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排序方式: 共有75条查询结果,搜索用时 15 毫秒
61.
Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen 总被引:10,自引:0,他引:10
A J Dessein M Begley C Demeure D Caillol J Fueri M G dos Reis Z A Andrade A Prata J C Bina 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(8):2727-2736
The aim of this work was to determine whether human resistance to Schistosoma mansoni was associated with increased antibody reactivity to certain larval surface Ag. To this end, young residents of a hyperendemic area were selected for their low or high susceptibility to reinfection after parasitologic cure, and the reactivity of their sera to individual larval surface Ag was determined at different times before and after treatment. The data showed that six Ag: 202, 165, 90 to 92, 85, 72, and 37 kDa are the principal targets on the larva of IgG in the sera of resistant subjects. The comparative study, by immunoblotting and ELISA on purified Ag, of the sera from high and low susceptibility subjects indicates that IgG reactivity toward the 37-kDa Ag may be associated with resistance. This work and ongoing vaccination trials carried out in mice suggest that the 37-kDa Ag may have vaccinating potentials. 相似文献
62.
The taste of polycose in hamsters 总被引:2,自引:2,他引:0
Hamsters show a preference for Polycose, a mixture of starch-derived
glucose polymers, that is as strong as their preference for sucrose.
However, in the hamster, taste aversions to Polycose may be less easily
acquired than taste aversions to sucrose and the qualitative aspects of
Polycose are unknown in this species. In order to examine the taste of
Polycose in the hamster, we utilized a taste-aversion protocol with two
conditioning trials. Animals were trained to avoid one of three different
conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM
sucrose with 100 mM Polycose. Control animals were conditioned with
deionized water. After the second conditioning trial, generalization
testing began for the three conditioning stimuli plus 3 mM citric acid, 300
mM KCI and 30 mM NaCl. The results showed that aversions to Polycose,
sucrose or the Polycose/sucrose mixture cross- generalized, demonstrating
that Polycose and sucrose share a common taste percept in the hamster. None
of the aversions generalized to NaCl, citric acid or KCI. In addition,
comparisons among the patterns of taste generalizations indicated that the
tastes of Polycose and sucrose also had distinct qualitative components.
Finally, although the taste of 100 mM Polycose was more salient than the
taste of 50 mM sucrose, the taste of sucrose could still be detected in a
mixture with Polycose.
相似文献
63.
Avice MN Sarfati M Triebel F Delespesse G Demeure CE 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(5):2748-2753
Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand structurally and genetically related to CD4. Although its expression is restricted to activated T cells and NK cells, the functions of LAG-3 remain to be elucidated. Here, we report on the expression and function of LAG-3 on proinflammatory bystander T cells that are activated in the absence of TCR engagement. LAG-3 is expressed at high levels on human T cells cocultured with autologous monocytes and IL-2 and synergizes with the low levels of CD40 ligand (CD40L) expressed on these cells to trigger TNF-alpha and IL-12 production by monocytes. Indeed, anti-LAG-3 mAb inhibits both IL-12 and IFN-gamma production in IL-2-stimulated cocultures of T cells and autologous monocytes. Soluble LAG-3Ig fusion protein markedly enhances IL-12 production by monocytes stimulated with infra-optimal concentrations of sCD40L, whereas it directly stimulates monocyte-derived dendritic cells (DC) for the production of TNF-alpha and IL-12, unravelling an enhanced responsiveness to MHC class II engagemenent in DC as compared with activated monocytes. Thus similar to CD40L, LAG-3 may be involved in the proinflammatory activity of cytokine-activated bystander T cells and most importantly it may directly activate DC. 相似文献
64.
65.
Behnam Abasht Frédérique Pitel Sandrine Lagarrigue Elisabeth Le Bihan-Duval Pascale Le Roy Olivier Demeure Florence Vignoles Jean Simon Larry Cogburn Sammy Aggrey Alain Vignal Madeleine Douaire 《遗传、选种与进化》2006,38(3):297-311
Quantitative trait loci (QTL) affecting fatness in male chickens were previously identified on chromosome 5 (GGA5) in a three-generation design derived from two experimental chicken lines divergently selected for abdominal fat weight. A new design, established from the same pure lines, produced 407 F2 progenies (males and females) from 4 F1-sire families. Body weight and abdominal fat were measured on the F2 at 9 wk of age. In each sire family, selective genotyping was carried out for 48 extreme individuals for abdominal fat using seven microsatellite markers from GGA5. QTL analyses confirmed the presence of QTL for fatness on GGA5 and identified a QTL by sex interaction. By crossing one F1 sire heterozygous at the QTL with lean line dams, three recombinant backcross 1 (BC1) males were produced and their QTL genotypes were assessed in backcross 2 (BC2) progenies. These results confirmed the QTL by sex interaction identified in the F2 generation and they allow mapping of the female QTL to less than 8 Mb at the distal part of the GGA5. They also indicate that fat QTL alleles were segregating in both fat and lean lines. 相似文献
66.
Bayesian adaptive sequence alignment algorithms 总被引:2,自引:1,他引:2
The selection of a scoring matrix and gap penalty parameters continues to
be an important problem in sequence alignment. We describe here an
algorithm, the 'Bayes block aligner, which bypasses this requirement.
Instead of requiring a fixed set of parameter settings, this algorithm
returns the Bayesian posterior probability for the number of gaps and for
the scoring matrices in any series of interest. Furthermore, instead of
returning the single best alignment for the chosen parameter settings, this
algorithm returns the posterior distribution of all alignments considering
the full range of gapping and scoring matrices selected, weighing each in
proportion to its probability based on the data. We compared the Bayes
aligner with the popular Smith-Waterman algorithm with parameter settings
from the literature which had been optimized for the identification of
structural neighbors, and found that the Bayes aligner correctly identified
more structural neighbors. In a detailed examination of the alignment of a
pair of kinase and a pair of GTPase sequences, we illustrate the
algorithm's potential to identify subsequences that are conserved to
different degrees. In addition, this example shows that the Bayes aligner
returns an alignment-free assessment of the distance between a pair of
sequences.
相似文献
67.
Marjolijn CE Bragt Jogchum Plat Marco Mensink Patrick Schrauwen Ronald P Mensink 《BMC endocrine disorders》2009,9(1):1-9
Background
The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).Methods
Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.Results
Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.Conclusion
Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.Trial registration
ClinicalTrials.gov, NCT00571090 相似文献68.
Ingolf Sommer Stefano Toppo Oliver Sander Thomas Lengauer Silvio CE Tosatto 《BMC bioinformatics》2006,7(1):364
Background
In the area of protein structure prediction, recently a lot of effort has gone into the development of Model Quality Assessment Programs (MQAPs). MQAPs distinguish high quality protein structure models from inferior models. Here, we propose a new method to use an MQAP to improve the quality of models. With a given target sequence and template structure, we construct a number of different alignments and corresponding models for the sequence. The quality of these models is scored with an MQAP and used to choose the most promising model. An SVM-based selection scheme is suggested for combining MQAP partial potentials, in order to optimize for improved model selection. 相似文献69.
70.
Kevin Demeure Fred Fack Elodie Duriez Katja Tiemann Amandine Bernard Anna Golebiewska Sébastien Bougnaud Rolf Bjerkvig Bruno Domon Simone P. Niclou 《Molecular & cellular proteomics : MCP》2016,15(2):481-492
Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future analysis in clinical GBM samples.In the context of glioblastoma (GBM)1, the quest for effective biomarkers is vital given that GBM is the most aggressive primary brain tumor in adults and no curative treatment is currently available (1). GBM is characterized by extensive invasion into the brain parenchyma, a high proliferation rate, neo-angiogenesis and significant cellular and molecular heterogeneity. Current treatment involves neurosurgery, radiotherapy and chemotherapy, yet the median life expectancy of affected patients is less than fifteen months. Recent efforts have focused on targeting the vascular endothelial growth factor (VEGF) system which is critical for tumor angiogenesis, however GBM quickly develop escape mechanisms leading to tumor progression (2, 3). Previous work from our group demonstrated that GBMs adapt to anti-VEGF treatment via a metabolic switch in tumor cells toward increased glycolysis (4, 5). This was accompanied by increased hypoxia and tumor cell invasion, with little or no effect on tumor growth (4). In agreement with these preclinical studies, two large scale clinical trials addressing the impact of bevacizumab, a VEGF targeting antibody, in newly diagnosed GBM patients reported disappointing results: although progression free survival appeared to be improved, no effect on overall survival was observed (6, 7). The evaluation of such studies are complicated by the fact that anti-angiogenic agents affect blood vessel permeability thereby directly modulating neuroimaging parameters used to determine treatment effects (8, 9). Thus there is a need for molecular biomarkers to adequately determine treatment response to anti-angiogenic agents.MS-based proteomics (10, 11) is widely used in the field of cancer research in particular in the context of biomarker development including discovery and verification. The application of the selected reaction monitoring (SRM) approach to proteomics reinforced the importance of MS in biomarker development (12–14). Indeed, SRM is a targeted proteomics approach that allows a precise and absolute quantification of previously selected marker candidates (15, 16). Moreover it can be applied in a supervised discovery phase for potential biomarkers (17, 18), i.e. the precise quantification of a wider range of selected biomarkers of interest by the use of stable isotope labeled (SIL) peptides in crude quality. Because of its high selectivity, sensitivity and accuracy, SRM, also named multiple reaction monitoring (MRM), is currently the reference method in targeted proteomics (14, 19).The aim of this study was to identify proteins that are altered by anti-angiogenic treatment, thereby providing biomolecular signatures of tumor response in GBM. Ultimately such protein markers could be evaluated for their utility as markers of efficacy that allow to discriminate responders from nonresponders. The study was focused on target proteins that may exhibit significant differences in protein expression reflecting the metabolic switch exhibited during anti-angiogenic therapy. An SRM workflow designed on a triple quadrupole platform (20), was developed and optimized in the context of GBM xenografts treated with bevacizumab in order to perform, in a supervised manner, a precise relative quantification of target proteins. We have previously shown that patient derived GBM xenografts developed in rodents faithfully reflect human pathology and allow a detailed analysis of the tumor and stromal compartments (4, 21–24). Furthermore xenograft models facilitate the access to control samples as well as the possibility of controlled interventional studies (25). The results presented herein demonstrate the feasibility of SRM to precisely quantify small changes in protein concentration after treatment. We highlight the importance of peptide selection, data normalization and consideration of the variability of target proteins within complex biological samples before assessing their concentration changes in subsequent comparative studies. From an initial set of 100 candidates, we screened 74 proteins and identified 32 responsive to anti-angiogenic treatment. We propose malectin, calnexin, lactate dehydrogenase A (LDHA), and isocitrate dehydrogenase (IDH) as novel response markers to anti-angiogenic therapy. 相似文献