bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is pegfilgrastim safe and effective in congenital neutropenia? An analysis of the French Severe Chronic Neutropenia registry
Authors: Beaupain Blandine , Leblanc Thierry , Reman Oumédaly , Hermine Olivier , Vannier Jean‐Pierre , Suarez Felipe , Lutz Patrick , Bordigoni Pierre , Jourdain Anne , Schoenvald Michele , Ouachee Marie , François Sylvie , Kohser Fréderic , Jardin Fabrice , Devouassoux Gilles , Bertrand Yves , Nove‐Josserand Raphaele , Donadieu Jean 
Published: July 2009

AbstractAimsTo examine the efficacy and safety of pegfilgrastim in patients with congenital neutropenia (CN).MethodsSeventeen patients enrolled in the French Severe CN Register received pegfilgrastim.ResultsMedian age at pegfilgrastim introduction was 19.1 years (range 3.9–52.3 years). In 14 cases pegfilgrastim replaced GCSF (filgrastim or lenograstim), after a median of 6.9 years of GCSF therapy. The dose of pegfilgrastim was usually one full vial per injection (except in five children, who received 1/6 to 1/2 a vial), resulting in a dose of between 50 and 286 µg/kg. The pegfilgrastim schedule ranged from two injections every 7 days to one injection every 30 days, with treatment‐free periods. The median interval between the first and last dose of pegfilgrastim was 0.8 years (0.01–4.1 years). The absolute neutrophil count tended to increase more strongly on pegfilgrastim than on GCSF, but the difference was not statistically significant. During pegfilgrastim therapy, a severe infection occurred in two patients and recurrent ENT infections in two other patients. Bone pain was reported by nine patients, anemia and thrombocytopenia occurred in one patient (WHO grade III), chronic urticaria occurred in one patient (WHO grade III), and a single pegfilgrastim injection was followed by respiratory distress and death 15 days later in a patient with GDSIb. At the last update, 10 patients had stopped receiving pegfilgrastim and seven patients were still receiving pegfilgrastim.ConclusionCompared to conventional GCSF, pegfilgrastim is more difficult to use in congenital neutropenia, with more frequent adverse events and sometimes poor efficacy. Pediatr Blood Cancer 2009;53:1068–1073. © 2009 Wiley‐Liss, Inc.
Family, demographic and illness‐related determinants of HRQL in children with brain tumours in the first year after diagnosis
Authors: Penn Anthony , Lowis Stephen P. , Stevens Michael C.G. , Hunt Linda P. , Shortman Robert I. , McCarter Renee J. , Pauldhas Darwin , Curran Andrew L. , Sharples Peta M. 
Published: July 2009

AbstractAimsTo evaluate the relationship between parent‐ and child‐report Health‐Related Quality of Life (HRQL) and demographic, tumour and family variables in children with a brain tumour in the first year after diagnosis and to identify determinants of HRQL at 12 months.ProcedureLongitudinal prospective study: Semi‐structured interviews took place approximately 1, 6 and 12 months after diagnosis. HRQL was measured using the self‐ and parent‐report PedsQL 4.0 Total Scale Score. Tumour and treatment variables considered included tumour site and grade, hydrocephalus at diagnosis, chemotherapy and radiotherapy. Family variables included measures of family function, family support and family stress, the primary carer's coping strategies and symptoms of depression and anxiety. Univariate analyses were used at all three time points, and to identify potential early predictors of HRQL at 1 year. Regression analysis was then used to identify the most important determinants of HRQL at 1 year.ResultsThirty‐five patients completed the 12‐month interviews. There were consistent significant negative correlations between concurrent family impact of illness and parent and self‐report HRQL, and positive correlations between concurrent family support and parent‐report HRQL. Treatment with radio‐ or chemotherapy correlated with child‐report HRQL only at some time points. Multivariate analysis showed infratentorial tumour site, and poor HRQL at 1 month best predicted poor self‐ and parent‐report HRQL at 12 months.ConclusionChildren with infratentorial tumours and poor HRQL early after diagnosis tend to have poor HRQL at 1 year. While family factors are important modulators of concurrent HRQL, they do not appear important in predicting HRQL. Pediatr Blood Cancer 2009;53:1092–1099. © 2009 Wiley‐Liss, Inc.
Epidemiology of bone tumours in children and young adults
Authors: Eyre Rachel , Feltbower Richard G. , Mubwandarikwa Emmanuel , Eden Tim O.B. , McNally Richard J.Q. 
Published: July 2009

AbstractAlthough the epidemiology of malignant bone tumours in children and young adults has been explored, no definitive causation of any specific tumour has yet been identified. We performed a literature review (1970–2008) to find all papers covering possible aetiological factors involved in the development of bone tumours in children and young adults. Several associations have been reported with some consistency: the presence of hernias and Ewing sarcoma; high fluoride exposure and osteosarcoma; and parental farming and residence on a farm, younger age at puberty and family history of cancer for all bone tumours, especially osteosarcoma. Clearly further research is needed to confirm or refute these putative risk factors. It is likely that studies of gene–environment interactions may prove to be the most fruitful of future research. Pediatr Blood Cancer 2009;53:941–952. © 2009 Wiley‐Liss, Inc.
Novel functional profiling approach combining reverse phase protein microarrays and human 3‐D ex vivo tissue cultures: Expression of apoptosis‐related proteins in human colon cancer
Authors: Pirnia Farzaneh , Pawlak Michael , Thallinger Gerhard G. , Gierke Berthold , Templin Markus F. , Kappeler Andi , Betticher Daniel C. , Gloor Beat , Borner Markus M. 
Published: July 2009

AbstractCancer is caused by a complex pattern of molecular perturbations. To understand the biology of cancer, it is thus important to look at the activation state of key proteins and signaling networks. The limited amount of available sample material from patients and the complexity of protein expression patterns make the use of traditional protein analysis methods particularly difficult. In addition, the only approach that is currently available for performing functional studies is the use of serial biopsies, which is limited by ethical constraints and patient acceptance. The goal of this work was to establish a 3‐D ex vivo culture technique in combination with reverse‐phase protein microarrays (RPPM) as a novel experimental tool for use in cancer research. The RPPM platform allows the parallel profiling of large numbers of protein analytes to determine their relative abundance and activation level. Cancer tissue and the respective corresponding normal tissue controls from patients with colorectal cancer were cultured ex vivo. At various time points, the cultured samples were processed into lysates and analyzed on RPPM to assess the expression of carcinoembryonic antigen (CEA) and 24 proteins involved in the regulation of apoptosis. The methodology displayed good robustness and low system noise. As a proof of concept, CEA expression was significantly higher in tumor compared with normal tissue (p<0.0001). The caspase 9 expression signal was lower in tumor tissue than in normal tissue (p<0.001). Cleaved Caspase 8 (p=0.014), Bad (p=0.007), Bim (p=0.007), p73 (p=0.005), PARP (p<0.001), and cleaved PARP (p=0.007) were differentially expressed in normal liver and normal colon tissue. We demonstrate here the feasibility of using RPPM technology with 3‐D ex vivo cultured samples. This approach is useful for investigating complex patterns of protein expression and modification over time. It should allow functional proteomics in patient samples with various applications such as pharmacodynamic analyses in drug development.
Use of narrow‐range peptide IEF to improve detection of lung adenocarcinoma markers in plasma and pleural effusion
Authors: Pernemalm Maria , De Petris Luigi , Eriksson Hanna , Brandén Eva , Koyi Hirsh , Kanter Lena , Lewensohn Rolf , Lehtiö Janne 
Published: July 2009

AbstractIn this study we applied narrow‐range peptide IEF to plasma or pleural effusion prior to LC/MS/MS. Two methods for narrow‐range IEF were run; IPG strips and free‐flow electrophoresis. Data from this study was compared with cell line data to evaluate the method performance in body fluids. To test the methods potential in quantitative biomarker discovery studies, plasma and pleural effusion from patients with lung adenocarcinoma (n=3) were compared with inflammatory pleuritis (n=3) using iTRAQ quantification. Using narrow‐range IEF on the peptide level we were able to identify and quantify 282 proteins in plasma and 300 proteins in pleural effusion. These body fluid proteomes demonstrated high degree of overlap; however, more proteins significantly differently altered levels related to adenenocarcinoma were found in pleural effusion compared with plasma, suggesting enrichment of lung tissue‐related proteins in pleural effusion. Nine proteins were chosen for initial validation with Western blot, and one protein (NPC2) was chosen for further validation using imunohistochemistry. Overall, the quantitative results from IEF/LC/MS/MS showed good correlation with the results from Western blot and imunohistochemistry, showing the potential of this methodology in quantitative biomarker discovery studies.
Identification of blood group A/A‐Leb/y and B/B‐Leb/y active glycotopes co‐expressed on the O‐glycans isolated from two distinct human ovarian cyst fluids
Authors: Yu Shin‐Yi , Yang Zhangung , Khoo Kay‐Hooi , Wu Albert M. 
Published: July 2009

AbstractAlthough the individual human blood group A and B determinants are well defined, their co‐expression pattern on a particular glycan carrier in individuals of blood group AB status has not been delineated. To address this issue, complex O‐glycans were isolated from two distinct sources of human ovarian cyst glycoproteins (HOC 89 and Cyst 19) and profiled by advanced MS analyses, in conjunction with defining their binding characteristics against a panel of lectins and monoclonal antibodies. The major O‐glycans of HOC 89 were found to correspond to sialyl Tn, mono‐ and di‐sialyl T structures, whereas those of Cyst 19 were apparently more heterogeneous and extended to larger sizes. A minimal structure that carries both A and B determinants on the same molecule was identified, in which the A epitope is attached directly to the core GalNAc, whereas the B epitope is preferentially located on the six arms of a core 2 structure. Both arms can be further extended with internal fucosylation that appears to be restricted to those non‐sialylated chains already carrying the terminal ABH determinants, thus giving rise to rather prominent A/B‐Leb/y glycotopes on larger O‐glycans.
Chronic ethanol feeding affects proteasome‐interacting proteins
Authors: Bousquet‐Dubouch Marie‐Pierre , Nguen Sheila , Bouyssié David , Burlet‐Schiltz Odile , French Samuel W. , Monsarrat Bernard , Bardag‐Gorce Fawzia 
Published: July 2009

AbstractStudies on alcoholic liver injury mechanisms show a significant inhibition of the proteasome activity. To investigate this phenomenon, we isolated proteasome complexes from the liver of rats fed ethanol chronically, and from the liver of their pair‐fed controls, using a non‐denaturing multiple centrifugations procedure to preserve proteasome‐interacting proteins (PIPs). ICAT and MS/MS spectral counting, further confirmed by Western blot, showed that the levels of several PIPs were significantly decreased in the isolated ethanol proteasome fractions. This was the case of PA28α/β proteasome activator subunits, and of three proteasome‐associated deubiquitinases, Rpn11, ubiquitin C‐terminal hydrolase 14, and ubiquitin carboxyl‐terminal hydrolase L5. Interestingly, Rpn13 C‐terminal end was missing in the ethanol proteasome fraction, which probably altered the linking of ubiquitin carboxyl‐terminal hydrolase L5 to the proteasome. 20S proteasome and most 19S subunits were however not changed but Ecm29, a protein known to stabilize the interactions between the 20S and its activators, was decreased in the isolated ethanol proteasome fractions. It is proposed that ethanol metabolism causes proteasome inhibition by several mechanisms, including by altering PIPs and proteasome regulatory complexes binding to the proteasome.
Large‐scale proteomic analysis of tyrosine‐phosphorylation induced by T‐cell receptor or B‐cell receptor activation reveals new signaling pathways
Authors: Matsumoto Masaki , Oyamada Koji , Takahashi Hidehisa , Sato Takamichi , Hatakeyama Shigetsugu , Nakayama Keiichi I. 
Published: July 2009

AbstractActivation of the T‐cell receptor (TCR) and that of the B‐cell receptor (BCR) elicits tyrosine‐phosphorylation of proteins that belongs to similar functional categories, but result in distinct cellular responses. Large‐scale analyses providing an overview of the signaling pathways downstream of TCR or BCR have not been described, so it has been unclear what components of these pathways are shared and which are specific. We have now performed a systematic analysis and provide a comprehensive list of tyrosine‐phosphorylated proteins (PY proteome) with quantitative data on their abundance in T cell, B cell, and nonlymphoid cell lines. Our results led to the identification of novel tyrosine‐phosphorylated proteins and signaling pathways not previously implicated in immunoreceptor signal transduction, such as clathrin, zonula occludens 2, eukaryotic translation initiation factor 3, and RhoH, suggesting that TCR or BCR signaling may be linked to downstream processes such as endocytosis, cell adhesion, and translation. Thus comparative and quantitative studies of tyrosine‐phosphorylation have the potential to expand knowledge of signaling networks and to promote understanding of signal transduction at the system level.
Proteomic profiling of Cronobacter turicensis 3032, a food‐borne opportunistic pathogen
Authors: Carranza Paula , Hartmann Isabel , Lehner Angelika , Stephan Roger , Gehrig Peter , Grossmann Jonas , Barkow‐Oesterreicher Simon , Roschitzki Bernd , Eberl Leo , Riedel Kathrin 
Published: July 2009

AbstractMembers of the genus Cronobacter are opportunistic pathogens for neonates and are often associated with contaminated milk powder formulas. At present little is known about the virulence mechanisms or the natural reservoir of these organisms. The proteome of Cronobacter turicensis 3032, which has recently caused two deaths, was mapped aiming at a better understanding of physiology and putative pathogenic traits of this clinical isolate. Our analyses of extracellular, surface‐associated and whole‐cell proteins by two complementary proteomics approaches, 1D‐SDS‐PAGE combined with LC‐ESI‐MS/MS and 2D‐LC‐MALDI‐TOF/TOF MS, lead to the identification of 832 proteins corresponding to a remarkable 19% of the theoretically expressed protein complement of C. turicensis. The majority of the identified proteins are involved in central metabolic pathways, translation, protein folding and stability. Several putative virulence factors, whose expressions were confirmed by phenotypic assays, could be identified: a macrophage infectivity potentiator involved in C. turicensis persistence in host cells, a superoxide dismutase protecting the pathogen against reactive oxygen species and an enterobactin‐receptor protein for the uptake of siderophore‐bound iron. Most interestingly, a chitinase and a metalloprotease that might act against insects and fungi but no casein hydrolysing enzymes were found, suggesting that there is an environmental natural habitat of C. turicensis 3032.
Shikonin inhibits fat accumulation in 3T3‐L1 adipocytes
Authors: Lee Haeyong , Kang Ryunhwa , Yoon Yoosik 
Published: July 2009

AbstractShikonin, 5,6‐dihydroxyflavone‐7‐glucuronic acid, is the main ingredient of Lithospermum erythrorhizon Sieb. et Zucc, and was reported to have various biological activities including antiinflammatory, anticancer, antimicrobial and others. This study aimed to elucidate, for the first time, the antiobesity activity of shikonin and its mechanism of action. Shikonin was found to inhibit fat droplet formation and triglyceride accumulation in 3T3‐L1 adipocytes. The half inhibitory concentration, IC50, for the inhibition of triglyceride accumulation was found to be 1.1 μM. The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following shikonin treatment. Shikonin also inhibited the ability of PPARγ and C/EBPα, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPARγ and C/EBPa were significantly down‐regulated following shikonin treatment. Among the upstream regulators of adipogenesis, only SREBP1C was found to be down‐regulated by shikonin. The results of this study suggest that shikonin down‐regulates the expression of SREBP1C and subsequently the expression of PPARγ and C/EBPα. Together, these changes result in the down‐regulation of lipid metabolizing enzymes and reduced fat accumulation. Copyright © 2009 John Wiley & Sons, Ltd.
The protective effects of hydroxytyrosol against UVB‐induced DNA damage in HaCaT cells
Authors: Guo Wei , An Yu , Jiang Liping , Geng Chengyan , Zhong Laifu 
Published: July 2009

AbstractThe chemoprotective effect of hydroxytyrosol (HT) against UVB‐induced DNA damage was investigated in a human skin keratinocyte cell line, HaCaT. The comet assay was used to monitor DNA strand breaks. Intracellular reactive oxygen species (ROS) formation was measured by flow cytometry using 2,7‐dichlorofluorescein diacetate (DCFH‐DA). The levels of oxidatively generated damage to DNA were estimated by immunocytochemistry analysis of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). The protein expression of p53 and NF‐κB was estimated by western blotting. The results showed that HT significantly reduced the DNA strand breaks caused by UVB. It was also found that HT reduced intracellular ROS formation and 8‐OHdG level caused by UVB. Furthermore, HT attenuated the expression of p53 and NF‐κB in a concentration‐dependent manner. These results strongly suggest that HT has a significant protective ability against UVB‐induced DNA damage and that oxidative stress plays an important part in it. Copyright © 2009 John Wiley & Sons, Ltd.
Empirically based modelling of radar‐rainfall uncertainties for a C‐band radar at different time‐scales
Authors: Villarini Gabriele , Krajewski Witold F. 
Published: July 2009

AbstractRadar‐based estimates of rainfall are affected by several sources of systematic and random errors. The propagation of these uncertainties is required for improving the understanding and interpretation of the results obtained when radar‐rainfall estimates are used as input or initial conditions. Despite the relevance of the problem, modelling of radar‐rainfall uncertainties is still at an early stage. The authors apply an empirically based model in which the relation between true rainfall and radar‐rainfall can be described as the product of a systematic distortion function (accounting for systematic biases) and random component (describing the remaining random errors). The proposed results are based on a large sample (more than six years) of data from a C‐band radar (Wardon Hill) located in southwest England. The true ground rainfall is approximated by rain gauge measurements from a highly dense network deployed in the Brue catchment, located about 40 km from the radar site.The authors present results from their modelling of the radar‐rainfall errors at four time‐scales of hydrologic interest (5‐ and 15‐minute, hourly and three‐hourly) and 2 km spatial resolution, discussing the impact of spatial sampling errors on the proposed results. Copyright © 2009 Royal Meteorological Society
Wavelet transform‐based analysis of periodicities and trends of Sakarya basin (Turkey) streamflow data
Authors: Partal Turgay 
Published: July 2009

AbstractIn this study, the wavelet transform and the Mann–Kendall test are used to determine possible trends in annual streamflow series. The wavelet analysis provides detailed information about the time‐frequency contents of the data. Using wavelet components of the original data, it was aimed to find which periodicities are mainly responsible for a trend in the original data. Also, the global wavelet spectra and the continuous wavelet transform (CWT) were used for the analysis of the streamflow data, in order to explain its time‐frequency characteristics. Annual streamflow series across Turkey were used for the detection of trends for the original data and the periodic wavelet components (obtained by discrete wavelet transform). It was found that some periodic events clearly affect the trend in the streamflow series. The DW4 component (16‐yearly periodic component) at the stations of the Sakarya basin is the effective periodic component and is responsible for producing a real trend in the data. The effects of regional differences on the wavelet‐trend analysis are studied using records of the stations located in different climate areas. DW2 (4‐yearly component) and DW3 (8‐yearly component) are the dominant periodic components of this data. This study aims to explain the trend structure in the data. Copyright © 2009 John Wiley & Sons, Ltd.
The relations between ‘standard’ fluvial habitat variables and turbulent flow at multiple scales in morphological units of a gravel‐bed river
Authors: Roy M. L. , Roy A. G. , Legendre P. 
Published: July 2009

AbstractFluvial fish habitat is often characterized by highly turbulent flow conditions. Several laboratory experiments suggest that unpredictable turbulent fluctuations can increase the swimming energy costs of fish. At the scale of fish habitat models, it can be hypothesized that turbulence can be captured by the combined effects of the standard habitat variables: depth, velocity and substrate. However, recent studies conducted at the reach scale suggest that turbulent properties are more controlled by the large‐scale bed morphology than by individual roughness elements. In this study, we investigate the spatial structure of turbulent flow and the potential relationships between ‘standard’ habitat variables and turbulent flow properties in pools and riffles of a shallow gravel‐bed river. The study explores these relations at multiple spatial scales. Mean turbulent properties and turbulent flow structures statistics were computed from 1932 near bed velocity time series sampled with acoustic Doppler velocimeters on a regular grid in four morphological units (two pools and two riffles) presenting a gradient of complexity. We used a novel multivariate variation partitioning analysis involving principal coordinates of neighbour matrices (PCNM) to partition turbulent flow properties into six significant spatial scales (VF: 0.35, F: 0.75, M: 1.25, L: 2, XL: 2.5 and XXL: 3 m). Between 45 and 70% of the variance of the turbulent flow properties were explained by the spatial PCNM. In the four units, turbulent properties exhibited a spatial dependence across the entire range of scales. However, the proportion of variation explained by the larger‐scaled PCNMs was higher in the most homogeneous units. In general, the spatial dependence of turbulent flow was lower in the riffles than in the pools, where the mean flow velocity was slower. The capacity of ‘standard’ fish habitat variables to explain turbulent properties was relatively low, especially in the smaller scales, but varied greatly between the units. From a practical point of view, this level of complexity suggests that turbulence should be considered as a ‘distinct’ ecological variable within the range of spatial scales included in this study. Further research should attempt to link the spatial scales of turbulent flow variability to benthic organism patchiness and fish habitat use. Copyright © 2009 John Wiley & Sons, Ltd.