bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular localization of Mayven following expression of wild type and mutant EGFP tagged cDNAs
Authors: Montague Paul , Kennedy Peter GE , Barnett Susan C 
Published: May 2010

Abstract

Background
Process formation by glial cells is crucial to their function. Mayven, an actin binding, multi-domain polypeptide, and member of the BTB-BACK-Kelch family have been shown to be important in oligodendrocyte process extension. To assess the role of Mayven in neural cell process extension we have tracked the subcellular distribution of exogenous Mayven following expression of a rat Mayven -EGFP cDNA in a variety of neural cell backgrounds and specifically in OEC tranfectants following drug treatment to disrupt the integrity of the cytoskeleton. A comparison was made between the subcellular localization following transient transfection of OECs with full-length Mayven cDNA and a series of mutant domain constructs.

Results
The subcellular location of Mayven in OEC transfectants showed a characteristic distribution with intense foci of staining towards the process tips corresponding to regions of accumulated Mayven overlapping in part with lammelipodial actin and was absent from the filipodia and the outer membrane. This signature pattern was also observed in Schwann cells, Oli-Neu cells, astrocytes and the neuroblastoma cell line B104 transfectants and resembled the exogenous and endogenous Mayven distribution in oligodendrocytes. This contrasted with the localization pattern in non-neural cells. There was a re-localization of Mayven in OEC transfectants following drug treatment to challenge the integrity of the actin cytoskeleton while breakdown of the microtubular component had no discernible impact on the accumulation of Mayven in the process tips. Deletion of the first three amino acids of the SH3 motif of the putative Fyn Kinase binding domain at the amino terminus significantly compromised this signature pattern as did the removal of the last Kelch repeat unit of six unit Kelch domain comprising the carboxyl terminus. In addition, there was a reduction in process length in mutant transfectants. Co-expression studies with a haemagglutinin (HA) tagged wild type Mayven cDNA and EGFP tagged mutant cDNAs suggested a homomeric interaction mediated by the BTB/POZ domain.

Conclusions
Exogenous Mayven is transported to the lamellipodia in neural transfectants associating with the actin cytoskeletal network. In addition to the importance of the internal BTB/POZ domain, this subcellular distribution pattern is dependent on the presence of an intact amino and carboxyl terminus.
Infection Probability Score, APACHE II and KARNOFSKY scoring systems as predictors of bloodstream infection onset in hematology-oncology patients
Authors: Apostolopoulou Eleni , Raftopoulos Vasilios , Terzis Konstantinos , Elefsiniotis Ioannis 
Published: May 2010

Abstract

Background
Bloodstream Infections (BSIs) in neutropenic patients often cause considerable morbidity and mortality. Therefore, the surveillance and early identification of patients at high risk for developing BSIs might be useful for the development of preventive measures. The aim of the current study was to assess the predictive power of three scoring systems: Infection Probability Score (IPS), APACHE II and KARNOFSKY score for the onset of Bloodstream Infections in hematology-oncology patients.

Methods
A total of 102 patients who were hospitalized for more than 48 hours in a hematology-oncology department in Athens, Greece between April 1st and October 31st 2007 were included in the study. Data were collected by using an anonymous standardized recording form. Source materials included medical records, temperature charts, information from nursing and medical staff, and results on microbiological testing. Patients were followed daily until hospital discharge or death.

Results
Among the 102 patients, Bloodstream Infections occurred in 17 (16.6%) patients. The incidence density of Bloodstream Infections was 7.74 per 1,000 patient-days or 21.99 per 1,000 patient-days at risk. The patients who developed a Bloodstream Infection were mainly females (p = 0.004), with twofold time mean length of hospital stay (p < 0.001), with fourfold time mean length of neutropenia (p < 0.001), with neutropenia < 500 (p < 0.001), suffered mainly from acute myeloid leukemia (p < 0.001), had been exposed to antibiotics (p = 0.045) and chemotherapy (p = 0.023), had a surgery (p = 0.048) and a Hickman catheter (p = 0.025) as compared to the patients without Bloodstream Infection. The best cut-off value of IPS for the prediction of a Bloodstream Infection was 10 with a sensitivity of 75% and specificity of 70.9%

Conclusion
Between the three different prognostic scoring systems, Infection Probability Score had the best sensitivity in predicting Bloodstream Infections.
MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia
Authors: Ferracin Manuela , Zagatti Barbara , Rizzotto Lara , Cavazzini Francesco , Veronese Angelo , Ciccone Maria , Saccenti Elena , Lupini Laura , Grilli Andrea , De Angeli Cristiano , Negrini Massimo , Cuneo Antonio 
Published: May 2010

Abstract

Background
Fludarabine, is one of the most active single agents in the treatment of chronic lymphocytic leukemia (CLL). Over time, however, virtually all CLL patients become fludarabine-refractory. To elucidate whether microRNAs are involved in the development of fludarabine resistance, we analyzed the expression of 723 human miRNAs before and 5-days after fludarabine mono-therapy in 17 CLL patients which were classified as responder or refractory to fludarabine treatment based on NCI criteria.

Results
By comparing the expression profiles of these two groups of patients, we identified a microRNA signature able to distinguish refractory from sensitive CLLs. The expression of some microRNAs was also able to predict fludarabine resistance of 12 independent CLL patients. Among the identified microRNAs, miR-148a, miR-222 and miR-21 exhibited a significantly higher expression in non-responder patients either before and after fludarabine treatment. After performing messenger RNA expression profile of the same patients, the activation of p53-responsive genes was detected in fludarabine responsive cases only, therefore suggesting a possible mechanism linked to microRNA deregulation in non-responder patients. Importantly, inhibition of miR-21 and miR-222 by anti-miRNA oligonucleotides induced a significant increase in caspase activity in fludarabine-treated p53-mutant MEG-01 cells, suggesting that miR-21 and miR-222 up-regulation may be involved in the establishment of fludarabine resistance.

Conclusions
This is the first report that reveals the existence of a microRNA profile that differentiate refractory and sensitive CLLs, either before and after fludarabine mono-therapy. A p53 dysfunctional pathway emerged in refractory CLLs and could contribute in explaining the observed miRNA profile. Moreover, this work indicates that specific microRNAs can be used to predict fludarabine resistance and may potentially be used as therapeutic targets, therefore establishing an important starting point for future studies.
Recent key advances in human immunodeficiency virus medicine and implications for China
Authors: Sun Kai , Zhou Shuntai , Chen Ray Y , Cohen Myron S , Zhang Fujie 
Published: May 2010

Abstract
In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program.
Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner
Authors: Rondini Elizabeth A , Walters Dianne M , Bauer Alison K 
Published: May 2010

Abstract

Background
Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation, a lung cancer risk factor. Vanadium pentoxide (V2O5) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans. In the current investigation we examined the influence of genetic background on susceptibility to V2O5-induced inflammation and evaluated whether V2O5 functions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice.

Results
A/J, BALB/cJ (BALB), and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 10 μg/g; i.p.) or corn oil followed by 5 weekly aspirations of V2O5 or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment. Susceptibility to V2O5-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid (BALF), and chemokines, transcription factor activity, and MAPK signaling were quantified in lung homogenates. We found that treatment of animals with MCA followed by V2O5 promoted lung tumors in both A/J (10.3 ± 0.9 tumors/mouse) and BALB (2.2 ± 0.36) mice significantly above that observed with MCA/PBS or V2O5 alone (P < 0.05). No tumors were observed in the B6 mice in any of the experimental groups. Mice sensitive to tumor promotion by V2O5 were also found to be more susceptible to V2O5-induced pulmonary inflammation and hyperpermeability (A/J>BALB>B6). Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1, higher NFκB and c-Fos binding activity, as well as sustained ERK1/2 activation in lung tissue.

Conclusions
In this study we demonstrate that V2O5, an occupational and environmentally relevant metal oxide, functions as an in vivo lung tumor promoter among different inbred strains of mice. Further, we identified a positive relationship between tumor promotion and susceptibility to V2O5-induced pulmonary inflammation. These findings suggest that repeated exposures to V2O5 containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways.
Semi-robotic 6 degree of freedom positioning for intracranial high precision radiotherapy; first phantom and clinical results
Authors: Wilbert Jürgen , Guckenberger Matthias , Polat Bülent , Sauer Otto , Vogele Michael , Flentje Michael , Sweeney Reinhart A 
Published: May 2010

Abstract

Background
To introduce a novel method of patient positioning for high precision intracranial radiotherapy.

Methods
An infrared(IR)-array, reproducibly attached to the patient via a vacuum-mouthpiece(vMP) and connected to the table via a 6 degree-of-freedom(DoF) mechanical arm serves as positioning and fixation system. After IR-based manual prepositioning to rough treatment position and fixation of the mechanical arm, a cone-beam CT(CBCT) is performed. A robotic 6 DoF treatment couch (HexaPOD™) then automatically corrects all remaining translations and rotations. This absolute position of infrared markers at the first fraction acts as reference for the following fractions where patients are manually prepositioned to within ± 2 mm and ± 2° of this IR reference position prior to final HexaPOD-based correction; consequently CBCT imaging is only required once at the first treatment fraction.
The preclinical feasibility and attainable repositioning accuracy of this method was evaluated on a phantom and human volunteers as was the clinical efficacy on 7 pilot study patients.

Results
Phantom and volunteer manual IR-based prepositioning to within ± 2 mm and ± 2° in 6DoF was possible within a mean(± SD) of 90 ± 31 and 56 ± 22 seconds respectively. Mean phantom translational and rotational precision after 6 DoF corrections by the HexaPOD was 0.2 ± 0.2 mm and 0.7 ± 0.8° respectively. For the actual patient collective, the mean 3D vector for inter-treatment repositioning accuracy (n = 102) was 1.6 ± 0.8 mm while intra-fraction movement (n = 110) was 0.6 ± 0.4 mm.

Conclusions
This novel semi-automatic 6DoF IR-based system has been shown to compare favourably with existing non-invasive intracranial repeat fixation systems with respect to handling, reproducibility and, more importantly, intra-fraction rigidity. Some advantages are full cranial positioning flexibility for single and fractionated IGRT treatments and possibly increased patient comfort.
Human difference in the genomic era: Facilitating a socially responsible dialogue
Authors: Knerr Sarah , Ramos Edward , Nowinski Juleigh , Dixon Keianna , Bonham Vence L 
Published: May 2010

Abstract

Background
The study of human genetic variation has been advanced by research such as genome-wide association studies, which aim to identify variants associated with common, complex diseases and traits. Significant strides have already been made in gleaning information on susceptibility, treatment, and prevention of a number of disorders. However, as genetic researchers continue to uncover underlying differences between individuals, there is growing concern that observed population-level differences will be inappropriately generalized as inherent to particular racial or ethnic groups and potentially perpetuate negative stereotypes.

Discussion
We caution that imprecision of language when conveying research conclusions, compounded by the potential distortion of findings by the media, can lead to the stigmatization of racial and ethnic groups.

Summary
It is essential that the scientific community and with those reporting and disseminating research findings continue to foster a socially responsible dialogue about genetic variation and human difference.
Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor
Authors: Komarova Svetlana , Roth Justin , Alvarez Ronald , Curiel David T , Pereboeva Larisa 
Published: May 2010

Abstract

Background
Mesenchymal Progenitor/Stem Cells (MSC) respond to homing cues providing an important mechanism to deliver therapeutics to sites of injury and tumors. This property has been confirmed by many investigators, however, the efficiency of tumor homing needs to be improved for effective therapeutic delivery. We investigated the feasibility of enhancing MSC tumor targeting by expressing an artificial tumor-binding receptor on the MSC surface.

Methods
Human MSC expressing an artificial receptor that binds to erbB2, a tumor cell marker, were obtained by transduction with genetically modified adenoviral vectors encoding an artificial receptor (MSC-AR). MSC-AR properties were tested in vitro in cell binding assays and in vivo using two model systems: transient transgenic mice that express human erbB2 in the lungs and ovarian xenograft tumor model. The levels of luciferase-labeled MSCs in erbB2-expressing targeted sites were evaluated by measuring luciferase activity using luciferase assay and imaging.

Results
The expression of AR enhanced binding of MSC-AR to erbB2-expressing cells in vitro, compared to unmodified MSCs. Furthermore, we have tested the properties of erbB2-targeted MSCs in vivo and demonstrated an increased retention of MSC-AR in lungs expressing erbB2. We have also confirmed increased numbers of erbB2-targeted MSCs in ovarian tumors, compared to unmodified MSC. The kinetic of tumor targeting by ip injected MSC was also investigated.

Conclusion
These data demonstrate that targeting abilities of MSCs can be enhanced via introduction of artificial receptors. The application of this strategy for tumor cell-based delivery could increase a number of cell carriers in tumors and enhance efficacy of cell-based therapy.
Requirement of ATM-dependent pathway for the repair of a subset of DNA double strand breaks created by restriction endonucleases
Authors: Suzuki Keiji , Takahashi Maiko , Oka Yasuyoshi , Yamauchi Motohiro , Suzuki Masatoshi , Yamashita Shunichi 
Published: May 2010

Background
DNA double strand breaks induced by DNA damaging agents, such ionizing radiation, are repaired by multiple DNA repair pathways including non-homologous end-joining (NHEJ) repair and homologous recombination (HR) repair. ATM-dependent DNA damage checkpoint regulates a part of DNA repair pathways, however, the exact role of ATM activity remains to be elucidated. In order to define the molecular structure of DNA double strand breaks requiring ATM activity we examined repair of DNA double strand breaks induced by different restriction endonucleases in normal human diploid cells treated with or without ATM-specific inhibitor.

Results
Synchronized G1 cells were treated with various restriction endonucleases. DNA double strand breaks were detected by the foci of phosphorylated ATM at serine 1981 and 53BP1. DNA damage was detectable 2 hours after the treatment, and the number of foci decreased thereafter. Repair of the 3'-protruding ends created by Pst I and Sph I was efficient irrespective of ATM function, whereas the repair of a part of the blunt ends caused by Pvu II and Rsa I, and 5'-protruding ends created by Eco RI and Bam HI, respectively, were compromised by ATM inhibition.

Conclusions
Our results indicate that ATM-dependent pathway plays a pivotal role in the repair of a subset of DNA double strand breaks with specific end structures.
Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels
Authors: Yeap Bu B , Chubb S A Paul , Flicker Leon , McCaul Kieran A , Ebeling Peter R , Beilby John P , Norman Paul E 
Published: May 2010

ObjectiveBone-derived undercarboxylated osteocalcin regulates insulin secretion and sensitivity in mice, and reduced serum total osteocalcin (TOC) is associated with diabetes in humans. However, the relationship between TOC levels and other cardiovascular risk factors is uncertain. We sought to determine whether serum TOC is associated with metabolic syndrome and its components in older men.DesignCross-sectional analysis from a population-based cohort of men aged ≥70 years.MethodsEarly morning sera were assayed for TOC. Insulin resistance was estimated using a homeostatic model (HOMA2-IR). Metabolic syndrome was defined according to NCEP-ATPIII criteria.ResultsTOC was assayed in 4047 men. Men who were not fasting and reported having bone fractures, Paget's disease, or bisphosphonate, glucocorticoid, or warfarin use were excluded, leaving 2765 men with metabolic syndrome present in 797 (28.8%). TOC was inversely associated with waist circumference, glucose, and triglyceride levels and HOMA2-IR (all P<0.001), and was lower in men with metabolic syndrome (mean±s.e.m.: 20.1±0.4 vs 21.4±0.2 μg/l, P=0.002). In multivariate analysis, men with TOC of 13.25–16.55 and <13.25 μg/l had 1.5- to 2-fold increased risk of metabolic syndrome compared with men with levels ≥30 μg/l. TOC remained associated with metabolic syndrome after adjustment for individual components, but not after adjusting for both waist circumference and glucose.ConclusionsIncreased waist circumference, reduced TOC, elevated glucose, and triglyceride levels are inter-related in aging men. Osteocalcin may lie in the causal pathway between central adiposity and insulin resistance. Further research is required to evaluate whether interventions which raise osteocalcin levels might decrease cardiovascular risk.
Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter ‘extended pilot study’
Authors: NILSSON LARS , ANDERSEN ANDERS NYBOE , LINDENBERG SVEND , HAUSKEN JON , ANDERSEN CLAUS YDING , KAHN JARL A 
Published: May 2010

AbstractTo enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when ≤ 5 follicles developed in a preceding cycle following a long agonist protocol with the use of > 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5 before expected start of menstruation and continued for 4–7 days. On cycle day 2–3 a starting dose of rFSH (300–400 IU/day) was given. At a leading follicle diameter of 14 mm, ganirelix administration was resumed until final oocyte maturation was induced with 10,000 IU hCG. GnRH antagonist only marginally affected the intercycle FSH rise; basal levels of FSH remained similar to those seen after 4 days of antagonist administration. The protocol effectively induced low LH levels and luteolysis, but daily administration of 350 IU rFSH (median) for 11 days only led to the collection of 3 oocytes in 49 oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release may improve the stimulation results in poor responders.
Continuous monitoring of fetal scalp temperature in labor: a new technology validated in a fetal lamb model
Authors: LAVESSON TONY , AMER‐WÅHLIN ISIS , HANSSON STEFAN , LEY DAVID , MARŠÁL KAREL , OLOFSSON PER 
Published: May 2010

AbstractObjective. To evaluate a new technical equipment for continuous recording of human fetal scalp temperature in labor. Design. Experimental animal study. Methods. Two temperature sensors were placed subcutaneously and intracranially on the forehead of 10 fetal lambs and connected to a temperature monitoring system. The system records temperatures simultaneously on‐line and stores data to be analyzed off‐line. Throughout the experiment, the fetus was oxygenated via the umbilical cord circulation. Asphyxia was induced by intermittent cord compression, as assessed by pH in jugular vein blood. The intracranial (ICT) and subcutaneous (SCT) temperatures were compared with simple and polynomial regression analyses. Main outcome measures. Absolute and delta ICT and SCT changes. Results. ICT and SCT were both successfully recorded in all 10 cases. With increasing acidosis, the temperatures decreased. The correlation coefficient between ICT and SCT had a range of 0.76–0.97 (median 0.88) by simple linear regression and 0.80–0.99 (median 0.89) by second grade polynomial regression. After an initial system stabilization period of 10 minutes, the delta temperature values (ICT minus SCT) were less than 1.5°C throughout the experiment in all but one case. Conclusions. The fetal forehead SCT mirrored the ICT closely, with the ICT being higher.