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排序方式: 共有112条查询结果,搜索用时 218 毫秒
81.
Justin L. McCarville Yotam Nisemblat Heather J. Galipeau Jennifer Jury Rinat Tabakman Ad Cohen Esmira Naftali Bela Neiman Efrat Halbfinger Joseph A. Murray Arivarasu N. Anbazhagan Pradeep K. Dudeja Alexander Varvak Jean-Christophe Leroux Elena F. Verdu 《PloS one》2014,9(11)
Celiac disease (CD) is an autoimmune disorder in individuals that carry DQ2 or DQ8 MHC class II haplotypes, triggered by the ingestion of gluten. There is no current treatment other than a gluten-free diet (GFD). We have previously shown that the BL-7010 copolymer poly(hydroxyethyl methacrylate-co-styrene sulfonate) (P(HEMA-co-SS)) binds with higher efficiency to gliadin than to other proteins present in the small intestine, ameliorating gliadin-induced pathology in the HLA-HCD4/DQ8 model of gluten sensitivity. The aim of this study was to investigate the efficiency of two batches of BL-7010 to interact with gliadin, essential vitamins and digestive enzymes not previously tested, and to assess the ability of the copolymer to reduce gluten-associated pathology using the NOD-DQ8 mouse model, which exhibits more significant small intestinal damage when challenged with gluten than HCD4/DQ8 mice. In addition, the safety and systemic exposure of BL-7010 was evaluated in vivo (in rats) and in vitro (genetic toxicity studies). In vitro binding data showed that BL-7010 interacted with high affinity with gliadin and that BL-7010 had no interaction with the tested vitamins and digestive enzymes. BL-7010 was effective at preventing gluten-induced decreases in villus-to-crypt ratios, intraepithelial lymphocytosis and alterations in paracellular permeability and putative anion transporter-1 mRNA expression in the small intestine. In rats, BL-7010 was well-tolerated and safe following 14 days of daily repeated administration of 3000 mg/kg. BL-7010 did not exhibit any mutagenic effect in the genetic toxicity studies. Using complementary animal models and chronic gluten exposure the results demonstrate that administration of BL-7010 is effective and safe and that it is able to decrease pathology associated with gliadin sensitization warranting the progression to Phase I trials in humans. 相似文献
82.
Jury EC Eldridge J Isenberg DA Kabouridis PS 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(11):7975-7983
It is shown in this study that the heparan sulfate proteoglycan agrin is overexpressed in T cells isolated from patients with the autoimmune disease systemic lupus erythematosus (SLE). Freshly isolated CD4(+) and CD8(+) subpopulations both exhibited higher expression over healthy controls, which however, gradually declined when cells were cultured in vitro. Agrin expression was induced following in vitro activation of cells via their Ag receptor, or after treatment with IFN-alpha, a cytokine shown to be pathogenic in lupus. Furthermore, serum from SLE patients with active disease was able to induce agrin expression when added to T cells from healthy donors, an increase that was partially blocked by neutralizing anti-IFN-alpha Abs. Cross-linking agrin with mAbs resulted in rapid reorganization of the actin cytoskeleton, activation of the ERK MAPK cascade, and augmentation of anti-CD3-induced proliferation and IL-10 production, indicating that agrin is a functional receptor in T cells. These results demonstrate that agrin expression in human T cells is regulated by cell activation and IFN-alpha, and may have an important function during cell activation with potential implications for autoimmunity. 相似文献
83.
Daniel EE Jury J Wang YF 《American journal of physiology. Gastrointestinal and liver physiology》2001,281(4):G1101-G1114
Immunochemical studies with light microscopy, confocal microscopy, and electron microscopy were used to examine proteins associated with caveolin (Cav) in canine lower esophageal sphincter. The main Cav was Cav-1. It appeared to be colocalized at the cell periphery, in punctate sites, with immunoreactivity to antibodies against different COOH- and NH2-terminal epitopes of neuronal nitric oxide (NO) synthase (nNOS). One COOH-terminal-directed antibody, made in guinea pig, was used to colocalize other immunoreactivities. Those that apparently colocalized with nNOS were L-Ca2+ channels, the PM Ca2+ pump, and, in part, calreticulin and calsequestrin. The large-conductance Ca2+-activated K+ (BK(Ca)) channels were located in discrete peripheral sites, some with Cav. Immunoreactivities not fully colocalized with nNOS were to the sarcoplasmic reticulum Ca2+ pump, connexins 43, 40, and 45, and vinculin. In patch-clamp studies, NO-driven outward currents, mainly through BK(Ca) channels, were inhibited by antibodies to Cav-1 and not by calmodulin and were restored by an NO donor. Several Ca2+-handling molecules are localized at the PM with and/or near Cav. This may allow intracellular calcium concentration levels to be controlled differently than those in the cytosol near caveolae. 相似文献
84.
It is generally accepted that crustaceans detect, and respond to, changes in water temperature, yet few studies have directly addressed their thermosensitivity. In this investigation a cardiac assay was used as an indicator that lobsters (Homarus americanus) sensed a change in temperature. The typical cardiac response of lobsters to a 1-min application of a thermal stimulus, either warmer (n = 19) or colder (n = 17) than the holding temperature of 15 degrees C, consisted of a short bradycardia (39.5 +/- 8.0 s) followed by a prolonged tachycardia (188.2 +/- 10.7 s). Lobsters exposed to a range of rates of temperature change (0.7, 1.4, 2.6, 5.0 degrees C/min) responded in a dose-dependent manner, with fewer lobsters responding at slower rates of temperature change. The location of temperature receptors could not be determined, but lesioning of the cardioregulatory nerves eliminated the cardiac response. Although the absolute detection threshold is not known, it is conservatively estimated that lobsters can detect temperature changes of greater than 1 degree C, and probably as small as 0.15 degrees C. A comparison of winter and summer lobsters, both held at 15 degrees C for more than 4 weeks, revealed that although their responses to temperature changes were similar, winter lobsters (n = 18) had a significantly lower baseline heart rate (34.8 +/- 4.4 bpm) and a shorter duration cardiac response (174 s) than summer lobsters (n = 18; 49.9 +/- 5.0 bpm, and 320 s respectively). This suggests that some temperature-independent seasonal modulation of cardiac activity may be occurring. 相似文献
85.
86.
Human combinatorial Fab library yielding specific and functional antibodies against the human fibroblast growth factor receptor 3 总被引:7,自引:0,他引:7
Rauchenberger R Borges E Thomassen-Wolf E Rom E Adar R Yaniv Y Malka M Chumakov I Kotzer S Resnitzky D Knappik A Reiffert S Prassler J Jury K Waldherr D Bauer S Kretzschmar T Yayon A Rothe C 《The Journal of biological chemistry》2003,278(40):38194-38205
The human combinatorial antibody library Fab 1 (HuCAL-Fab 1) was generated by transferring the heavy and light chain variable regions from the previously constructed single-chain Fv library (Knappik, A., Ge, L., Honegger, A., Pack, P., Fischer, M., Wellnhofer, G., Hoess, A., W?lle, J., Plückthun, A., and Virnek?s, B. (2000) J. Mol. Biol. 296, 57-86), diversified in both complementarity-determining regions 3 into a novel Fab display vector, yielding 2.1 x 10(10) different antibody fragments. The modularity has been retained in the Fab display and screening plasmids, ensuring rapid conversion into various antibody formats as well as antibody optimization using prebuilt maturation cassettes. HuCAL-Fab 1 was challenged against the human fibroblast growth factor receptor 3, a potential therapeutic antibody target, against which, to the best of our knowledge, no functional antibodies could be generated so far. A unique screening mode was designed utilizing recombinant functional proteins and cell lines differentially expressing fibroblast growth factor receptor isoforms diversified in expression and receptor dependence. Specific Fab fragments with subnanomolar affinities were isolated by selection without any maturation steps as determined by fluorescence flow cytometry. Some of the selected Fab fragments completely inhibit target-mediated cell proliferation, rendering them the first monoclonal antibodies against fibroblast growth factor receptors having significant function blocking activity. This study validates HuCAL-Fab 1 as a valuable source for the generation of target-specific antibodies for therapeutic applications. 相似文献
87.
88.
Gang Dai Noel W. Dunn Gwen E. Allison Karen L. Jury Ping Su Ping Zhu 《Biotechnology letters》2000,22(9):721-725
A random mutation strategy using mutator strain, Epicurian coli XL1-Red, was applied to a plasmid, pND018, constructed by inserting a Lactococcus lacis bacteriophage resistance gene (abiI) into a L. lactis/E. coli shuttle vector (pDL278), to introduce random mutations throughout the plasmid. Following transformation of the mutated plasmid library to a plasmid free and phage sensitive strain of L. lactis (LM0230), mutated plasmids were screened by cross-streaking and efficiency of plaquing (EOP) assays. Two strains with enhanced resistance were obtained, as well as several phage sensitive strains. Repeated transformation of the mutated plasmids to LM0230 confirmed that the observed phenotypes were caused by mutations located on the plasmids. The EOP values and plaque morphology of two enhanced phage resistance mutants were characterized at 30°C and 37°C. These results indicate that this simple procedure can be applied to generate modified plasmids with improved phage resistance, which may be of commercial value. 相似文献
89.
We used flow cytometry to measure the nuclear DNA content in erythrocytes of 27 salamandrid species. Across these species, diploid genome size varied more than 2 fold (51.3-104.4 pg). According to genome size and geographic distribution, 3 groups of newt species were recognized: West Palearctics with smaller amounts of nuclear DNA; Nearctic, with intermediate values; and East Asiatic, with higher genome sizes. Viviparous West Palearctic salamanders differed from most of the oviparous West Palearctic newts in possessing larger genome sizes. The nuclear DNA content strongly correlates with species range limits. At the same temperature, embryos of salamandrid species with larger genome sizes have a markedly longer developmental time than those with smaller genomes. We present an analysis of the relationships between the amount of nuclear DNA and water temperature at the breeding sites. 相似文献
90.
Renata Sõukand Yanina Hrynevich Julia Prakofjewa Tatsiana Valodzina Iryna Vasilyeva Jury Paciupa Aliaksandra Shrubok Aliaksei Hlushko Yana Knureva Yulia Litvinava Siarhei Vyskvarka Hanna Silivonchyk Alena Paulava Mare Kõiva Raivo Kalle 《Journal of ethnobiology and ethnomedicine》2017,13(1):54