bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of severe acute respiratory syndrome coronavirus structural proteins in virus‐like particle assembly
Authors: Nakauchi Mina , Kariwa Hiroaki , Kon Yasuhiro , Yoshii Kentaro , Maeda Akihiko , Takashima Ikuo 
Published: December 2008

ABSTRACTSARS‐CoV has four major structural proteins: the N, S, M, and E proteins. To investigate the mechanism of SARS‐CoV assembly, we cloned the genes encoding these four proteins into the eukaryotic expression vector pCAGGS and transfected them into 293T cells. When all four expression vectors were co‐transfected VLP formed, as confirmed using electron microscopy. Using a rabbit polyclonal antibody specific to the N protein, N‐protein‐containing particles similar in size to the VLP were also observed by immunoelectron microscopy, indicating that the VLP contained the N protein. Co‐immunoprecipitation analyses demonstrated an interaction between the N and M proteins, suggesting that N protein binds directly to M protein to be incorporated into VLP.
A WT1 protein‐derived, naturally processed 16‐mer peptide, WT1332, is a promiscuous helper peptide for induction of WT1‐specific Th1‐type CD4+ T cells
Authors: Fujiki Fumihiro , Oka Yoshihiro , Kawakatsu Mai , Tsuboi Akihiro , Nakajima Hiroko , Elisseeva Olga A. , Harada Yukie , Li Zheyu , Tatsumi Naoko , Kamino Eriko , Shirakata Toshiaki , Nishida Sumiyuki , Taniguchi Yuki , Kawase Ichiro , Oji Yusuke , Sugiyama Haruo 
Published: December 2008

ABSTRACTThe Wilms' tumor gene WT1 is overexpressed in various tumors, and the WT1 protein has been demonstrated to be an attractive target antigen for cancer immunotherapy. A WT1 protein‐derived 16‐mer peptide, WT1332 (KRYFKLSHLQMHSRKH), which was naturally generated through processing in cells and could elicit Th1‐type CD4+ helper T cell responses with an HLA‐DRB1*0405‐restriction has previously been identified by us. In the present study, it has been demonstrated that WT1332 can induce WT1332‐specific CD4+ T cell responses with the restriction of not only HLA‐DRB1*0405 but also HLA‐DRB1*1501, ‐DRB1*1502, or ‐DPB1*0901. These HLA class II‐restricted WT1332‐specific CD4+ T cell lines produced IFN‐γ but neither IL‐4 nor IL‐10 with WT1332 stimulation, thus showing a Th1‐type cytokine profile. Furthermore, HLA‐DRB1*1501 or ‐DRB1*1502‐restricted WT1332‐specific CD4+ T cell lines responded to WT1‐expressing transformed cells in an HLA‐DRB1‐restricted manner, which is consistent with our previous finding that WT1332 is a naturally processed peptide. These results indicate that the natural peptide, WT1332, is a promiscuous WT1‐specific helper epitope. WT1332 is expected to apply to cancer patients with various types of HLA class II as a WT1‐specific helper peptide in combination with HLA class I‐restricted WT1 peptides.
A comparative study of bone marrow and peripheral blood CD34+ myeloblasts in acute myeloid leukaemia
Authors: Cheung Alice M. S. , Chow Howard C. H. , Liang Raymond , Leung Anskar Y. H. 
Published: December 2008

SummaryTo examine the differences between primitive bone marrow (BM) and peripheral blood (PB) myeloblasts in acute myeloid leukaemia (AML), we compared CD34+ myeloblasts of paired BM and PB samples from 14 AML patients in terms of surface phenotype, homing and engraftment in a xenogeneic transplantation model, and gene expression, based on microarray studies and quantitative polymerase chain reaction. While there was no significant difference in surface phenotypes between these two populations, in vivo assay showed significantly better homing potential of PB CD34+ cells than BM CD34+ cells. Significant correlation between homing and engraftment in AML samples was also noted. In addition, gene expression profiling of CD34+ cells from five paired BM and PB leukaemic samples showed that genes involved in G‐protein and prostaglandin signalling, chemotaxis and stress response, cell proliferation and apoptosis were down‐regulated in PB CD34+ myeloblasts. These data suggested that circulating primitive myeloblasts in AML are functionally different from those residing in the marrow compartment, and such differences may be partly regulated by the BM microenvironment.
Longitudinal follow up of elevated pulmonary artery pressures in children with sickle cell disease
Authors: Pashankar Farzana D. , Carbonella Judith , Bazzy‐Asaad Alia , Friedman Alan 
Published: December 2008

SummaryElevated pulmonary artery pressures (PAP) occur in approximately 30% of children with sickle cell disease. In adults, pulmonary hypertension is significantly associated with mortality. There are no data on the long term significance in children. Nineteen children with SS/Sß0 thalassaemia had elevated PAP, defined as tricuspid regurgitant jet velocity (TRV) ≥2·5 m/s on screening echocardiograms. They were prospectively followed for 23 months (range 19–31 months). Patients with initial TRV ≥ 3 or TRV ≥ 2·5 m/s on repeat echocardiogram had cardiopulmonary evaluation and were offered treatment with hydroxyurea. Associated conditions like asthma and obstructive sleep apnea were treated. 18/19 patients had follow‐up echocardiograms. These showed normalization of TRV in 8 patients. Risk factors associated with persistent elevation were higher TRV on initial echocardiogram (P = 0·01), lower haemoglobin (P = 0·003) and lower oxygen saturation (P = 0·03). Five patients with persistently elevated PAP were treated with hydroxyurea. Mean right ventricular pressure dropped from 40·16 to 29·26 (P = 0·017) after 3–6 months and to 23·6 mmHg (P = 0·002) after 9–12 months on treatment. In conclusion (i) At borderline elevation of TRV there is intrapatient variability and echocardiograms should be repeated for confirmation. (ii) Elevated PAP are reversible in children with early detection and treatment with hydroxyurea.
Primary tumour diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma
Authors: Verburg Frederik A. , Mäder Uwe , Luster Markus , Reiners Christoph 
Published: December 2008

SummaryObjective  To study the relationship between primary tumour size and the risk of advanced disease features (multifocal or locally invasive disease, lymph‐node or distant metastases) in differentiated thyroid carcinoma (DTC).Design  A retrospective chart review study.Patients  The study sample comprised 935 papillary (PTC) and 291 follicular thyroid carcinoma (FTC) patients treated in our hospital from 1978 to 2007.Measurements  Kaplan–Meier analyses and log‐rank tests were performed to calculate tumour size‐adjusted cumulative risk of advanced disease features.Results  Accounting for primary tumour diameter, there were no significant differences in cumulative risks of multifocal carcinoma (P = 0·12) or distant metastases (P = 0·49) between PTC and FTC. PTC showed higher cumulative risks of local invasion (P < 0·0001) or lymph‐node metastases (P < 0·0001). The cumulative risk of tumour multifocality increased 5%/cm of primary tumour diameter. The cumulative risk of local invasion or lymph‐node metastases in PTC and of distant metastases in DTC increased exponentially at a threshold tumour diameter of 10 mm. In FTC, lymph‐node metastases are associated almost exclusively with primary tumours showing extrathyroidal growth.Conclusions  Starting with a 1 cm primary tumour diameter, increasing tumour size is associated with an exponentially increasing risk of local invasion or lymph‐node or distant metastases of DTC. The current classification of carcinomas < 2 cm as T1 is therefore questionable.
Does preterm birth influence the response to growth hormone treatment in short, small for gestational age children?
Authors: De Kort Sandra W. K. , Willemsen Ruben H. , Van Der Kaay Danielle C. M. , Duivenvoorden Hugo J. , Hokken‐Koelega Anita C. S. 
Published: December 2008

SummaryObjective  To investigate whether prematurity has an independent influence on the response to GH treatment in short, small for gestational age (SGA) children.Design  A longitudinal 3‐year GH study.Patients  A total of 392 prepubertal non‐GH‐deficient, short SGA children, comprising 138 preterm (< 36 weeks) and 254 term (≥ 36 weeks) children.Measurements  Height, weight, head circumference, skinfolds and serum IGF‐I and IGFBP‐3 levels were measured before start of GH treatment and after 6 months, 1, 2 and 3 years of treatment.Results  Preterm short SGA children were significantly lighter and shorter at birth after correction for gestational age than term short SGA children (P < 0·001). At start of GH treatment, preterm children were significantly shorter than term children when height was corrected for target height (TH). Preterm children were also significantly leaner as shown by a lower body mass index (BMI) standard deviation score (SDS) and a lower sum of four skinfolds SDS. Prematurity had no influence on childhood IGF‐I and IGFBP‐3 levels. The response to GH treatment was similar for preterm and term SGA children.Conclusions  Within a population of short SGA children, prematurity is associated with a smaller size for gestational age and a shorter height corrected for TH and leaner phenotype in childhood. The response to GH treatment is similar for preterm and term short SGA children.
Enhanced proatherogenic inflammation after recombinant human TSH administration in patients monitored for thyroid cancer remnant
Authors: Desideri Giovambattista , Bocale Raffaella , Milardi Domenico , Ghiadoni Lorenzo , Grassi Davide , Necozione Stefano , Taddei Stefano , Di Orio Ferdinando , Pontecorvi Alfredo , Ferri Claudio 
Published: December 2008

SummaryObjective  To evaluate the effect of recombinant human TSH (rhTSH) on biomarkers of vascular endothelial cell and platelet activation in patients monitored for thyroid carcinoma remnant.Methods  Circulating levels of soluble(s) intercellular adhesion molecule (sICAM)‐1 and sE‐selectin, as indices of vascular endothelial cell activation, of sP‐selectin and sCD40 ligand (sCD40L), as indices of platelet activation, and of 8‐iso‐prostaglandin F2α (8‐iso‐PGF2α), as an index of lipid peroxidation, were evaluated in 20 patients (16 females, 48·0 ± 13·6 years) at baseline and after intramuscular rhTSH injection (0·9 mg/day on two consecutive days).Results  At baseline, serum TSH values were below normal whereas free T3 and free T4 were within the normal range. After rhTSH injection, serum TSH increased significantly but free T3 and free T4 remained unchanged. Concomitantly, plasma sICAM‐1 concentrations increased significantly (from 155·9 ± 39·1 to 183·6 ± 38·1 ng/ml, P < 0·03), as did those of sE‐selectin (from 74·8 ± 15·4 to 91·4 ± 12·2 ng/ml, P < 0·0006), sP‐selectin (from 56·4 ± 13·7 to 72·2 ± 14·9 ng/ml, P < 0·002), sCD40L (from 2·1 ± 0·9 to 2·8 ± 1·1 ng/ml, P < 0·03) and total 8‐iso‐PGF2α(from 238·5 ± 47·0 to 307·8 ± 41·2 pg/l, P < 0·0001). Changes in circulating levels of sCD40L were directly correlated with changes in levels of plasma total 8‐iso‐PGF2α (r = 0·523, P < 0·02) and sP‐selectin (r = 0·480, P < 0·03).Conclusions  Supraphysiological concentrations of rhTSH might exert proatherogenic effects by promoting activation of vascular endothelial cells and platelets probably through enhanced oxidative stress.
Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension
Authors: Haymart Megan R. , Glinberg Simone L. , Liu Jing , Sippel Rebecca S. , Jaume Juan C. , Chen Herbert 
Published: December 2008

SummaryBackground  It has previously been shown that higher serum TSH is associated with increased thyroid cancer incidence and advanced‐stage disease. In the healthy adult population, mean TSH increases with age. As age over 45 years is a known prognostic indicator for thyroid cancer, it is important to know whether higher TSH in patients with thyroid cancer occurs independent of age.Objective  To determine the relationship between higher TSH, cancer and age.Design  A retrospective cohort study.Patients and methods  A total of 1361 patients underwent thyroid surgery between May 1994 and December 2007 at a single institution. Of these patients, 954 had pathological data, preoperative TSH and complete surgical history available. Data were analysed in relation to age and TSH.Results  Mean TSH was significantly higher in cancer patients regardless of age < 45 years or ≥ 45 years (P = 0·046 and P = 0·027, respectively). When examining age groups < 20, 20–44, 45–59 and ≥ 60 years, there was a trend of rising mean TSH with age. Despite the rise in the benign subgroups, mean TSH was consistently higher in those with cancer vs. those without. On multivariate analysis, higher TSH was independently associated with cancer (P = 0·039) and pathological features of Hashimoto's thyroiditis (P = 0·001) but not with age (P = 0·557). On multivariate analysis of high‐risk features associated with poor prognosis, there was a significant association between higher TSH and extrathyroidal extension (P = 0·002), whereas there was no clear relationship with age, tumour size > 4 cm, and distant metastases.Conclusion  Independent of age, thyroid cancer incidence correlates with higher TSH. Higher TSH is associated with extrathyroidal extension of disease.
Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence
Authors: Preiss David , Sattar Naveed 
Published: December 2008

SummaryIt is well‐established that serum total‐cholesterol, LDL‐cholesterol, low HDL‐cholesterol and calculated indices such as total cholesterol : HDL‐cholesterol ratio or less commonly used indices such as non‐HDL cholesterol are strongly predictive of cardiovascular events. Serum triglycerides, by contrast, are only modestly associated with coronary heart disease (CHD) in multivariate analysis and incorporation of triglycerides into prediction algorithms is therefore unlikely to improve their prediction capability. Meta‐analysis of studies including > 90 000 subjects has provided robust evidence that statins reduce important clinical end‐points. These included a 12% fall in all‐cause mortality, 19% fall in CHD mortality and 23% fall in CHD mortality or myocardial infarction. Furthermore there are high quality data showing additional benefit of intensive statin therapy over standard statin therapy for secondary prevention of cardiovascular disease. However, meta‐analysis of 10 fibrate trials has shown inconsistent evidence of vascular benefit and non‐cardiovascular mortality has been slightly but consistently elevated in most fibrate trials and in meta‐analysis. The general use of fibrates for cardiovascular risk reduction can therefore not be supported at present. Other second line agents such as bile acid sequestrants, nicotinic acid and omega‐3 fatty acid supplements have been evaluated in a few randomized controlled studies in which cardiovascular benefit has been found but clearly further data are required to properly establish their use in clinical practice. Ongoing studies such as ACCORD, IMPROVE‐IT, ASCEND, ORIGIN and HPS2‐THRIVE should assist in answering outstanding questions over the next 5 years.
Characterization of the promoter region of the human PARG gene and its response to PU.1 during differentiation of HL‐60 cells
Authors: Uchiumi Fumiaki , Sakakibara Gakushi , Sato Junko , Tanuma Sei‐ichi 
Published: December 2008

The metabolism of poly(ADP‐ribose) plays important roles in the nuclear function of mammalian cells. Previously, we analyzed expression of the poly(ADP‐ribose) glycohydrolase (PARG) gene during HL‐60 cell differentiation and found that expression was greatly reduced by 4 h after 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) treatment and returned to the initial level within 20 h. In the present study, a 2.1‐kb fragment of the 5′‐flanking (promoter) region of the human PARG gene was isolated from the HL‐60 genome by polymerase chain reaction and ligated into a luciferase‐expression vector, pGL3, to generate the pPARG‐Luc#2 reporter plasmid. Deletion analysis revealed that a 75‐nt sequence is required for basal promoter activity and TPA responsiveness. Mutations in this 75‐nt sequence reduced promoter activity and the TPA response of HL‐60 cells. TFSEARCH analysis revealed that Ets family binding motifs are located in the 75‐nt sequence. Chromatin immunoprecipitation assay, electrophoretic mobility shift assay and competition analysis indicated that PU.1 (Spi‐1) binds to the 75‐nt sequence. Moreover, co‐transfection of HL‐60 cells with a PU.1 expression plasmid and pPARG‐Luc indicated that PU.1 down‐regulate the PARG promoter. These results suggest that PARG gene expression is modulated by PU.1 during TPA‐induced differentiation of HL‐60 cells.
Evaluation of trap capture in a geographically closed population of brown treesnakes on Guam
Authors: Tyrrell Claudine L. , Christy Michelle T. , Rodda Gordon H. , Yackel Adams Amy A. , Ellingson Aaron R. , Savidge Julie A. , Dean‐Bradley Kathy , Bischof Richard 
Published: December 2008

SummaryOpen population mark–recapture analysis of unbounded populations accommodates some types of closure violations (e.g. emigration, immigration). In contrast, closed population analysis of such populations readily allows estimation of capture heterogeneity and behavioural response, but requires crucial assumptions about closure (e.g. no permanent emigration) that are suspect and rarely tested empirically.In 2003, we erected a double‐sided barrier to prevent movement of snakes in or out of a 5‐ha semi‐forested study site in northern Guam. This geographically closed population of >100 snakes was monitored using a series of transects for visual searches and a 13 × 13 trapping array, with the aim of marking all snakes within the site. Forty‐five marked snakes were also supplemented into the resident population to quantify the efficacy of our sampling methods. We used the programmarkto analyse trap captures (101 occasions), referenced to census data from visual surveys, and quantified heterogeneity, behavioural response, and size bias in trappability. Analytical inclusion of untrapped individuals greatly improved precision in the estimation of some covariate effects.A novel discovery was that trap captures for individual snakes consisted of asynchronous bouts of high capture probability lasting about 7 days (ephemeral behavioural effect). There was modest behavioural response (trap happiness) and significant latent (unexplained) heterogeneity, with small influences on capture success of date, gender, residency status (translocated or not), and body condition.Trapping was shown to be an effective tool for eradicating large brown treesnakesBoiga irregularis(>900 mm snout‐vent length, SVL).Synthesis and applications.Mark–recapture modelling is commonly used by ecological managers to estimate populations. However, existing models involve making assumptions about either closure violations or response to capture. Physical closure of our population on a landscape scale allowed us to determine the relative importance of covariates influencing capture probability (body size, trappability periods, and latent heterogeneity). This information was used to develop models in which different segments of the population could be assigned different probabilities of capture, and suggests that modelling of open populations should incorporate easily measured, but potentially overlooked, parameters such as body size or condition.
Estimating survival and movements using both live and dead recoveries: a case study of oystercatchers confronted with habitat change
Authors: Duriez Olivier , Sæther Stein A. , Ens Bruno J. , Choquet Rémi , Pradel Roger , Lambeck Rob H. D. , Klaassen Marcel 
Published: December 2008

SummaryAnimals facing partial habitat loss can try to survive in the remaining habitat or emigrate. Effects on survival and movements should be studied simultaneously since survival rates may be underestimated if emigrants are not considered, and since emigrants may experience reduced survival.We analysed movements and survival of adult wintering oystercatcherHaematopus ostralegusin response to the 1986–1987 partial closure of the Oosterschelde in the Dutch Delta. This reduced by one‐third the tidal area of this major European wintering area for waders.We developed a novel variant of a multistate capture–recapture model allowing simultaneous estimation of survival and movement between sites using a mixture of data (live recaptures and dead recoveries). We used a two‐step process, first estimating movements between sites followed by site‐specific survival rates.Most birds were faithful to their ringing site. Winter survival was negatively affected by winter severity and was lowest among birds changing wintering site (i.e. moving outside of the Oosterschelde).During mild winters, survival rates were very high, and similar to before the closure in both changed and unchanged sectors of the Oosterschelde. However, the combined effect of habitat loss with severe winters decreased the survival of birds from changed sectors and induced emigration.The coastal engineering project coincided with three severe winters and high food stock, making assessment of its effects difficult. However, the habitat loss seems to have had less impact on adult survival and movements than did winter severity.Synthesis and applications. Human‐induced habitat change may result in population decline through costly emigration or reduced survival or reproduction of individuals that stay. Long‐term monitoring of marked individuals helps to understand how populations respond to environmental change, but site‐specific survival and movement rates should be integrated in the same model in order to maximize the information yield. Our modelling approach facilitates this because it allows the inclusion of recoveries from outside the study area.
Guild‐specific responses of bats to landscape composition and configuration in fragmented Amazonian rainforest
Authors: Klingbeil Brian T. , Willig Michael R. 
Published: December 2008

Summary

Habitat loss and fragmentation are serious threats to biodiversity, especially in the Amazon Basin, where biodiversity is greatest and deforestation is continuing at an alarming rate. Nonetheless, little is known about the responses of biotas to spatially explicit aspects of landscape structure.
Bats are a promising indicator group for studying consequences of forest fragmentation in the Neotropics. Therefore, population‐ and assemblage‐level responses of bats to landscape composition and configuration were quantified at each of three focal scales (circles of 1‐, 3‐, and 5‐km radii) at 14 sites in lowland Amazonia.
Responses to landscape characteristics were scale‐dependent. Abundance and richness were higher in moderately fragmented forest than in continuous forest. Moreover, the abundance of each of nine frugivorous species decreased with increasing forest cover.
The abundance of frugivores probably responded to landscape composition (e.g. percentage forest, mean patch density) because of an increase in early successional fruits and flowers in areas with reduced canopy cover. In contrast, abundances of gleaning animalivores responded to landscape configuration (e.g. edge density), probably by exploiting low‐contrast edges (i.e. closed canopy forest patches embedded in secondary forest) while foraging and travelling between higher quality resource patches.
Synthesis and applications. Species‐ and ensemble‐specific responses to aspects of landscape structure suggest that both compositional and configurational aspects need to be managed effectively in conservation planning. However, conservation decisions based on associations of biodiversity metrics (e.g. richness, diversity and rarity) with landscape structure may be problematic as they are composite characteristics that mask individual responses and potentially reflect only patterns of the dominant species or groups.