bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel negative regulatory function of the phosphoprotein associated with glycosphingolipid-enriched microdomains: blocking Ras activation
Authors: Smida Michal , Posevitz-Fejfar Anita , Horejsi Vaclav , Schraven Burkhart , Lindquist Jonathan A. 
Published: March 2007

AbstractIn primary human T cells, anergy induction results in enhanced p59Fyn activity. Because Fyn is the kinase primarily responsible for the phosphorylation of PAG (the phosphoprotein associated with glycosphingolipid-enriched microdomains), which negatively regulates Src-kinase activity by recruiting Csk (the C-terminal Src kinase) to the membrane, we investigated whether anergy induction also affects PAG. Analysis of anergic T cells revealed that PAG is hyperphosphorylated at the Csk binding site, leading to enhanced Csk recruitment and inhibitory tyrosine phosphorylation within Fyn. This together with enhanced phosphorylation of a tyrosine within the SH2 domain of Fyn leads to the formation of a hyperactive conformation, thus explaining the enhanced Fyn kinase activity. In addition, we have also identified the formation of a multiprotein complex containing PAG, Fyn, Sam68, and RasGAP in stimulated T cells. We demonstrate that PAG-Fyn overexpression is sufficient to suppress Ras activation in Jurkat T cells and show that this activity is independent of Csk binding. Thus, in addition to negatively regulating Src family kinases by recruiting Csk, PAG also negatively regulates Ras by recruiting RasGAP to the membrane. Finally, by knocking down PAG, we demonstrate both enhanced Src kinase activity and Ras activation, thereby establishing PAG as an important negative regulator of T-cell activation.
Proposed classification of lymphoid neoplasms for epidemiologic research from the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph)
Authors: Morton Lindsay M. , Turner Jennifer J. , Cerhan James R. , Linet Martha S. , Treseler Patrick A. , Clarke Christina A. , Jack Andrew , Cozen Wendy , Maynadié Marc , Spinelli John J. , Costantini Adele Seniori , Rüdiger Thomas , Scarpa Aldo , Zheng Tongzhang , Weisenburger Dennis D. 
Published: March 2007

Abstract
Recent evidence suggests that there is etiologic heterogeneity among the various subtypes of lymphoid neoplasms. However, epidemiologic analyses by disease subtype have proven challenging due to the numerous clinical and pathologic schemes used to classify lymphomas and lymphoid leukemias over the last several decades. On behalf of the International Lymphoma Epidemiology Consortium (InterLymph) Pathology Working Group, we present a proposed nested classification of lymphoid neoplasms to facilitate the analysis of lymphoid neoplasm subtypes in epidemiologic research. The proposed classification is based on the World Health Organization classification of lymphoid neoplasms and the International Classification of Diseases–Oncology, Third Edition (ICD-O-3). We also provide a translation into the proposed classification from previous classifications, including the Working Formulation, Revised European-American Lymphoma (REAL) classification, and ICD-O-2. We recommend that epidemiologic studies include analyses by lymphoma subtype to the most detailed extent allowable by sample size. The standardization of groupings for epidemiologic research of lymphoma subtypes is essential for comparing subtype-specific reports in the literature, harmonizing cases within a single study diagnosed using different systems, as well as combining data from multiple studies for the purpose of pooled analysis or meta-analysis, and will probably prove to be critical for elucidating etiologies of the various lymphoid neoplasms.
RSV-infected airway epithelial cells cause biphasic up-regulation of CCR1 expression on human monocytes
Authors: Morrison Paul T , Thomas Lynette H , Sharland Mike , Friedland Jon S 
Published: March 2007

AbstractRespiratory syncytial virus (RSV) infection can cause extensive airway inflammation, which is orchestrated by chemokines and their receptors. RSV-infected epithelial cells secrete many cytokines and chemokines, but little is known about regulation of chemokine receptors on target cells. We investigated the effects of conditioned media (CM) from RSV-infected epithelial cells on monocyte CCR1, CCR2, and CCR5 expression. RSV-CM but not control-CM stimulated a biphasic increase in cell-surface CCR1, and levels peaked at 36 h and 96 h poststimulation. Similar CCR1 up-regulation occurred on monocyte-derived macrophages. Cytochlasin D and colchicine blocked both peaks of expression, demonstrating requirement of a functional cytoskeleton. Intracellular staining revealed little internal sequestration of CCR1 protein, and CCR1 up-regulation was inhibited by actinomycin D and cycloheximide, indicating that both waves of RSV-CM-induced surface CCR1 expression were dependent on de novo transcription and protein synthesis. Cytokine-neutralizing experiments showed that the effects of RSV-CM were decreased by blocking TNF-α (percent inhibition=51±2.3% at 36 h peak and 42±7.7% at 96 h peak) and to a lesser extent, IL-1 (percent inhibition=32±7.2% at 36 h and 23±2.9% at 96 h). In summary, RSV-CM causes a biphasic up-regulation of surface CCR1 on monocytes, which is dependent on an intact cytoskeleton, requires new gene transcription and protein synthesis, and is mediated in part by the proinflammatory cytokines TNF-α and IL-1.
MDP-induced interleukin-1β processing requires Nod2 and CIAS1/NALP3
Authors: Pan Qilin , Mathison John , Fearns Colleen , Kravchenko Vladimir V , Da Silva Correia Jean , Hoffman Hal M , Kobayashi Koichi S , Bertin John , Grant Ethan P , Coyle Anthony J , Sutterwala Fayyaz S , Ogura Yasunori , Flavell Richard A , Ulevitch Richard J 
Published: April 2007

AbstractNucleotide-binding oligomerization domain (Nod)2 is a sensor of muramyl dipeptides (MDP) derived from bacterial peptidoglycan. Nod2 also plays a role in some autoinflammatory diseases. Cold-induced autoinflammatory syndrome 1 (CIAS1)/NACHT domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NALP3) has been suggested to be sufficient for MDP-dependent release of mature IL-1β, but the role of Nod2 in this process is unclear. Using mice bearing selective gene deletions, we provide in vitro and in vivo data showing that MDP-induced IL-1β release requires Nod2 and CIAS1/NALP3 as well as receptor-interacting protein-2 (Rip2), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1. In contrast, MDP-dependent IL-6 production only requires Nod2 and Rip2. Together, our data provide a new understanding of this important pathway of IL-1β production and allow for further studies of the role of these proteins within the broader context of inflammatory disease.
CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity
Authors: Sadhu Chanchal , Ting Harold J , Lipsky Brian , Hensley Kelly , Garcia-Martinez Leon F , Simon Scott I , Staunton Donald E 
Published: March 2007

AbstractCD11c, a member of the leukointegrin family, is expressed prominently on tissue macrophages and dendritic cells and binds to complement fragment (iC3b), provisional matrix molecules (fibrinogen), and the Ig superfamily cell adhesion molecule, ICAM-1. CD11c has been proposed to function in phagocytosis, cell migration, and cytokine production by monocytes/macrophages as well as induction of T cell proliferation by Langerhans cells. Using assays to quantify CD11c-mediated cell adhesion, we demonstrate that CD11c recognizes ICAM-2 and VCAM-1. The CD11c-binding site on VCAM-1 appears to be different from that used by the integrin α4. CD11c and α4β1 contributed to monocyte capture and transmigration on inflamed human aortic endothelial cells. We discovered that the anti-mouse CD11c mAb N418 blocks CD11c binding to iC3b, ICAM-1, and VCAM-1. Treatment of mice with N418 reduced SRBC-induced delayed-type hypersensitivity significantly. CD11c appeared to contribute predominantly to the sensitization phase and somewhat less to the response to SRBC challenge. This suggests a novel role for CD11c during leukocyte recruitment, antigen uptake, and the survival of APC.
Health-Related Quality of Life in Younger Patients With Chronic Lymphocytic Leukemia Treated With Fludarabine Plus Cyclophosphamide or Fludarabine Alone for First-Line Therapy: A Study by the German CLL Study Group
Authors: Eichhorst Barbara F. , Busch Raymonde , Obwandner Tanja , Kuhn-Hallek Ingrid , Herschbach Peter , Hallek Michael 
Published: March 2007

Purpose To date, only a few studies have evaluated the health-related quality of life (HRQOL) of patients with chronic lymphocytic leukemia (CLL) receiving chemotherapy. Therefore, the German CLL Study Group assessed HRQOL in younger patients with advanced CLL receiving first-line chemotherapy with fludarabine or fludarabine plus cyclophosphamide (FC). Patients and Methods Three hundred seventy-five patients younger than 66 years with advanced CLL were randomly assigned to receive either fludarabine alone (fludarabine 25 mg/m2/d for 5 days intravenously [IV], repeated every 28 days) or FC (fludarabine 30 mg/m2/d for 3 days IV plus cyclophosphamide 250 mg/m2/d for 3 days, repeated every 28 days). Six courses of treatment were planned to be administered. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was sent to all patients at baseline and after 6, 12, and 24 months. Results Eighty-nine percent of 362 included patients completed at least one questionnaire (163 fludarabine- and 158 FC-treated patients). Comparing the baseline levels of 249 CLL patients with the general German population, significant differences in nearly all HRQOL scales were assessed between the two groups. A multivariate analysis showed no significant differences in all HRQOL scales between both arms. In both treatment arms, symptoms such as fatigue, insomnia, and appetite loss improved to lower levels after the end chemotherapy. Except for lower physical status, no significant difference in HRQOL between male and female patients was evaluated. Conclusion Fludarabine-based treatment seems to improve HRQOL little to moderately in younger patients with advanced CLL. No significant difference between fludarabine- and FC-treated patients was observed.
Plasma Cytokine and Soluble Receptor Signature Predicts Outcome of Patients With Classical Hodgkin's Lymphoma: A Study From the Groupe d'Etude des Lymphomes de l'Adulte
Authors: Casasnovas René-Olivier , Mounier Nicolas , Brice Pauline , Divine Marine , Morschhauser Franck , Gabarre Jean , Blay Jean-Yves , Voillat Laurent , Lederlin Pierre , Stamatoullas Aspasia , Bienvenu Jacques , Guiguet Michel , Intrator Liliane , Grandjean Monique , Brière Josette , Ferme Christophe , Salles Gilles 
Published: March 2007

Purpose Approximately 15% of patients with localized and 30% with disseminated classical Hodgkin's lymphoma fail to respond or relapse after first-line treatment. Usual prognosis scoring systems are actually unable to identify this small subset of patients with good confidence, pointing out the need for additional prognostic biomarkers. Patients and Methods We prospectively analyzed the prognosis value of plasma levels of tumor necrosis factor (TNF), its soluble receptors TNF-R1 and TNF-R2, IL-10, IL1-RA, IL-6, and soluble CD30 (sCD30) when taken before any treatment in 519 consecutive patients with a first diagnosis of classical Hodgkin's lymphoma. Results Levels of TNFα higher than 46 pg/mL, TNF-R1 higher than 3 ng/mL, TNF-R2 higher than 5 ng/mL, IL-10 higher than 30 pg/mL, IL1-RA higher than 668 pg/mL, IL-6 higher than 30 pg/mL, and sCD30 higher than 80 U/mL were associated with poor event-free and overall survival. In multivariate analysis, high levels of IL1-RA, IL-6, and sCD30 were independent poor prognosis factors, and the cytokine signature based on their combination allowed the stratification of patients in four prognosis classes, reaching a 5-year event-free survival probability of 92%, 85%, 76%, and 15%, respectively. This index was more potent than other scoring systems to predict patient event-free survival, and remained independent from the international prognostic score (P < .001), adding significant prognostic information to its predictive power. Conclusion Plasma cytokine signature is sufficient to predict disease-related outcome in classical Hodgkin's lymphoma, and allows the identification of patients with very high risk of treatment failure.
Effect of Lugol Solution on Thyroid Gland Blood Flow and Microvessel Density in the Patients with Graves’ Disease
Authors: Erbil Yeşim , Ozluk Yasemin , Giriş Murat , Salmaslıoglu Artur , Issever Halim , Barbaros Umut , Kapran Yersu , Özarmağan Selçuk , Tezelman Serdar 
Published: March 2007

Abstract
Context: Although some endocrine surgeons administer Lugol solution to decrease thyroid gland vascularity, there is still not an agreement on its effectiveness.
Objective: The aims of this clinical trial are to evaluate thyroid blood flow and microvessel density in patients with Graves’ disease who received Lugol solution treatment preoperatively.
Design: This was a prospective clinical trial.
Setting: This clinical trial took place at a tertiary referral center.
Method: Thirty-six patients were randomly assigned to receive either preoperative treatment with Lugol solution (group 1, n = 17) or no preoperative treatment with Lugol solution (group 2, n = 19).
Main Outcome Measures: Blood flow through the thyroid arteries of patients with Graves’ disease was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed by immunohistochemical and Western blot analysis of the level of expression of CD-34 in thyroid tissue. The weight and blood loss of the thyroid gland were measured in all patients.
Results: The mean blood flow, MVD, CD-34 expression, and blood loss in group 1 patients were significantly lower than those in group 2 patients. There was a negative correlation between Lugol solution treatment and blood flow (rs = −0.629; P = 0.0001), blood loss (rs = −0.621; P = 0.0001), MVD (rs = −0.865; P = 0.0001), and CD-34 expression (rs = −0.865; P = 0.0001). According to logistic regression analysis, Lugol solution treatment resulted in a 9.33-fold decreased rate of intraoperative blood loss.
Conclusion: Preoperative Lugol solution treatment decreased the rate of blood flow, thyroid vascularity, and intraoperative blood loss during thyroidectomy.
V2O5·nH2O Crystalline Nanosheets: Hydrothermal Fabrication and Structure Evolution
Authors: Hu Xiao Kai , Ma De Kun , Liang Jian Bo , Xiong Sheng Lin , Li Jiang Ying , Qian Yi Tai 
Published: March 2007

Abstract
V2O5·nH2O nanosheets are fabricated hydrothermally with the acidified peroxovanadate solution at 200 °C for 12 h. The X-ray diffraction suggests that V2O5·nH2O nanosheets display lamellar ordering along c-axis direction. Transmission electron microscopy, field-emission scanning electron microscopy, and selected area electron diffraction indicate that V2O5·nH2O nanosheets are very thin in thickness and micron-sized in lateral dimension, and they are two-dimensional crystallites. X-ray photoelectron spectroscopy and thermogravimetric analysis are utilized to confirm the elemental composition of nanosheets. The formation process of nanosheets is also discussed in terms of time- and temperature-controlled experiments.
Electrochemistry of Self-assembled Ultra-thin Films Composed of Chloroperoxidase and Polyions
Authors: Lu Zhongqing , Hou Wenjing , Wu Xiaqin , Li Hexing , Chen Jun 
Published: March 2007

Abstract
Direct electron transfer between chloroperoxidase (CPO) from Caldariomyces fumago and gold electrode has been achieved by layer-by-layer adsorption of CPO and polydimethyldiallylammonium chloride (PDDA) monolayers on a gold electrode. QCM frequency shift demonstrated monolayer formed during each adsorption. Electrochemical characterization studies show thin layer properties of these PDDA–CPO–PDDA films. The PDDA–CPO–PDDA ultra-thin films were stable, up to 97% electrochemical activity remained after two days storage in phosphate buffer pH 5.
Patients’ experiences of Western-style acupuncture: The influence of acupuncture ‘dose’, self-care strategies and integration
Authors: Paterson Charlotte 
Published: March 2007

Objectives To investigate patients’ perspectives of the process and outcome of Western-style acupuncture for chronic health problems. To use these results to inform the provision of acupuncture in health services in the UK. Methods A purposive sample of 18 patients who were having Western-style acupuncture, for the first time, for a health problem of at least three months duration, were interviewed twice over a four-month period using semi-structured interviews. Using a constant comparative method, the data were analysed across cases and within cases. Results The interviewees complained of chronic pain and moderate or severe disability which was resistant to conventional treatment. Their experience of acupuncture was diverse and varied according to the ‘dosage’ of acupuncture received, the inclusion of self-care strategies, and their relationship with the practitioner. These three factors were interlinked and constituted individual styles of practice for each practitioner. The majority of patients benefited in terms of complete or partial relief of pain and disability, and reduction in conventional medication. However, some patients were disappointed by the treatment, distressed about ‘wasting people's time’, and about the lack of continuity of care. People who benefited most had good general health and a single problem. Conclusions Patients showed discerning judgement regarding the ‘dosage’ of acupuncture they required, and combined acupuncture with exercises to good effect. Publicly funded health services should provide an acupuncture service that provides the optimal ‘dosage’ and uses pain relief to promote self-care. Further research to investigate the benefits of a service that combines Western-style and traditional acupuncture is planned.
Socioeconomic inequality in small area use of elective total hip replacement in the English National Health Service in 1991 and 2001
Authors: Cookson Richard , Dusheiko Mark , Hardman Geoffrey 
Published: March 2007

Objectives To compare socioeconomic inequality in small area use of elective total hip replacement in the English National Health Service (NHS) in 1991 and 2001. Methods Hospital Episode Statistics and Census data were aggregated to a common geography of ‘frozen’ 1991 English electoral wards. The Townsend deprivation score was used as the primary indicator of socioeconomic status for each ward, and the sensitivity analysis used other Census indicators. Two main measures of inequality were examined: the indirectly age-sex standardized utilization rate ratio between most and least deprived quintile groups, and the concentration index of deprivation-related inequality in age-sex standardized utilization ratios between small areas. Each standardized utilization ratio is the observed use divided by the expected use, if each age and sex group in the study population had the same use rate as the national population. Results In both years, observed use was below expected use for the bottom third of areas by socioeconomic status. The standardized utilization rate ratio between top and bottom Townsend quintiles fell from 1.41 (95% confidence interval [CI] 1.36-1.47) in 1991 to 1.27 (95% CI 1.23-1.32) in 2001. The proportionate increase in use required to bring the bottom quintile to the level of top thus fell significantly from 41% to 27%. The Town-send-based concentration index also fell from 0.069 (95% CI 0.059-0.079) in 1991 to 0.060 (95% CI 0.050-0.071) in 2001, although this fall was not statistically significant (P=0.085). Other socioeconomic indicators yielded a similar pattern. Conclusions Socioeconomic small area inequality in use of total hip replacement appears to have fallen between 1991 and 2001. One possible explanation is that increased hip replacement rates in the 1990s may have lowered barriers to access, thus allowing this health technology to diffuse further among lower socio-economic groups.
Describing the impact of health services and policy research
Authors: Kuruvilla Shyama , Mays Nicholas , Walt Gill 
Published: March 2007

Objectives In an essentially applied area of research, there are particular pressures on health services and policy researchers to describe the impact of their work. However, specialized research impact assessments often require skills and resources beyond those available to individual researchers, and ad hoc accounts impose a considerable burden to generate. Further, these idiosyncratic accounts may not facilitate comparative analysis to inform research management, practice and assessment. This paper describes an initial attempt to develop a methodical approach to identify and describe research impact. Methods A Research Impact Framework was developed, drawing on the literature and interviews with researchers at the London School of Hygiene and Tropical Medicine, and was used to structure impact narratives of selected research projects. These narratives were based on semi-structured interviews with principal investigators and documentary analysis of the projects. Results Using the framework as a guide, researchers were relatively easily and methodically able to identify and present impacts of their work. Researchers’ narratives contained verifiable evidence and highlighted a wide range of areas in which health services and policy research has impact. The standardized structure of the narratives also facilitated analysis across projects. Factors thought to positively influence the impact of research included researchers’ continued involvement in research and policy networks, established track records in the field, and the ability to identify and use key influencing events, such as ‘policy windows’. Conclusions The framework helped develop research impact narratives and facilitated comparisons across projects, highlighting issues for research management and assessment.
Tied to the job: Affective and relational components of nurse retention
Authors: Barron David , West Elizabeth , Reeves Rachel 
Published: March 2007

Objective To investigate whether affective and relational components of nurses’ experience of work have a significant impact on their intentions to leave either the job or the nursing profession in models that control forother factors (sociodemographic, work conditions, perceptions of quality of care) that are known to affect career decisions. Method An exploratory, cross-sectional postal survey of 2880 nurses in grades A-I in 20 National Health Service (NHS) Hospital Trusts, 11 in inner London and nine in outer London, was carried out between January and July 2002, looking at nurses’ intention to leave their current job or the nursing profession. The data were analysed using logistic regression with robust standard errors. Results In models that controlled for known sources of job dissatisfaction, relationships with supervisors and managers were found to have a significant effect on respondents’ career intentions. Feeling valued by the Trust and by society was very important. Nurses seemed to distinguish between local problems that are the responsibility of the Trust and those, such as levels of pay, that could only be solved at the national level. Conclusion Nurses’ career intentions are complex and multifactorial. Feelings of being valued and listened to play a role, as well as the individual and job-related characteristics. The study highlights the role of supervisors and managers in retaining staff and suggests that investment in robust systems of communication, conflict resolution and security could slow nurse turnover. The NHS as an employer may be most interested in the role of pay in nurse retention, and the general public in how societal attitudes and verbal abuse shape nurses’ career decisions.