bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459
Authors: Singh Dave , Cadden Paul , Hunter Michael , Pearce Collins Lisa , Perkins Mike , Pettipher Roy , Townsend Elizabeth , Vinall Shân , O'Connor Brian 
Published: April 2012

CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D2-driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients.A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days’ treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study.There was a 25.4% (95% CI 5.1–45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p=0.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p=0.002). PGD2-induced blood eosinophil shape changeex vivowas assessed at day 7 (n=7). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8– -0.4%; p=0.048).OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma.
Early life lung function and respiratory outcome in the first year of life
Authors: van Putte-Katier Nienke , van der Gugten Anne C. , Uiterwaal Cuno S.P.M. , de Jong Brita M. , Numans Mattijs E. , Kimpen Jan L.L. , Verheij Theo J.M. , van der Ent Cornelis K. 
Published: April 2012

Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors.Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires.836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance (Rrs) and time constant (τrs) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance (Crs) were associated with a decreased risk for wheeze and cough.Rrs,Crsandτrsmeasured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.
Diagnosis-related deterioration of lung function after extracorporeal membrane oxygenation
Authors: Spoel Marjolein , Laas Roxanne , Gischler Saskia J. , Hop Wim J.C. , Tibboel Dick , de Jongste Johan C. , Ijsselstijn Hanneke 
Published: April 2012

The aim of the study was to assess lung function longitudinally after neonatal extracorporeal membrane oxygenation (ECMO), and to identify any effects of diagnosis and perinatal characteristics.121 neonatal ECMO-treated children (70 with meconium aspiration syndrome, 20 congenital diaphragmatic hernia and 31 with other diagnoses) performed a total of 191 lung function measurements at 5, 8 and/or 12 yrs. We assessed dynamic and static lung volumes, reversibility of airway obstruction and diffusion capacity.Mean SDS forced expiratory volume in 1 s (FEV1) at 5 yrs before and after bronchodilation (-0.51 and 0.07) was significantly higher than at 8 (-0.79 and -0.4; p<0.04) and 12 yrs (-1.10 and -0.52; p<0.003). Mean SDS for all spirometric parameters before and after bronchodilation were significantly lower in the congenital diaphragmatic hernia group compared with the other diagnostic groups (all p≤0.025). A significant volume of trapped air was observed in 86% patients with congenital diaphragmatic hernia, 50% with meconium aspiration syndrome and 58% with other diagnoses. After bronchodilation, mean SDS FEV1and forced vital capacity were negatively influenced by duration of ventilation (both p<0.001) and duration of ECMO (p=0.003 and p=0.02, respectively).Long-term pulmonary sequelae after neonatal ECMO-treatment mainly occur in congenital diaphragmatic hernia patients and tend to deteriorate over time.
Decreased cerebrovascular response to CO2in post-menopausal females with COPD: role of oxidative stress
Authors: Hartmann Sara E. , Pialoux Vincent , Leigh Richard , Poulin Marc J. 
Published: April 2012

Chronic obstructive pulmonary disease (COPD) is associated with cerebrovascular abnormalities and an overproduction of reactive oxygen species. We hypothesised that COPD patients have oxidant-related cerebrovascular dysfunction. Our main objective was to evaluate cerebrovascular reactivity and its relationship with oxidative stress in females with COPD.We studied eight females with moderate COPD and 10 healthy female control subjects of similar age. Transcranial Doppler ultrasound assessed cerebral blood flow (CBF) velocity during hypercapnia. Plasma was assessed at rest for DNA oxidation, advanced oxidation protein products, lipid peroxidation, nitrotyrosine, antioxidant enzyme activity (glutathione peroxidase and catalase) and end-products of nitric oxide metabolism.Moderate COPD patients showed decreased cerebrovascular sensitivity to carbon dioxide (CO2) (COPD 1.17±0.54versuscontrol 2.15±0.73 cm·s−1·mmHg−1; p<0.01). COPD patients had higher levels of DNA and lipid oxidation, advanced oxidation protein products and higher glutathione peroxidase activity (p<0.05). Controlling for measures of oxidative stress (DNA and lipid oxidation, and advanced oxidation protein product) eliminates statistically significant differences between the COPD and control groups in the CBF sensitivity to CO2.Females with moderate COPD were found to have cerebrovascular dysfunction. Our results suggest that increased levels of systemic oxidative stress may have implications in the cerebrovascular dysfunction observed during hypercapnia in COPD.
Domestic use of cleaning sprays and asthma activity in females
Authors: Le Moual Nicole , Varraso Raphaelle , Siroux Valérie , Dumas Orianne , Nadif Rachel , Pin Isabelle , Zock Jan-Paul , Kauffmann Francine 
Published: April 2012

We aimed to study the associations between the household use of cleaning sprays and asthma symptoms and control of asthma, in females from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA).Data were available for 683 females (mean age 44 yrs, 55% never smokers, 439 without asthma and 244 with current asthma). Both domestic exposures and asthma phenotypes (asthma symptom score, current asthma, poorly-controlled asthma (56%)) were evaluated as previously described in the European Community Respiratory Health Survey. Associations between the use of sprays and asthma phenotypes were evaluated using logistic and nominal regressions, adjusted for age, smoking, body mass index and occupational exposures.Significant associations were observed between the weekly use of at least two types of sprays and a high asthma symptom score (OR (95% CI) 2.50 (1.54–4.03)) compared with a null score. Consistent results were observed for current asthma (1.67 (1.08–2.56)) and poorly-controlled asthma (2.05 (1.25–3.35)) compared with females without asthma. The association for current asthma was higher in females not reporting avoidance of polluted places (2.12 (1.27–3.54)) than in those reporting such avoidance (0.99 (0.53–1.85)).The common use of household cleaning sprays is positively associated with a high asthma symptom score, current asthma and poorly-controlled asthma in females.
Is it time for home treatment of pulmonary embolism?
Authors: Lankeit Mareike , Konstantinides Stavros 
Published: April 2012

Acute pulmonary embolism (PE) is a frequent cause of death, but not all patients are at high risk of an adverse early outcome. It has been proposed that selected patients may be considered for early discharge and home treatment, but it was only recently that improved risk assessment strategies permitted advances in the identification of low-risk PE.Clinical prediction rules, such as the Pulmonary Embolism Severity Index (PESI), and laboratory biomarkers, particularly natriuretic peptides and cardiac troponins, appeared capable of excluding severe PE and serious comorbidity.Recently, two randomised trials and two prospective cohort studies investigated the feasibility and safety of outpatient treatment. All excluded patients with haemodynamic instability and serious comorbidity, but only one trial used a validated clinical score (PESI) for patient inclusion, and only one cohort study employed a biomarker test. Overall, 90-day outcome was favourable and the results appear promising.To optimise patient selection, future trials will need to test simplified clinical scores combined with high-sensitivity biomarker assays, and it will have to be determined whether echocardiography and/or compression ultrasonography are also required before discharge. Furthermore, ongoing trials will show whether new oral anticoagulants are a safe and cost-effective option for managing patients out of hospital.
Distribution patterns of influenza virus receptors and viral attachment patterns in the respiratory and intestinal tracts of seven avian species
Authors: Costa Taiana , Chaves Aida J , Valle Rosa , Darji Ayub , van Riel Debby , Kuiken Thijs , Majó Natàlia , Ramis Antonio 
Published: April 2012

Abstract
This study assessed the presence of sialic acid α-2,3 and α-2,6 linked glycan receptors in seven avian species. The respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, golden pheasant, ostrich, and mallard were tested by means of lectin histochemistry, using the lectins Maackia amurensis agglutinin II and Sambucus nigra agglutinin, which show affinity for α-2,3 and α-2,6 receptors, respectively. Additionally, the pattern of virus attachment (PVA) was evaluated with virus histochemistry, using an avian-origin H4N5 virus and a human-origin seasonal H1N1 virus. There was a great variation of receptor distribution among the tissues and avian species studied. Both α-2,3 and α-2,6 receptors were present in the respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, and golden pheasant. In ostriches, the expression of the receptor was basically restricted to α-2,3 in both the respiratory and intestinal tracts and in mallards the α-2,6 receptors were absent from the intestinal tract. The results obtained with the lectin histochemistry were, in general, in agreement with the PVA. The differential expression and distribution of α-2,3 and α-2,6 receptors among various avian species might reflect a potentially decisive factor in the emergence of new viral strains.
Consumers' experiences and values in conventional and alternative medicine paradigms: a problem detection study (PDS)
Authors: Emmerton Lynne , Fejzic Jasmina , Tett Susan E 
Published: April 2012

Abstract

Background
This study explored consumer perceptions of complementary and alternative medicine (CAM) and relationships with CAM and conventional medicine practitioners.
A problem detection study (PDS) was used. The qualitative component to develop the questionnaire used a CAM consumer focus group to explore conventional and CAM paradigms in healthcare. 32 key issues, seven main themes, informed the questionnaire (the quantitative PDS component - 36 statements explored using five-point Likert scales.)

Results
Of 300 questionnaires distributed (Brisbane, Australia), 83 consumers responded. Results indicated that consumers felt empowered by using CAM and they reported positive relationships with CAM practitioners. The perception was that CAM were used most effectively as long-term therapy (63% agreement), but that conventional medicines would be the best choice for emergency treatment (81% agreement). A majority (65%) reported that doctors appeared uncomfortable about consumers' visits to CAM practitioners. Most consumers (72%) believed that relationships with and between health practitioners could be enhanced by improved communication. It was agreed that information sharing between consumers and healthcare practitioners is important, and reported that "enough" information is shared between CAM practitioners and consumers. Consumers felt comfortable discussing their medicines with pharmacists, general practitioners and CAM practitioners, but felt most comfortable with their CAM practitioners.

Conclusions
This PDS has emphasized the perceived importance of open communication between consumers, CAM and conventional providers, and has exposed areas where CAM consumers perceive that issues exist across the CAM and conventional medicine paradigms. There is a lot of information which is perceived as not being shared at present and there are issues of discomfort and distrust which require resolution to develop concordant relationships in healthcare. Further research should be based on optimisation of information sharing, spanning both conventional and CAM fields of healthcare, due to both the relevance of concordance principles within CAM modalities and the widespread use of CAM by consumers.
The pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestation in Ethiopia: a retrospective study
Authors: Berhe Tesfaye , Melkamu Yilma , Amare Amanuel 
Published: April 2012

Abstract

Background
Even though the prevalence of HIV infection among the adult population in Ethiopia was estimated to be 2.2% in 2008, the studies on the pattern of neurological manifestations are rare. The aim of this retrospective study was to assess the pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestations.

Methods
Medical records of 347 patients (age ≥13 years) admitted to Tikur Anbesa Hospital from September 2002 to August 2009 were reviewed and demographic and clinical data were collected.

Results
Data from 347 patients were analysed. The mean age was 34.6 years. The diagnosis of HIV was made before current admission in 33.7% and 15.6% were on antiretroviral therapy (ART). Causes of neurological manifestation were: cerebral toxoplasmosis (36.6%), tuberculous meningitis (22.5%), cryptococcal meningitis (22.2%) and bacterial meningitis (6.9%). HIV-encephalopathy, primary central nervous system (CNS) lymphoma and progressive multifocal leukoencephalopathy were rare in our patients. CD4 count was done in 64.6% and 89.7% had count below 200/mm3[mean = 95.8, median = 57] and 95.7% were stage IV. Neuroimaging was done in 38% and 56.8% had mass lesion. The overall mortality was 45% and the case-fatality rates were: tuberculous meningitis (53.8%), cryptococcal meningitis (48.1%), cerebral toxoplasmosiss (44.1%) and bacterial meningitis (33.3%). Change in sensorium and seizure were predictors of mortality.

Conclusions
CNS opportunistic infections were the major causes of neurological manifestations of HIV/AIDS and were associated with high mortality and morbidity. Almost all patients had advanced HIV disease at presentation. Early diagnosis of HIV, prophylaxis and treatment of opportunistic infections, timely ART, and improving laboratory services are recommended. Mortality was related to change in sensorium and seizure.
Induction of superficial zone protein (SZP)/lubricin/PRG 4 in muscle-derived mesenchymal stem/progenitor cells by transforming growth factor-β1 and bone morphogenetic protein-7
Authors: Andrades José A , Motaung Shirley C , Jiménez-Palomo Pedro , Claros Silvia , López-Puerta José M , Becerra José , Schmid Thomas M , Reddi A Hari 
Published: April 2012

Abstract
Introduction
Articular cartilage (AC) is an avascular tissue with precise polarity and organization. The three distinct zones are: surface, middle and deep. The production and accumulation of the superficial zone protein (SZP), also known as lubricin, by the surface zone is a characteristic feature of AC. To date, there is a wealth of evidence showing differentiation of AC from mesenchymal stem cells. Most studies that described chondrogenic differentiation did not focus on AC with characteristic surface marker SZP/lubricin. The present investigation was initiated to determine the induction of SZP/lubricin in skeletal muscle-derived mesenchymal stem/progenitor cells (MDMSCs) by transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7).

Methods
MDMSCs were cultured as a monolayer at a density of 1 × 105 cells/well in 12-well tissue culture plates. Cell cultures were treated for 3, 7 and 10 days with TGF-β1 and BMP-7. The medium was analyzed for SZP. The cells were used to isolate RNA for RT-PCR assays for SZP expression.

Results
The SZP/lubricin increased in a time-dependent manner on Days 3, 7 and 10 in the medium. As early as Day 3, there was a three-fold increase in response to 3 ng/ml of TGF-β1 and 300 ng/ml of BMP-7. This was confirmed by immunochemical localization of SZP as early as Day 3 after treatment with TGF-β1. The expression of SZP mRNA was enhanced by TGF-β1.

Conclusions
The present investigation demonstrated the efficient and reproducible induction of SZP/lubricin accumulation by TGF-β1 and BMP-7 in skeletal MDMSCs. Optimization of the experimental conditions may permit the utility of MDMSCs in generating surface zone-like cells with phenotypic markers of AC and, therefore, constitute a promising cell source for tissue engineering approaches of superficial zone cartilage.
Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)
Authors: Fagin Ursula , Pitann Silke , Gross Wolfgang L , Lamprecht Peter 
Published: April 2012

Abstract

Introduction

Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polarization.

Methods

Multicolor flow cytometry was used to analyze CCR4, CCR6, and intracellular cytokine expression of T cells from whole blood of GPA-patients (n = 26) and healthy controls (n = 20). CCR7 and CD45RA were included for phenotypic characterization.

Results

We found a significant increase in the percentages of circulating CCR4+ and CCR6+ cells within the total CD4+ T cell population in GPA. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T cells between GPA and healthy controls. CCR4 and CCR6 expression was largely confined to central (TCM) and effector memory T cells (TEM, TEMRA). A significant increase in the frequency of CCR4+ and CCR6+ TEMRA and CCR6+ TCM was shown in GPA. Of note, we could dissect CCR4 and CCR6 expressing CCR7+CD45RAmed very early memory T cells (TVEM) from genuine CCR7+CD45RAhigh naïve T cells lacking CCR4 and CCR6 expression for peripheral tissue-migration within the CCR7+CD45RA+ compartment. The frequencies of CCR4+ and CCR6+ TVEM were also significantly increased in GPA. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR6+ cell subsets and IL-4+ cells in the CRR4+ cell subset when compared with CD4+ cells lacking CCR4 and CCR6 expression.

Conclusions

Increased frequencies of circulating CCR4+ and CCR6+ memory T cell subsets including hitherto unreported TVEM suggest persistent T cell activation with the accumulation of CCR4+ and CCR6+ cells in GPA. CCR4 and CCR6 could be involved in the recruitment of T cells including cytokine-producing subsets to inflamed sites in GPA.
Immune regulation of Rab proteins expression and intracellular transport
Authors: Pei Gang , Bronietzki Marc , Gutierrez Maximiliano Gabriel 
Published: April 2012

Abstract
Review on the immune signals that regulate Rab protein expression and transport, and the consequences during the immune response.
Compartmentalization in cells of the immune system, the focus of this review, facilitates the spatiotemporal organization of cellular responses essential for specialized immune functions. In this process of compartment maintenance, Rab proteins are central regulators of protein-mediated transport and fusion of intracellular structures. It is widely believed that the intracellular concentration of proteins that regulate intracellular transport, including Rab proteins, is constitutively mantained. However, there is a growing body of evidence indicating that transcriptional rates of Rab proteins can be modified. This process is especially evident during immune activation and argues that after activation, these cells require higher levels of Rab proteins. The aim of this review is to discuss evidence showing the increasing links between Rab protein expression and intracellular transport, particularly in monocytes and macrophages. We highlight here biological processes in which the expression of Rab GTPases is selectively regulated, leading to the activation of specific intracellular routes. Further, we focus on the immune regulation of intracellular transport after cytokine activation and microbial infection, with an emphasis in mycobacterial infection.