bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive value for progression to tuberculosis by IGRA and TST in immigrant contacts
Authors: Kik S. V. , Franken W. P. J. , Mensen M. , Cobelens F. G. J. , Kamphorst M. , Arend S. M. , Erkens C. , Gebhard A. , Borgdorff M. W. , Verver S. 
Published: October 2009

The authors determined the positive predictive value (PPV) for progression to tuberculosis (TB) of two interferon-γ release assays (IGRAs), QuantiFERON-TB® Gold In-tube (QFT-GIT) and T-SPOT.TB®, and the tuberculin skin test (TST) in immigrants contacts.Immigrant close contacts of sputum smear-positive TB patients were included when aged ≥16 yrs and their TST result was ≥5 mm 0 or 3 months after diagnosis of the index patient. Contacts were followed for the next 2 yrs for development of TB disease.Of 339 immigrant contacts with TST ≥5 mm, 324 and 299 had valid results of QFT-GIT and T-SPOT.TB®, respectively. Nine contacts developed active TB. One patient had not been tested with TST, while another patient had not been tested with QFT-GIT and T-SPOT.TB®. The PPV for progression to TB during this period was 9/288 = 3.1% (95% CI 1.3–5.0%) for TST ≥10 mm, 7/184 = 3.8% (95% CI 1.7–5.9%) for TST ≥15 mm, 5/178 = 2.8% (95% CI 1.0–4.6%) for QFT-GIT and 6/181 = 3.3% (95% CI 1.3–5.3%) for T-SPOT.TB®. Sensitivity was 100%, 88%, 63% and 75%, respectively.The predictive values of QFT-GIT, T-SPOT.TB® and TST for progression to TB disease among immigrant close contacts were comparable.
A model of chronic lung allograft rejection in the rat
Authors: Jungraithmayr W. , Vogt P. , Inci I. , Hillinger S. , Arni S. , Korom S. , Weder W. 
Published: October 2009

Bronchiolitis obliterans, the pathological hallmark of chronic pulmonary rejection, severely impacts long-term survival following lung transplantation. However, experimental reproduction of this pathophysiological phenomenon has not been achieved with contemporaryin vivomodels. Here, a model of chronic rejection is described, with sensitised recipients receiving unilateral orthotopic rat lung transplants.Lewis rats, sensitised with skin from brown Norway rats 7 days before receiving left lung transplants from donors that were Lewis×brown Norway F1hybrids, were analysed during day 21–84. The development of chronic rejection was modulated by a treatment with rapamycin and cyclosporin, and characterised histologically, immunohistochemically and by reverse transcriptase PCR.Characteristic histopathological changes leading to chronic rejection were induced over time by an initial treatment with cyclosporin in the presence of continuous rapamycin application. At day 84, fibrotic lesions replaced the respiratory epithelium within small bronchioles, with strong expression of smooth muscle α-actin and upregulation of mRNA for T-helper cell type-1 cytokines, smooth muscle α-actin, transforming growth factor-β and CC chemokine ligand 5, but decreased forkhead box protein P3 gene expression.A reproducible and clinically relevant experimental set-up for progressive chronic rejection in rat pulmonary allografts is described. This model will permit better understanding of the pathological changes of small airways during the development of bronchiolitis obliterans, and may serve as anin vivoset-up for testing the efficacy of novel therapeutic interventions.
Optimal positive airway pressure predicts oral appliance response to sleep apnoea
Authors: Tsuiki S. , Kobayashi M. , Namba K. , Oka Y. , Komada Y. , Kagimura T. , Inoue Y. 
Published: October 2009

Patients with less severe obstructive sleep apnoea (OSA) are usually prescribed oral appliances and/or smaller optimal nasal continuous positive airway pressure (PnCPAP) in nCPAP therapy. We hypothesised that OSA patients with greaterPnCPAPwould not respond favourably to oral appliances.Oral appliances were inserted in nCPAP users after washing-out the nCPAP effect. Follow-up polysomnography was undertaken with the adjusted oral appliance in place. The predictability ofPnCPAPwas evaluated with receiver-operating characteristic (ROC) curves.The median baseline apnoea/hypopnoea index (AHI) was reduced with the oral appliance from 36 to 12 events·h−1in 35 patients. When responders were defined as patients showing a follow-up AHI of <5 events·h−1with >50% reduction in baseline AHI, the area under the ROC curve forPnCPAPwas 0.76. The best cut-off value ofPnCPAPturned out to be 10.5 cmH2O with a high negative predictive value (0.93) and a low negative likelihood ratio (0.18).OSA patients with aPnCPAPof >10.5 cmH2O are unlikely to respond to oral appliance therapy. This prediction is clinically helpful to both OSA patients and medical personnel in discussing oral appliances as a temporary substitute and/or alternative for nCPAP.
Respiratory medicines for children: current evidence, unlicensed use and research priorities
Authors: Smyth A. R. , Barbato A. , Beydon N. , Bisgaard H. , de Boeck K. , Brand P. , Bush A. , Fauroux B. , de Jongste J. , Korppi M. , O’Callaghan C. , Pijnenburg M. , Ratjen F. , Southern K. , Spencer D. , Thomson A. , Vyas H. , Warris A. , Merkus P. J. 
Published: October 2009

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies.Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g.dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the β-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency.We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.
Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis
Authors: Zappala C. J. , Latsi P. I. , Nicholson A. G. , Colby T. V. , Cramer D. , Renzoni E. A. , Hansell D. M. , du Bois R. M. , Wells A. U. 
Published: October 2009

In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence of significant change in pulmonary functional tests (PFTs) has been a major constraint. The prognostic value of “marginal” changes in PFTs in IPF and fibrotic non-specific interstitial pneumonia (NSIP) was evaluated.In patients with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DL,CO) trends at 6 months were categorised as “significant” (FVC >10%;DL,CO>15%) or “marginal” (FVC 5–10%;DL,CO7.5–15%). Proportional hazards analysis and time-dependent receiver operating characteristic methodology were used to examine PFT trends against mortality.In IPF, reductions in FVC were significant in 22 cases (26%) and marginal in 19 cases (23%). Mortality was higher in patients with a significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54–5.06; p<0.001) and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19–4.50; p = 0.01) than in those with stable disease. Progression-free survival was lower when the decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19–4.60; p = 0.01). Marginal changes inDL,COin IPF and marginal changes in FVC andDL,COin fibrotic NSIP did not provide useful prognostic information.Marginal change in FVC in IPF denotes a poor outcome. These findings are applicable to clinical practice and to the selection of patients with more progressive disease for therapeutic studies.
Anti-apoptotic effects of Z α1-antitrypsin in human bronchial epithelial cells
Authors: Greene C. M. , Miller S. D. W. , Carroll T. P. , Oglesby I. K. , Ahmed F. , O'Mahony M. , Taggart C. C. , McElvaney N. G. , O'Neill S. J. 
Published: October 2009

α1-antitrypsin (α1-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of α1-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z α1-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved.Control, M variant α1-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-κB activation and induced expression of a selection of pro- and anti-apoptotic genes.Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-κB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-κB. cIAP1 expression was increased in ZAATversusMAAT bronchial biopsies.The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.
CHD5 is down-regulated through promoter hypermethylation in gastric cancer
Authors: Wang Xian , Lau Kenneth KK , So Leo KY , Lam Yun Wah 
Published: October 2009

Abstract

Background
Nonhistone chromosomal proteins in concert with histones play important roles in the replication and repair of DNA and in the regulation of gene expression. The deregulation of these proteins can contribute to the development of a variety of diseases such as cancer. As a nonhistone chromosomal protein, chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as the product of a novel tumor suppressor gene (TSG), promoting the transcription of p19
ink4a
and p16
arf
. The inactivation of CHD5 was achieved partly through genetic deletion since it is located in 1p36, a region frequently deleted in human tumors. In this study, we aim to study the involvement of CHD5 in gastric cancer, the second most common cancer worldwide.

Methods
CHD5 expression in a panel of gastric cancer cells were determined by quantitative RT-PCR. The methylation of CHD5 was evaluated by methylation specific PCR and bisulfite genome sequencing. The effect of CHD5 on growth of gastric cancer cells was tested by colony formation assay.

Results
CHD5 expression was down-regulated in all of gastric cancer cell lines used (100%, 7/7) and significantly restored after pharmacological demethylation. Methylation of CHD5 promoter was detected in all of seven gastric cancer cell lines and in the majority of primary gastric carcinoma tissues examined (73%, 11/15). Finally, ectopic expression of CHD5 in gastric cancer cells led to a significant growth inhibition.

Conclusion
CHD5 was a TSG epigenetically down-regulated in gastric cancer.
Characterization of the oxidative stress stimulon and PerR regulon of Campylobacter jejuni
Authors: Palyada Kiran , Sun Yi-Qian , Flint Annika , Butcher James , Naikare Hemant , Stintzi Alain 
Published: October 2009

Abstract

Background
During gut colonization, the enteric pathogen Campylobacter jejuni must surmount the toxic effects of reactive oxygen species produced by its own metabolism, the host immune system, and intestinal microflora. Elucidation of C. jejuni oxidative stress defense mechanisms is critical for understanding Campylobacter pathophysiology.

Results
The mechanisms of oxidative stress defense in C. jejuni were characterized by transcriptional profiling and phenotypic analysis of wild-type and mutant strains. To define the regulon of the peroxide-sensing regulator, PerR, we constructed an isogenic ΔperR mutant and compared its transcriptome profile with that of the wild-type strain. Transcriptome profiling identified 104 genes that belonged to the PerR regulon. PerR appears to regulate gene expression in a manner that both depends on and is independent of the presence of iron and/or H2O2. Mutation of perR significantly reduced motility. A phenotypic analysis using the chick colonization model showed that the ΔperR mutant exhibited attenuated colonization behavior. An analysis of changes in the transcriptome induced by exposure to H2O2, cumene hydroperoxide, or menadione revealed differential expression of genes belonging to a variety of biological pathways, including classical oxidative stress defense systems, heat shock response, DNA repair and metabolism, fatty acid biosynthesis, and multidrug efflux pumps. Mutagenic and phenotypic studies of the superoxide dismutase SodB, the alkyl-hydroxyperoxidase AhpC, and the catalase KatA, revealed a role for these proteins in oxidative stress defense and chick gut colonization.

Conclusion
This study reveals an interplay between PerR, Fur, iron metabolism and oxidative stress defense, and highlights the role of these elements in C. jejuni colonization of the chick cecum and/or subsequent survival.
Genetic effect of CysLTR2 polymorphisms on its mRNA synthesis and stabilization
Authors: Shin Jeong-Ah , Chang Hun Soo , Park Se-Min , Jang An-Soo , Park Sung Woo , Park Jong Sook , Uh Soo-Taek , Il Lim Gune , Rhim Taiyoun , Kim Mi-Kyeong , Choi Inseon S , Chung Il Yup , Park Byung Lae , Shin Hyoung Doo , Park Choon-Sik 
Published: October 2009

AbstractBackgroundWe previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of theCysLTR2gene.MethodsWe measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics havinght1+/+andht2+/+. A gel retardation assay was used to identify nuclear protein binding to the c.-819 promoter site. The function of promoter and 3'-UTR were assessed using pGL3 luciferase and pEGFP reporter system, respectively.ResultsWe found that the expression of CysLTR2 protein was higher in B cell lines of asthmatics havinght2+/+than in those havinght1+/+. PMA/ionomycin induced higher mRNA expression of CysLTR2 in B cell lines fromht2+/+asthmatics than those fromht1+/+asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding affinity with a probe containingc.-819T thanone containingc.-819G. The luciferase activity of thec.-819Ttype ofCysLTR2promoter was higher than that of thec.-819Gtype. EGFP expression was higher in the EGFP-c.2078T3'-UTR fusion construct than in thec.2078Cconstruct.ConclusionThe sequence variants ofCysLTR2may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity.
Managing insecticide resistance in malaria vectors by combining carbamate-treated plastic wall sheeting and pyrethroid-treated bed nets
Authors: Djènontin Armel , Chabi Joseph , Baldet Thierry , Irish Seth , Pennetier Cédric , Hougard Jean-Marc , Corbel Vincent , Akogbéto Martin , Chandre Fabrice 
Published: October 2009

Abstract

Background
Pyrethroid resistance is now widespread in Anopheles gambiae, the major vector for malaria in sub-Saharan Africa. This resistance may compromise malaria vector control strategies that are currently in use in endemic areas. In this context, a new tool for management of resistant mosquitoes based on the combination of a pyrethroid-treated bed net and carbamate-treated plastic sheeting was developed.

Methods
In the laboratory, the insecticidal activity and wash resistance of four carbamate-treated materials: a cotton/polyester blend, a polyvinyl chloride tarpaulin, a cotton/polyester blend covered on one side with polyurethane, and a mesh of polypropylene fibres was tested. These materials were treated with bendiocarb at 100 mg/m2 and 200 mg/m2 with and without a binding resin to find the best combination for field studies. Secondly, experimental hut trials were performed in southern Benin to test the efficacy of the combined use of a pyrethroid-treated bed net and the carbamate-treated material that was the most wash-resistant against wild populations of pyrethroid-resistant An. gambiae and Culex quinquefasciatus.

Results
Material made of polypropylene mesh (PPW) provided the best wash resistance (up to 10 washes), regardless of the insecticide dose, the type of washing, or the presence or absence of the binding resin. The experimental hut trial showed that the combination of carbamate-treated PPW and a pyrethroid-treated bed net was extremely effective in terms of mortality and inhibition of blood feeding of pyrethroid-resistant An. gambiae. This efficacy was found to be proportional to the total surface of the walls. This combination showed a moderate effect against wild populations of Cx. quinquefasciatus, which were strongly resistant to pyrethroid.

Conclusion
These preliminary results should be confirmed, including evaluation of entomological, parasitological, and clinical parameters. Selective pressure on resistance mechanisms within the vector population, effects on other pest insects, and the acceptability of this management strategy in the community also need to be evaluated.
Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase
Authors: Dar Mohd J , Monel Blandine , Krishnan Lavanya , Shun Ming-Chieh , Di Nunzio Francesca , Helland Dag E , Engelman Alan 
Published: October 2009

AbstractBackgroundThe 18 residue tail abutting the SH3 fold that comprises the heart of the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by structural biology. To ascertain the role of the tail region in integrase function and HIV-1 replication, a set of deletion mutants that successively lacked three amino acids was constructed and analyzed in a variety of biochemical and virus infection assays. HIV-1/2 chimers, which harbored the analogous 23-mer HIV-2 tail in place of the HIV-1 sequence, were also studied. Because integrase mutations can affect steps in the replication cycle other than integration, defective mutant viruses were tested for integrase protein content and reverse transcription in addition to integration. The F185K core domain mutation, which increases integrase protein solubility, was furthermore analyzed in a subset of mutants.ResultsPurified proteins were assessed for in vitro levels of 3' processing and DNA strand transfer activities whereas HIV-1 infectivity was measured using luciferase reporter viruses. Deletions lacking up to 9 amino acids (1-285, 1-282, and 1-279) displayed near wild-type activitiesin vitroand during infection. Further deletion yielded two viruses, HIV-11-276and HIV-11-273, that displayed approximately two and 5-fold infectivity defects, respectively, due to reduced integrase function. Deletion mutant HIV-11-270and the HIV-1/2 chimera were non-infectious and displayed approximately 3 to 4-fold reverse transcription in addition to severe integration defects. Removal of four additional residues, which encompassed the C-terminal β strand of the SH3 fold, further compromised integrase incorporation into virions and reverse transcription.ConclusionHIV-11-270, HIV-11-266, and the HIV-1/2 chimera were typed as class II mutant viruses due to their pleiotropic replication defects. We speculate that residues 271-273 might play a role in mediating the known integrase-reverse transcriptase interaction, as their removal unveiled a reverse transcription defect. The F185K mutation reduced thein vitroactivities of 1-279 and 1-276 integrases by about 25%. Mutant proteins 1-279/F185K and 1-276/F185K are therefore highlighted as potential structural biology candidates, whereas further deleted tail variants (1-273/F185K or 1-270/F185K) are less desirable due to marginal or undetectable levels of integrase function.
Ocular disorders as the prevailing manifestations of antiphospholipid syndrome: a case series
Authors: Tsironi Evangelia , Gatselis Nikolaos , Kotoula Maria G , Zachou Kalliopi , Pefkianaki Maria , Zacharaki Fani , Chatzoulis Dimitrios Z , Dalekos George N 
Published: October 2009

Abstract

Introduction
Antiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome.

Case presentation
All the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuro-ophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them.

Conclusion
Due to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization.