bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat the acquired von Willebrand syndrome
Authors: Tiede Andreas , Rand Jacob H. , Budde Ulrich , Ganser Arnold , Federici Augusto B. 
Published: May 2011

AbstractThe acquired von Willebrand syndrome (AVWS) is a bleeding disorder that is frequently unrecognized or is misdiagnosed as von Willebrand disease. AVWS is characterized by structural or functional defects of von Willebrand factor (VWF) that are secondary to autoimmune, lymphoproliferative or myeloproliferative, malignant, cardiovascular, or other disorders. VWF abnormalities in these disorders can result from (1) antibody-mediated clearance or functional interference, (2) adsorption to surfaces of transformed cells or platelets, or (3) increased shear stress and subsequent proteolysis. Diagnosis can be challenging as no single test is usually sufficient to prove or exclude AVWS. Furthermore, there are no evidence-based guidelines for management. Treatments of the underlying medical condition, including chemo/radiotherapy, surgery, or immunosuppressants can result in remission of AVWS, but is not always feasible and successful. Because of the heterogeneous mechanisms of AVWS, more than one therapeutic approach is often required to treat acute bleeds and for prophylaxis during invasive procedures; the treatment options include, but are not limited to, desmopressin, VWF-containing concentrates, intravenous immunoglobulin, plasmapheresis or recombinant factor VIIa. Here, we review the management of AVWS with an overview on the currently available evidence and additional considerations for typical treatment situations.
A genome-wide association study identifies novel loci associated with susceptibility to chronic myeloid leukemia
Authors: Kim Dong Hwan (Dennis) , Lee Seung-Tae , Won Hong-Hee , Kim Seonwoo , Kim Min-Ji , Kim Hee-Jin , Kim Sun-Hee , Kim Jong-Won , Kim Hyeoung-Joon , Kim Yeo-Kyeoung , Sohn Sang Kyun , Moon Joon Ho , Jung Chul Won , Lipton Jeffrey H. 
Published: May 2011

Abstract
In the current study, we identified 2 genetic markers for susceptibility to chronic myeloid leukemia (CML) using a genome-wide analysis. A total of 2744 subjects (671 cases and 2073 controls) were included, with 202 Korean CML patients and 497 control subjects enrolled as a discovery set. Significant findings in the discovery set were validated in a second Korean set of 237 patients and 1000 control subjects and in an additional Canadian cohort of European descent, including 232 patients and 576 control subjects. Analysis revealed significant associations of 2 candidate loci, 6q25.1 and 17p11.1, with CML susceptibility, with the lowest combined P values of 2.4 × 10−6 and 1.3 × 10−12, respectively. Candidate genes in those regions include RMND1, AKAP12, ZBTB2, and WSB1. The locus 6q25.1 was validated in both Korean and European cohorts, whereas 17p11.1 was validated only in the Korean cohort. These findings suggest that genetic variants of 6q25.1 and 17p11.1 may predispose one to the development of CML.
Development and characterization of APRIL antagonistic monoclonal antibodies for treatment of B-cell lymphomas
Authors: Guadagnoli Marco , Kimberley Fiona C. , Phan Uyen , Cameron Katherine , Vink Paul M. , Rodermond Hans , Eldering Eric , Kater Arnon P. , van Eenennaam Hans , Medema Jan Paul 
Published: May 2011

Abstract
APRIL (A proliferation-inducing ligand) is a TNF family member that binds two TNF receptor family members, TACI and BCMA. It shares these receptors with the closely related TNF family member, B-cell activating factor (BAFF). Contrary to BAFF, APRIL binds heparan sulfate proteoglycans (HSPGs), which regulates cross-linking of APRIL and efficient signaling. APRIL was originally identified as a growth promoter of solid tumors, and more recent evidence defines APRIL also as an important survival factor in several human B-cell malignancies, such as chronic lymphocytic leukemia (CLL). To target APRIL therapeutically, we developed two anti–human APRIL antibodies (hAPRIL.01A and hAPRIL.03A) that block APRIL binding to BCMA and TACI. Their antagonistic properties are unique when compared with a series of commercially available monoclonal anti–human APRIL antibodies as they prevent in vitro proliferation and IgA production of APRIL-reactive B cells. In addition, they effectively impair the CLL-like phenotype of aging APRIL transgenic mice and, more importantly, block APRIL binding to human B-cell lymphomas and prevent the survival effect induced by APRIL. We therefore conclude that these antibodies have potential for further development as therapeutics to target APRIL-dependent survival in B-cell malignancies.
Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful?
Authors: Meyer K.C. , Raghu G. 
Published: May 2011

Although the application of thoracic high-resolution computed tomography (HRCT) to clinical pulmonology has revolutionised the diagnostic approach to patients with suspected interstitial lung disease (ILD), additional testing is often needed to make a confident ILD diagnosis.Bronchoalveolar lavage (BAL) can play a significant role in making an accurate and confident diagnosis of specific forms of ILD. When BAL is used in conjunction with comprehensive clinical information and HRCT, BAL nucleated immune cell patterns can frequently provide useful information for diagnostic evaluation and lessen the need to proceed to more invasive procedures, such as surgical lung biopsy.Additionally, BAL can identify confounding conditions, such as infection or malignancy. However, BAL technique, and protocols for processing and analysing BAL fluid are critically important for providing useful information.This perspective reviews the current status of using BAL as a diagnostic tool for the diagnosis of ILD.
A 5-aza-2′-deoxycytidine/valproate combination induces cytotoxic T-cell response against mesothelioma
Authors: Leclercq S. , Gueugnon F. , Boutin B. , Guillot F. , Blanquart C. , Rogel A. , Padieu M. , Pouliquen D. , Fonteneau J-F. , Grégoire M. 
Published: May 2011

Malignant pleural mesothelioma (MPM) is an aggressive tumour with a limited response to conventional therapy. The aim of this study was to evaluate the anticancer effect of a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-azaCdR), and two histone deacetylase inhibitors, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA).Human mesothelioma cells were treated with each epigenetic drug, either alone or in combinations. The cytotoxic effects on treated cells and the expression of specific tumour antigens were evaluated. The recognition of treated cells by a specific CD8+ T-cell clone was also measured. Additionally, the effect of combined treatments was tested in a murine model of mesothelioma.We showed that VPA and SAHA synergised with 5-azaCdR to kill MPM cells and induce tumour antigen expression in the remaining living tumour cells. As a consequence, tumour cells expressing these antigens were recognised and lysed by specific CD8+ cytotoxic T-cells.In vivo, treatment with 5-azaCdR/VPA inhibited tumour growth, and promoted lymphocyte infiltration and an immune response against tumour cells.Appropriate epigenetic drug combinations, in addition to inducing mesothelioma cell death, also affect the immunogenic status of these cells. This property could be exploited in clinical investigations to develop MPM treatments combining chemotherapeutic and immunotherapeutic approaches.
TACE/TGF-α/EGFR regulates CXCL8 in bronchial epithelial cells exposed to particulate matter components
Authors: Øvrevik J. , Refsnes M. , Totlandsdal A.I. , Holme J.A. , Schwarze P.E. , Låg M. 
Published: May 2011

Airborne particulate matter (PM) may induce or exacerbate neutrophilic airway disease by triggering the release of inflammatory mediators, such as CXC chemokine ligand (CXCL)8, from the airway epithelium. It is still unclear which PM components are driving CXCL8 responses, as most candidates occur at low concentrations in the dusts. We therefore hypothesised that different PM constituents may contribute through common mechanisms to induce CXCL8.Human bronchial epithelial cells (BEAS-2B) were exposed to different PM components (Zn2+/Fe2+salts, 1-nitropyrene, lipopolysaccharide and diesel exhaust/mineral particles). Gene expression patterns were detected by real-time PCR array. CXCL8 responses were measured by real-time PCR and ELISA. CXCL8 regulation was assessed with a broad inhibitor panel and neutralising antibodies. Epidermal growth factor receptor (EGFR) phosphorylation was examined by immunoprecipitation and Western blotting.Component-induced gene expression was mainly linked to nuclear factor-κB, Ca2+/protein kinase C, phospholipase C, low-density lipoprotein and mitogenic signalling. Many inhibitors attenuated CXCL8 release induced by all PM components, but to varying extents. However, EGFR inhibition strongly reduced CXCL8 release induced by all test compounds and selected compounds increased EGFR phosphorylation. Interference with transforming growth factor (TGF)-α or tumour necrosis factor-α-converting enzyme (TACE), which mediates TGF-α ectodomain shedding, also attenuated CXCL8 release.Different PM constituents induced CXCL8 partly through similar signalling pathways but the relative importance of the different pathways varied. However, TACE/TGF-α/EGFR signalling appears to be a convergent pathway regulating innate immune responses of airway epithelial cells upon exposure to multiple airborne pollutants.
Association between domestic mould and mould components, and asthma and allergy in children: a systematic review
Authors: Tischer C. , Chen C-M. , Heinrich J. 
Published: May 2011

Critical reviews over the past 10 yrs have found increased respiratory and allergic health outcomes for children living in damp and mouldy environments. However, recent studies have suggested that early childhood exposure to specific mould components may actually protect children from developing allergy.We conducted a systematic review of observational studies published in English from January 1980 to July 2010. This review was conducted according to systematic guidelines for Meta-analyses of Observational Studies in Epidemiology (MOOSE). The literature was searched using a computerised bibliographic database, PubMed. In order to increase the quality of the reviewed studies, meta-analyses of the effects of visible mould exposure on allergic health outcomes were performed and we evaluated the findings according to the Bradford Hill criteria for evidence of causation.The literature search identified 1,398 peer-reviewed scientific publications, and 61 studies that fulfilled the inclusion criteria were included in this review. We observed increased risks of allergic respiratory health outcomes in children exposed to visible mould and mould spores. These findings were confirmed by the results of the meta-analysis and in line with the evaluation criteria according to Bradford Hill. Visible mould was positively associated with asthma (OR 1.49 (95% CI 1.28–1.72)), wheeze (OR 1.68 (95% CI 1.48–1.90)) and allergic rhinitis (OR 1.39 (95% CI 1.28–1.51)). However, there was a tendency of lower risk for allergic health outcomes in children exposed to mould-derived components such as (1,3)-β-d-glucan and extracellular polysaccharides.These findings suggest that home environments with visible mould and mould spore exposure increase the risk of allergic respiratory health outcomes in children. However, further investigations are needed to examine the effects of exposure to mould-derived components as the current literature is inconclusive. In order to disentangle the different effects of overall microbial exposure on children’s health, research should focus on specific microbial markers in the home, in combination with new assessment techniques including molecular methods.
E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids
Authors: Ierodiakonou D. , Postma D.S. , Koppelman G.H. , Boezen H.M. , Gerritsen J. , ten Hacken N. , Timens W. , Vonk J.M. 
Published: May 2011

E-cadherins form intercellular junctions that maintain epithelial integrity. Epithelial integrity is impaired in asthma and can be restored by inhaled corticosteroids (ICSs). Our aim was to investigate the association ofCDH1gene polymorphisms (single-nucleotide polymorphisms (SNPs)) with airway remodelling, inflammation and forced expiratory volume in 1 s (FEV1) decline in asthma patients and assess whether ICSs modulate these effects.Bronchial biopsies of 138 asthmatics were available (population 1). Associations of 17 haplotype-tagging SNPs with epithelial E-cadherin expression, biopsy parameters and FEV1/vital capacity (VC) ratio were tested. FEV1and VC data were collected in 281 asthmatics with 30-yr follow-up (population 2). Linear mixed-effect models were used to assess associations of SNPs with FEV1decline.Seven out of the 17 SNPs were associated with airway remodelling, three with CD8+ T-cell counts, two with eosinophil counts and seven with FEV1decline. All associations occurred only in patients using ICS. In general, alleles associated with less remodelling correlated with less FEV1decline and higher FEV1/VC. Decreased epithelial E-cadherin expression was associated with five SNPs in non-ICS users.In conclusion, our data show thatCDH1polymorphisms are associated with epithelial E-cadherin expression and suggest that epithelial adhesion is an important contributor to airway remodelling and lung function in asthma. These effects are modified by the use of inhaled corticosteroids.
GC/MS based metabolomics: development of a data mining system for metabolite identification by using soft independent modeling of class analogy (SIMCA)
Authors: Tsugawa Hiroshi , Tsujimoto Yuki , Arita Masanori , Bamba Takeshi , Fukusaki Eiichiro 
Published: May 2011

Abstract

Background
The goal of metabolomics analyses is a comprehensive and systematic understanding of all metabolites in biological samples. Many useful platforms have been developed to achieve this goal. Gas chromatography coupled to mass spectrometry (GC/MS) is a well-established analytical method in metabolomics study, and 200 to 500 peaks are routinely observed with one biological sample. However, only ~100 metabolites can be identified, and the remaining peaks are left as "unknowns".

Result
We present an algorithm that acquires more extensive metabolite information. Pearson's product-moment correlation coefficient and the Soft Independent Modeling of Class Analogy (SIMCA) method were combined to automatically identify and annotate unknown peaks, which tend to be missed in routine studies that employ manual processing.

Conclusions
Our data mining system can offer a wealth of metabolite information quickly and easily, and it provides new insights, particularly into food quality evaluation and prediction.
Integration Host Factor (IHF) binds to the promoter region of the phtD operon involved in phaseolotoxin synthesis in P. syringaepv. phaseolicola NPS3121
Authors: Arvizu-Gómez Jackeline Lizzeta , Hernández-Morales Alejandro , Pastor-Palacios Guillermo , Brieba Luis G , Álvarez-Morales Ariel 
Published: May 2011

Abstract

Background

Pseudomonas syringae pv. phaseolicola, the causal agent of halo blight disease in beans, produces a toxin known as phaseolotoxin, in whose synthesis participate a group of genes organized within the genome in a region known as the "Pht cluster". This region, which is thought to have been acquired by horizontal gene transfer, includes 5 transcriptional units, two monocistronic (argK, phtL) and three polycistronic (phtA, phtD, phtM), whose expression is temperature dependent. So far, the regulatory mechanisms involved in phaseolotoxin synthesis have not been elucidated and the only well-established fact is the requirement of low temperatures for its synthesis. In this work, we searched for regulatory proteins that could be involved in phaseolotoxin synthesis, focusing on the regulation of the phtD operon.

Results
In this study we identified the global regulator IHF (Integration Host Factor), which binds to the promoter region of the phtD operon, exerting a negative effect on the expression of this operon. This is the first regulatory protein identified as part of the phaseolotoxin synthesis system. Our findings suggest that the Pht cluster was similarly regulated in the ancestral cluster by IHF or similar protein, and integrated into the global regulatory mechanism of P. syringae pv. phaseolicola, after the horizontal gene transfer event by using the host IHF protein.

Conclusion
This study identifies the IHF protein as one element involved in the regulation of phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121 and provides new insights into the regulatory mechanisms involved in phaseolotoxin production.
The burden of physical activity on type 2 diabetes public healthcare expenditures among adults: a retrospective study
Authors: Codogno Jamile S , Fernandes Rômulo A , Sarti Flávia M , Freitas Júnior Ismael F , Monteiro Henrique L 
Published: May 2011

Abstract

Background
Determinants of public healthcare expenditures in type 2 diabetics are not well investigated in developing nations and, therefore, it is not clear if higher physical activity decreases healthcare costs. The purpose of this study was to analyze the relationship between physical activity and the expenditures in public healthcare on type 2 diabetes mellitus treatment.

Methods
Cross-sectional study carried out in Brazil. A total of 121 type 2 diabetics attended to in two Basic Healthcare Units were evaluated. Public healthcare expenditures in the last year were estimated using a specific standard table. Also evaluated were: socio-demographic variables; chronological age; exogenous insulin use; smoking habits; fasting glucose test; diabetic neuropathy and anthropometric measures. Habitual physical activity was assessed by questionnaire.

Results
Age (r = 0.20; p = 0.023), body mass index (r = 0.33; p = 0.001) and waist-to-hip ratio (r = 0.20; p = 0.025) were positively related to expenditures on medication for the treatment of diseases other than diabetes. Insulin use was associated with increased expenditures. Higher physical activity was associated with lower expenditure, provided medication for treatment of diseases other than diabetes (OR = 0.19; p = 0.007) and medical consultations (OR = 0.26; p = 0.029).

Conclusions
Type 2 diabetics with higher enrollment in physical activity presented consistently lower healthcare expenditures for the public healthcare system.
Delay in diagnosis of muscle disorders depends on the subspecialty of the initially consulted physician
Authors: Spuler Simone , Stroux Andrea , Kuschel Franziska , Kuhlmey Adelheid , Kendel Friederike 
Published: May 2011

Abstract

Background
New therapeutic strategies in muscular dystrophies will make a difference in prognosis only if they are begun early in the course of the disease. Therefore, we investigated factors that influence the time to diagnosis in muscle dystrophy patients.

Methods
A sample of 101 patients (mean age 49 years; range 19-80; 44% women) with diagnosed muscle dystrophies from neurological practices and the neuromuscular specialty clinic in Berlin, Germany, was invited to participate. Time from first consultation to diagnosis, subspecialty of physician, and sociodemographic data were assessed with self-report questionnaires. The association between time to diagnosis and potential predictors (subspecialty of initially consulted physician, diagnoses, gender, and age at onset) was modeled with linear regression analysis.

Results
The mean time span between first health-care contact and diagnosis was 4.3 years (median 1). The diagnostic delay was significantly longer if patients were initially seen by a non-neurological specialist compared to a general practitioner (5.2 vs. 3.5 years, p = 0.047). Other factors that were independently associated with diagnostic delay were female gender and inherited muscle disease.

Conclusion
Action to improve clinical awareness of muscle diseases in non-neurological specialists is needed.
Assessment of psychosocial functioning and its risk factors in children with pectus excavatum
Authors: Ji Yi , Liu Wenying , Chen Siyuan , Xu Bing , Tang Yunman , Wang Xuejun , Yang Gang , Cao Liming 
Published: May 2011

Abstract

Background
Psychosocial functioning is poor in patients with pectus excavatum (PE). However, a comprehensive understanding of this issue does not exist. The aim of this study was to assess the severity of psychosocial problems as associated with PE, as well as to identify its risk factors.

Methods
A comparative study was performed at the Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital in Chengdu, China. Patients age 6 to 16 who admitted to the outpatient department for the evaluation or treatment for PE were included in the study. In addition to parental reports of child psychosocial problems on the Achenbach Child Behavior Checklist (CBCL), parents also filled in other structured questionnaires, including socio-demographic variables, patients' medical and psychological characteristics. The severity of malformation was assessed by CT scan. For comparison, an age- and gender- matched control group was recruited from the general population. The socio-demographic and scores on CBCL were compared between patients and control subjects. Univariate and multivariate analysis were performed to examine risk factors for psychosocial problems in patients.

Results
No statistically significant differences were found with respect to social-demographic variables between children with PE and control subjects. Compared with control subjects, children with PE displayed higher prevalence of psychosocial problems in the different scales of the CBCL questionnaire such as 'withdraw', 'anxious-depressed', 'social problems' and 'total problems'. Both univariate and multivariate analyses suggested that age, severity of malformation, and being teased about PE were significantly associated with patients' psychosocial problems.

Conclusions
The information derived from this study supports the opinion that children with PE have more psychosocial problems than children from the general population. Multiple medical and psychosocial factors were associated with patients' impairment of psychosocial functioning.