Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE). Previous ...studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mouse models of cancer are essential in furthering our understanding both of the mechanisms that drive tumor development and the immune response that develops in parallel, and also in providing a ...platform for testing novel anti-cancer therapies. The majority of solid tumor models available rely on the injection of existing cancer cell lines into naïve hosts which, while providing quick and reproducible model systems, typically lack the development of a tumor microenvironment that recapitulates those seen in human cancers. Administration of the carcinogen 3-methylcholanthrene (MCA), allows tumors to develop in situ, forming a tumor microenvironment with an established stroma and vasculature. This article provides a detailed set of protocols for the administration of MCA into mice and the subsequent monitoring of tumors. Protocols are also provided for some of the routinely used downstream applications that can be used for MCA tumors.
Five-axis machine tools, consisting of three translational axes and two rotary axes, are increasingly being used for complex surface machining. This paper proposes a new sensitivity analysis method ...to elucidate the relationship between the tool trajectory error and the error motions of the feed axes. Based on the free-curve trajectory during simultaneous five-axis machining, a surface coordinate system is created for each tool center point, to define the tool trajectory and the trajectory errors. Then, a novel sensitivity coefficient is defined to investigate the relationship between the trajectory error and the error motions. It is shown that the proposed sensitivity analysis method can successfully determine whether the trajectory is sensitive to the error motions, based on sensitivity analyses performed during conic frustum machining and S-shaped machining tests. Moreover, the sensitivity analysis method can also predict the effects of the error motion source, such as the reversal errors. In the future, we intend to study other types of machining processes, such as ball-end milling, as well.
•A novel sensitivity analysis method is proposed.•The Proposed method can analyze the influence of error motions of each feed axis.•The proposed method can help the users of five-axis machining tools.
To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with ...rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI.
A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated.
Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively.
US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.
CA125, a coelomic epithelium-related antigen, is expressed in both normal and pathological conditions. In this study, we compared the glycosylation of CA125 antigen from amniotic fluid and the ...ovarian carcinoma cell line OVCAR-3, in order to detect possible differences as a specific marker of their origin. Antigens from both sources were radiolabelled and subsequently subjected to the affinity chromatography, using plant lectins differing in carbohydrate specificity as ligands. A common chromatographic scheme was applied to all columns, i.e. they were eluted with: a) washing buffer to wash out non-bound and low-affinity bound fractions, b) a solution of inhibitory sugar and c) a low pH buffer, to release the high affinity bound fractions. CA125 antigen from each source was found to be heterogeneous in respect to the existence of multiple glycoforms, with O-linked glycan chains predominating. However, the binding patterns of both N- and O-linked glycan-reactive lectins indicated distinct differences in carbohydrate composition between CA125 antigen isolated from amniotic fluid and OVCAR-3 cell line. The observed specificites of CA125-oligosaccharide chains might be of special importance from the biomedical aspect, in terms of their possible use for clinical evaluation of gynecological functions in health and disease.
Dengue virus cocirculates globally as four serotypes (DENV1 to -4) that vary up to 40% at the amino acid level. Viral strains within a serotype further cluster into multiple genotypes. Eliciting a ...protective tetravalent neutralizing antibody response is a major goal of vaccine design, and efforts to characterize epitopes targeted by polyclonal mixtures of antibodies are ongoing. Previously, we identified two E protein residues (126 and 157) that defined the serotype-specific antibody response to DENV1 genotype 4 strain West Pac-74. DENV1 and DENV2 human vaccine sera neutralized DENV1 viruses incorporating these substitutions equivalently. In this study, we explored the contribution of these residues to the neutralization of DENV1 strains representing distinct genotypes. While neutralization of the genotype 1 strain TVP2130 was similarly impacted by mutation at E residues 126 and 157, mutation of these residues in the genotype 2 strain 16007 did not markedly change neutralization sensitivity, indicating the existence of additional DENV1 type-specific antibody targets. The accessibility of antibody epitopes can be strongly influenced by the conformational dynamics of virions and modified allosterically by amino acid variation. We found that changes at E domain II residue 204, shown previously to impact access to a poorly accessible E domain III epitope, impacted sensitivity of DENV1 16007 to neutralization by vaccine immune sera. Our data identify a role for minor sequence variation in changes to the antigenic structure that impacts antibody recognition by polyclonal immune sera. Understanding how the many structures sampled by flaviviruses influence antibody recognition will inform the design and evaluation of DENV immunogens.
Dengue virus (DENV) is an important human pathogen that cocirculates globally as four serotypes. Because sequential infection by different DENV serotypes is associated with more severe disease, eliciting a protective neutralizing antibody response against all four serotypes is a major goal of vaccine efforts. Here, we report that neutralization of DENV serotype 1 by polyclonal antibody is impacted by minor sequence variation among virus strains. Our data suggest that mechanisms that control neutralization sensitivity extend beyond variation within antibody epitopes but also include the influence of single amino acids on the ensemble of structural states sampled by structurally dynamic virions. A more detailed understanding of the antibody targets of DENV-specific polyclonal sera and factors that govern their access to antibody has important implications for flavivirus antigen design and evaluation.
CA125 antigen is a high molecular mass, structurally heterogeneous, mucin-type molecule expressed during embryonic development as well as in adult human tissues. This study was aimed at investigating ...its mucin-related property of ferning, as a general complementary way of characterization. Pregnancy-associated CA125 antigen (pCA125) was examined using light, transmission and scanning electron microscopy and compared with cancer-derived CA125 antigen (cCA125). The results obtained for spread-out, air-dried pCA125 and cCA125 samples revealed clear differences in the patterns of crystalline as well as amorphous material. Thus, the fern-like crystals were mainly sparsely distributed and their morphology was atypical. The extent of crystallization of pCA125 was moderately lower than that of cCA125 antigen, whereas variation in the size and spatial organization of fern crystals was evident. Besides the material with a crystalline appearance, differences in the organic substrate were also noticeable. In contrast to the sponge-like appearance of pCA125, cCA125 had a more compact structure. These initial data may be relevant for relating biochemical properties of CA125 antigen with its morphology as a basis for elucidating its still obscure function under different physiological conditions.
To examine possible associations between dietary factors and gastric cancer risk among residents in the area of Nis, Serbia.
This hospital based case-control study was conducted at the Clinical ...Centre Nis between 2005 and 2006. Cases (n=102) with histologically confirmed gastric cancer and matched non-cancer patients (controls, n=204) were interviewed. Diet was assessed using a food frequency questionnaire and odds ratios (OR), 95% confidence interval (95% CI), and p-trends were calculated across tertiles of intake.
High intake of salt, salty meals and hot food were associated with higher risk of gastric cancer. After searching for potential confounders, multivariate logistic regression analysis showed elevated risk for the highest vs. the lowest tertile of intake for smoked and barbecue meat (OR 4.21; 95% CI 1.43-12.37), processed meat (OR 9.17; 95% CI 2.78-15.23), desert (OR 2.85; 95% CI 1.28-6.38), potatoes (OR 4.79; 95% CI 1.44-5.94), pickled vegetables (OR 2.02; 95% CI 1.21-3.0) and milk (OR 5.08; 95% CI 1.59-10.16) intake but reduced for citrus fruits (OR= 0.13, 95% CI 0.03- 0.53), other fruits (OR 0.05; 95% CI 0.02-0.18), allium vegetables (e.g. onion, garlic, leek) (OR 0.11; 95% CI 0.02-0.60) and cooked meat intake (OR 0.07; 95% CI 0.02-0.27). Intake of bread, dairy, fish, legumes and raw and cooked vegetables was not significantly related with gastric cancer risk.
A low risk diet for gastric cancer in the area of Nis should include increased fruits and alliums vegetables consumption and limited processed meat, salt, preserved food, deserts, potatoes and milk intake.
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