bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of tissue‐specific autoantigens in the hematopoietic cells leads to activation‐induced cell death of autoreactive T cells in the secondary lymphoid organs
Authors: Zheng Xincheng , Yin Lijie , Liu Yang , Zheng Pan 
Published: September 2004

AbstractMany tissue‐specific antigens are expressed in specialized cells called peripheral antigen‐expressing cells (PAE) in the thymus and can induce central tolerance. While thymic medullary epithelial cells are the prototypic PAE that express peripheral antigens via an aire‐dependent mechanism, some studies also describe bone marrow (BM)‐derived dendritic cells (DC) and macrophages as PAE in both the thymus and secondary lymphoid organs. However, the role of these cells in development of tolerance to tissue‐specific antigens has not been elucidated. Here we use BM radiation chimeric mice to study the existence of hematopoietic PAE and their contribution to tolerance to tissue‐specific antigens. Our results reveal that BM‐derived PAE exist in both central and secondary lymphoid organs and that the expression of peripheral antigens in the BM‐derived cells does not correlate with aire expression. Using double‐transgenic mice expressing TCR specific for a model antigen expressed under the control of a prostate‐specific promoter, we show that expression of self antigen in PAE of non‐hematopoietic origin is both necessary and sufficient to induce clonal deletion. Surprisingly, while BM‐derived PAE fail to induce clonal deletion, they do cause the activation‐induced cell death of autoreactive cells in the secondary lymphoid organs. Thus, BM‐derived PAE have a distinct function in the maintenance of tolerance to tissue‐specific antigens.
Cross‐reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H
Authors: Elkington Rebecca , Shoukry Naglaa H. , Walker Susan , Crough Tania , Fazou Chrysa , Kaur Amitinder , Walker Christopher M. , Khanna Rajiv 
Published: September 2004

AbstractAlthough the importance of CD4+ T cell responses to human cytomegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4+ CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA‐DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HCMV isolates revealed that the gB and gH epitope sequences recognized by human CD4+ T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4+ CTL. More importantly, we show that gB‐specific T cells from humans can also efficiently lyse peptide‐sensitized Patr‐DR7+ cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class II lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.
High levels of neutralizing IL‐6 autoantibodies in 0.1% of apparently healthy blood donors
Authors: Galle Pia , Svenson Morten , Bendtzen Klaus , Hansen Morten B. 
Published: September 2004

AbstractIL‐6‐specific autoantibodies (aAb‐IL‐6) have been reported in diseased and healthy individuals. We recently established a model for aAb‐IL‐6 in different mouse strains, based on vaccination with immunogenic IL‐6 analogues, in which titers of aAb‐IL‐6 above 1,000 resulted in an in vivo IL‐6 deficiency. Here, we examined aAb‐IL‐6 in 4,230 blood donors. Stable low titers of aAb‐IL‐6 were found in 9% of the donors, while 1% had titers ranging from 64 to greater than 10,000. Such aAb‐IL‐6‐positive donors appeared normal with no overt signs of pathology. Natural and recombinant forms of IL‐6 bound avidly to their IgG, and their plasma strongly neutralized IL‐6 in vitro. Slightly elevated concentrations of IL‐6 exclusively in the form of IL‐6‐IgG complexes were present in their circulation. The complexes did not contain soluble IL‐6 receptors. Titers of 0.1% of the blood donors were as positive as the vaccination‐induced IL‐6‐deficient mice. Such donors might be IL‐6 deficient, and if so, IL‐6 seems be dispensable for several months in otherwise healthy individuals. Such highly positive donors also explain why normal human IgG for pharmaceutical use may contain high anti‐IL‐6 activity. Finally, transfusion of plasma with a high titer of aAb‐IL‐6 might, temporally, render a recipient IL‐6 deficient.
The corticosteroid‐induced inhibitory effect on NK cell function reflects down‐regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity
Authors: Vitale Chiara , Chiossone Laura , Cantoni Claudia , Morreale Giuseppe , Cottalasso Francesca , Moretti Sara , Pistorio Angela , Haupt Riccardo , Lanino Edoardo , Dini Giorgio , Moretta Lorenzo , Mingari Maria Cristina 
Published: September 2004

AbstractCorticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft‐versus‐host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5 days of culture in IL‐2. Such cultured NK cells also failed to express the IL‐2‐inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected.
Catalytic Adsorptive Stripping Voltammetry of Molybdenum: Redox Kinetic Measurements
Authors: Quentel François , Mirčeski Valentin 
Published: September 2004

AbstractThe electrode mechanism of Mo(VI) reduction was studied under catalytic adsorptive stripping mode by means of square‐wave voltammetry (SWV). Mo(VI) creates a stable surface active complex with mandelic acid. The electrode reaction of Mo(VI)‐mandelic acid system undergoes as one‐electron reduction, exhibiting properties of a surface electrode process. In the presence of chlorate, bromate, and hydrogen peroxide, the electrode reaction is transposed into a catalytic mechanism. The experimental results are compared with the recent theory for surface catalytic reaction, enabling qualitative characterization of the electrode mechanism in the presence of different catalytic agents. Utilizing both the method of “split SW peaks” and “quasireversible maximum” the standard redox rate constant of Mo(VI)‐mandelic acid system was estimates as ks=150±5 s−1. By fitting the experimental and theoretical results, the following catalytic rate constants have been estimated: (8.0±0.5)×104 mol−1 dm3 s−1, (1.0±0.1)×105 mol−1 dm3 s−1, and (3.2±0.1)×106 mol−1 dm3 s−1, for hydrogen peroxide, chlorate, and bromate, respectively.
A Selective Voltammetric Method for Uric Acid Detection at a Glassy Carbon Electrode Modified with Electrodeposited Film Containing DNA and Pt‐Fe(III) Nanocomposites
Authors: Wang Shuqing , Lu Liping , Lin Xiangqin 
Published: September 2004

AbstractA novel biosensor by electrochemical codeposited Pt‐Fe(III) nanocomposites and DNA film was constructed and applied to the detection of uric acid (UA) in the presence of high concentration of ascorbic acid (AA). Based on its strong catalytic activity toward the oxidation of UA and AA, the modified electrode resolved the overlapping voltammetric response of UA and AA into two well‐defined peaks with a large anodic peak difference (ΔEpa) of about 380mV. The catalytic peak current obtained from differential pulse voltammetry (DPV) was linearly dependent on the UA concentration from 3.8×10−6 to 1.6×10−4 M (r=0.9967) with coexistence of 5.0×10−4 M AA. The detection limit was 1.8×10−6 M (S/N=3) and the presence of 20 times higher concentration of AA did not interfere with the determination. The modified electrode shows good sensitivity, selectivity and stability.
Adsorptive Stripping Voltammetry of Rifamycins at Unmodified and Surfactant‐Modified Carbon Paste Electrodes
Authors: Gutiérrez‐Fernández Sonia , Blanco‐López M. C. , Lobo‐Castañón M. Jesús , Miranda‐Ordieres Arturo J. , Tuñón‐Blanco Paulino 
Published: September 2004

AbstractThe electrochemical behavior of the antibiotics rifampicin and rifamycin SV is investigated by cyclic voltammetry at carbon paste and in situ surfactant modified carbon paste electrodes. Both antibiotics adsorb on the unmodified electrodes and show a reversible redox process due to the oxidation of the 6,9‐dihydroxynaphthalene moiety to the corresponding naphthoquinone. This process is used as analytical signal for developing adsorptive voltammetric methods for the determination of the antibiotics. Experimental parameters, such as pH of the supporting electrolyte, accumulation potential and time are optimized. After accumulation from acidic solutions (0.1 M KCl pH 2 or HCl 0.2 M) at −0.1 or 0 V for 3 min, the differential pulse oxidation peak current changes linearly with the antibiotic concentration in the range 3.5×10−10 M −5.4×10−9 M or 5×10−11 M −1.0×10−9 M for rifampicin and rifamycin SV, respectively. Rifamycin SV is not accumulated on carbon paste electrodes modified in situ with the anionic surfactant sodium dodecyl sulfate, whereas rifampicin is readily accumulated on this modified electrodes resulting in a signal enhancement and allowing rifampicin determinations without interference from rifamycin SV. On the other hand, selective determination of rifamycin SV in the presence of rifampicin is achieved by using carbon paste electrodes in situ modified with the cationic surfactant cetyltrimethylammonium chloride.
Speciation of Arsenic by Potentiometric Stripping Analysis Using Gold(III) Solution as Chemical Reoxidant and a Wall‐Jet Flow Cell
Authors: Muñoz Emma , Palmero Susana 
Published: September 2004

AbstractA simple procedure is described for the potentiometric stripping of arsenic with a wall‐jet cell by means of potentiostatic co‐deposition of gold and arsenic at a glassy‐carbon electrode and subsequent chemical stripping with Au(III). Optimum medium containing 160 mg L−1 of Au(III) in HCl 0.1 M, where it is possible to speciate As(III) and As(V). As(V) was electrodeposited directly without prior chemical reduction at working electrode. As(III) was first determined at an electrodeposition potential of −0.1 V. Afterwards, total arsenic was determined by an electrodeposition potential of −0.7 V, from the area of peak obtained of the differential stripping potentiogram by using the standard addition method. The original As(V) concentration in the sample was calculated by difference. The possibilities of the optimized method were demonstrated by determinations of As(III), As(V) and total arsenic in samples of polluted water.
Comparison of prospective and retrospective methods for haplotype inference in case‐control studies
Authors: Satten Glen A. , Epstein Michael P. 
Published: September 2004

AbstractWe compare bias and power of three methods for haplotype inference on disease risk using unphased genotype data from a case‐control study. We examine the prospective score test of Schaid et al. ([2002] Am. J. Hum. Genet 70:425–434), a novel modification of the prospective estimating equations of Zhao et al. ([2003] Am. J. Hum. Genet. 72:1231–1250) and the retrospective likelihood of Epstein and Satten ([2003] Am. J. Hum. Genet. 73:1316–1329). We find that all three approaches are roughly comparable when the haplotype effect on disease odds follows a multiplicative model. However, for dominant and recessive models of haplotype effect, the retrospective‐likelihood method has increased efficiency with respect to the prospective methods. As all three methods assume haplotype frequencies are in Hardy‐Weinberg Equilibrium (HWE), we compare the robustness of each procedure to departures from HWE. We find the prospective methods are robust to departure from HWE, while the retrospective‐likelihood method is biased for dominant and recessive models of haplotype effect. To remedy this limitation of the retrospective‐likelihood method, we propose a modification that allows for a non‐negative fixation index (common to all haplotype pairs) and show it dramatically reduces the bias of the retrospective likelihood when HWE is violated. Published 2004 Wiley‐Liss, Inc.
Algorithms for inferring haplotypes
Authors: Niu Tianhua 
Published: September 2004

AbstractHaplotype phase information in diploid organisms provides valuable information on human evolutionary history and may lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to human diseases. Molecular haplotyping methods are labor‐intensive, low‐throughput, and very costly. Therefore, algorithms based on formal statistical theories were shown to be very effective and cost‐efficient for haplotype reconstruction. This review covers 1) population‐based haplotype inference methods: Clark's algorithm, expectation‐maximization (EM) algorithm, coalescence‐based algorithms (pseudo‐Gibbs sampler and perfect/imperfect phylogeny), and partition‐ligation algorithm implemented by a fully Bayesian model (Haplotyper) or by EM (PLEM); 2) family‐based haplotype inference methods; 3) the handling of genotype scoring uncertainties (i.e., genotyping errors and raw two‐dimensional genotype scatterplots) in inferring haplotypes; and 4) haplotype inference methods for pooled DNA samples. The advantages and limitations of each algorithm are discussed. By using simulations based on empirical data on the G6PD gene and TNFRSF5 gene, I demonstrate that different algorithms have different degrees of sensitivity to various extents of population diversities and genotyping error rates. Future development of statistical algorithms for addressing haplotype reconstruction will resort more and more to ideas based on combinatorial mathematics, graphical models, and machine learning, and they will have profound impacts on population genetics and genetic epidemiology with the advent of the human HapMap. © 2004 Wiley‐Liss, Inc.
The role of haplotypes in candidate gene studies
Authors: Clark Andrew G. 
Published: September 2004

AbstractHuman geneticists working on systems for which it is possible to make a strong case for a set of candidate genes face the problem of whether it is necessary to consider the variation in those genes as phased haplotypes, or whether the one‐SNP‐at‐a‐time approach might perform as well. There are three reasons why the phased haplotype route should be an improvement. First, the protein products of the candidate genes occur in polypeptide chains whose folding and other properties may depend on particular combinations of amino acids. Second, population genetic principles show us that variation in populations is inherently structured into haplotypes. Third, the statistical power of association tests with phased data is likely to be improved because of the reduction in dimension. However, in reality it takes a great deal of extra work to obtain valid haplotype phase information, and inferred phase information may simply compound the errors. In addition, if the causal connection between SNPs and a phenotype is truly driven by just a single SNP, then the haplotype‐based approach may perform worse than the one‐SNP‐at‐a‐time approach. Here we examine some of the factors that affect haplotype patterns in genes, how haplotypes may be inferred, and how haplotypes have been useful in the context of testing association between candidate genes and complex traits. © 2004 Wiley‐Liss, Inc.
Tag SNP selection for association studies
Authors: Stram Daniel O. 
Published: September 2004

AbstractThis report describes current methods for selection of informative single nucleotide polymorphisms (SNPs) using data from a dense network of SNPs that have been genotyped in a relatively small panel of subjects. We discuss the following issues: (1) Optimal selection of SNPs based upon maximizing either the predictability of unmeasured SNPs or the predictability of SNP haplotypes as selection criteria. (2) The dependence of the performance of tag SNP selection methods upon the density of SNP markers genotyped for the purpose of haplotype discovery and tag SNP selection. (3) The likely power of case‐control studies to detect the influence upon disease risk of common disease‐causing variants in candidate genes in a haplotype‐based analysis. We propose a quasi‐empirical approach towards evaluating the power of large studies with this calculation based upon the SNP genotype and haplotype frequencies estimated in a haplotype discovery panel. In this calculation, each common SNP in turn is treated as a potential unmeasured causal variant and subjected to a correlation analysis using the remaining SNPs. We use a small portion of the HapMap ENCODE data (488 common SNPs genotyped over approximately a 500 kb region of chromosome 2) as an illustrative example of this approach towards power evaluation. © 2004 Wiley‐Liss, Inc.
The influence of novel bioactive glasses on in vitro osteoblast behavior
Authors: Foppiano Silvia , Marshall Sally J. , Marshall Grayson W. , Saiz Eduardo , Tomsia Antoni P. 
Published: September 2004

AbstractImplant success requires a direct bond between bone and implant surface. Bioinert implants, such as titanium alloys, are commonly plasma‐spray–coated with a bone‐bonding, bioactive material such as hydroxyapatite. Such coatings tend to be chemically and topographically inhomogeneous without reproducible properties. A family of bioactive glasses that can be enameled and reliably adheres to titanium alloy has been developed. In this study the cytocompatibility of two of these glass compositions was tested in the as‐cast condition. The effects of these glasses on the early and late events of osseous tissue formation in vitro were determined with MC3T3‐E1.4 mouse osteoblast‐like cells. MC3T3‐E1.4 cells were cultured on glasses containing 55 and 50 wt % SiO2, with titanium alloy (Ti6Al4V) and tissue culture polystyrene as controls. Cellular adhesion and proliferation, and alkaline phosphatase activity were studied over 5 to 15 days in culture. Qualitative and quantitative assays of mineralization were conducted. The osteoblast‐like cells showed increased proliferation when grown on a bioactive glass containing 50 wt % silica. However, the adhesion, differentiation and mineralization behavior were similar on both glass compositions used in this study. These bioactive glasses proved to be cytocompatible substrata for osteoblast‐like cell culture, and yielded higher cellular proliferation than titanium alloy. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 242–249, 2004
Efficacy and cytotoxicity of cationic‐agent–mediated nonviral gene transfer into osteoblasts
Authors: Kim Soo‐Woo , Ogawa Takahiro , Tabata Yasuhiko , Nishimura Ichiro 
Published: September 2004

AbstractEx vivo gene transfer into osteoblastic cells is an advantageous strategy for bone tissue engineering. This study investigated the efficacy and cytotoxicity of in vitro cationic‐agent–mediated nonviral gene transfer into osteoblasts. Various cationic agents, lipid, gelatin, and polyethylenimine (PEI) were tested. Each was formulated in various concentrations to form a complex with plasmid DNA encoding red fluorescent protein. The cationic agent/DNA complexes were transfected into human fetal osteoblastic cell line and rat bone‐marrow–derived primary osteoblasts, as well as NIH 3T3 fibroblast controls. Rat primary osteoblasts were transfected more with cationic lipid and PEI agents than with gelatin carrier, yielding transfection efficacy up to 18.1% and 12.7 %, respectively. In contrast, human fetal osteoblastic cell line was transfected more with cationic lipid and gelatin than with PEI. There was a positive correlation between the lipid and PEI doses and cytotoxicity. When the lipid and PEI were used to transfect the rat primary osteoblasts in a dose that yielded the highest transfection efficacy, cell survival rates decreased as low as 40%. When their transfection efficacies into primary osteoblasts were compromised at two thirds of the highest value, that is, 12.6% and 8.3% for the lipid and PEI, respectively, the cell survival rate was nearly 80%. Cationic gelatin was associated with cell survival rates over 60 % in any cell type, regardless of the doses tested. These results suggest that different types of osteoblastic cells may possess different ability to the uptake and expression of cationic‐agent–bound DNA. There seemed to be agent‐specific threshold doses that dropped the cell survival rate. Cationic‐agent–mediated nonviral gene transfer into osteoblastic cells may be successful when the agent‐ and dose‐dependent transfection efficacy and cytotoxicity are optimized. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 308–315, 2004
Biodegradability and cell‐mediated contraction of porous collagen scaffolds: The effect of lysine as a novel crosslinking bridge
Authors: Ma Lie , Gao Changyou , Mao Zhengwei , Zhou Jie , Shen Jiacong 
Published: September 2004

AbstractA novel crosslinking method was adopted to modify the porous collagen scaffolds by using a water‐soluble carbodiimide, 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide (EDAC) and N‐hydroxysuccinimide (NHS) in the presence of lysine, which functions as a crosslinking bridge. In vitro biodegradation tests proved that in the presence of lysine the biostability of the EDAC crosslinked scaffolds was greatly enhanced. The biostability of the resultant scaffolds was also elucidated as a function of the concentrations of lysine and EDAC/NHS. Compared to the Col‐DHT, the ability of the Col‐EDAC and the Col/Lys to resist cell‐mediated contraction (CMC) was greatly enhanced. Yet no obvious difference between the Col‐EDAC and the Col/Lys was found with respect to CMC. SEM observations showed that the microstructure of the crosslinked scaffolds could be largely preserved after fibroblast seeding. As a result, MTT assays proved that the fibroblasts in the Col/Lys scaffolds proliferated faster compared to the DHT‐treated one on the assumption that the cell viability was preserved to a similar level. Histological section results indicated that the Col/Lys scaffolds had the ability to accelerate the cell infiltration and proliferation. All these results demonstrated that this novel crosslinking method is an effective way to achieve a collagen scaffold with improved biostability and a more stable structure, which can resist cell‐mediated contraction. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 334–342, 2004