bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant
Authors: Ay Cihan , Jungbauer Lea V , Sailer Thomas , Tengler Theres , Koder Silvia , Kaider Alexandra , Panzer Simon , Quehenberger Peter , Pabinger Ingrid , Mannhalter Christine 
Published: May 2007

AbstractBackground: The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain.Methods: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age- and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event.Results: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) μg/L vs 36.8 (11.0) μg/L, P &lt;0.001. The unadjusted odds ratio (OR) for sP-selectin &gt;55.1 μg/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7–23.3; P &lt;0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1–31.2; P &lt;0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%). sP-selectin concentrations were lower in this subgroup than in noncarriers: 31.3 (7.9) μg/L vs 44.1 (14.1) μg/L; P &lt;0.001).Conclusions: Increased sP-selectin concentrations are associated with VTE and genotype status. sP-selectin concentrations are lower in individuals carrying the P-selectin Pro715 variant than in those without this variant.
Magnetic Control of an Electrochemical Microfluidic Device with an Arrayed Immunosensor for Simultaneous Multiple Immunoassays
Authors: Tang Dianping , Yuan Ruo , Chai Yaqin 
Published: May 2007

Abstract
Background: Methods based on magnetic bead probes have been developed for immunoassay, but most involve complicated labeling or stripping procedures and are unsuitable for routine use.
Methods: We synthesized magnet core/shell NiFe2O4/SiO2 nanoparticles and fabricated an electrochemical magnetic controlled microfluidic device for the detection of 4 tumor markers. The immunoassay system consisted of 5 working electrodes and an Ag/AgCl reference electrode integrated on a glass substrate. Each working electrode contained a different antibody immobilized on the NiFe2O4/SiO2 nanoparticle surface and was capable of measuring a specific tumor marker using noncompetitive electrochemical immunoassay.
Results: Under optimal conditions, the multiplex immunoassay enabled the simultaneous detection of 4 tumor markers. The sensor detection limit was &lt;0.5 μg/L (or &lt;0.5 kunits/L) for most analytes. Intra- and interassay imprecisions (CVs) were &lt;4.5% and 8.7% for analyte concentrations &gt;5 μg/L (or &gt;5 kunits/L), respectively. No nonspecific adsorption was observed during a series of procedures to detect target proteins, and electrochemical cross-talk (CV) between neighboring sites was &lt;10%.
Conclusion: This immunoassay system offers promise for label-free, rapid, simple, cost-effective analysis of biological samples. Importantly, the chip-based immunosensor could be suitable for use in the mass production of miniaturized lab-on-a-chip devices and open new opportunities for protein diagnostics and biosecurity.
High-Throughput Quantitative Profiling of Serum N-Glycome by MALDI-TOF Mass Spectrometry and N-Glycomic Fingerprint of Liver Fibrosis
Authors: Kam Richard KT , Poon Terence CW , Chan Henry LY , Wong Nathalie , Hui Alex Y , Sung Joseph JY 
Published: May 2007

AbstractBackground: The use of MALDI-TOF mass spectrometry (MS) in quantitative glycan profiling has not been reported. In this study, we attempted to establish a high-throughput quantitative assay for profiling serum N-glycome, and we applied the new assay to identifying serum N-glycans for diagnosis of liver fibrosis and cirrhosis.Methods: N-glycans from whole serum proteins in 2 μL serum were released by enzymatic digestion, cleaned up by hydrophilic chromatography, and subsequently quantitatively profiled with a linear MALDI-TOF MS system, which was originally designed for quantitative proteomic profiling. Serum N-glycome profiles from 46 patients with chronic hepatitis B infection and with different degrees of liver fibrosis were examined.Results: The intra- and interassay CVs of peak intensities of the standard N-glycans were &lt;8% and &lt;17%, respectively. When the assay was applied to the analysis of serum N-glycome profiles, 17 peaks were found to be potential biomarkers for detection of liver fibrosis/cirrhosis. Linear regression analysis revealed that 4 peaks of 1341.5, 1829.7, 1933.3, and 2130.3 m/z (all P &lt;0.005) had complementary value in detecting liver fibrosis and included them, but not any serological markers, in the diagnostic model. Leave-one-out cross-validation showed the diagnostic model could identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5), both at 85% accuracy.Conclusion: This is the first study to illustrate the quantitative aspect of MALDI-TOF MS in N-glycome profiling and the first study to reveal the potential value of the serum N-glycan profile for identifying liver fibrosis.
Multiplex Assay for Comprehensive Genotyping of Genes Involved in Drug Metabolism, Excretion, and Transport
Authors: Daly Thomas M , Dumaual Carmen M , Miao Xin , Farmen Mark W , Njau Reuben K , Fu Dong-Jing , Bauer Nancy L , Close Sandra , Watanabe Nancy , Bruckner Carsten , Hardenbol Paul , Hockett Richard D 
Published: May 2007

Abstract
Background: Drug metabolism is a multistep process by which the body disposes of xenobiotic agents such as therapeutic drugs. Genetic variation in the enzymes involved in this process can lead to variability in a patient’s response to medication.
Methods: We used molecular-inversion probe technology to develop a multiplex genotyping assay that can simultaneously test for 1227 genetic variants in 169 genes involved in drug metabolism, excretion, and transport. Within this larger set of variants, we performed analytical validation of a clinically defined core set of 165 variants in 27 genes to assess accuracy, imprecision, and dynamic range.
Results: In a test set of 91 samples, genotyping accuracy for the core set probes was 99.8% for called genotypes, with a 1.2% no-call (NC) rate. The majority of the core set probes (133 of 165) had ≤1 genotyping failure in the test set; a subset of 12 probes was responsible for the majority of failures (mainly NC). Genotyping results were reproducible upon repeat testing with overall within- and between-run variation of 1.1% and 1.4%, respectively—again, primarily NCs in a subset of probes. The assay showed stable genotyping results over a 6-fold range of input DNA.
Conclusions: This assay generates a comprehensive assessment of a patient’s metabolic genotype and is a tool that can provide a more thorough understanding of patient-to-patient variability in pharmacokinetic responses to drugs.
Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry
Authors: la Marca Giancarlo , Malvagia Sabrina , Pasquini Elisabetta , Innocenti Marzia , Donati Maria Alice , Zammarchi Enrico 
Published: May 2007

AbstractBackground: The expansion of newborn screening programs has increased the number of newborns diagnosed with inborn errors of metabolism in the presymptomatic phase, but it has also increased the number of costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we aimed to develop a rapid liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots.Methods: We studied newborn screening spots from 250 healthy controls; 124 from infants with abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed patients. Whole blood was eluted from a 3.2-mm dried blood spot by a CH3CN/H2O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray without derivatization. Total analysis time was 5 min per sample.Results: The assays were linear up to 3300 nmol/L for both metabolites. Intra- and interassay imprecision data were 3.6%–8% and 3.1%–6%, respectively, for MMA and 5.2%–20% and 3.6%–17% for 3OH-PA. Limit of detection and limit of quantitation were 1.95 and 4.2 μmol/L, respectively, for MMA and 8 and 10 μmol/L for 3OH-PA. The recoveries were 92.9%–106.1%. No deterioration was noted on the columns after 500 chromatographic runs. If the new method had been used as a 2nd-tier test for the 124 samples, only the 5 true positives would have been recalled for additional samples, and the positive predictive value would have been 100%.Conclusions: This method has the potential to markedly reduce false-positive results and the associated costs and anxiety. It may also be suitable for diagnosing and routinely monitoring blood spots for methylmalonic aciduria and propionic acidemia.
Increased Dentate Neurogenesis After Grafting of Glial Restricted Progenitors or Neural Stem Cells in the Aging Hippocampus
Authors: Hattiangady Bharathi , Shuai Bing , Cai Jingli , Coksaygan Turhan , Rao Mahendra S. , Shetty Ashok K. 
Published: May 2007

Abstract
Neurogenesis in the dentate gyrus (DG) declines severely by middle age, potentially because of age-related changes in the DG microenvironment. We hypothesize that providing fresh glial restricted progenitors (GRPs) or neural stem cells (NSCs) to the aging hippocampus via grafting enriches the DG microenvironment and thereby stimulates the production of new granule cells from endogenous NSCs. The GRPs isolated from the spinal cords of embryonic day 13.5 transgenic F344 rats expressing human alkaline phosphatase gene and NSCs isolated from embryonic day 9 caudal neural tubes of Sox-2:EGFP transgenic mice were expanded in vitro and grafted into the hippocampi of middle-aged (12 months old) F344 rats. Both types of grafts survived well, and grafted NSCs in addition migrated to all layers of the hippocampus. Phenotypic characterization revealed that both GRPs and NSCs differentiated predominantly into astrocytes and oligodendrocytic progenitors. Neuronal differentiation of graft-derived cells was mostly absent except in the dentate subgranular zone (SGZ), where some of the migrated NSCs but not GRPs differentiated into neurons. Analyses of the numbers of newly born neurons in the DG using 5′-bromodeoxyuridine and/or doublecortin assays, however, demonstrated considerably increased dentate neurogenesis in animals receiving grafts of GRPs or NSCs in comparison with both naïve controls and animals receiving sham-grafting surgery. Thus, both GRPs and NSCs survive well, differentiate predominantly into glia, and stimulate the endogenous NSCs in the SGZ to produce more new dentate granule cells following grafting into the aging hippocampus. Grafting of GRPs or NSCs therefore provides an attractive approach for improving neurogenesis in the aging hippocampus.
Disclosure of potential conflicts of interest is found at the end of this article.
Effects of HOXB4 Overexpression on Ex Vivo Expansion and Immortalization of Hematopoietic Cells from Different Species
Authors: Zhang Xiao-Bing , Schwartz Jeffrey L. , Humphries R. Keith , Kiem Hans-Peter 
Published: May 2007

Abstract
Overexpression of the human HOXB4 has been shown to induce the expansion and self-renewal of murine hematopoietic stem cells. In preparation for clinical studies, we wished to investigate the effects of HOXB4 on cells from other species, in particular preclinical large animals such as dogs and nonhuman primates. Thus, we transduced CD34+ cells from nonhuman primates, dogs, and humans with a HOXB4-expressing gammaretroviral vector and a yellow fluorescent protein-expressing control vector. Compared with the control vector, HOXB4 overexpression resulted in a much larger increase in colony-forming cells in dog cells (28-fold) compared with human peripheral blood, human cord blood, and baboon cells (two-, four-, and fivefold, respectively). Furthermore, we found that HOXB4 overexpression resulted in immortalization with sustained growth (&gt;12 months) of primitive hematopoietic cells from mice and dogs but not from monkeys and humans. This difference correlated with increased levels of retrovirally overexpressed HOXB4 in dog and mouse cells compared with human and nonhuman primate cells. The immortalized cells did not show any evidence of insertional mutagenesis or chromosomal abnormalities. Competitive congenic transplantation experiments showed that HOXB4-expanded mouse cells engrafted well after 1 or 3 months of expansion, and no leukemia was observed in mice. Our findings suggest that the growth promoting effects of HOXB4 are critically dependent on HOXB4 expression levels and that this can result in important species-specific differences in potency.
Disclosure of potential conflicts of interest is found at the end of this article.
Generation of Insulin-Producing Islet-Like Clusters from Human Embryonic Stem Cells
Authors: Jiang Jianjie , Au Melinda , Lu Kuanghui , Eshpeter Alana , Korbutt Gregory , Fisk Greg , Majumdar Anish S. 
Published: May 2007

Abstract
Recent success in pancreatic islet transplantation has energized the field to discover an alternative source of stem cells with differentiation potential to β cells. Generation of glucose-responsive, insulin-producing β cells from self-renewing, pluripotent human ESCs (hESCs) has immense potential for diabetes treatment. We report here the development of a novel serum-free protocol to generate insulin-producing islet-like clusters (ILCs) from hESCs grown under feeder-free conditions. In this 36-day protocol, hESCs were treated with sodium butyrate and activin A to generate definitive endoderm coexpressing CXCR4 and Sox17, and CXCR4 and Foxa2. The endoderm population was then converted into cellular aggregates and further differentiated to Pdx1-expressing pancreatic endoderm in the presence of epidermal growth factor, basic fibroblast growth factor, and noggin. Soon thereafter, expression of Ptf1a and Ngn3 was detected, indicative of further pancreatic differentiation. The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide. The temporal pattern of pancreas-specific gene expression in the hESC-derived ILCs showed considerable similarity to in vivo pancreas development, and the final population contained representatives of the ductal, exocrine, and endocrine pancreas. The hESC-derived ILCs contained 2%–8% human C-peptide-positive cells, as well as glucagon- and somatostatin-positive cells. Insulin content as high as 70 ng of insulin/μg of DNA was measured in the ILCs, representing levels higher than that of human fetal islets. In addition, the hESC-derived ILCs contained numerous secretory granules, as determined by electron microscopy, and secreted human C-peptide in a glucose-dependent manner.
Disclosure of potential conflicts of interest is found at the end of this article.
Directed Sibling Cord Blood Banking for Transplantation: The 10-Year Experience in the National Blood Service in England
Authors: Smythe Jon , Armitage Sue , McDonald Dorothy , Pamphilon Derwood , Guttridge Martin , Brown Juliette , Green Ann , Brown Colin , Warwick Ruth M. , Lankester Alan , Fehily Deirdre , Contreras Marcela , Navarrete Cristina , Watt Suzanne M. 
Published: May 2007

Abstract
Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation. Although UCB is often collected from unrelated donors, directed umbilical cord blood (DCB) from sibling donors also provides an important source of UCB for transplantation. This report summarizes the experience in collection, testing, storage, and transplantation of DCB units by the National Blood Service for England and North Wales over 10 years. Eligibility for collection was based on an existing sibling suffering from a disease that may be treated by stem cell transplantation or a family history that could result in the birth of a sibling with a disease that could be treated by stem cell transplantation. Collections were made on the provision that the sibling's clinician was willing to financially support the collection and to take responsibility for medical review of the mother and potential recipient. Given the high investment in UCB banking and the introduction of new regulations and mandatory licensing under the European Union Tissues and Cells Directive and those proposed in the U.S., this report details the procedures that we have used for DCB donations, the outcome data where donations have been used for transplantation, and it provides some timely recommendations for best practices.
Disclosure of potential conflicts of interest is found at the end of this article.
Rho Inhibition Induces Migration of Mesenchymal Stromal Cells
Authors: Jaganathan Bithiah Grace , Ruester Brigitte , Dressel Lars , Stein Stefan , Grez Manuel , Seifried Erhard , Henschler Reinhard 
Published: May 2007

AbstractAlthough mesenchymal stromal cells (MSCs) are being increasingly used as cell therapeutics in clinical trials, the mechanisms that regulate their chemotactic migration behavior are incompletely understood. We aimed to better define the ability of the GTPase regulator of cytoskeletal activation, Rho, to modulate migration induction in MSCs in a transwell chemotaxis assay. We found that culture-expanded MSCs migrate poorly toward exogenous phospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in transwell assays. Moreover, plasma-induced chemotactic migration of MSCs was even inhibited after pretreatment with LPA. LPA treatment activated intracellular Rho and increased actin stress fibers in resident MSCs. Very similar cytoskeletal changes were observed after microinjection of a cDNA encoding constitutively active RhoA (RhoAV14) in MSCs. In contrast, microinjection of cDNA encoding Rho inhibitor C3 transferase led to resolution of actin stress fibers, appearance of a looser actin meshwork, and increased numbers of cytoplasmic extensions in the MSCs. Surprisingly, in LPA-pretreated MSCs migrating toward plasma, simultaneous addition of Rho inhibitor C2I-C3 reversed LPA-induced migration suppression and led to improved migration. Moreover, addition of Rho inhibitor C2I-C3 resulted in an approximately 3- to 10-fold enhancement of chemotactic migration toward LPA, S1P, as well as platelet-derived growth factor or hepatocyte growth factor. Thus, inhibition of Rho induces rearrangement of actin cytoskeleton in MSCs and renders them susceptible to induction of migration by physiological stimuli.Disclosure of potential conflicts of interest is found at the end of this article.
An Expedient Variant of Heck Reaction of Alkenyl Nonaflates: Homogeneous Ligand‐Free Palladium Catalysis at Room Temperature
Authors: Vogel Michael A. K. , Stark Christian B. W. , Lyapkalo Ilya M. 
Published: May 2007

AbstractA mechanistic study on the ligand‐free room‐temperature Heck reaction of alkenyl nonafluorobutanesulfonates (nonaflates) is described. Kinetic data obtained from poisoning experiments, centrifugation and variation of catalyst loading consistently provide evidence for a homogeneous palladium catalysis unprecedented in Heck chemistry. The Heck reaction of alkenyl perfluorobutanesulfonates represents a remarkably robust, active and efficient catalytic system generally applicable to the coupling with a broad range of terminal olefins including non‐activated ones under ambient conditions. It features insensitivity towards atmospheric oxygen and moisture, furnishing uniformly high yields of the anticipated coupling products without the necessity to purify commercial reagents and solvents.
Mesocellular Foam‐Supported Catalysts: Enhanced Activity and Recyclability for Ring‐Closing Metathesis
Authors: Lim Jaehong , Lee Su Seong , Riduan Siti Nurhanna , Ying Jackie Y. 
Published: May 2007

AbstractAlthough ring‐closing metathesis (RCM) has been one of the most powerful methodologies for creating cyclic compounds, the pharmaceutical industry has not yet widely adopted this process commercially due to the high costs and leaching problems of homogeneous ruthenium catalysts. To circumvent these problems, we have immobilized the second‐generation Hoveyda–Grubbs catalyst effectively onto siliceous mesocellular foam (MCF). The open and interconnected pores of MCF facilitated ligand immobilization and substrate diffusion. We have observed that the ligand and metal loadings significantly affected the catalytic activity and recyclability. Enhanced recyclability by suppression of ruthenium leaching was achieved by using excess immobilized ligands. The resulting novel heterogenized catalysts demonstrated excellent activity and reusability for the RCM of various types of substrates.
Alkylation of Ammonium Salts Catalyzed by Imidazolium‐Based Ionic Liquid Catalysts
Authors: Zheng Zhuo Qun , Wang Jie , Wu Ting Hua , Zhou Xiao Ping 
Published: May 2007

AbstractQuaternary ammonium salts were synthesized from ammonium salts and dialkyl carbonates over imidazolium ionic liquid catalysts. The reaction gave almost stoichiometric amounts of the quaternary ammonium salts for halides and nitrates. It was found that the electron‐donating property of the alkyl moieties of ammonium cations, the electrophilic nature of the alkyl group of the carbonate, the acidity of the acid that the anion of the ammonium salt corresponds to, and the steric hindrance of the ammonium salts and the dialkyl carbonates are the key factors that influence the yields of quaternary ammonium salts. Strong electron‐donating alkyl groups on the nitrogen atom of the ammonium salt, electron‐withdrawing groups on the methylene carbon of dialkyl carbonate, and weaker steric hindrance of the starting ammonium salts and dialkyl carbonates favor the alkylation reaction of ammonium salts.
Development of Efficient and Reusable Diarylphosphinopolystyrene‐Supported Palladium Catalysts for CC Bond Forming Cross‐Coupling Reactions
Authors: Schweizer Stéphane , Becht Jean‐Michel , Le Drian Claude 
Published: May 2007

AbstractShort and versatile syntheses of reusable diarylphosphinopolystyrene‐supported palladium catalysts 3a–j are described. The bis(o‐tolyl)phosphino catalyst 3b is particularly efficient for the Suzuki and Sonogashira cross‐couplings, whereas the bis(m‐tolyl)phosphino catalyst 3c is the most active catalyst for Heck reactions. The couplings are performed under non‐anhydrous reaction conditions and require only low amounts of supported palladium (0.5 mequivs. for Suzuki–Miyaura, 1.0 mequiv. for Sonogashira and 0.5 mequivs. for Heck reactions could be sufficient). Catalysts 3a–j are recovered by filtration and can be reused more than four times with no loss of efficiency.