bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immunosuppressive drug FK778 induces regulatory activity in stimulated human CD4+CD25− T cells
Authors: Kreijveld Ellen , Koenen Hans J. P. M. , Hilbrands Luuk B. , van Hooff Hans J. P. , Joosten Irma 
Published: August 2006

AbstractThe induction of transplantation tolerance involves a T-cell–mediated process of immune regulation. In clinical transplantation, the use of immunosuppressive drugs that promote or facilitate this process would be highly desirable. Here, we investigated the tolerance-promoting potential of the immunosuppressive drug FK778, currently under development for clinical therapy. Using a human allogeneic in vitro model we showed that, upon T-cell receptor (TCR) triggering, FK778 induced a regulatory phenotype in CD4+CD25− T cells. Purified CD4+CD25− T cells primed in the presence of FK778 showed hyporesponsiveness upon restimulation with alloantigen in the absence of the drug. This anergic state was reversible by exogenous interleukin-2 (IL-2) and was induced independent of naturally occurring CD4+CD25+ regulatory T cells. Pyrimidine restriction was a crucial requirement for the de novo induction of regulatory activity by FK778. The FK778-induced anergic cells showed suppressor activity in a cell-cell contact–dependent manner; were CD25high, CD45RO+, CD27−, and CD62L−; and expressed cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and FoxP3. The cells revealed delayed p27kip1 degradation and enhanced phosphorylation of STAT3. In conclusion, the new drug FK778 shows tolerizing potential through the induction of a regulatory T-cell subset in CD4+CD25− T cells.
Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk of therapy-related acute myeloid leukemia
Authors: Jawad Mays , Seedhouse Claire Helen , Russell Nigel , Plumb Mark 
Published: August 2006

AbstractStudies of radiation-induced acute myeloid leukemia (AML) in mice suggest that the number of target stem cells is a risk factor, and the HLX1 homeobox gene, which is important for hematopoietic development, is a candidate gene. The distribution of the C/T-3′ untranslated region (UTR) polymorphism in HLX1 in patients with AML and therapy-related AML (t-AML) compared with controls was therefore determined. The presence of the variant HLX1 allele significantly increases the risk of t-AML (OR = 3.36, 95% CI, 1.65-6.84). The DNA repair gene RAD51 (135G/C-5′ UTR) polymorphism also increases t-AML risk, and when combined analysis was performed on both RAD51 and HLX1 variant alleles, a synergistic 9.5-fold increase (95% CI, 2.22-40.64) in the risk of t-AML was observed. We suggest that the HLX1 polymorphism has an effect on stem cell numbers, whereas an increased DNA repair capacity (RAD51) will suppress apoptosis, a genetic interaction that may increase the number of genomes at risk during cancer therapy.
Caveolin-1 and -2 in airway epithelium: expression and in situ association as detected by FRET-CLSM
Authors: Krasteva Gabriela , Pfeil Uwe , Drab Marek , Kummer Wolfgang , König Peter 
Published: August 2006

Abstract

Background
Caveolae are involved in diverse cellular functions such as signal transduction, cholesterol homeostasis, endo- and transcytosis, and also may serve as entry sites for microorganisms. Hence, their occurrence in epithelium of the airways might be expected but, nonetheless, has not yet been examined.

Methods
Western blotting, real-time quantitative PCR analysis of abraded tracheal epithelium and laser-assisted microdissection combined with subsequent mRNA analysis were used to examine the expression of cav-1 and cav-2, two major caveolar coat proteins, in rat tracheal epithelium. Fluorescence immunohistochemistry was performed to locate caveolae and cav-1 and -2 in the airway epithelium of rats, mice and humans. Electron-microscopic analysis was used for the identification of caveolae. CLSM-FRET analysis determined the interaction of cav-1α and cav-2 in situ.

Results
Western blotting and laser-assisted microdissection identified protein and transcripts, respectively, of cav-1 and cav-2 in airway epithelium. Real-time quantitative RT-PCR analysis of abraded tracheal epithelium revealed a higher expression of cav-2 than of cav-1. Immunoreactivities for cav-1 and for cav-2 were co-localized in the cell membrane of the basal cells and basolaterally in the ciliated epithelial cells of large airways of rat and human. However, no labeling for cav-1 or cav-2 was observed in the epithelial cells of small bronchi. Using conventional double-labeling indirect immunofluorescence combined with CLSM-FRET analysis, we detected an association of cav-1α and -2 in epithelial cells. The presence of caveolae was confirmed by electron microscopy. In contrast to human and rat, cav-1-immunoreactivity and caveolae were confined to basal cells in mice. Epithelial caveolae were absent in cav-1-deficient mice, implicating a requirement of this caveolar protein in epithelial caveolae formation.

Conclusion
These results show that caveolae and caveolins are integral membrane components in basal and ciliated epithelial cells, indicating a crucial role in these cell types. In addition to their physiological role, they may be involved in airway infection.
Text mining of full-text journal articles combined with gene expression analysis reveals a relationship between sphingosine-1-phosphate and invasiveness of a glioblastoma cell line
Authors: Natarajan Jeyakumar , Berrar Daniel , Dubitzky Werner , Hack Catherine , Zhang Yonghong , DeSesa Catherine , Van Brocklyn James R , Bremer Eric G 
Published: August 2006

Abstract

Background
Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in various cellular processes such as migration, proliferation, and survival. To date, the impact of S1P on human glioblastoma is not fully understood. Particularly, the concerted role played by matrix metalloproteinases (MMP) and S1P in aggressive tumor behavior and angiogenesis remains to be elucidated.

Results
To gain new insights in the effect of S1P on angiogenesis and invasion of this type of malignant tumor, we used microarrays to investigate the gene expression in glioblastoma as a response to S1P administration in vitro. We compared the expression profiles for the same cell lines under the influence of epidermal growth factor (EGF), an important growth factor. We found a set of 72 genes that are significantly differentially expressed as a unique response to S1P. Based on the result of mining full-text articles from 20 scientific journals in the field of cancer research published over a period of five years, we inferred gene-gene interaction networks for these 72 differentially expressed genes. Among the generated networks, we identified a particularly interesting one. It describes a cascading event, triggered by S1P, leading to the transactivation of MMP-9 via neuregulin-1 (NRG-1), vascular endothelial growth factor (VEGF), and the urokinase-type plasminogen activator (uPA). This interaction network has the potential to shed new light on our understanding of the role played by MMP-9 in invasive glioblastomas.

Conclusion
Automated extraction of information from biological literature promises to play an increasingly important role in biological knowledge discovery. This is particularly true for high-throughput approaches, such as microarrays, and for combining and integrating data from different sources. Text mining may hold the key to unraveling previously unknown relationships between biological entities and could develop into an indispensable instrument in the process of formulating novel and potentially promising hypotheses.
Trends in drop out, drug free discharge and rates of re-presentation: a retrospective cohort study of drug treatment clients in the North West of England
Authors: Beynon Caryl M , Bellis Mark A , McVeigh Jim 
Published: August 2006

Abstract

Background
Governments aim to increase treatment participation by problematic drug users. In the UK this has been achieved by fiscal investment, an expanded workforce, reduced waiting times and coercive measures (usually criminal justice (CJ) led). No assessment of these measures on treatment outcomes has been made. Using established monitoring systems we assessed trends in 'dropped out' and 'discharged drug free' (DDF), since the launch of the national drug strategy, and rates of treatment re-presentation for these cohorts.

Methods
A longitudinal dataset of drug users (1997 to 2004/05, n = 26,415) was used to identify people who dropped out of, and were DDF from, services for years 1998 to 2001/02, and re-presentations of these people in years to 2004/05. Trends in drop out and DDF, baseline comparisons of those DDF and those who dropped out and outcome comparisons for those referred from the CJ system versus other routes of referral were examined using chi square. Logistic regression analyses identified variables predicting drop out versus DDF and subsequent re-presentation versus no re-presentation.

Results
The proportion of individuals dropping out has increased from 7.2% in 1998 to 9.6% in 2001/02 (P < 0.001). The proportion DDF has fallen from 5.8% to 3.5% (P < 0.001). Drop out was more likely in later years, by those of younger age and by CJ referrals. The proportion re-presenting to treatment in the following year increased from 27.8% in 1998 to 44.5% in 2001/02 (P < 0.001) for those DDF, and from 22.9% to 48.6% (P < 0.001) for those who dropped out. Older age and prior treatment experience predicted re-presentation. Outcome (drop out or DDF) did not predict re-presentation.

Conclusion
Increasing numbers in treatment is associated with an increased proportion dropping out and an ever-smaller proportion DDF. Rates of drop out are significantly higher for those coerced into treatment via the CJ system. Rates of re-presentation are similar for those dropping out and those DDF. Encouragingly, those who need to re-engage with treatment, particularly those who drop out, are doing so more quickly. The impact of coercion on treatment outcomes and the appropriateness of aftercare provision require further consideration.
Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer
Authors: Kollermann Jens , Kempkensteffen Carsten , Helpap Burkhard , Schrader Mark , Krause Hans , Muller Markus , Miller Kurt , Schostak Martin 
Published: August 2006

Abstract

Background
In spite of excellent cure rates for prostate cancer patients with favorable tumor characteristics, patients with unfavorable characteristics after radical prostatectomy are still at a significantly increased risk of tumor progression. Early adjuvant hormonal therapy (AHT) has been shown to be of prognostic benefit in these patients. Unfortunately initiation and duration of early AHT in the individual patient is based on statistic data. PSA, as the standard prostate marker is neither able to reliably indicate minimal residual tumor disease in the early postoperative phase, nor can it be used for therapy monitoring due to the suppressive effect of hormonal therapy on PSA production. Promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1-HM) has been shown to be the most common DNA alteration of primary prostatic carcinoma which, when used as a marker, is supposed to be able to overcome some of the disadvantages of PSA. However until now information on the impact of hormonal therapy on the detection of GSTP1-HM is lacking. The purpose of our study was to assess the impact of endocrine therapy on the detection of GSTP1-HM by methylation-specific PCR (MSP) in prostate cancer.

Methods
Paraffin embedded tumor samples from the radical prostatectomy (RP) specimens from 15 patients after hormonal therapy (HT) (mean 8 months) were assessed by MSP. In 8 of the patients the GSTP-1 status of the tumors before HT was assessed on the corresponding initial diagnostic biopsies.

Results
Following HT MSP showed GSTP1-HM in 13/15 of the RP specimens. In two patients analysis of the RP specimens failed to show GSTP1-HM. All initial tumor samples (8/8 biopsy specimens) showed GSTP1-HM, including both patients negative for GSTP1 HM in the corresponding RP specimen.

Conclusion
In most cases hormonal therapy appears to not alter GSTP1 HM detection. However the change from a positive to a negative GSTP1 HM status in a subset of the patients may point to an, at least partial androgen dependency. Further studies on a larger cohort of patients are necessary to assess its frequency and the exact hormonal interactions.
UniPep - a database for human N-linked glycosites: a resource for biomarker discovery
Authors: Zhang Hui , Loriaux Paul , Eng Jimmy , Campbell David , Keller Andrew , Moss Pat , Bonneau Richard , Zhang Ning , Zhou Yong , Wollscheid Bernd , Cooke Kelly , Yi Eugene C , Lee Hookeun , Peskind Elaine R , Zhang Jing , Smith Richard D , Aebersold Ruedi 
Published: August 2006

AbstractThere has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N-linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep http://www.unipep.org - a database of human N-linked glycosites - as a resource for biomarker discovery.
A genome-wide approach to identify genetic loci with a signature of natural selection in the Irish population
Authors: Mattiangeli Valeria , Ryan Anthony W , McManus Ross , Bradley Daniel G 
Published: August 2006

Abstract
Background
In this study we present a single population test (Ewens-Waterson) applied in a genomic context to investigate the presence of recent positive selection in the Irish population. The Irish population is an interesting focus for the investigation of recent selection since several lines of evidence suggest that it may have a relatively undisturbed genetic heritage.

Results
We first identified outlier single nucleotide polymorphisms (SNPs), from previously published genome-wide data, with high FST branch specification in a European-American population. Eight of these were chosen for further analysis. Evidence for selective history was assessed using the Ewens-Watterson's statistic calculated using Irish genotypes of microsatellites flanking the eight outlier SNPs. Evidence suggestive of selection was detected in three of these by comparison with a population-specific genome-wide empirical distribution of the Ewens-Watterson's statistic.

Conclusion
The cystic fibrosis gene, a disease that has a world maximum frequency in Ireland, was among the genes showing evidence of selection. In addition to the demonstrated utility in detecting a signature of natural selection, this approach has the particular advantage of speed. It also illustrates concordance between results drawn from alternative methods implemented in different populations.
Are Statewide Trauma Registries Comparable? Reaching for a National Trauma Dataset
Authors: Mann N. Clay , Guice Karen , Cassidy Laura , Wright Dagan , Koury Julie 
Published: August 2006

Abstract
Background:
Statewide trauma registries have proliferated in the last decade, suggesting that information could be aggregated to provide an accurate depiction of serious injury in the United States.
Objectives:
To determine whether variability exists in the composition and content of statewide trauma registries, specifically addressing case‐acquisition, case‐definition (inclusion criteria), and registry‐coding conventions.
Methods:
A cross‐sectional, two‐part survey was administered to managers of all statewide trauma registries. State trauma registrars also provided inclusion and exclusion criteria from their state registry and abstracted a clinical vignette designed to identify coding inconsistencies.
Results:
Thirty‐two states maintain a centralized registry, but requirements for data submission vary significantly. Inclusion and exclusion criteria also vary, particularly for nontraumatic injuries. Coding conventions adopted by states for vague or missing information are dissimilar. When abstractions of the clinical vignette are compared, only 19% and 47% of states provided similar quantity or content for injury e‐coding and diagnostic coding, respectively. Injury severity scores (based on diagnostic coding) demonstrated a range from 2 to 18.
Conclusions:
Statewide trauma registries are prevalent but vary significantly in composition and content. Standardizing inclusion criteria, variable definitions, and coding conventions would greatly enhance the usability of an aggregated, national trauma registry.
An Emergency Department–based Vaccination Program: Overcoming the Barriers for Adults at High Risk for Vaccine‐preventable Diseases
Authors: Rimple Diane , Weiss Steven J. , Brett Meghan , Ernst Amy A. 
Published: August 2006

Abstract
Background:
More than 10% of the population visit emergency departments (ED) every year. Many of these patients are not up‐to‐date on routine vaccinations that could prevent future illnesses. The ED could significantly impact these vaccination trends.
Objectives:
This study was a feasibility study to determine whether patients would be amenable to an ED‐based program that provided appropriate immunizations when they were at high risk for these diseases. In addition, the authors sought to identify barriers that predict high‐risk patients who did not receive immunizations before ED presentation and to identify barriers that predict those high‐risk unvaccinated patients who are unwilling to receive vaccinations when offered in the ED.
Methods:
This study was a prospective cross‐sectional study of all patients arriving in the ED at one inner‐city trauma center between 10 am and 10 pm over the course of a three‐week intervention period. The subjects completed a survey that included information about their risk of influenza (flu) and pneumococcal disease, their immunization history, and their perceptions of their need for immunization. Demographic information collected included insurance status, age, gender, and primary language. All high‐risk patients who were not current with their immunizations were offered vaccination. The primary outcome was improvement in vaccination coverage based on an ED surveillance and treatment system for vaccinations. The secondary outcomes were barriers to successful vaccination before ED presentation and barriers to acceptance of vaccination in the ED. Results were compared using chi‐square test and confidence interval analysis. Characteristics of barriers to immunization were determined using a logistic regression model. A p‐value < 0.05 was considered significant.
Results:
A total of 674 subjects were entered into the study. Vaccination of subjects at high risk for flu increased significantly from 16% before to 83% after ED evaluation and treatment, and vaccination of subjects at high risk for pneumococcal disease increased significantly from 18% before to 84% after ED evaluation and treatment. Significant barriers to vaccination before ED presentation were lack of insurance (odds ratio [OR] = 0.31 for flu, 0.22 for pneumococcal disease), age younger than 50 years (OR = 0.18 for flu, 0.24 for pneumococcal disease), and no perceived need for vaccination (OR = 0.07 for flu). The sole significant barrier to vaccine administration in the ED was perceived need for vaccination (OR = 0.32 for flu).
Conclusions:
An ED‐based vaccination program is both feasible and successful. Other than a shortage of vaccine, the only ED barrier to vaccination (perceived need) might be overcome with patient education.
Emergency Department Treatment of Viral Gastritis Using Intravenous Ondansetron or Dexamethasone in Children
Authors: Stork Christine M. , Brown Kathleen M. , Reilly Tracey H. , Secreti LaLaina , Brown Lawrence H. 
Published: August 2006

Abstract Objectives To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. Methods This double‐blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10–20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi‐square test, Kruskal–Wallis test, Mantel–Haenszel test, and analysis of variance, with p < 0.05 considered significant. Results A total of 166 subjects were enrolled; data for analysis were available for 44 NS‐treated patients, 46 ondansetron‐treated patients, and 47 dexamethasone‐treated patients. Hospital admission occurred in nine patients (20.5%) receiving placebo (NS alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%) receiving dexamethasone, with ondansetron significantly different from placebo (p = 0.02). Similarly, at two hours, more ondansetron‐treated patients (39 [86.6%]) tolerated oral hydration than NS‐treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. Conclusions In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.