bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue
Authors: Brown Lewis M. , Helmke Steve M. , Hunsucker Stephen W. , Netea‐Maier Romana T. , Chiang Simon A. , Heinz David E. , Shroyer Kenneth R. , Duncan Mark W. , Haugen Bryan R. 
Published: June 2006

AbstractIn order to better understand basic mechanisms of tumor development and identify potential new biomarkers, we have performed difference gel electrophoresis (DIGE) and peptide mass fingerprinting on pooled protein extracts from patients with papillary thyroid carcinoma (PTC) compared with matched normal thyroid tissue. Image analysis of DIGE gels comparing PTC and matched normal thyroid tissue protein indicated that 25% of the protein spots were differentially expressed at a 2.5‐fold cutoff and 35% at two‐fold. Comparison between two different pools of protein from normal thyroid tissues revealed differential protein expression of only 4% at 2.5‐fold and 6% at two‐fold cutoff. One hundred ninety‐two protein spots were identified by MALDI‐TOFMS, representing 90 distinct proteins. Excluding albumin, globins and thyroglobulin, imaging software determined 31 proteins to be differentially expressed at the two‐fold (or greater) level. Individual gel comparisons (PTC vs. matched normal) from five patients established that 15/31 (48%) of these proteins exhibited statistically significant differential expression. Previously identified molecular markers in this group of proteins include cathepsin B, cytokeratin 19, and galectin‐3. Novel differentially expressed proteins include S100A6, moesin, HSP70 (BiP), peroxiredoxin 2, protein phosphatase 2, selenium binding protein 1, vitamin D binding protein, and proteins involved in mitochondrial function. The use of two‐dimensional gel electrophoresis (2DGE) revealed a significantly altered protein mass and/or pI in 10%–15% of proteins, suggesting alternatively spliced forms and other posttranslational modification of proteins revealed by this approach. We confirmed S100A6 as a potentially useful biomarker using immunohistochemical analysis (85% sensitivity and 69% specificity for distinguishing benign from malignant thyroid neoplasms). In summary, proteomic analysis of PTC using DIGE and mass spectrometry has confirmed several known biomarkers, uncovered novel potential biomarkers, and provided insights into global pathophysiologic changes in PTC. Many of the differences observed would not have been detected by genomic or other proteomic approaches. © 2006 Wiley‐Liss, Inc.
Temperature and solvent dependent NMR studies on mangiferin and complete NMR spectral assignments of its acyl and methyl derivatives
Authors: Faizi Shaheen , Zikr‐ur‐Rehman Sadia , Ali Muhammad , Naz Aneela 
Published: June 2006

AbstractBy employing concerted 1 and 2D NMR techniques, exact NMR spectral assignments have been made of the acyl (2–7) and methyl (8 and 9) derivatives of mangiferin (1) isolated from the leaves of Bombax ceiba. Derivatives 2, 8 and 9 have been reported in literature, while 3–7 represent new compounds. The acetates 2 and 3 were found to be unstable and were converted into the same penta‐acetate 4 at room temperature. Extensive NMR studies on mangiferin (1) and its derivatives showed that H‐4 exchanges with deuterium of the solvent molecule more easily. This exchange under acidic conditions occurred at that position (C‐4) where electrophilic substitution reactions can easily take place. This is the first report describing the exchange of C‐4 proton of mangiferin (1), or any other xanthone, with deuterium of solvent molecules. Copyright © 2006 John Wiley & Sons, Ltd.
SodaConstructing knowledge through exploratoids
Authors: Svarovsky Gina Navoa , Shaffer David Williamson 
Published: June 2006

AbstractIn this article, we describe a preliminary study that integrates research on engineering design activities for K‐12 students with work on microworlds as learning tools. Here, we extend these bodies of research by exploring whether—and how—authentic recreations of engineering practices can help students develop conceptual understanding of physics. We focus on the design–build–test (DBT) cycle used by professional engineers in simulation‐based rapid modeling. In this experiment, middle‐school students worked for 10 hr during a single weekend to solve engineering design challenges using SodaConstructor, a Java‐based microworld, as a simulation environment. As a result of the experiment, students learned about center of mass. Our data further suggest that in the process of simulation‐based modeling, rapid iterations of the DBT cycle progressively linked students' interest in the design activities and understanding of the concept of center of mass. We suggest that these rapid iterations of the DBT cycle functioned as exploratoids: short fragments of exploratory action in a microworld that cumulatively develop interest in and understanding of important scientific concepts. © 2006 Wiley Periodicals, Inc. J Res Sci Teach
Do antidepressants influence mood patterns? A naturalistic study in bipolar disorder
Authors: Bauer M. , Rasgon N. , Grof P. , Glenn T. , Lapp M. , Marsh W. , Munoz R. , Suwalska A. , Baethge C. , Bschor T. , Alda M. , Whybrow P.C. 
Published: June 2006

AbstractThis prospective, longitudinal study compared the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. One hundred and eighty-two patients with bipolar disorder self-reported mood and psychiatric medications for 4 months using a computerized system (ChronoRecord) and returned 22,626 days of data. One hundred and four patients took antidepressants, 78 did not. Of the antidepressants taken, 95% were selective serotonin or norepinephrine reuptake inhibitors, or second-generation antidepressants. Of the patients taking an antidepressant, 91.3% were concurrently taking a mood stabilizer. The use of antidepressants did not influence the daily rate of switching from depression to mania or the rate of rapid cycling, independent of diagnosis of bipolar I or II. The primary difference in mood pattern was the time spent normal or depressed. Patients taking antidepressants frequently remained in a subsyndromal depression. In this naturalistic study using self-reported data, patients with bipolar disorder who were taking antidepressants—overwhelmingly not tricyclics and with a concurrent mood stabilizer—did not experience an increase in the rate of switches to mania or rapid cycling compared to those not taking antidepressants. Antidepressants had little impact on the mood patterns of bipolar patients taking mood stabilizers.
Quality of life following emergency liver transplantation for acute liver failure
Authors: Sargent Suzanne , Wainwright Steven P. 
Published: June 2006

ABSTRACT Introduction. Liver transplantation is an accepted and successful therapy for both acute and chronic liver diseases (CLDs), with good survival outcomes. Whilst the study of health‐related quality of life (HRQoL) post transplantation for CLDs have been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF) patients. Patients and methods. Data were collected using between‐method triangulation; however, only the quantitative element of the study is reported here. Measuring eight health domains, we distributed the short form 36 (SF‐36) questionnaire by post to 96 acute and chronic transplant recipients. Differences between the groups were measured using both parametric and non‐parametric t‐tests. Results. Overall, the patients showed a satisfactory HRQoL; there were no differences between either acute or chronic transplant groups in seven of the eight domains of quality of life. Among the patients transplanted for ALF, there were no differences in HRQoL between patients transplanted for paracetamol hepatotoxicity compared with other indications, and no variations in HRQoL related to recipient gender, employment or length of survival post transplantation. When compared with the UK SF‐36 normal values to the ALF transplant recipients, there was a significantly lower physical functioning and role emotional scores. Conclusion. Regardless of aetiology, most of recipients transplanted for ALF have a HRQoL comparable with chronic transplant recipients.
A critical discourse analysis of provision of end‐of‐life care in key UK critical care documents
Authors: Pattison Natalie 
Published: June 2006

ABSTRACTThis article highlights certain practical and professional difficulties in providing end‐of‐life (EOL) care for patients in critical care units and explores discourses arising from guidelines for critical care services. Background : A significant number of patients die in critical care after decisions to withdraw or withhold treatment. Guidelines for provision of critical care suggest, wherever possible, moving patients out of critical care at the EOL. This may not necessarily be conducive to a ‘good death’ for patients or their loved ones. There is a moral responsibility for both nurses and doctors to ensure that decision‐making around EOL issues is sensitively implemented, that decisions about care includes families, patients when able, nurses and doctors, and that good EOL care is provided. Methods : A critical discourse analysis (CDA) of four key UK critical care documents published since 1996. Findings and recommendations : The key documents give little clear guidance about how to provide EOL care in critical care. Discourses include the power dynamic in critical care between professions, families and patients, and how this impacts on provision of EOL care. Difficulties encountered include dilemmas at discharge and paternalism in decision‐making. The technological environment can act as a barrier to good EOL care, and critical care nurses are at risk of assuming the dominant medical model of care. Nurses, however, are in a prime position to ensure that decision‐making is an inclusive process, patient needs are paramount, the practical aspects of withdrawal lead to a smooth transition in goals of care and that comfort measures are implemented.
Does the efficacy of supplemental oxygen for the prevention of postoperative nausea and vomiting depend on the measured outcome, observational period or site of surgery?
Authors: Turan A. , Apfel C. C. , Kumpch M. , Danzeisen O. , Eberhart L. H. J. , Forst H. , Heringhaus C. , Isselhorst C. , Trenkler S. , Trick M. , Vedder I. , Kerger H. 
Published: June 2006

SummaryHigh intra‐operative oxygen concentration reportedly reduces postoperative nausea and vomiting (PONV), but recent data are conflicting. Therefore, we tested whether the effectiveness of supplemental oxygen depends on the endpoint (nausea vs. vomiting), observation interval (early vs. late) or surgical field (abdominal vs. non‐abdominal). We randomly assigned 560 adult patients undergoing various elective procedures with a PONV risk of at least 40% to intra‐operative 80% (supplemental) or 30% oxygen (control). Potential confounding factors were similar between groups. Incidences of nausea were similar in the groups during early (12% (supplemental) vs. 10% (control), p = 0.43) and late intervals, 26%vs. 20%, p = 0.09, as were the incidences of vomiting (early: 2%vs. 3%, p = 0.40; late: 8%vs. 9%, p = 0.75). Supplemental oxygen was no more effective at reducing PONV in abdominal (40%vs. 31%, p = 0.37) than in non‐abdominal surgery (25%vs. 21%, p = 0.368). Thus, supplemental oxygen was unable to reduce PONV independent of the endpoint, observational period or site of surgery.
Proteasome inhibition as novel treatment strategy in leukaemia
Authors: Vink J. , Cloos J. , Kaspers G. J. L. 
Published: June 2006

SummaryFollowing its success in multiple myeloma (MM), proteasome inhibition has become a topic of interest as novel treatment strategy of cancer. By simultaneously affecting multiple pathways in the cancer cell, such as deregulation of the programmed degradation of many cellular proteins, proteasome inhibition causes rapid apoptosis of these cells. Both in rapidly proliferating leukaemic cell lines and in primary leukaemic cells isolated from patients, proteasome inhibition results in antileukaemic activity. The normal counterparts of these cells are much more resistant to proteasome inhibitors (PI), thereby resulting in a favourable therapeutic index. Importantly, while leukaemic stem cells are sensitive to proteasome inhibition, normal haematopoietic stem cells are still viable after drug exposure. Nowadays, many PIs are being identified; bortezomib is the most well known since obtaining Food and Drug Administration approval for clinical use in MM. This review summarises the biological and clinical aspects of proteasome inhibition and discusses the potential role of these inhibitors in the treatment of leukaemia.
Manipulation of prothrombin concentration improves response to high‐dose factor VIIa in a cell‐based model of haemophilia
Authors: Allen Geoffrey A. , Hoffman Maureane , Roberts Harold R. , Monroe Dougald M. 
Published: June 2006

SummaryClinical reports suggest that treatment regimens employing both activated prothrombin complex concentrates (aPCCs) and recombinant activated factor VII (rFVIIa) may control the bleeding in patients with haemophilia who fail to respond to either agent alone. We hypothesised that increased concentrations of prothrombin, as may be observed after the infusion of aPCCs, favourably influence parameters of thrombin generation in haemophilia treated with high‐dose rFVIIa. We examined the effect of varied prothrombin and rFVIIa concentrations on thrombin generation in a model of haemophilia. At all concentrations of rFVIIa, increased prothrombin concentrations led to increases in the peak and rate of thrombin generation. In assays with the highest concentrations of prothrombin and rFVIIa, peak thrombin actually equalled that measured in the model of normal haemostasis. The significant impact of prothrombin concentration on the effect of rFVIIa in vitro may explain the improved haemostasis reported with concurrent use of aPCCs and rFVIIa. These results imply that persons with plasma prothrombin levels at either end of the ‘normal’ range could have significantly different responses to similar rFVIIa doses. Furthermore, these results suggest that increasing plasma prothrombin concentration prior to rFVIIa administration may offer advantages over the use of rFVIIa alone in the treatment of haemophilic bleeding.
Costimulation of naive human CD4+ T cells through intercellular adhesion molecule‐1 promotes differentiation to a memory phenotype that is not strictly the result of multiple rounds of cell division
Authors: Kohlmeier Jacob E. , Chan Marcia A. , Benedict Stephen H. 
Published: June 2006

SummaryThe process by which naive T cells become activated, differentiate into effector cells and ultimately generate long‐lived memory cells is dependent upon a number of factors, including the costimulatory signals received by the T cell. To best understand the multiple events involved, it is important to understand the potential contributions by individual signalling proteins using both in vitro and in vivo studies. Here, the potential for costimulation through intercellular adhesion molecule‐1 (ICAM‐1; CD54), resident on the surface of naive human T cells, to influence differentiation was investigated. Costimulation of naive T cells through ICAM‐1 resulted in expansive cell division, high interleukin‐2 production, and protection from apoptosis. Prolonged culture led to outgrowth of a subpopulation of cells with a highly differentiated CD45RA– CD11ahi CD27– phenotype. In this respect, costimulation through ICAM‐1 was similar to costimulation through CD28 and different from costimulation through leucocyte function‐associated antigen‐1. The CD45RA– CD11ahi CD27– cells responded to suboptimal stimulation through the T‐cell receptor alone with a more robust proliferative response compared with naive cells from the same subject. These cells also secreted higher levels of T helper type 1 cytokines in response to lower levels of stimulation than their naive counterparts. The surface phenotype and more sensitive response characteristics suggest the creation of a memory T‐cell subpopulation as a result of costimulation through ICAM‐1. Finally, generation of this memory population was the result of specific costimulatory signals, and not merely because of a high number of cell divisions. These data reveal a new role for resident ICAM‐1 to influence the differentiation of naive T cells.
Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index.
Authors: TESTA R. , TESTA E. , GIANNINI E. , BORRO P. , MILAZZO S. , ISOLA L. , CEPPA P. , LANTIERI P. B. , RISSO D. 
Published: June 2006

Abstract.Objectives.  Noninvasive evaluation of fibrosis is an on‐going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging.Design.  We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients.Results.  Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score ≤ 2) versus evident (score > 2) fibrosis: BMI (24 ± 2 vs. 26 ± 2, P = 0.0007), AST (56 ± 36 vs. 88 ± 65, P = 0.0159), ALT (92 ± 54 vs. 139 ± 108, P = 0.0290), PLT (220 ± 64 vs. 173 ± 61, P = 0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133 ± 786 vs. 1540 ± 681, P = 0.0003), AST/platelet count ratio index (APRI) (0.80 ± 0.87 vs. 1.51 ± 1.47, P = 0.0010), ABT%d/h30 min (10.8 ± 4.5 vs. 7.6 ± 3.8, P = 0.0007), ABT%d/cum120 min (8.9 ± 3.3 vs. 6.5 ± 3.1, P = 0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: −0.569 +(BMI × 0.107) + (APRI × 0.169)−(PLT/SPD × 0.304), and Model 2: 2.376 + (APRI × 0.152)−(ABTd/h30 × 0.043)−(PLT/SPD × 0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score.Conclusion.  These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.
Migration and recovery of the genetic diversity during the increasing density phase in cyclic vole populations
Authors: BERTHIER K. , CHARBONNEL N. , GALAN M. , CHAVAL Y. , COSSON J.‐F. 
Published: June 2006

AbstractIn cyclic populations, high genetic diversity is currently reported despite the periodic low numbers experienced by the populations during the low phases. Here, we report spatio‐temporal monitoring at a very fine scale of cyclic populations of the fossorial water vole (Arvicola terrestris) during the increasing density phase. This phase marks the transition from a patchy structure (demes) during low density to a continuous population in high density. We found that the genetic diversity was effectively high but also that it displayed a local increase within demes over the increasing phase. The genetic diversity remained relatively constant when considering all demes together. The increase in vole abundance was also correlated with a decrease of genetic differentiation among demes. Such results suggest that at the end of the low phase, demes are affected by genetic drift as the result of being small and geographically isolated. This leads to a loss of local genetic diversity and a spatial differentiation among demes. This situation is counterbalanced during the increasing phase by the spatial expansion of demes and the increase of the effective migration among differentiated demes. We provide evidences that in cyclic populations of the fossorial water voles, the relative influence of drift operating during low density populations and migration occurring principally while population size increases interacts closely to maintain high genetic diversity.
Evidence for Golgi‐independent transport from the early secretory pathway to the plastid in malaria parasites
Authors: Tonkin Christopher J. , Struck Nicole S. , Mullin Kylie A. , Stimmler Luciana M. , McFadden Geoffrey I. 
Published: June 2006

SummaryThe malaria parasite Plasmodium falciparum harbours a relict plastid (termed the apicoplast) that has evolved by secondary endosymbiosis. The apicoplast is surrounded by four membranes, the outermost of which is believed to be part of the endomembrane system. Nuclear‐encoded apicoplast proteins have a two‐part N‐terminal extension that is necessary and sufficient for translocation across these four membranes. The first domain of this N‐terminal extension resembles a classical signal peptide and mediates translocation into the secretory pathway, whereas the second domain is homologous to plant chloroplast transit peptides and is required for the remaining steps of apicoplast targeting. We explored the initial, secretory pathway component of this targeting process using green fluorescent reporter protein constructs with modified leaders. We exchanged the apicoplast signal peptide with signal peptides from other secretory proteins and observed correct targeting, demonstrating that apicoplast targeting is initiated at the general secretory pathway of P. falciparum. Furthermore, we demonstrate by immunofluorescent labelling that the apicoplast resides on a small extension of the endoplasmic reticulum (ER) that is separate from the cis‐Golgi. To define the position of the apicoplast in the endomembrane pathway in relation to the Golgi we tracked apicoplast protein targeting in the presence of the secretory inhibitor Brefeldin A (BFA), which blocks traffic between the ER and Golgi. We observe apicoplast targeting in the presence of BFA despite clear perturbation of ER to Golgi traffic by the inhibitor, which suggests that the apicoplast resides upstream of the cis‐Golgi in the parasite's endomembrane system. The addition of an ER retrieval signal (SDEL) – a sequence recognized by the cis‐Golgi protein ERD2 – to the C‐terminus of an apicoplast‐targeted protein did not markedly affect apicoplast targeting, further demonstrating that the apicoplast is upstream of the Golgi. Apicoplast transit peptides are thus dominant over an ER retention signal. However, when the transit peptide is rendered non‐functional (by two point mutations or by complete deletion) SDEL‐specific ER retrieval takes over, and the fusion protein is localized to the ER. We speculate either that the apicoplast in P. falciparum resides within the ER directly in the path of the general secretory pathway, or that vesicular trafficking to the apicoplast directly exits the ER.