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211.
Delphine Mariotte Beno?t Dupont Radj Gervais Marie-Pierre Galais Dominique Laroche Aurore Tranchant Elisabeth Comby Karine Bouhier-Leporrier Jean-Marie Reimund Brigitte Le Mauff 《MABS-AUSTIN》2011,3(4):396-401
Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3–4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p = 0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3–4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.Key words: anti-cetuximab antibodies, ELISA, hypersensitivity, therapeutic monoclonal antibody, ROC 相似文献
212.
Andrés O Rönn AC Bonhomme M Kellermann T Crouau-Roy B Doxiadis G Verschoor EJ Goossens B Domingo-Roura X Bruford MW Bosch M Syvänen AC 《Molecular ecology resources》2008,8(3):529-539
Chimpanzee populations are diminishing as a consequence of human activities, and as a result this species is now endangered. In the context of conservation programmes, genetic data can add vital information, for instance on the genetic diversity and structure of threatened populations. Single nucleotide polymorphisms (SNP) are biallelic markers that are widely used in human molecular studies and can be implemented in efficient microarray systems. This technology offers the potential of robust, multiplexed SNP genotyping at low reagent cost in other organisms than humans, but it is not commonly used yet in wild population studies. Here, we describe the characterization of new SNPs in Y-chromosomal intronic regions in chimpanzees and also identify SNPs from mitochondrial genes, with the aim of developing a microarray system that permits the simultaneous study of both paternal and maternal lineages. Our system consists of 42 SNPs for the Y chromosome and 45 SNPs for the mitochondrial genome. We demonstrate the applicability of this microarray in a captive population where genotypes accurately reflected its large pedigree. Two wild-living populations were also analysed and the results show that the microarray will be a useful tool alongside microsatellite markers, since it supplies complementary information about population structure and ecology. SNP genotyping using microarray technology, therefore, is a promising approach and may become an essential tool in conservation genetics to help in the management and study of captive and wild-living populations. Moreover, microarrays that combine SNPs from different genomic regions could replace microsatellite typing in the future. 相似文献
213.
Laure-Emmanuelle Zaragosi Brigitte Wdziekonski Kevin Le Brigand Phi Villageois Bernard Mari Rainer Waldmann Christian Dani Pascal Barbry 《Genome biology》2011,12(7):R64
Background
In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation. 相似文献214.
Volodymyr Trotsiuk Florian Hartig Maxime Cailleret Flurin Babst David I. Forrester Andri Baltensweiler Nina Buchmann Harald Bugmann Arthur Gessler Mana Gharun Francesco Minunno Andreas Rigling Brigitte Rohner Jonas Stillhard Esther Thürig Peter Waldner Marco Ferretti Werner Eugster Marcus Schaub 《Global Change Biology》2020,26(4):2463-2476
The response of forest productivity to climate extremes strongly depends on ambient environmental and site conditions. To better understand these relationships at a regional scale, we used nearly 800 observation years from 271 permanent long‐term forest monitoring plots across Switzerland, obtained between 1980 and 2017. We assimilated these data into the 3‐PG forest ecosystem model using Bayesian inference, reducing the bias of model predictions from 14% to 5% for forest stem carbon stocks and from 45% to 9% for stem carbon stock changes. We then estimated the productivity of forests dominated by Picea abies and Fagus sylvatica for the period of 1960–2018, and tested for productivity shifts in response to climate along elevational gradient and in extreme years. Simulated net primary productivity (NPP) decreased with elevation (2.86 ± 0.006 Mg C ha?1 year?1 km?1 for P. abies and 0.93 ± 0.010 Mg C ha?1 year?1 km?1 for F. sylvatica). During warm–dry extremes, simulated NPP for both species increased at higher and decreased at lower elevations, with reductions in NPP of more than 25% for up to 21% of the potential species distribution range in Switzerland. Reduced plant water availability had a stronger effect on NPP than temperature during warm‐dry extremes. Importantly, cold–dry extremes had negative impacts on regional forest NPP comparable to warm–dry extremes. Overall, our calibrated model suggests that the response of forest productivity to climate extremes is more complex than simple shift toward higher elevation. Such robust estimates of NPP are key for increasing our understanding of forests ecosystems carbon dynamics under climate extremes. 相似文献
215.
Bernadette A.S. J?ger Charlotte Finkenzeller Carolin Bock Leonie Majunke Julia K. Jueckstock Ulrich Andergassen Julia K. Neugebauer Aurelia Pestka Thomas W.P. Friedl Udo Jeschke Wolfgang Janni Sophie F. Doisneau-Sixou Brigitte K. Rack 《Translational oncology》2015,8(6):509-516
BACKGROUND: We evaluated both estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status on disseminated tumor cells (DTCs) in the bone marrow of 54 patients with early breast cancer and compared these with the corresponding primary tumor (PT). MATERIALS AND METHODS: Bone marrow aspirates were obtained at the time of first surgery, and ER and HER2 status on DTCs was assessed simultaneously by immunocytochemistry using a triple fluorescence staining method. RESULTS: The median number of DTCs was 13 (range 1-95). The concordance rate between ER status on DTC and PT was 74%. Patients with an ER-positive PT were significantly more likely to have at least one ER-positive DTC (34 out of 42) than patients with an ER-negative PT (6 out of 12; P = .031). Thirty-nine (93%) of the 42 patients with ER-positive PT had at least one ER-negative DTC. The concordance rate between HER2 status on DTC and PT was 52%. The probability of having at least one HER2-positive DTC was not related to the HER2 status of the PT (P = 0.56). Twenty-two (46%) of the 48 patients with a HER2-negative PT had at least one HER2-positive DTC. All the six patients with a HER2-positive PT had at least one HER2-negative DTC. CONCLUSION: Taken together, our study confirms that ER and/or HER2 status may differ between DTC and PT. This discordance could be important for patients lacking ER or HER2 expression on the PT but showing ER-positive or HER2-positive DTC because they might benefit from an endocrine and/or HER2-targeted therapy. 相似文献
216.
217.
In this study, we addressed why Caenorhabditis elegans males are inefficient at fertilizing their hermaphrodites. During copulation, hermaphrodites generally move away from males before they become impregnated. C. elegans hermaphrodites reproduce by internal self-fertilization, so that copulation with males is not required for species propagation. The hermaphroditic mode of reproduction could potentially relax selection for genes that optimize male mating behavior. We examined males from hermaphroditic and gonochoristic (male-female copulation) Caenorhabditis species to determine if they use different sensory and motor mechanisms to control their mating behavior. Instead, we found through laser ablation analysis and behavioral observations that hermaphroditic C. briggsae and gonochoristic C. remanei and Caenorhabditis species 4, PB2801 males produce a factor that immobilizes females during copulation. This factor also stimulates the vulval slit to widen, so that the male copulatory spicules can easily insert. C. elegans and C. briggsae hermaphrodites are not affected by this factor. We suggest that sensory and motor execution of mating behavior have not significantly changed among males of different Caenorhabditis species; however, during the evolution of internal self-fertilization, hermaphrodites have lost the ability to respond to the male soporific-inducing factor. 相似文献
218.
Horizontal gene transfer and homologous recombination drive the evolution of the nitrogen-fixing symbionts of Medicago species 下载免费PDF全文
Using nitrogen-fixing Sinorhizobium species that interact with Medicago plants as a model system, we aimed at clarifying how sex has shaped the diversity of bacteria associated with the genus Medicago on the interspecific and intraspecific scales. To gain insights into the diversification of these symbionts, we inferred a topology that includes the different specificity groups which interact with Medicago species, based on sequences of the nodulation gene cluster. Furthermore, 126 bacterial isolates were obtained from two soil samples, using Medicago truncatula and Medicago laciniata as host plants, to study the differentiation between populations of Sinorhizobium medicae, Sinorhizobium meliloti bv. meliloti, and S. meliloti bv. medicaginis. The former two can be associated with M. truncatula (among other species of Medicago), whereas the last organism is the specific symbiont of M. laciniata. These bacteria were characterized using a multilocus sequence analysis of four loci, located on the chromosome and on the two megaplasmids of S. meliloti. The phylogenetic results reveal that several interspecific horizontal gene transfers occurred during the diversification of Medicago symbionts. Within S. meliloti, the analyses show that nod genes specific to different host plants have spread to different genetic backgrounds through homologous recombination, preventing further divergence of the different ecotypes. Thus, specialization to different host plant species does not prevent the occurrence of gene flow among host-specific biovars of S. meliloti, whereas reproductive isolation between S. meliloti bv. meliloti and S. medicae is maintained even though these bacteria can cooccur in sympatry on the same individual host plants. 相似文献
219.
Differential expression of two related amino acid transporters with differing substrate specificity in Arabidopsis thaliana 总被引:5,自引:3,他引:5
Marion Kwart Brigitte Hirner Sabine Hummel Wolf B. Frommer 《The Plant journal : for cell and molecular biology》1993,4(6):993-1002
A general amino acid permease cDNA ( AAP2 ) was isolated from Arabidopsis by complementation of a yeast mutant defective in citrulline uptake. Direct transport measurements in yeast show that the protein mediates uptake of l -[14 C]-citrulline and l -[14 C]-proline. Detailed analyses of the substrate specificity by competition studies demonstrate that all proteogenic amino acids are recognized by the carrier, including those that represent the major transport forms of reduced nitrogen in many species, i.e. glutamine, glutamate and asparagine. Thus, AAP2 is less selective as compared with AAP1 and transports basic amino acids such as histidine as shown by expression in a histidine transport-deficient yeast strain. The predicted polypeptide of 53 kDa is highly hydrophobic with 12 putative membrane-spanning regions and shows significant homologies to the Arabidopsis broad specificity permease AAP1, and a limited homology to bacterial branched chain amino acid transporters, but not to any other known proteins. Alterations in the charged residues as compared with AAP1 in four regions might be involved in the difference in selectivity towards basic amino acids. Both genes are highly expressed in developing pods indicating a role in supplying the developing seeds with reduced nitrogen. AAP2 is selectively expressed in the stem and might therefore play a role in xylem-to-phloem transfer of amino acids during seed filling. Furthermore in situ hybridization shows that both genes are expressed in the vascular system of cotyledons in developing seedlings. 相似文献
220.
Dos Vultos T Mestre O Rauzier J Golec M Rastogi N Rasolofo V Tonjum T Sola C Matic I Gicquel B 《PloS one》2008,3(2):e1538