bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineation of precursors in murine spleen that develop in contact with splenic endothelium to give novel dendritic-like cells
Authors: Tan Jonathan K. H. , Periasamy Pravin , O'Neill Helen C. 
Published: March 2010

AbstractHematopoietic cell lineages are best described in terms of distinct progenitors with limited differentiative capacity. To distinguish cell lineages, it is necessary to define progenitors and induce their differentiation in vitro. We previously reported in vitro development of immature dendritic-like cells (DCs) in long-term cultures (LTCs) of murine spleen, and in cocultures of spleen or bone marrow (BM) over splenic endothelial cell lines derived from LTCs. Cells produced are phenotypically distinct CD11bhiCD11cloCD8−MHC-II− cells, tentatively named L-DCs. Here we delineate L-DC progenitors as different from known DC progenitors in BM and DC precursors in spleen. The progenitor is contained within the lineage-negative (Lin)−c-kit+ subset in neonatal and adult spleen. This subset has multipotential reconstituting ability in mice. In neonatal spleen, the progenitor is further enriched within the c-kitlo and CD34+ subsets of Lin−c-kit+ cells. These cells seed cocultures of splenic endothelial cells, differentiating to give L-DCs that can activate T cells. L-DC progenitors are distinguishable from described splenic CD11clo DC precursors and from Fms-like tyrosine kinase 3+ DC progenitors in BM. Overall, this study confirms that LTCs are a physiologically relevant culture system for in vitro development of a novel DC type from spleen progenitors.
NF-κB balances vascular regression and angiogenesis via chromatin remodeling and NFAT displacement
Authors: Aurora Arin B. , Biyashev Dauren , Mirochnik Yelena , Zaichuk Tetiana A. , Sánchez-Martinez Cristina , Renault Marie-Ange , Losordo Douglas , Volpert Olga V. 
Published: March 2010

Abstract
Extracellular factors control the angiogenic switch in endothelial cells (ECs) via competing survival and apoptotic pathways. Previously, we showed that proangiogenic and antiangiogenic factors target the same signaling molecules, which thereby become pivots of angiogenic balance. Here we show that in remodeling endothelium (ECs and EC precursors) natural angiogenic inhibitors enhance nuclear factor-κB (NF-κB) DNA binding, which is critical for antiangiogenesis, and that blocking the NF-κB pathway abolishes multiple antiangiogenic events in vitro and in vivo. NF-κB induction by antiangiogenic molecules has a dual effect on transcription. NF-κB acts as an activator of proapoptotic FasL and as a repressor of prosurvival cFLIP. On the FasL promoter, NF-κB increases the recruitment of HAT p300 and acetylated histones H3 and H4. Conversely, on cFLIP promoter, NF-κB increases histone deacetylase 1 (HDAC1), decreases p300 and histone acetylation, and reduces the recruitment of NFAT, a transcription factor critical for cFLIP expression. Finally, we found a biphasic effect, when HDAC inhibitors (HDACi) were used to test the dependence of pigment epithelial-derived factor activity on histone acetylation. The cooperative effect seen at low doses switches to antagonistic as the concentrations increase. Our study defines an interactive transcriptional network underlying angiogenic balance and points to HDACi as tools to manipulate the angiogenic switch.
Hematopoietic stem cell transplantation for multiple myeloma beyond 2010
Authors: Bladé Joan , Rosiñol Laura , Cibeira Maria Teresa , Rovira Montserrat , Carreras Enric 
Published: March 2010

AbstractAutologous stem cell transplantation (ASCT) is considered the gold standard in the frontline therapy of younger patients with multiple myeloma because it results in higher complete remission (CR) rates and longer event-free survival than conventional chemotherapy. The greatest benefit from ASCT is obtained in patients achieving CR after transplantation, the likelihood of CR being associated with the M-protein size at the time of transplantation. The incorporation of novel agents results in higher pre- and posttransplantation CR rates. Induction with bortezomib-containing regimens is encouraging in patients with poor-risk cytogenetics. However, longer follow-up is required to assess the impact of this increased CR on long-term survival. The results of posttransplantation consolidation/maintenance with new drugs are encouraging. All this indicates that, in the era of novel agents, high-dose therapy should be optimized rather than replaced. Because of its high transplantation-related mortality, myeloablative allografting has been generally replaced by reduced-intensity conditioning (reduced intensity conditioning allogeneic transplantation). The best results are achieved after a debulky ASCT, with a progression-free survival plateau of 25% to 30% beyond 6 years from reduced intensity conditioning allogeneic transplantation. The development of novel reduced-intensity preparative regimens and peri- and posttransplantation strategies aimed at minimizing graft-versus-host disease, and enhancing the graft-versus-myeloma effect are key issues.
The transcription factor Gfi1 regulates G-CSF signaling and neutrophil development through the Ras activator RasGRP1
Authors: de la Luz Sierra Maria , Sakakibara Shuhei , Gasperini Paola , Salvucci Ombretta , Jiang Kan , McCormick Peter J. , Segarra Marta , Stone Jim , Maric Dragan , Zhu Jinfang , Qian Xiaolan , Lowy Douglas R. , Tosato Giovanna 
Published: March 2010

AbstractThe transcription factor growth factor independence 1 (Gfi1) and the growth factor granulocyte colony-stimulating factor (G-CSF) are individually essential for neutrophil differentiation from myeloid progenitors. Here, we provide evidence that the functions of Gfi1 and G-CSF are linked in the regulation of granulopoiesis. We report that Gfi1 promotes the expression of Ras guanine nucleotide releasing protein 1 (RasGRP1), an exchange factor that activates Ras, and that RasGRP1 is required for G-CSF signaling through the Ras/mitogen–activated protein/extracellular signal-regulated kinase (MEK/Erk) pathway. Gfi1-null mice have reduced levels of RasGRP1 mRNA and protein in thymus, spleen, and bone marrow, and Gfi1 transduction in myeloid cells promotes RasGRP1 expression. When stimulated with G-CSF, Gfi1-null myeloid cells are selectively defective at activating Erk1/2, but not signal transducer and activator of transcription 1 (STAT1) or STAT3, and fail to differentiate into neutrophils. Expression of RasGRP1 in Gfi1-deficient cells rescues Erk1/2 activation by G-CSF and allows neutrophil maturation by G-CSF. These results uncover a previously unknown function of Gfi1 as a regulator of RasGRP1 and link Gfi1 transcriptional control to G-CSF signaling and regulation of granulopoiesis.
Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups
Authors: Limdi Nita A. , Wadelius Mia , Cavallari Larisa , Eriksson Niclas , Crawford Dana C. , Lee Ming-Ta M. , Chen Chien-Hsiun , Motsinger-Reif Alison , Sagreiya Hersh , Liu Nianjun , Wu Alan H. B. , Gage Brian F. , Jorgensen Andrea , Pirmohamed Munir , Shin Jae-Gook , Suarez-Kurtz Guilherme , Kimmel Stephen E. , Johnson Julie A. , Klein Teri E. , Wagner Michael J. 
Published: March 2010

AbstractWarfarin-dosing algorithms incorporating CYP2C9 and VKORC1 −1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than Asians or blacks. Herein, we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1 −1639G>A among Asians (n = 1103), blacks (n = 670), and whites (n = 3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 −1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the −1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.
Leukemia-associated minor histocompatibility antigen discovery using T-cell clones isolated by in vitro stimulation of naive CD8+ T cells
Authors: Bleakley Marie , Otterud Brith E. , Richardt Julia L. , Mollerup Audrey D. , Hudecek Michael , Nishida Tetsuya , Chaney Colette N. , Warren Edus H. , Leppert Mark F. , Riddell Stanley R. 
Published: March 2010

AbstractT-cell immunotherapy that targets minor histocompatibility (H) antigens presented selectively by recipient hematopoietic cells, including leukemia, could prevent and treat leukemic relapse after hematopoietic cell transplantation without causing graft-versus-host disease. To provide immunotherapy that can be applied to a majority of transplantation recipients, it is necessary to identify leukemia-associated minor H antigens that result from gene polymorphisms that are balanced in the population and presented by common human leukocyte antigen alleles. Current approaches for deriving minor H antigen–specific T cells, which provide essential reagents for the molecular identification and characterization of the polymorphic genes that encode the antigens, rely on in vivo priming and are often unsuccessful. We show that minor H antigen–specific cytotoxic T lymphocyte precursors are found predominantly in the naive CD8+ T-cell subset and provide an efficient strategy for in vitro priming of native T cells to generate T cells to a broad diversity of minor H antigens presented with common human leukocyte antigen alleles. We used this approach to derive a panel of stable cytotoxic T lymphocyte clones for discovery of genes that encode minor H antigens and identify a novel antigen expressed on acute myeloid leukemia stem cells and minimally in graft-versus-host disease target tissues.
Altered neuromuscular control mechanisms of the trapezius muscle in fibromyalgia
Authors: Gerdle Björn , Grönlund Christer , Karlsson Stefan J , Holtermann Andreas , Roeleveld Karin 
Published: March 2010

Abstract

Background
fibromyalgia is a relatively common condition with widespread pain and pressure allodynia, but unknown aetiology. For decades, the association between motor control strategies and chronic pain has been a topic for debate. One long held functional neuromuscular control mechanism is differential activation between regions within a single muscle. The aim of this study was to investigate differences in neuromuscular control, i.e. differential activation, between myalgic trapezius in fibromyalgia patients and healthy controls.

Methods
27 fibromyalgia patients and 30 healthy controls performed 3 minutes bilateral shoulder elevations with different loads (0-4 Kg) with a high-density surface electromyographical (EMG) grid placed above the upper trapezius. Differential activation was quantified by the power spectral median frequency of the difference in EMG amplitude between the cranial and caudal parts of the upper trapezius. The average duration of the differential activation was described by the inverse of the median frequency of the differential activations.

Results
the median frequency of the differential activations was significantly lower, and the average duration of the differential activations significantly longer in fibromyalgia compared with controls at the two lowest load levels (0-1 Kg) (p < 0.04), but not at the two highest load levels (2 and 4 Kg).

Conclusion
these findings illustrate a different neuromuscular control between fibromyalgia patients and healthy controls during a low load functional task, either sustaining or resulting from the chronic painful condition. The findings may have clinical relevance for rehabilitation strategies for fibromyalgia.
Cell cycle-dependent regulation of the bi-directional overlapping promoter of human BRCA2/ZAR2 genes in breast cancer cells
Authors: Misra Smita , Sharma Shvetank , Agarwal Anupriya , Khedkar Sheetal V , Tripathi Manish K , Mittal Mukul K , Chaudhuri Gautam 
Published: March 2010

AbstractBackgroundBRCA2 gene expression is tightly regulated during the cell cycle in human breast cells. The expression of BRCA2 gene is silenced at the G0/G1 phase of cell growth and is de-silenced at the S/G2 phase. While studying the activity of BRCA2 gene promoter in breast cancer cells, we discovered that this promoter has bi-directional activity and the product of the reverse activity (a ZAR1-like protein, we named ZAR2) silences the forward promoter at the G0/G1 phase of the cell. Standard techniques like cell synchronization by serum starvation, flow cytometry, N-terminal or C-terminal FLAG epitope-tagged protein expression, immunofluorescence confocal microscopy, dual luciferase assay for promoter evaluation, and chromatin immunoprecipitation assay were employed during this study.ResultsHumanBRCA2gene promoter is active in both the forward and the reverse orientations. This promoter is 8-20 fold more active in the reverse orientation than in the forward orientation when the cells are in the non-dividing stage (G0/G1). When the cells are in the dividing state (S/G2), the forward activity of the promoter is 5-8 folds higher than the reverse activity. The reverse activity transcribes the ZAR2 mRNA with 966 nt coding sequence which codes for a 321 amino acid protein. ZAR2 has two C4 type zinc fingers at the carboxyl terminus. In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. In the dividing cells, ZAR2 is trapped in the cytoplasm.ConclusionsBRCA2gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. Subcellular location of ZAR2 and its expression from the reverse promoter of the BRCA2 gene are stringently regulated in a cell cycle dependent manner. ZAR2 binds to BRCA2/ZAR2 bi-directional promoterin vivoand is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells.
Effects of lovastatin on breast cancer cells: a proteo-metabonomic study
Authors: Klawitter Jelena , Shokati Touraj , Moll Vanessa , Christians Uwe , Klawitter Jost 
Published: March 2010

Abstract
Introduction
Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation and reduction of signals driving cell proliferation and survival responses.

Methods
In this study we evaluated the effects of lovastatin acid and lactone on breast cancer MDAMB231 and MDAMB468 cells using a combination of proteomic and metabonomic profiling techniques.

Results
Lovastatin inhibited proliferation of breast cancer cell lines. MDAMB231 cells were more sensitive to its effects, and in most cases lovastatin acid showed more potency towards the manipulation of protein expression than lovastatin lactone. Increased expression of Rho inhibitor GDI-2 stabilized the non-active Ras homolog gene family member A (RhoA) leading to a decreased expression of its active, membrane-bound form. Its downstream targets cofilin, CDC42 and G3BP1 are members of the GTPase family affected by lovastatin. Our data indicated that lovastatin modulated the E2F1-pathway through the regulation of expression of prohibitin and retinoblastoma (Rb). This subsequently leads to changes of E2F-downstream targets minichromosome maintenance protein 7 (MCM7) and MutS homolog 2 (MSH2). Lovastatin also regulated the AKT-signaling pathway. Increased phosphatase and tensin homolog (PTEN) and decreased DJ-1 expression lead to a down-regulation of the active pAkt. Lovastatin's involvement in the AKT-signaling pathway was confirmed by an upregulation of its downstream target, tumor progressor NDRG1. Metabolic consequences to lovastatin exposure included suppression of glycolytic and Krebs cycle activity, and lipid biosynthesis.

Conclusions
The combination of proteomics and metabonomics enabled us to identify several key targets essential to the antitumor activity of lovastatin. Our results imply that lovastatin has the potential to reduce the growth of breast cancer cells.
The Rate and Costs Attributable to Intravenous Patient-Controlled Analgesia Errors
Authors: Meissner Brian , Nelson Winnie , Hicks Rodney (Rod) , Sikirica Vanja , Gagne Josh , Schein Jeff 
Published: March 2010

Purpose To estimate the rates and costs of intravenous patient-controlled analgesia (IV PCA) errors from the hospital or integrated health system perspective. Methods This study used a cost-accounting methodology to estimate the costs attributable to IV PCA errors in the United States. Data for the study were obtained from the MEDMARX and Manufacturer and User Facility Device Experience (MAUDE) datasets, published literature, and expert opinions. MEDMARX is a voluntary, anonymous, medication-error-reporting database owned and operated by the United States Pharmacopeia. MAUDE is a mandatory, device-error-reporting database maintained by the US Food and Drug Administration. Levels of care rendered as a result of the IV PCA errors were estimated by applying clinical assumptions (validated by an expert advisory panel) to each of the 7 error consequences considered in this analysis. Variable and opportunity costs (2006 values) were considered, including medication, laboratory, lost revenue, and labor. The corresponding costs were applied to the error consequences to derive the estimated mean cost for each error cause. The numbers of errors documented in each dataset and the published literature were used to extrapolate the rate of IV PCA errors annually. Results The average cost per error event was $733 in the MEDMARX dataset and $552 in the MAUDE dataset. Harmful IV PCA errors were 120 to 250 times more costly than nonharmful errors. The annual error rates were estimated as 407 IV PCA-related errors and 17 device-related errors per 10,000 people within the United States. Conclusion: Analysis of 2 datasets, MEDMARX and MAUDE, revealed that IV PCA medication- and device-related errors are costly to hospitals and integrated health systems and represent a significant burden on the US health system. This study provided a novel approach to estimating the associated costs of undesired IV PCA-related events. Additional research is needed to validate the methodology (as applied to this area) and results.
Nortriptyline Cardiac Toxicity Resulting from a Probable Interaction with Telithromycin
Authors: Thomason Angela R. , Waldrop Bruce A. , Price Sherry O. 
Published: March 2010

ObjectiveTo report a case of probable nortriptyline toxicity associated with a combination of telithromycin and nortriptyline.Case SummaryA 50-year-old white woman was admitted to the hospital with new-onset palpitations after taking 5 days of telithromycin in combination with nortriptyline. On admission her electrocardiograph showed atrioventricular nodal reentry tachycardia. The patient was also hypotensive, with a blood pressure of 90/45 mm Hg. She had been taking nortriptyline 150 mg daily at bedtime for 10 years without complications. The final day of telithromycin therapy was completed, and nortriptyline was discontinued on admission. The tachycardia subsided with a dose of diltiazem.DiscussionIt is suspected that the cardiovascular symptoms observed in the patient are the result of nortriptyline toxicity caused by inhibition of CYP2D6 by telithromycin. Limited evidence shows that telithromycin may be an inhibitor of CYP2D6. An assessment of causation of the adverse effects using the Drug Interaction Probability Scale suggests a probable interaction between telithromycin and nortriptyline.ConclusionIt is recommended that clinicians remain aware of possible interactions between telithromycin and known CYP2D6 substrates such as nortriptyline. Should telithromycin therapy be required, close monitoring of the potential adverse effects and/or plasma drug levels of patients taking interacting drugs is warranted.
Rufinamide
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: March 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The May 2009 monograph topics are febuxostat, antithrombin (recombinant), calcitriol ointment, trabectedin, and tesamorelin. The class review is on drugs used in the therapy of benign prostatic hyperplasia, and the DUE is on febuxostat.
Reactivity of measurement in health psychology: How much of a problem is it? What can be done about it?
Authors: French David P. , Sutton Stephen 
Published: March 2010

Purpose. Measurement reactivity is defined as being present where measurement results in changes in the people being measured. The main aim of this review is to provide an overview of the current state of knowledge concerning the extent and nature of psychological measurement affecting people who complete the measures. Other aims are to describe how this may affect conclusions drawn in health psychology research and to outline where more research is needed.Methods. Narrative review.Results. Several studies, using a variety of methods, have found measurement procedures to alter subsequent cognition, emotion, and behaviour. In many instances, the effects obtained were of up to medium size. However, the extent to which such studies are representative is not clear: do other studies which find no reactive effects of measurement not exist or do they exist but are not reported?Conclusions. Although measurement reactivity can yield medium‐sized effects, our understanding of this phenomenon is still rudimentary. We do not know the precise circumstances that are likely to result in measurement reactivity: we cannot predict when problems are more likely to arise. There is a particular absence of studies of the mechanisms by which measurement reactivity arises. There is a need for a systematic review of this literature, which should aim to quantify the extent of measurement reactivity effects and to provide a firmer evidence base for theorizing about the sources of reactivity.