and humidity are correlated with AU incidence. Seasonality of several acute respiratory viral infections, the most prominent associated trigger of AU, coincides with the observed AU seasonality, suggesting a potential linkage. However, this needs to be elucidated from larger epidemiological studies.
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A 5-year venom immunotherapy protocol with 50 ?g maintenance dose: safety and efficacy in school children.
Pediatr Allergy Immunol
PUBLISHED: 01-16-2011
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Venom immunotherapy (VIT) has been shown to be an effective and safe treatment for preventing sting-induced anaphylaxis in patients with systemic reactions to hymenoptera stings. A remaining problem is the relative effectiveness and safety of different immunotherapy protocols used with respect to maintenance dose, injection interval, and duration.
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Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg- mothers.
Cell. Mol. Immunol.
PUBLISHED: 07-26-2010
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Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active-passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg(+)) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg(+)/HBeAg(-) mothers. Blood was collected from 46 HBsAg(+) mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg(+) mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon (IFN)-? concentrations were determined by ELISA. HBsAg-induced production of IL-2, IL-5, IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination. All neonates were HBsAg(-) and responded to vaccination. Increased IFN-? production following HBcAg stimulation was seen in 30.4% of neonates born to HBsAg(+)/HBeAg(-) mothers. Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation, whereas IL-5, IL-6 and IL-10 cytokine responses were not significantly different. Almost one-third of uninfected neonates developed viral antigen-induced IFN-? production, suggesting that they had been exposed to virions or viral derivatives. This encounter, however, did not impair their T-cell responses to vaccination.
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Whole blood interferon-? release assay is a useful tool for the diagnosis of tuberculosis infection particularly among Bacille Calmette Guèrin-vaccinated children.
Pediatr. Infect. Dis. J.
PUBLISHED: 07-10-2010
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The performance of QuantiFERON-tuberculosis (TB) Gold-In-Tube assay was compared with the tuberculin skin test for the diagnosis of TB among children. It was shown that among non-Bacille Calmette Guèrin immunized children, agreement between tests was excellent both in those with TB disease and in TB contacts. Among Bacille Calmette Guèrin-immunized children, agreement was fair in those with active disease and poor among TB contacts. It is concluded that QuantiFERON-TB Gold-In-Tube compares with the tuberculin skin test in the diagnosis of TB disease and latent tuberculosis infection in TB contacts among children and has enhanced specificity.
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Nitric oxide, ammonia, and CRP levels in cirrhotic patients with hepatic encephalopathy: is there a connection?
J. Clin. Gastroenterol.
PUBLISHED: 05-25-2010
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Comparison of nitric oxide (NO) levels in cirrhotic patients with and without hepatic encephalopathy (HE), evaluation of possible correlation between HE and other clinical or laboratory characteristics, and estimation of utilization of NO levels in clinical practice.
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Dendritic cells in uninfected infants born to hepatitis B virus-positive mothers.
Clin. Vaccine Immunol.
PUBLISHED: 05-12-2010
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Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-alpha) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-alpha production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-alpha production until the age of 6 months and inhibits IFN-alpha responses triggered by the TLR7 pathway.
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Corneal infiltrates after corneal collagen cross-linking.
J Refract Surg
PUBLISHED: 03-23-2010
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To present a case of advancing keratoconus treated with corneal collagen cross-linking (CXL) with ultraviolet A (UVA) light and riboflavin complicated with sterile infiltrates.
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Viral respiratory tract infections and asthma: the course ahead.
J. Allergy Clin. Immunol.
PUBLISHED: 03-15-2010
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Inquiries into the relationships between viral respiratory tract illnesses and the inception and exacerbation of asthma are being facilitated by recent advances in research approaches and technology. In this article we identify important knowledge gaps and future research questions, and we discuss how new investigational tools, including improved respiratory tract virus detection techniques, will permit current and future researchers to define these relationships and the host, virus, developmental, and environmental mechanisms that regulate them. A better understanding of these processes should facilitate the development of improved strategies for the prevention and treatment of virus-induced wheezing illnesses and asthma exacerbations and, possibly, the ultimate goal of discovering effective approaches for the primary prevention of asthma.
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Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkins lymphoma.
Ann. Hematol.
PUBLISHED: 03-15-2010
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Apoptosis-related proteins play an important role in lymphoma cell death during chemotherapy. In our study, we investigated the prognostic significance of CD95, BCL2, and P53 expression in extranodal non-Hodgkins lymphoma (NHL). We examined 71 patients with extranodal NHL [45 diffuse large B-cell lymphomas (DLBCLs) and 26 mucosa-associated lymphoid tissue lymphomas (MALTLs)], 35 male and 36 female, with a median age of 65.8 years. The most common site of origin was the stomach (N = 31). Paraffin-embedded specimens were analyzed immunohistochemically for CD95, BCL2, and P53 expression. Multivariate analysis revealed that in DLBCLs, positive CD95 and negative BCL2 expression were independent prognostic factors for overall survival. We reached the same conclusion for MALTLs, with positive CD95 and negative P53 expression. In DLBCLs, the 5-year overall survival rate was 71.5% for the CD95-positive cases and 35% for the CD95-negative cases (p = 0.004) and the 5-year overall survival was significantly better in BCL2-negative cases (70.8%) when compared to BCL2-positive cases (37%; p = 0.009). In MALTLs, the 5-year overall survival rate for the CD95-positive and CD95-negative groups was 89.5% and 42.9%, respectively (p = 0.004) and the 5-year overall survival rate was 50% for the P53-positive cases and 88.9% for the P53-negative cases (p = 0.016). In conclusion, positive CD95 expression proved to be a good prognostic factor of overall survival in both extranodal DLBCLs and MALTLs. In contrast, positive expression of BCL2 and P53 was found to be unfavorably associated with survival in extranodal DLBCLs and MALTLs, respectively.
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HOX A10 and HOX A11 mutation scan in congenital malformations of the female genital tract.
Reprod. Biomed. Online
PUBLISHED: 02-03-2010
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Homeobox (HOX) genes encode a number of transcription factors, expressed along the developmental axis of the female genital tract during the embryonic period. Because HOX A10 and HOX A11 genes are expressed in the embryonic paramesonephric (Müllerian) ducts, abnormally low expression by mutant HOX A10 and HOX A11 genes might cause genital tract anomalies. This case-control study examined if one or more mutations in the HOX A10 and HOX A11 genes are included in the pathogenesis of the female genital tract anomalies. Blood samples were obtained from 30 women diagnosed with malformations of the genital tract (18 with septate uterus, three with bicornuate uterus, two with didelphys uterus, two with unicornuate uterus and five with aplasia/dysplasia) and 100 normal controls. DNA samples prepared from blood leukocytes were used as templates for polymerase chain reaction amplification of DNA fragments from HOX A10 and HOX A11 genes. The gene fragments were tested for DNA sequence differences using single-strand conformation polymorphism analysis and sequenced when genetic variation was detected. No subject showed a plausible causative mutation in HOX A10 or HOX A11; the sole variant observed (P38R) found in a patient with septate uterus was also present in her clinically normal mother.
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Hyperchloremic metabolic acidosis due to deferasirox in a patient with beta thalassemia major.
Ann Pharmacother
PUBLISHED: 11-24-2009
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To report a case of hyperchloremic metabolic acidosis in a patient with beta thalassemia major secondary to treatment with deferasirox due to iron overload.
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Association of nutrient intake and wheeze or asthma in a Greek pre-school population.
Pediatr Allergy Immunol
PUBLISHED: 09-09-2009
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The rise of asthma prevalence in children observed the last years might be related to several dietary factors/components as suggested by several researchers. We aimed to evaluate the potential relationship between certain nutrients intake and asthma occurrence in a population of pre-school children. In the framework of the cross-sectional study Growth, Exercise and Nutrition Epidemiological Study In pre-schoolers, data were collected from 1964 children, aged 24-72 months, living in five different counties in Greece. The International Study of Asthma and Allergies in Childhood questionnaire was used to assess asthma related outcomes. Dietary intake was assessed with 3 days diet records. The prevalence of ever wheeze, current wheeze and diagnosed asthma was 37.7%, 27.5% and 10.5% respectively. Dietary intake of magnesium had a 0.5% and 0.6% increase in the reported risk of current wheeze and diagnosed asthma respectively. On the contrary a decrease in the prevalence of ever (OR: 0.997, 95% CI: 0.995-1.000) and current wheeze (OR: 0.996, 95% CI: 0.993-0.999) was associated with vitamin C intake. Calcium intake slightly decreased the risk of current wheeze (OR: 0.999, 95% CI: 0.998-0.999). An increase of 2% of the risk of reporting ever or current wheeze was associated with mono-unsaturated fatty acid intake. Magnesium intake was the only independent predictor for doctors diagnosed asthma. We conclude that dietary intake of vitamin C and calcium seem to have a protective effect on the incidence of wheeze in pre-school children, whereas magnesium and mono-unsaturated fatty acid may have a harmful role.
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Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-17-2009
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The purpose of this study was to investigate the co-expression of survivin, c-erbB2, and COX-2 in endometrial cancer tissues and evaluate its prognostic significance in endometrial cancer
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Association of passive exposure of pregnant women to environmental tobacco smoke with asthma symptoms in children.
Pediatr Allergy Immunol
PUBLISHED: 08-14-2009
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Environmental tobacco smoke (ETS) is a significant risk factor for the presence and increased severity of asthma- and allergy-related symptoms in children. Smoking during pregnancy has detrimental effects on asthma-associated outcomes in childhood. Whether passive exposure of pregnant women to ETS may also lead to asthma in their offspring, is not known. The aim of this study was to investigate the association of passive exposure of pregnant women to ETS and asthma- and/or allergy-related symptoms in Preschool children. Cross-sectional data were collected with questionnaires from 2374 Preschool children, recruited from public and private nurseries and day-care centers. Parental smoking was significantly associated with wheezing symptoms in their children. Mothers active smoking during pregnancy significantly increased the risk for occurrence of asthma symptoms and/or medically diagnosed asthma in Preschool children in a dose-dependent manner. Passive exposure to ETS, mainly during the third trimester of pregnancy, was significantly associated with asthma- and allergy-related symptoms after adjusting for several confounders in a multivariate analysis (current wheeze: OR = 1.42, 95% CI = 1.06-1.91, pruritic rash ever: OR= 1.45, 95% CI = 1.01-2.08). Passive exposure of pregnant women to ETS during the third trimester is positively associated with asthma- and allergy-related symptoms in their Preschool age children. Public health policies should be oriented not only towards smoking cessation, but also reinforce elimination of ETS exposure of pregnant women.
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Atypical atrial myxomas in two asymptomatic patients: a case report.
Cardiovasc Ultrasound
PUBLISHED: 07-24-2009
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Atypical cardiac myxomas are a rare occurrence and may present with a variety of clinical manifestations depending on the morphology and location.
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Mesna preserves hepatocyte regenerating capacity following liver radiofrequency ablation under Pringle maneuver.
J. Surg. Res.
PUBLISHED: 07-18-2009
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The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration.
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Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna.
J. Gastroenterol. Hepatol.
PUBLISHED: 07-03-2009
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We investigated the role of the prophylactic administration of the antioxidant 2-mercaptoethane sulfonate (mesna) on the hepatocyte-regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver.
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Attenuation of propofol tolerance conferred by remifentanil co-administration does not reduce propofol toxicity in rabbits under prolonged mechanical ventilation.
J. Surg. Res.
PUBLISHED: 06-05-2009
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Prolonged sedation with propofol at high doses may lead to fatal multi-organ dysfunction, know as propofol infusion syndrome. We tested the hypothesis that propofol plus remifentanil co-administration attenuates propofol tolerance to its sedative effect and assessed if such an effect has an impact on propofol toxicity in rabbits under prolonged mechanical ventilation.
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The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity.
J Asthma
PUBLISHED: 06-02-2009
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To determine the effect of montelukast on asthma during the allergy season in children with persistent asthma and seasonal aeroallergen sensitivity.
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The longest wheal diameter is the optimal measurement for the evaluation of skin prick tests.
Int. Arch. Allergy Immunol.
PUBLISHED: 05-18-2009
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Mean diameter or longest diameter are the 2 most frequently used parameters for wheal response assessment after skin prick testing (SPT). We aimed to compare these 2 parameters taking as gold standard the surface of the wheal skin response.
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Comparison of four nasal sampling methods for the detection of viral pathogens by RT-PCR-A GA(2)LEN project.
J. Virol. Methods
PUBLISHED: 04-15-2009
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The aim of this study was to compare the efficacy and patient discomfort between four techniques for obtaining nasal secretions. Nasal secretions from 58 patients with symptoms of a common cold, from three clinical centers (Amsterdam, Lodz, Oslo), were obtained by four different methods: swab, aspirate, brush, and wash. In each patient all four sampling procedures were performed and patient discomfort was evaluated by a visual discomfort scale (scale 1-5) after each procedure. Single pathogen RT-PCRs for Rhinovirus (RV), Influenza virus and Adenovirus, and multiplex real-time PCR for RV, Enterovirus, Influenza virus, Adenovirus, Respiratory Syncytial Virus (RSV), Parainfluenza virus, Coronavirus, Metapneumovirus, Bocavirus and Parechovirus were performed in all samples. A specific viral cause of respiratory tract infection was determined in 48 patients (83%). In these, the detection rate for any virus was 88% (wash), 79% (aspirate), 77% (swab) and 74% (brush). The degree of discomfort reported was 2.54 for swabs, 2.63 for washes, 2.68 for aspirates and 3.61 for brushings. Nasal washes yielded the highest rate of viral detection without excessive patient discomfort. In contrast, nasal brushes produced the lowest detection rates and demonstrated the highest level of discomfort.
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Dendritic cells in viral bronchiolitis.
Expert Rev Clin Immunol
PUBLISHED: 02-24-2009
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Dendritic cells (DCs) are major antigen-presenting cells that constitute a link between innate and adaptive immune responses, and are critical in the processes of control and elimination of viral infections. On the other hand, there is a large body of data strongly implicating respiratory viruses in morbidity during infancy through the induction of lower respiratory tract infections, such as bronchiolitis, and later on in childhood and adult life, mainly due to their association with asthma exacerbations. Little is known, however, about the precise role of DCs in human respiratory tract infections. This review focuses on current data, both from in vivo and in vitro studies, that highlight the interplay between DCs and the viral causes of bronchiolitis.
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The mini-resectoscope: a new instrument for office hysteroscopic surgery.
Acta Obstet Gynecol Scand
PUBLISHED: 02-12-2009
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Outpatient hysteroscopy has become well-established for the investigation abnormal uterine bleeding. Although "See and Treat" clinics have been widely introduced, the types of procedures offered are limited, and many patients with intrauterine pathology continue to be admitted as in-patients for hysteroscopic surgery. We wanted to investigate the feasibility and acceptability of surgery for small intrauterine lesions without the need for general anesthesia by using a miniature resectoscope.
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Bacterial translocation in a rat model of large volume hepatic radiofrequency ablation.
J. Surg. Res.
PUBLISHED: 01-12-2009
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In this experimental study, we investigated the possibility of bacterial translocation, constituting a potential cause of infectious complications, after performing large volume hepatic radiofrequency ablation (RFA).
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Acute asthma exacerbations in childhood: risk factors, prevention and treatment.
Expert Rev Respir Med
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Asthma is a heterogeneous disease more appropriately seen as a syndrome rather than a single pathologic entity. Although it can remain quiescent for extended time periods, the inflammatory and remodeling processes affect the bronchial milieu and predispose to acute and occasionally severe clinical manifestations. The complexity underlying these episodes is enhanced during childhood, an era of ongoing alterations and maturation of key biological systems. In this review, the authors focus on such sudden-onset events, emphasizing on their diversity on the basis of the numerous asthma phenotypes.
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Research needs in allergy: an EAACI position paper, in collaboration with EFA.
Nikolaos G Papadopoulos, Ioana Agache, Sevim Bavbek, Beatrice M Bilo, Fulvio Braido, Victòria Cardona, Adnan Custovic, Jan Demonchy, Pascal Demoly, Philippe Eigenmann, Jacques Gayraud, Clive Grattan, Enrico Heffler, Peter W Hellings, Marek Jutel, Edward Knol, Jan Lötvall, Antonella Muraro, Lars K Poulsen, Graham Roberts, Peter Schmid-Grendelmeier, Chrysanthi Skevaki, Massimo Triggiani, Ronald Vanree, Thomas Werfel, Breda Flood, Susanna Palkonen, Roberta Savli, Pia Allegri, Isabella Annesi-Maesano, Francesco Annunziato, Dario Antolin-Amerigo, Christian Apfelbacher, Miguel Blanca, Ewa Bogacka, Patrizia Bonadonna, Matteo Bonini, Onur Boyman, Knut Brockow, Peter Burney, Jeroen Buters, Indre Butiene, Moises Calderon, Lars Olaf Cardell, Jean-Christoph Caubet, Sevcan Celenk, Ewa Cichocka-Jarosz, Cemal Cingi, Mariana Couto, Nicolette Dejong, Stefano Del Giacco, Nikolaos Douladiris, Filippo Fassio, Jean-Luc Fauquert, Javier Fernández, Montserrat Fernandez Rivas, Marta Ferrer, Carsten Flohr, James Gardner, Jon Genuneit, Philippe Gevaert, Anna Groblewska, Eckard Hamelmann, Hans Jürgen Hoffmann, Karin Hoffmann-Sommergruber, Lilit Hovhannisyan, Valérie Hox, Frode L Jahnsen, Omer Kalayci, Ayse Füsun Kalpaklioglu, Jörg Kleine-Tebbe, George Konstantinou, Marcin Kurowski, Susanne Lau, Roger Lauener, Antti Lauerma, Kirsty Logan, Antoine Magnan, Joanna Makowska, Heidi Makrinioti, Paraskevi Mangina, Felicia Manole, Adriano Mari, Angel Mazon, Clare Mills, Ervinç Mingomataj, Bodo Niggemann, Gunnar Nilsson, Markus Ollert, Liam O'Mahony, Serena O'Neil, Gianni Pala, Alberto Papi, Gianni Passalacqua, Michael Perkin, Oliver Pfaar, Constantinos Pitsios, Santiago Quirce, Ulrike Raap, Monika Raulf-Heimsoth, Claudio Rhyner, Paula Robson-Ansley, Rodrigo Rodrigues Alves, Zeljka Roje, Carmen Rondón, Odilija Rudzeviciene, Franziska Rueff, Maia Rukhadze, Gabriele Rumi, Cansin Sackesen, Alexandra F Santos, Annalisa Santucci, Christian Scharf, Carsten Schmidt-Weber, Benno Schnyder, Jürgen Schwarze, Gianenrico Senna, Svetlana Sergejeva, Sven Seys, Andrea Siracusa, Isabel Skypala, Milena Sokolowska, François Spertini, Radoslaw Spiewak, Aline Sprikkelman, Gunter Sturm, Ines Swoboda, Ingrid Terreehorst, Elina Toskala, Claudia Traidl-Hoffmann, Carina Venter, Berber Vlieg-Boerstra, Paul Whitacker, Margitta Worm, Paraskevi Xepapadaki, Cezmi A Akdis.
Clin Transl Allergy
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In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
Clin Transl Allergy
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Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europes policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
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Allergic airway diseases in childhood - marching from epidemiology to novel concepts of prevention.
Pediatr Allergy Immunol
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In the past years, a wide range of epidemiological, clinical, and experimental studies have produced remarkable advances in the field of respiratory allergies in childhood. By the recent investigations on epidemiological trends, risk factors, and prevention of asthma and allergic rhinitis, various exiting concepts have been challenged, and novel innovative approaches have been developed. Pediatric Allergy and Immunology (PAI), with a number of highly relevant contributions between 2010 and 2012, has become an important forum in this area. The prevalence of asthma in some developed countries may have reached a plateau, while in developing countries, where the prevalence was previously low, allergic diseases are still on the increase. A wide array of risk and protective factors, including hygiene, infections, outdoor and indoor air pollution, allergen exposure, breast-feeding practices, nutrition, and obesity, play a multifaceted role in shaping the observed worldwide trends of respiratory allergies. Under the guidance of recent research, prediction and prevention strategies in the clinical practice are progressively changing, the focus moving away from avoidance of allergen exposure and toward tolerance induction.
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The genomic signature of human rhinoviruses A, B and C.
PLoS ONE
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Human rhinoviruses are single stranded positive sense RNA viruses that are presented in more than 50% of acute upper respiratory tract infections. Despite extensive studies on the genetic diversity of the virus, little is known about the forces driving it. In order to explain this diversity, many research groups have focused on protein sequence requirements for viable, functional and transmissible virus but have missed out an important aspect of viral evolution such as the genomic ontology of the virus. This study presents for the first time the genomic signature of 111 fully sequenced HRV strains from all three groups HRV-A, HRV-B and HRV-C. We observed an HRV genome tendency to eliminate CpG and UpA dinucleotides, coupling with over-representation of UpG and CpA. We propose a specific mechanism which describes how rapid changes in the HRV genomic sequence can take place under the strict control of conservation of the polypeptide backbone. Moreover, the distribution of the observed under- and over-represented dinucleotides along the HRV genome is presented. Distance matrice tables based on CpG and UpA odds ratios were constructed and viewed as heatmaps and distance trees. None of the suppressions can be attributed to codon usage or in RNA secondary structure requirements. Since viral recognition is dependent on RNA motifs rich in CpG and UpA, it is possible that the overall described genome evolution mechanism acts in order to protect the virus from host recognition.
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Molecular and immunological characterization of Tri a 36, a low molecular weight glutenin, as a novel major wheat food allergen.
J. Immunol.
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Wheat is an essential element in our nutrition but one of the most important food allergen sources. Wheat allergic patients often suffer from severe gastrointestinal and systemic allergic reactions after wheat ingestion. In this study, we report the molecular and immunological characterization of a new major wheat food allergen, Tri a 36. The cDNA coding for a C-terminal fragment of Tri a 36 was isolated by screening a wheat seed cDNA expression library with serum IgE from wheat food-allergic patients. Tri a 36 is a 369-aa protein with a hydrophobic 25-aa N-terminal leader peptide. According to sequence comparison it belongs to the low m.w. glutenin subunits, which can be found in a variety of cereals. The mature allergen contains an N-terminal domain, a repetitive domain that is rich in glutamine and proline residues, and three C-terminal domains with eight cysteine residues contributing to intra- and intermolecular disulfide bonds. Recombinant Tri a 36 was expressed in Escherichia coli and purified as soluble protein. It reacted with IgE Abs of ?80% of wheat food-allergic patients, showed IgE cross-reactivity with related allergens in rye, barley, oat, spelt, and rice, and induced specific and dose-dependent basophil activation. Even after extensive in vitro gastric and duodenal digestion, Tri a 36 released distinct IgE-reactive fragments and was highly resistant against boiling. Thus, recombinant Tri a 36 is a major wheat food allergen that can be used for the molecular diagnosis of, and for the development of specific immunotherapy strategies against, wheat food allergy.
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Effect of clarithromycin on acute asthma exacerbations in children: an open randomized study.
Pediatr Allergy Immunol
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Asthma exacerbations are major contributors to asthma morbidity and rather difficult to treat. There is inconclusive evidence that macrolide antibiotics may have an effect on asthma exacerbations through their antibacterial and/or anti-inflammatory properties. The aim of the study was to evaluate the efficacy of clarithromycin on medium-term asthma activity when given as an add-on therapy in children with acute asthma.
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Molecular Characterization of Recombinant Mus a 5 Allergen from Banana Fruit.
Mol. Biotechnol.
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Allergy to banana fruit appears to have become an important cause of fruit allergy in Europe. Among five allergens that have been found, beta-1,3-glucanase denoted as Mus a 5 was identified as a candidate allergen for the component-resolved allergy diagnosis of banana allergy. Because of the variations in protein levels in banana fruit, in this study Mus a 5 was produced as a fusion protein with glutathione-S-transferase in Escherichia coli. The recombinant Mus a 5 was purified under native conditions by a combination of affinity, ion-exchange, and reversed phase chromatography. N-terminal sequence was confirmed by Edman degradation and 55 % of the primary structure was identified by mass fingerprint, while the secondary structure was assessed by circular dichroism spectroscopy. IgG reactivity of recombinant protein was shown in 2-D immunoblot with anti-Mus a 5 antibodies, while IgG and IgE binding to natural Mus a 5 was inhibited with the recombinant Mus a 5 in immunoblot inhibition test. IgE reactivity of recombinant Mus a 5 was shown in ELISA within a group of ten persons sensitized to banana fruit. Recombinant Mus a 5 is a novel reagent suitable for the component-resolved allergy diagnosis of banana allergy.
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