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排序方式: 共有282条查询结果,搜索用时 15 毫秒
61.
Zhu R Mancini-Bourgine M Zhang XM Bayard F Deng Q Michel ML 《Journal of virology》2011,85(19):10201-10212
Plasmid DNA vaccines serve in a wide array of applications ranging from prophylactic vaccines to potential therapeutic tools against infectious diseases and cancer. In this study, we analyzed the mechanisms underlying the activation of natural killer (NK) cells and their potential role in adaptive immunity during DNA-based immunization against hepatitis B virus surface antigen in mice. We observed that the mature Mac-1(+) CD27(-) NK cell subset increased in the liver of mice early after DNA injection, whereas the number of the less mature Mac-1(+) CD27(+) NK cells in the liver and spleen was significantly reduced. This effect was attributed to bacterial sequences present in the plasmid backbone rather than to the encoded antigen and was not observed in immunized MyD88-deficient mice. The activation of NK cells by plasmid-DNA injection was associated with an increase in their effector functions that depended on the expressed antigen. Maturation of NK cells was abrogated in the absence of T cells, suggesting that cross talk exists between NK cells and antigen-specific T cells. Taken together, our data unravel the mechanics of plasmid vector-induced maturation of NK cells and plasmid-encoded antigen-dependent activation of NK cells required for a crucial role of NK cells in DNA vaccine-induced immunogenicity. 相似文献
62.
Background: The accurate duplication and packaging of the genome is an absolute prerequisite to the segregation of chromosomes in mitosis. To understand the process of cell-cycle chromosome dynamics further, we have performed the first detailed characterization of a mutation affecting mitotic chromosome condensation in a metazoan. Our combined genetic and cytological approaches in Drosophila complement and extend existing work employing yeast genetics and Xenopus in vitro extract systems to characterize higher-order chromosome structure and function.Results: Two alleles of the ORC2 gene were found to cause death late in larval development, with defects in cell-cycle progression (delays in S-phase entry and metaphase exit) and chromosome condensation in mitosis. During S-phase progression in wild-type cells, euchromatin replicates early and heterochromatin replicates late. Both alleles disrupted the normal pattern of chromosomal replication, with some euchromatic regions replicating even later than heterochromatin. Mitotic chromosomes were irregularly condensed, with the abnormally late replicating regions of euchromatin exhibiting the greatest problems in mitotic condensation.Conclusions: The results not only reveal novel functions for ORC2 in chromosome architecture in metazoans, they also suggest that the correct timing of DNA replication may be essential for the assembly of chromatin that is fully competent to undergo mitotic condensation. 相似文献
63.
A. Toutain Nathalie Ronce Benoît Dessay Laura Robb Christine Francannet Martine Le Merrer Marie-Louise Briard Josseline Kaplan Claude Moraine 《Human genetics》1997,99(2):256-261
Nance-Horan syndrome (NHS) is an X-linked disease characterized by severe congenital cataract with microcornea, distinctive
dental findings, evocative facial features and mental impairment in some cases. Previous linkage studies have placed the NHS
gene in a large region from DXS143 (Xp22.31) to DXS451 (Xp22.13). To refine this localization further, we have performed linkage
analysis in four families. As the maximum expected Lod score is reached in each family for several markers in the Xp22.31–p22.13
region and linkage to the rest of the X chromosome can be excluded, our study shows that NHS is a genetically homogeneous
condition. An overall maximum two-point Lod score of 9.36 (θ = 0.00) is obtained with two closely linked markers taken together,
DXS207 and DXS1053 in Xp22.2. Recombinant haplotypes indicate that the NHS gene lies between DXS85 and DXS1226. Multipoint
analysis yields a maximum Lod score of 9.45 with the support interval spanning a 15-cM region that includes DXS16 and DXS1229/365.
The deletion map of the Xp22.3–Xp21.3 region suggests that the phenotypic variability of NHS is not related to gross rearrangement
of sequences of varying size but rather to allelic mutations in a single gene, presumably located proximal to DXS16 and distal
to DXS1226. Comparison with the map position of the mouse Xcat mutation supports the location of the NHS gene between the GRPR and PDHA1 genes in Xp22.2.
Received: 14 June 1996 / Revised: 10 October 1996 相似文献
64.
Joana M. Murad Susanne H. Baumeister Lillian Werner Heather Daley Hélène Trébéden-Negre Jake Reder Charles L. Sentman David Gilham Frederic Lehmann Sarah Snykers Marie-Louise Sentman Terri Wade Adam Schmucker Michael W. Fanger Glenn Dranoff Jerome Ritz Sarah Nikiforow 《Cytotherapy》2018,20(7):952-963
Background aims
Adoptive cell therapy employing natural killer group 2D (NKG2D) chimeric antigen receptor (CAR)-modified T cells has demonstrated preclinical efficacy in several model systems, including hematological and solid tumors. We present comprehensive data on manufacturing development and clinical production of autologous NKG2D CAR T cells for treatment of acute myeloid leukemia and multiple myeloma (ClinicalTrials.gov Identifier: NCT02203825). An NKG2D CAR was generated by fusing native full-length human NKG2D to the human CD3ζ cytoplasmic signaling domain. NKG2D naturally associates with native costimulatory molecule DAP10, effectively generating a second-generation CAR against multiple ligands upregulated during malignant transformation including MIC-A, MIC-B and the UL-16 binding proteins.Methods
CAR T cells were infused fresh after a 9-day process wherein OKT3-activated T cells were genetically modified with replication-defective gamma-retroviral vector and expanded ex vivo for 5 days with recombinant human interleukin-2.Results
Despite sizable interpatient variation in originally collected cells, release criteria, including T-cell expansion and purity (median 98%), T-cell transduction (median 66% CD8+ T cells), and functional activity against NKG2D ligand-positive cells, were met for 100% of healthy donors and patients enrolled and collected. There was minimal carryover of non–T cells, particularly malignant cells; both effector memory and central memory cells were generated, and inflammatory cytokines such as granulocyte colony-stimulating factor, RANTES, interferon-γ and tumor necrosis factor-α were selectively up-regulated.Conclusions
The process resulted in production of required cell doses for the first-in-human phase I NKG2D CAR T clinical trial and provides a robust, flexible base for further optimization of NKG2D CAR T-cell manufacturing. 相似文献65.
Control of phosphorus loading and flushing as restoration methods for Lake Veluwe,The Netherlands 总被引:10,自引:0,他引:10
As a result of high nutrient loading Lake Veluwe suffered from an almost permanent bloom of the blue-green algaOscillatoria agardhii Gomont. In 1979, the phosphorus loading of the lake was reduced from approx. 3 to 1 g P.m–2.a–1. Moreover, since then the lake has been flushed during winter periods with water low in phosphorus. This measure aimed primarily at interrupting the continuous algal bloom. The results of these measures show a sharp decline of total-phosphorus values from 0.40–0.60 mg P.l–1 (before 1980) to 0.10–0.20 mg P.l–1 (after 1980). Summer values for chlorophylla dropped from 200–400 mg.m–3 to 50–150 mg.m–3.The increase in transparency of the lake water was relatively small, from summer values of 15–25 cm before the implementation of the measures to 25–45 cm afterwards. The disappointing transparency values may be explained by the decreasing chlorophylla and phosphorus content of the algae per unit biovolume. Blue-green algae are gradually loosing ground. In the summer of 1985 green algae and diatoms dominated the phytoplankton for the first time since almost 20 years. To achieve the ultimate water quality objectives (transparency values of more than 100 cm in summer), the phosphorus loading has to be reduced further. 相似文献
66.
Paulie Staffan Koho Hannu Ben-Aissa Hedi Hansson Yngve Lundblad Marie-Louise Perlmann Peter 《Cancer immunology, immunotherapy : CII》1984,17(3):165-172
Summary Spleen cells from BALB/c mice immunized with cells derived from transitional cell carcinomas (TCC) of the human urinary bladder were fused with mouse myeloma Sp 2/0 Ag14 cells. Monoclonal antibodies from six established hybridomas were investigated for specificity in a cell ELISA and in indirect immunofluorescence against a large panel of fixed intact cells. Three of the antibodies reacted with half or more of the eight bladder tumors and with a few unrelated tumors. They did not react at all with malignant or normal cells of hematopoietic origin. A fourth antibody reacted with seven of eight bladder tumors. It also reacted weakly with a prostatic carcinoma, with five of six malignant or transformed B cell lines, and with a subpopulation of normal lymphocytes, but not with any of the other cells on the test panel. These four antibodies did not react with cells derived from normal urothelium. The results suggest that these antibodies might recognize cell-type-restricted antigens associated with malignancy. Another antibody reacted with almost all urothelium-derived cells. It also reacted with three of three melanomas but not with any other cells on the panel. The sixth antibody reacted with 32 of the 37 cells tested. The spectrum of reactivities displayed by the antibody suggested that it recognizes HLA antigens.
Abbreviations used in this paper: TCC, transitional cell carcinoma of the urinary bladder; TAA, tumor-associated antigens; ELISA, enzyme-linked immunosorbent assay; NBCS, newborn calf serum; PBS, phosphate-buffered saline, pH 7.2; ALP, alkaline phosphatase; GDA, glutardialdehyde; BSA, bovine serum albumin; IF, indirect immunofluorescence; LCL, lymphoblastoid cell lines: B-lymphocytes transformed in vitro with Epstein-Barr virus 相似文献
67.
Summary In a review of information on 444 patients with sporadic retinoblastoma, a correlation with increased fathers'age was demonstrated and no correlation with was found in the unilateral form. These data favor the hypothesis that the bilateral form is caused by a germinal mutation and the unilateral form is due to somatic mutations.
Zusammenfassung In einer Übersicht über 444 Patienten mit sporadischem Retinoblastom wurde eine Erhöhung des väterlichen Alters demonstriert. Bei den einseitigen Fällen wurde eine solche Erhöhung jedoch nicht gefunden. Die Daten sprechen dafür, daß die doppelseitige Form durch Keimzell-Mutation verursacht ist, während die einseitige form auf somatische Mutationen zurückgeht.相似文献
68.
Jenny Knapp Jean-Mathieu Bart Patrick Giraudoux Marie-Louise Glowatzki Isabelle Breyer Francis Raoul Peter Deplazes Georg Duscher Karel Martinek Pavol Dubinsky Marie-Hélène Guislain Florence Cliquet Thomas Romig Andrzej Malczewski Bruno Gottstein Renaud Piarroux 《PLoS neglected tropical diseases》2009,3(6)
Background
Alveolar echinococcosis (AE) is a severe helminth disease affecting humans, which is caused by the fox tapeworm Echinococcus multilocularis. AE represents a serious public health issue in larger regions of China, Siberia, and other regions in Asia. In Europe, a significant increase in prevalence since the 1990s is not only affecting the historically documented endemic area north of the Alps but more recently also neighbouring regions previously not known to be endemic. The genetic diversity of the parasite population and respective distribution in Europe have now been investigated in view of generating a fine-tuned map of parasite variants occurring in Europe. This approach may serve as a model to study the parasite at a worldwide level.Methodology/Principal Findings
The genetic diversity of E. multilocularis was assessed based upon the tandemly repeated microsatellite marker EmsB in association with matching fox host geographical positions. Our study demonstrated a higher genetic diversity in the endemic areas north of the Alps when compared to other areas.Conclusions/Significance
The study of the spatial distribution of E. multilocularis in Europe, based on 32 genetic clusters, suggests that Europe can be considered as a unique global focus of E. multilocularis, which can be schematically drawn as a central core located in Switzerland and Jura Swabe flanked by neighbouring regions where the parasite exhibits a lower genetic diversity. The transmission of the parasite into peripheral regions is governed by a “mainland–island” system. Moreover, the presence of similar genetic profiles in both zones indicated a founder event. 相似文献69.
Dominique Joly Marie-Louise Cariou Tendai Mhlanga-Mutangadura Daniel Lachaise 《Genetica》2010,138(1):139-152
It is commonly recognized that speciation does not necessarily imply extensive variation between populations, and what the
speciation process per se consists of still remains an unanswered question. We advocate here that the variation of male terminalia
does not necessarily result in noticeable reproductive isolation. We report whether there is invariance or variance of traits
central to sexual selection processes (i.e. male terminalia and sperm length) compared to traits which are generally assumed
to vary more neutrally (i.e. allozymes) in the strictly Afrotropical forest-dwelling continental species Drosophila teissieri. Three geographic blocks can be recognized along the present range of the species. Our data suggest that the components of
the species integrity do not obey the variance/invariance alternative consistently. Male terminalia and allozymes show extensive
variation while sperm length distribution is strikingly similar between the geographic blocks. It is therefore inferred that
sperm length might be one of the major targets of stabilizing selection. Finally, it is suggested that the striking fit between
the extent of sperm heteromorphism (within male) and sperm polymorphism (between males) is instrumental in maintaining the
species integrity. 相似文献