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11.
Christina Brunke Stefan Lohse Stefanie Derer Matthias Peipp Peter Boross Christian Kellner Thomas Beyer Michael Dechant Louise Royle Li Phing Liew Jeanette HW Leusen Thomas Valerius 《MABS-AUSTIN》2013,5(6):936-945
Antibodies of human IgA isotype are critical components of the mucosal immune system, but little is known about their immunotherapeutic potential. Compared with IgG antibodies, IgA molecules carry a C-terminal tail piece extension of 18 amino acids with a free cysteine at position 471. This cysteine is required for the formation of dimeric IgA antibodies, but may impair molecular characteristics of monomeric IgA antibodies as therapeutic reagents. Thus, we generated and characterized a d471-mutated antibody against the epidermal growth factor receptor (EGFR) and compared it to its respective IgA2 m(1) wild type antibody. Both wild type and mutated IgA antibodies demonstrated similar EGFR binding and were similarly efficient in inhibiting EGF binding and in blocking EGF-mediated cell proliferation. Recruitment of Fc-mediated effector functions like antibody-dependent cell-mediated cytotoxicity by monocytes, macrophages or PMN was similar, but the d471-mutated IgA exhibited different biochemical properties compared with wild type antibody. As expected, mutated IgA did not form stable dimers in the presence of human joining (J)-chain, but we also observed reduced levels of dimeric aggregates in the absence of J-chain. Furthermore, glycoprofiling revealed different glycosylation patterns for both antibodies, including considerably less mannosylation of d471-mutated antibodies. Overall, our results demonstrate that the deletion of the C-terminal cysteine of IgA2 did not affect the investigated effector functions compared with wild type antibody, but it improved biochemical properties of an IgA2 m(1) antibody against EGFR, and may thereby assist in exploring the immunotherapeutic potential of recombinant IgA antibodies. 相似文献
12.
Magdalena Winiarska Kamil Bojarczuk Beata Pyrzynska Jacek Bil Marta Siernicka Michal Dwojak Malgorzata Bobrowicz Nina Miazek Piotr Zapala Agnieszka Zagozdzon Magdalena Krol Aleksandra Syta Paulina Podszywalow-Bartnicka Zofia Pilch Anna Dabrowska-Iwanicka Przemyslaw Juszczynski Dimitar G Efremov Mikolaj Slabicki Thorsten Zenz Aude Le Roy Daniel Olive Tomasz P Rygiel Jeanette HW Leusen Jakub Golab 《MABS-AUSTIN》2014,6(5):1300-1313
13.
María Teruel Carmen P Simeon Jasper Broen Madelon C Vonk Patricia Carreira Maria Teresa Camps Rosa García-Portales Esmeralda Delgado-Frías Maria Gallego Gerard Espinosa the Spanish Scleroderma Group Lorenzo Beretta Paolo Airó Claudio Lunardi Gabriela Riemekasten Torsten Witte Thomas Krieg Alexander Kreuter J?rg HW Distler Nicolas Hunzelmann Bobby P Koeleman Alexandre E Voskuyl Annemie J Schuerwegh Miguel ángel González-Gay Timothy RDJ Radstake Javier Martin 《Arthritis research & therapy》2012,14(3):R154-6
Introduction
The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc).Methods
In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes.Results
No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis.Conclusions
Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc. 相似文献14.
Maas RH Bakker RR Boersma AR Bisschops I Pels JR de Jong E Weusthuis RA Reith H 《Biotechnology for biofuels》2008,1(1):14
Introduction
The limited availability of fossil fuel sources, worldwide rising energy demands and anticipated climate changes attributed to an increase of greenhouse gasses are important driving forces for finding alternative energy sources. One approach to meeting the increasing energy demands and reduction of greenhouse gas emissions is by large-scale substitution of petrochemically derived transport fuels by the use of carbon dioxide-neutral biofuels, such as ethanol derived from lignocellulosic material. 相似文献15.
Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. 总被引:21,自引:12,他引:9 下载免费PDF全文
Murine gammaherpesvirus 68 (gamma HV-68; also referred to as MHV-68) is a gammaherpesvirus which infects murid rodents. Previous studies showed that CD8 T cells are important for controlling gamma HV-68 replication during the first 2 weeks of infection and suggested a role for B cells in latent or persistent gamma HV-68 infection. To further define the importance of B cells and CD8 T cells during acute and chronic gamma HV-68 infection, we examined splenic infection in mice with null mutations in the transmembrane domain of the mu-heavy-chain constant region (MuMT; B-cell and antibody deficient) or in the beta2-microglobulin gene (beta2 -/-; CD8 deficient). Immunocompetent mice infected intraperitoneally with gamma HV-68 demonstrated peak splenic titers 9 to 10 days postinfection, cleared infectious virus 15 to 20 days postinfection, and harbored low levels of latent virus at 6 weeks postinfection. Beta2-/- mice showed peak splenic gamma HV-68 titers similar to those of normal mice but were unable to clear infectious virus completely from the spleen, demonstrating persistent infectious virus 6 weeks postinfection. These data indicate that CD8 T cells are important for clearing infectious gamma HV-68 from the spleen. Infected MuMT mice did not demonstrate detectable infectious gamma HV-68 in the spleen at any time after infection, indicating that mature B lymphocytes are necessary for acute splenic infection by gamma HV-68. Despite the lack of measurable acute infection, MuMT spleen cells harbored latent virus 6 weeks postinfection at a level about 100-fold higher than that in normal mice. These data demonstrate establishment of latency by a herpesvirus in an organ in the absence of acute viral replication in that organ. In addition, they demonstrate that gamma HV-68 can establish latency in a cell type other than mature B lymphocytes. 相似文献
16.
Distribution and conservation of mobile elements in the genus Drosophila 总被引:13,自引:1,他引:12
Essentially nothing is known of the origin, mode of transmission, and
evolution of mobile elements within the genus Drosophila. To better
understand the evolutionary history of these mobile elements, we examined
the distribution and conservation of homologues to the P, I, gypsy, copia,
and F elements in 34 Drosophila species from three subgenera. Probes
specific for each element were prepared from D. melanogaster and hybridized
to genomic DNA. Filters were washed under conditions of increasing
stringency to estimate the similarity between D. melanogaster sequences and
their homologues in other species. The I element homologues show the most
limited distribution of all elements tested, being restricted to the
melanogaster species group. The P elements are found in many members of the
subgenus Sophophora but, with the notable exception of D. nasuta, are not
found in the other two subgenera. Copia-, gypsy-, and F-element homologues
are widespread in the genus, but their similarity to the D. melanogaster
probe differs markedly between species. The distribution of copia and P
elements and the conservation of the gypsy and P elements is inconsistent
with a model that postulates a single ancient origin for each type of
element followed by mating-dependent transmission. The data can be
explained by horizontal transmission of mobile elements between
reproductively isolated species.
相似文献
17.
Sheran HW Law Rudolf SS Wu Patrick KS Ng Richard MK Yu Richard YC Kong 《BMC molecular biology》2006,7(1):15-13
Background
Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs. 相似文献18.
Yan Boucher Camilla L Nesbø Michael J Joss Andrew Robinson Bridget C Mabbutt Michael R Gillings WFord Doolittle HW Stokes 《BMC evolutionary biology》2006,6(1):3-14
Background
Integrons are genetic elements capable of the acquisition, rearrangement and expression of genes contained in gene cassettes. Gene cassettes generally consist of a promoterless gene associated with a recombination site known as a 59-base element (59-be). Multiple insertion events can lead to the assembly of large integron-associated cassette arrays. The most striking examples are found in Vibrio, where such cassette arrays are widespread and can range from 30 kb to 150 kb. Besides those found in completely sequenced genomes, no such array has yet been recovered in its entirety. We describe an approach to systematically isolate, sequence and annotate large integron gene cassette arrays from bacterial strains. 相似文献19.
Da-Chuan Cheng Christian Billich Shing-Hong Liu Horst Brunner Yi-Chen Qiu Yu-Lin Shen Hans Jürgen Brambs Arno Schmidt-Trucksäss Uwe HW Schütz 《Biomedical engineering online》2011,10(1):26
Background
Systematic aerobe training has positive effects on the compliance of dedicated arterial walls. The adaptations of the arterial structure and function are associated with the blood flow-induced changes of the wall shear stress which induced vascular remodelling via nitric oxide delivered from the endothelial cell. In order to assess functional changes of the common carotid artery over time in these processes, a precise measurement technique is necessary. Before this study, a reliable, precise, and quick method to perform this work is not present. 相似文献20.
在韩国境内Potentilla fragarioides var.sprengeliana的遗传多样 … 总被引:1,自引:0,他引:1
根据22个等位酶位点遗传变异,探讨了韩国境内委陵菜(Potentilla fragarioides L.var.sprengeliana)的遗传多样性和种群结构。酶位点的多态位点百分比为59.1%。种和种群水平上的遗传多样性比较高,分别为Hes=0.210,Hep=0.199;而种群的分化水平则相对较低(GST=0.074)。19个种群中随机交配的偏差为FIS=0.331。每代迁移数的间接估计 相似文献