bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency
Authors: Morales-Aza Begonia , Glennie Sarah J. , Garcez Tomaz Pereira , Davenport Victoria , Johnston Sarah L. , Williams Neil A. , Heyderman Robert S. 
Published: February 2009

AbstractThe importance of T cells in the generation of antigen-specific B-cell immunity has been extensively described, but the role B cells play in shaping T-cell memory is uncertain. In healthy controls, exposure to Neisseria meningitidis in the upper respiratory tract is associated with the generation of memory T cells in the mucosal and systemic compartments. However, we demonstrate that in B cell–deficient subjects with X-linked agammaglobulinemia (XLA), naturally acquired T-cell memory responses to meningococcal antigens are reduced compared with healthy control patients. This difference is not found in T-cell memory to an obligate respiratory pathogen, influenza virus. Accordingly, we show that meningococcal antigens up-regulate major histocompatibility complex (MHC) class II, CD40, CD86/80 expression on mucosal and systemic associated B cells and that antigen presentation stimulates T-cell proliferation. A similar reduction in N meningitidis but not influenza antigen–specific T-cell memory was observed in subjects with X-linked hyper IgM syndrome (X-HIM), implicating the interaction of CD40-CD40L in this process. Together, these data implicate B cells in the induction and maintenance of T-cell memory to mucosal colonizing bacteria such as N meningitidis and highlight the importance of B cells beyond antibody production but as a target for immune reconstitution.
The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies
Authors: Nahimana Aimable , Attinger Antoine , Aubry Dominique , Greaney Peter , Ireson Christopher , Thougaard Annemette V. , Tjørnelund Jette , Dawson Keith M. , Dupuis Marc , Duchosal Michel A. 
Published: February 2009

Abstract
APO866 inhibits nicotinamide phosphoribosyltransferase (NMPRTase), a key enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis from the natural precursor nicotinamide. Intracellular NAD is essential for cell survival, and NAD depletion resulting from APO866 treatment elicits tumor cell death. Here, we determine the in vitro and in vivo sensitivities of hematologic cancer cells to APO866 using a panel of cell lines (n = 45) and primary cells (n = 32). Most cancer cells (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], mantle cell lymphoma [MCL], chronic lymphocytic leukemia [CLL], and T-cell lymphoma), but not normal hematopoietic progenitor cells, were sensitive to low concentrations of APO866 as measured in cytotoxicity and clonogenic assays. Treatment with APO866 decreased intracellular NAD and adenosine triphosphate (ATP) at 24 hours and 48 to72 hours, respectively. The NAD depletion led to cell death. At 96 hours, APO866-mediated cell death occurred in a caspase-independent mode, and was associated with mitochondrial dysfunction and autophagy. Further, in vivo administration of APO866 as a single agent prevented and abrogated tumor growth in animal models of human AML, lymphoblastic lymphoma, and leukemia without significant toxicity to the animals. The results support the potential of APO866 for treating hematologic malignancies.
A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration
Authors: McKimmie Clive S. , Moore Mark , Fraser Alasdair R. , Jamieson Thomas , Xu Damo , Burt Claire , Pitman Nick I. , Nibbs Robert J. , McInnes Iain B. , Liew Foo Y. , Graham Gerard J. 
Published: February 2009

AbstractToll-like receptors orchestrate rapid local protective innate-immune responses to invading pathogens and optimize leukocyte priming of subsequent adaptive responses. Paradoxically, systemic excess of the TLR2 ligand, bacterial lipoprotein (BLP), suppresses peripheral inflammatory responses. Here, we demonstrate that this phenomenon is regulated via the TLR2-dependent, cell-autonomous down-regulation of inflammatory chemokine receptor expression on a variety of leukocyte subsets. Remarkably, BLP mediated no effect on constitutive chemokine receptor expression. By tracking adoptively transferred wild-type and TLR2−/− leukocytes in vivo, we observed that BLP mediated chemokine receptor switching directed leukocytes away from inflamed sites toward secondary lymphoid organs. These data highlight a novel role for TLR ligands, such as BLP, in regulating leukocyte retention and migration away from innate immune lesions via discrete constitutive and inflammatory chemokine receptor regulation.
Interleukin-1 receptor-related protein ST2 suppresses the initial stage of bleomycin-induced lung injury
Authors: Mato N. , Fujii M. , Hakamata Y. , Kobayashi E. , Sato A. , Hayakawa M. , Ohto-Ozaki H. , Bando M. , Ohno S. , Tominaga S. , Sugiyama Y. 
Published: February 2009

Acute lung injury has a range of causes, and occasionally leads to lethal respiratory failure. Despite advances in treatment, acute lung injury continues to have a high mortality rate, and thus a new therapeutic approach is needed. ST2 is an interleukin (IL)-1 receptor-related protein, and its expression is induced by various inflammatory responses. Recently, ST2 has been speculated to exert anti-inflammatory effects; therefore, we investigated the role of the ST2 in the murine model of acute lung injury.To elucidate the function of ST2in vivo, mice that transiently overexpressed ST2 protein were prepared using the hydrodynamic gene transfer method, and lung injury was induced by intratracheal administration of bleomycin.In bleomycin-treated ST2-overexpressing mice, the increase of neutrophils in the bronchoalveolar lavage fluid (BALF) was markedly suppressed. Additionally, the levels of tumour necrosis factor-α and IL-6, as well as the concentration of albumin, in BALF were reduced compared with those of controls. Furthermore, the pulmonary architecture in ST2-overexpressing mice remained almost normal, and the survival rate was significantly improved.From these results, we concluded that ST2 has the potential to suppress the initial stage of acute lung injury, and therefore it may be a useful reagent for the treatment of acute lung injury.
Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness
Authors: Sharma S. , Murphy A. J. , Soto-Quiros M. E. , Avila L. , Klanderman B. J. , Sylvia J. S. , Celedón J. C. , Raby B. A. , Weiss S. T. 
Published: February 2009

Vascular endothelial growth factor (VEGF) is an angiogenic factor implicated in asthma severity. The objective of the present study was to determine whether VEGF single nucleotide polymorphisms (SNPs) are associated with asthma, lung function and airway responsiveness.The present authors analysed 10 SNPs in 458 white families in the Childhood Asthma Management Program (CAMP). Tests of association with asthma, lung function and airway responsiveness were performed using PBAT software (Golden Helix, Inc. Bozeman, MT, USA; available atwww.goldenhelix.com). Family and population-based, revpeated measures analysis of airflow obstruction were conducted. Replication studies were performed in 412 asthmatic children and their parents from Costa Rica.Associations with asthma, lung function and airway responsiveness were observed in both cohorts. SNP rs833058 was associated with asthma in both cohorts. This SNP was also associated with increased airway responsiveness in both populations. An association of rs4711750 and its haplotype with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio in both cohorts was observed. Longitudinal analysis in CAMP confirmed an association of rs4711750 with FEV1/FVC decline over ∼4.5 yrs of observation.VEGF polymorphisms are associated with childhood asthma, lung function and airway responsiveness in two populations, suggesting that VEGF polymorphisms influence asthma susceptibility, airflow obstruction and airways responsiveness.
Leptin receptor polymorphisms and lung function decline in COPD
Authors: Hansel N. N. , Gao L. , Rafaels N. M. , Mathias R. A. , Neptune E. R. , Tankersley C. , Grant A. V. , Connett J. , Beaty T. H. , Wise R. A. , Barnes K. C. 
Published: February 2009

Only a fraction of all smokers develop chronic obstructive pulmonary disease (COPD), suggesting a large role for genetic susceptibility. The leptin receptor (LEPR) is present in human lung tissue and may play a role in COPD pathogenesis. The present study examined the association between genetic variants in theLEPRgene and lung function decline in COPD.In total, 429 European Americans were randomly selected from the National Heart Lung and Blood Institute Lung Health Study. 36 single nucleotide polymorphisms (SNPs) inLEPRwere genotyped using the IlluminaTMGoldenGate platform (Broad Institute, Cambridge, MA, USA). Mean annual decline in forced expiratory volume in 1 s % predicted over the 5-yr period was calculated using linear regression. Linear regression models were also used to adjust for potential confounders. In addition,in vivoexpression of the receptor gene was assessed with immunohistochemistry on lungs from smoke-exposed inbred mice.We identified significant associations (p<0.05) between lung function decline and 21 SNPs. Haplotype analyses confirmed several of these associations seen with individual markers. Immunohistochemistry results in inbred mice strains support a potential role of LEPR in COPD pathogenesis.We identified genetic variants in theLEPRgene significantly associated with lung function decline in a population of smokers with COPD. Our results support a role forLEPRas a novel candidate gene for COPD.
Interferon-γ release assays do not identify more children with active tuberculosis than the tuberculin skin test
Authors: Kampmann B. , Whittaker E. , Williams A. , Walters S. , Gordon A. , Martinez-Alier N. , Williams B. , Crook A. M. , Hutton A-M. , Anderson S. T. 
Published: February 2009

Data are lacking on the performance of interferon-γ release assays (IGRAs) in children. Although IGRAs are recommended for screening for latent tuberculosis infection (LTBI), many clinicians wish to employ them as a diagnostic test for active tuberculosis (TB). The objective of the present study was to compare the performance of the two commercially available IGRAs and the tuberculin skin test (TST) side-by-side in children with active TB and LTBI.In a prospective study, 209 children were investigated for active (n = 91) or latent TB (n = 118). TST, QuantiFERON-TB Gold In-tube (QFG-IT; Cellestis, Carnegie, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK) assays were simultaneously used.For culture-confirmed active TB, the sensitivity of the TST was 83%, compared with 80% for QFG-IT and 58% for T-SPOT.TB. IGRAs did not perform significantly better than TST, although QFG-IT was significantly better than T-SPOT.TB. The agreement between QFG-IT and T-SPOT.TB in culture-confirmed TB was poor at 66.7%. In LTBI, the agreement between QFG-IT and T-SPOT.TB was very good (92%) with moderate agreement between TST and T-SPOT.TB (75%) and QFG-IT and TST (77%).A negative interferon-γ release assay should not dissuade paediatricians from diagnosing and treating presumed active tuberculosis. If used for diagnosis of latent tuberculosis infection, interferon-γ release assays could significantly reduce the numbers of children receiving chemoprophylaxis. Very good concordance between both tests was found.
Validation of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis
Authors: Murray M. P. , Turnbull K. , MacQuarrie S. , Pentland J. L. , Hill A. T. 
Published: February 2009

Health-related quality of life is a potentially important marker for evaluating existing and new therapies in bronchiectasis. The Leicester Cough Questionnaire (LCQ) is a symptom specific questionnaire designed to assess the impact of cough severity, a major symptom of bronchiectasis. This study aimed to validate the LCQ in bronchiectasis.The validity, responsiveness and reliability of the LCQ were assessed as follows: ability to discriminate severe and mild disease; change in score following antibiotic treatment for exacerbations; repeatability over a 6-month period in stable disease; and comparison with the St George's Respiratory Questionnaire (SGRQ).In total, 120 patients (51 with severe disease, 29 with moderate disease and 40 with mild disease) completed the LCQ and SGRQ. The area under the receiver–operator curve was good for both severe and mild disease (0.84 and 0.80 respectively, p<0.0001). Following 2 weeks' antibiotic treatment, the median LCQ score (interquartile range) improved from 11.3 (9.3–13.7) to 17.8 (15–18.8) (p<0.0001). The LCQ score was repeatable over 6 months in stable disease (intraclass correlation coefficient of 0.96 (95%CI 0.93–0.97), p<0.0001). Correlation between the LCQ and SGRQ scores was -0.7 in both stable disease and exacerbations (p<0.0001).The LCQ can discriminate disease severity, is responsive to change and is reliable for use in non-cystic fibrosis bronchiectasis.
Secretion of flagellin by the LEE-encoded type III secretion system of enteropathogenic Escherichia coli
Authors: Badea Luminita , Beatson Scott A , Kaparakis Maria , Ferrero Richard L , Hartland Elizabeth L 
Published: February 2009

Abstract

Background
Enteropathogenic Escherichia coli (EPEC) is an attaching and effacing (A/E) pathogen that possesses a type III secretion system (T3SS) encoded within the locus of enterocyte effacement (LEE). The LEE is essential for A/E lesion formation and directs the secretion and translocation of multiple LEE-encoded and non-LEE encoded effector proteins into the cytosol of infected cells. In this study we used proteomics to compare proteins exported to the culture supernatant by wild type EPEC E2348/69, a ΔespADB mutant and a ΔescF T3SS mutant.

Results
We observed that flagellin was consistently and strongly present in the secretome of wild type EPEC and the ΔespADB mutant but present only weakly in the secretome of the ΔescF mutant. Given the ancestral relationship between the flagella export apparatus and virulence associated T3SSs, we investigated whether FliC could utilise the LEE-encoded T3SS for export. In the absence of a functional flagella export apparatus, we showed that FliC could be secreted by the LEE-encoded T3SS and stimulate (Toll-like receptor 5) TLR5 signalling but could not confer motility.

Conclusion
Since the secretion of FliC during A/E lesion formation would presumably be disadvantageous for the pathogen, we propose that virulence associated T3SSs and flagella T3SSs have evolved through a system of chaperones and complex regulatory pathways to be functional at different times to ensure that FliC secretion does not occur during T3SS effector translocation.
Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses
Authors: Fu Li-Yun , Jia Hu-Liang , Dong Qiong-Zhu , Wu Jin-Cai , Zhao Yue , Zhou Hai-Jun , Ren Ning , Ye Qin-Hai , Qin Lun-Xiu 
Published: February 2009

Abstract

Background
Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes.

Methods
We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tomor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test.

Results
With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes.

Conclusion
TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis.
Multinational development of a questionnaire assessing patient satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' (PACT-Q©)
Authors: Prins Martin H , Marrel Alexia , Carita Paulo , Anderson David , Bousser Marie-Germaine , Crijns Harry , Consoli Silla , Arnould Benoit 
Published: February 2009

AbstractBackgroundThe side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment.MethodsA conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions.ResultsInitial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated.ConclusionThe PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and psychometric properties have been tested and are presented in a separate manuscript.
The endogenous production of hydrogen sulphide in intrauterine tissues
Authors: Patel Pushpa , Vatish Manu , Heptinstall John , Wang Rui , Carson Ray J 
Published: February 2009

Abstract

Background
Hydrogen sulphide is a gas signalling molecule which is produced endogenously from L-cysteine via the enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). The possible role of hydrogen sulphide in reproduction has not yet been fully investigated. It has been previously demonstrated that hydrogen sulphide relaxes uterine smooth muscle in vitro. The aim of the present study was to investigate the endogenous production of hydrogen sulphide in rat and human intrauterine tissues in vitro.

Methods
The production of hydrogen sulphide in rat and human intrauterine tissues was measured in vitro using a standard technique. The expression of CBS and CSE was also investigated in rat and human intrauterine tissues via Western blotting. Furthermore, the effects of nitric oxide (NO) and low oxygen conditions on the production rates of hydrogen sulphide were investigated.

Results
The order of hydrogen sulphide production rates (mean +/- SD, n = 4) for rat tissues were: liver (777 +/- 163 nM/min/g) > uterus (168 +/- 100 nM/min/g) > fetal membranes (22.3 +/- 15.0 nM/min/g) > placenta (11.1 +/- 4.7 nM/min/g), compared to human placenta (200 +/- 102 nM/min/g). NO significantly increased hydrogen sulphide production in rat fetal membranes (P < 0.05). Under low oxygen conditions the production of hydrogen sulphide was significantly elevated in human placenta, rat liver, uterus and fetal membranes (P < 0.05). Western blotting (n = 4) detected the expression of CBS and CSE in all rat intrauterine tissues, and in human placenta, myometrium, amnion and chorion.

Conclusion
Rat and human intrauterine tissues produce hydrogen sulphide in vitro possibly via CBS and CSE enzymes. NO increased the production of hydrogen sulphide in rat fetal membranes. The augmentation of hydrogen sulphide production in human intrauterine tissues in a low oxygen environment could have a role in pathophysiology of pregnancy.
Production and purification of immunologically active core protein p24 from HIV-1 fused to ricin toxin B subunit in E. coli
Authors: Donayre-Torres Alberto J , Esquivel-Soto Ernesto , Gutiérrez-Xicoténcatl María deLourdes , Esquivel-Guadarrama Fernando R , Gómez-Lim Miguel A 
Published: February 2009

AbstractBackgroundGag protein from HIV-1 is a polyprotein of 55 kDa, which, during viral maturation, is cleaved to release matrix p17, core p24 and nucleocapsid proteins. The p24 antigen contains epitopes that prime helper CD4 T-cells, which have been demonstrated to be protective and it can elicit lymphocyte proliferation. Thus, p24 is likely to be an integral part of any multicomponent HIV vaccine. The availability of an optimal adjuvant and carrier to enhance antiviral responses may accelerate the development of a vaccine candidate against HIV. The aim of this study was to investigate the adjuvant-carrier properties of the B ricin subunit (RTB) when fused to p24.ResultsA fusion between ricin toxin B subunit and p24 HIV (RTB/p24) was expressed inE. coli. Affinity chromatography was used for purification of p24 alone and RTB/p24 from cytosolic fractions. Biological activity of RTB/p24 was determined by ELISA and affinity chromatography using the artificial receptor glycoprotein asialofetuin. Both assays have demonstrated that RTB/p24 is able to interact with complex sugars, suggesting that the chimeric protein retains lectin activity. Also, RTB/p24 was demonstrated to be immunologically active in mice. Two weeks after intraperitoneal inoculation with RTB/p24 without an adjuvant, a strong anti-p24 immune response was detected. The levels of the antibodies were comparable to those found in mice immunized with p24 alone in the presence of Freund adjuvant. RTB/p24 inoculated intranasally in mice, also elicited significant immune responses to p24, although the response was not as strong as that obtained in mice immunized with p24 in the presence of the mucosal adjuvant cholera toxin.ConclusionIn this work, we report the expression inE. coliof HIV-1 p24 fused to the subunit B of ricin toxin. The high levels of antibodies obtained after intranasal and intraperitoneal immunization of mice demonstrate the adjuvant-carrier properties of RTB when conjugated to an HIV structural protein. This is the first report in which a eukaryotic toxin produced inE. coliis employed as an adjuvant to elicit immune responses to p24 HIV core antigen.