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81.
Malinge S Ragu C Della-Valle V Pisani D Constantinescu SN Perez C Villeval JL Reinhardt D Landman-Parker J Michaux L Dastugue N Baruchel A Vainchenker W Bourquin JP Penard-Lacronique V Bernard OA 《Blood》2008,112(10):4220-4226
Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. To gain insight into the oncogenic process leading to acute megakaryoblastic leukemia (AMKL), we performed sequence analyses of a subset of oncogenes known to be activated in human myeloid and myeloproliferative disorders. In a series of human AMKL samples from both Down syndrome and non-Down syndrome patients, mutations were identified within KIT, FLT3, JAK2, JAK3, and MPL genes, with a higher frequency in DS than in non-DS patients. The novel mutations were analyzed using BaF3 cells, showing that JAK3 mutations were activating mutations. Finally, we report a novel constitutively active MPL mutant, MPLT487A, observed in a non-Down syndrome childhood AMKL that induces a myeloproliferative disease in mouse bone marrow transplantation assay. 相似文献
82.
Hättenschwiler S Gasser P 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(5):1519-1524
Most of the terrestrial net primary production enters the decomposer system as dead organic matter, and the subsequent recycling of C and nutrients are key processes for the functioning of ecosystems and the delivery of ecosystem goods and services. Although climatic and substrate quality controls are reasonably well understood, the functional role of biodiversity for biogeochemical cycles remains elusive. Here we ask how altering litter species diversity affects species-specific decomposition rates and whether large litter-feeding soil animals control the litter diversity-function relationship in a temperate forest ecosystem. We found that decomposition of a given litter species changed greatly in the presence of litters from other cooccurring species despite unaltered climatic conditions and litter chemistry. Most importantly, soil fauna determined the magnitude and direction of litter diversity effects. Our data show that litter species richness and soil fauna interactively determine rates of decomposition in a temperate forest, suggesting a combination of bottom-up and top-down controls of litter diversity effects on ecosystem C and nutrient cycling. These results provide evidence that, in ecosystems supporting a well developed soil macrofauna community, animal activity plays a fundamental role for altered decomposition in response to changing litter diversity, which in turn has important implications for biogeochemical cycles and the long-term functioning of ecosystems with ongoing biodiversity loss. 相似文献
83.
Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma 总被引:8,自引:0,他引:8 下载免费PDF全文
Yu MY Bartosch B Zhang P Guo ZP Renzi PM Shen LM Granier C Feinstone SM Cosset FL Purcell RH 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(20):7705-7710
The role of humoral immunity in hepatitis C virus (HCV) infections is uncertain. Nevertheless, there is increasing evidence for neutralizing antibodies to HCV in the serum or plasma of chronically infected individuals. Immune globulins prepared by ethanol fractionation of plasma had long been considered safe until a commercial immune globulin product, Gammagard, prepared from plasma from which units containing anti-HCV had been excluded, transmitted HCV to recipients. Studies suggested that the exclusion might have removed neutralizing antibodies from the plasma and hence compromised the safety of the resulting immune globulins. In the present study, by using chimpanzees and a recently validated in vitro system based on neutralization of infectious HCV pseudoparticles, we found broadly reactive neutralizing and protective antibodies in experimental immune globulin preparations made from anti-HCV-positive donations. Neutralizing antibodies were also found in Gammagard lots made from unscreened plasma that did not transmit hepatitis C but not in Gammagard lots, which were prepared from anti-HCV-screened plasma, that did transmit hepatitis C. The results provide an explanation for the mechanism by which the safety of this product was compromised. Immune globulins made from anti-HCV-positive plasma and containing broadly reactive neutralizing antibodies may provide a method of preventing HCV infection. 相似文献
84.
Alpha-fetoprotein,the major fetal serum protein,is not essential for embryonic development but is required for female fertility 总被引:6,自引:0,他引:6
Gabant P Forrester L Nichols J Van Reeth T De Mees C Pajack B Watt A Smitz J Alexandre H Szpirer C Szpirer J 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(20):12865-12870
The alpha-fetoprotein gene (Afp) is a member of a multigenic family that comprises the related genes encoding albumin, alpha-albumin, and vitamin D binding protein. The biological role of this major embryonic serum protein is unknown although numerous speculations have been made. We have used gene targeting to show that AFP is not required for embryonic development. AFP null embryos develop normally, and individually transplanted homozygous embryos can develop in an AFP-deficient microenvironment. Whereas mutant homozygous adult males are viable and fertile, AFP null females are infertile. Our analyses of these mice indicate that the defect is caused by a dysfunction of the hypothalamic/pituitary system, leading to anovulation. 相似文献
85.
Cédric Rat Gaelle Quereux Christelle Riviere Sophie Clouet Rémy Senand Christelle Volteau Brigitte Dreno Jean-Michel Nguyen 《Annals of family medicine》2014,12(1):21-28
PURPOSE
Targeted interventions to reduce the risk and increase the early detection of melanoma have the potential to save lives. We aimed to assess the effect of such an intervention on patient prevention behavior.METHODS
We conducted a pilot clustered randomized controlled trial, comparing a targeted screening and education intervention with a conventional information-based campaign in 20 private surgeries in western France. In the intervention group, 10 general practitioners identified patients at elevated risk for melanoma with a validated assessment tool, the Self-Assessment Melanoma Risk Score (SAMScore), examined their skin, and counseled them using information leaflets. In the control group, 10 general practitioners displayed a poster and the leaflets in their waiting room and examined patients’ skin at their own discretion. The main outcome measures were sunbathing and skin self-examinations among patients at elevated risk, assessed 5 months later with a questionnaire.RESULTS
Analyses were based on 173 patients. Compared with control patients, intervention patients were more likely to remember the campaign (81.4% vs 50.0%, P = .0001) and to correctly identify their elevated risk of melanoma (71.1% vs 42.1%, P = .001). Furthermore, intervention patients had higher levels of prevention behaviors: they were less likely to sunbathe in the summer (24.7% vs 40.8%, P = .048) and more likely to have performed skin self-examinations in the past year (52.6% vs 36.8%, P = .029). The intervention was not associated with any clear adverse effects, although there were trends whereby intervention patients were more likely to worry about melanoma and to consult their general practitioner again about the disease.CONCLUSIONS
The combination of use of the SAMScore and general practitioner examination and counseling during consultations is an efficient way to promote patient behaviors that may reduce melanoma risk. Extending the duration of follow-up and demonstrating an impact on morbidity and mortality remain major issues for further research. 相似文献86.
Pau Abrisqueta Julio Delgado Miguel Alcoceba Ana Carla Oliveira Javier Loscertales Jose A. Hernández-Rivas Christelle Ferrà Raul Cordoba Lucrecia Yáñez Angeles Medina Cristina Motlló Gloria Iacoboni Guillermo Villacampa Marcos González Francesc Bosch 《British journal of haematology》2020,190(6):854-863
Richter syndrome (RS) is an uncommon evolution of chronic lymphocytic leukaemia (CLL) with a dismal prognosis. Clinical-biological features predicting outcome and best therapeutic approach for these patients remain to be established. In this study, 128 patients with RS, including 112 diffuse large B-cell lymphoma (DLBCL)-type RS, 15 Hodgkin lymphoma (HL)-type RS, and one plasmablastic lymphoma, were identified in 11 centres of the Spanish CLL Study Group (GELLC). The median overall survival (OS) was 5·9 months for DLBCL-type RS and 30·8 months for HL-type RS. Eastern Cooperative Oncology Group Performance Status, haemoglobin level, platelet count, serum lactate dehydrogenase and β2-microglobulin levels, tumour protein p53 (TP53) abnormalities in the CLL clone concomitant to RS, number of prior therapies, and clonal relationship between CLL and RS, were associated with OS in patients with DLBCL-type RS. A platelet count of <100 × 109/l, prior CLL therapy (0 vs. ≥1), and presence of TP53 alterations maintained an independent prognostic impact in the multivariate analysis. Patients without any of these factors had a better clinical outcome, with a median OS of 75·3 months, while patients with one or two or more of these factors presented a median OS of 25·5 and 3 months, respectively. Although OS of patients with RS is generally poor, a proportion of patients achieved prolonged survival. Treatment of RS remains a medical need, and further therapeutic approaches with novel therapies are warranted. 相似文献
87.
88.
Limited plastic potential of the left ventral premotor cortex in speech articulation: Evidence From intraoperative awake mapping in glioma patients 下载免费PDF全文
Kim van Geemen Guillaume Herbet Sylvie Moritz‐Gasser Hugues Duffau 《Human brain mapping》2014,35(4):1587-1596
Objectives: Despite previous lesional and functional neuroimaging studies, the actual role of the left ventral premotor cortex (vPMC), i.e., the lateral part of the precentral gyrus, is still poorly known. Experimental design:We report a series of eight patients with a glioma involving the left vPMC, who underwent awake surgery with intraoperative cortical and subcortical language mapping. The function of the vPMC, its subcortical connections, and its reorganization potential are investigated in the light of surgical findings and language outcome after resection. Principal observations: Electrostimulation of both the vPMC and subcortical white matter tract underneath the vPMC, that is, the anterior segment of the lateral part of the superior longitudinal fascicle (SLF), induced speech production disturbances with anarthria in all cases. Moreover, although some degrees of redistribution of the vPMC have been found in four patients, allowing its partial resection with no permanent speech disorders, this area was nonetheless still detected more medially in the precentral gyrus in the eight patients, despite its invasion by the glioma. Moreover, a direct connection of the vPMC with the SLF was preserved in all cases. Conclusions: Our original data suggest that the vPMC plays a crucial role in the speech production network and that its plastic potential is limited. We propose that this limitation is due to an anatomical constraint, namely the necessity for the left vPMC to remain connected to the lateral SLF. Beyond fundamental implications, such knowledge may have clinical applications, especially in surgery for tumors involving this cortico‐subcortical circuit. Hum Brain Mapp 35:1587–1596, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
89.
M. Bozi D. Papadimitriou R. Antonellou M. Moraitou M. Maniati D. K. Vassilatis S. G. Papageorgiou A. Leonardos G. Tagaris G. Malamis D. Theofilopoulos S. Kamakari E. Stamboulis G. M. Hadjigeorgiou A. Athanassiadou H. Michelakakis A. Papadimitriou T. Gasser L. Stefanis 《European journal of neurology》2014,21(7):963-968
90.
Caroline Plazanet Christelle Arrondel François Chavant Marie-Claire Gubler 《Pediatric nephrology (Berlin, Germany)》2014,29(7):1221-1230