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排序方式: 共有693条查询结果,搜索用时 109 毫秒
61.
Bourges D Zhan Y Brady JL Braley H Caminschi I Prato S Villadangos JA Lew AM 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(9):5678-5685
Systemic delivery of Ag usually induces poor mucosal immunity. To improve the CD8 T cell response at mucosal sites, we targeted the Ag to MAdCAM-1, a mucosal addressin cell adhesion molecule expressed mainly by high endothelial venules (HEV) in mesenteric lymph nodes (MLN) and Peyer's patches of gut-associated lymphoid tissue. When chemical conjugates of anti-MAdCAM-1 Ab and model Ag OVA were injected i.v., a greatly enhanced proliferative response of Ag-specific OT-I CD8 T cells was detected in MLN. This was preceded by prolonged accumulation, up to 2 wk, of the anti-MAdCAM OVA conjugate on HEV of Peyer's patches and MLN. In contrast, nontargeted OVA conjugate was very inefficient in inducing OT-I CD8 T cell proliferation in MLN and required at least 20-fold more Ag to induce a comparable response. In addition, MAdCAM targeting elicits an endogenous OVA-specific CD8 T cell response, evident by IFN-gamma production and target killing. Induced response offers protection against an OVA-expressing B cell lymphoma. We propose that the augmentation of gut CD8 T cell responses by MAdCAM targeting is due to both accumulation of Ag in the HEV and conversion of a soluble Ag to a cell-associated one, allowing cross-presentation by DCs. 相似文献
62.
Bernard L Vaudaux P Huggler E Stern R Fréhel C Francois P Lew D Hoffmeyer P 《FEMS immunology and medical microbiology》2007,49(3):425-432
Polymorphonuclear neutrophils, a first line of defence against invading microbial pathogens, may be attracted by inflammatory mediators triggered by ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles released from orthopaedic prostheses. Phagocytosis of UHMWPE particles by neutrophils may indirectly compromise their phagocytic-bactericidal mechanisms, thus enhancing host susceptibility to microbial infections. In an in vitro assay, pre-exposure of purified human neutrophils to UHMWPE micrometre- and submicrometre-sized wear particles interfered with subsequent Staphylococcos aureus uptake in a heterogeneous way, as assessed by a dual label fluorescence microscopic assay that discriminated intracellular rhodamine-labelled UHMWPE particles from fluorescein isothiocyanate-labelled S. aureus. Indeed, a higher percentage (44%) of neutrophils having engulfed UHMWPE particles lost the ability to phagocytize S. aureus, compared with UHMWPE-free neutrophils (<3%). Pre-exposure of neutrophils to UHMWPE wear particles did not impair but rather stimulated their oxidative burst response in a chemoluminescence assay. The presence of UHMWPE wear particles did not lead to significant overall consumption of complement-mediated opsonic factors nor decreased surface membrane display of neutrophil complement receptors. In conclusion, engulfment of UHMWPE wear particles led to inactivation of S. aureus uptake in nearly half of the neutrophil population, which may potentially impair host clearance mechanisms against pyogenic infections. 相似文献
63.
Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) accelerate spatial learning and facilitate memory retention and retrieval by binding competitively to the catalytic site of the enzyme and inhibiting its catalytic activity. IRAP belongs to the M1 family of Zn2+-dependent aminopeptidases characterized by a catalytic domain that contains two conserved motifs, the HEXXH(X)18E Zn2+-binding motif and the GXMEN exopeptidase motif. To elucidate the role of GXMEN in binding peptide substrates and competitive inhibitors, site-directed mutagenesis was performed on the motif. Non-conserved mutations of residues G428, A429 and N432 resulted in mutant enzymes with altered catalytic activity, as well as divergent changes in kinetic properties towards the synthetic substrate leucine beta-naphthylamide. The affinities of the IRAP inhibitors angiotensin IV, Nle1-angiotensin IV, and LVV-hemorphin-7 were selectively decreased. Substrate degradation studies using the in vitro substrates vasopressin and Leu-enkephalin showed that replacement of G428 by either D, E or Q selectively abolished the catalysis of Leu-enkephalin, while [A429G]IRAP and [N432A]IRAP mutants were incapable of cleaving both substrates. These mutational studies indicate that G428, A429 and N432 are important for binding of both peptide substrates and inhibitors, and confirm previous results demonstrating that peptide IRAP inhibitors competitively bind to its catalytic site. 相似文献
64.
Anna CC Aguiar Ananda C Cunha Isabela Penna Ceravolo Regina A Correia Gon?alves Arildo JB Oliveira Antoniana Ursine Krettli 《Memórias do Instituto Oswaldo Cruz》2015,110(7):906-913
Several species of Aspidosperma plants are used to treat diseases in
the tropics, including Aspidosperma ramiflorum, which acts against
leishmaniasis, an activity that is experimentally confirmed. The species, known as
guatambu-yellow, yellow peroba,
coffee-peroba andmatiambu, grows in the Atlantic
Forest of Brazil in the South to the Southeast regions. Through a guided
biofractionation of A. ramiflorum extracts, the plant activity
against Plasmodium falciparum was evaluated in vitro for toxicity
towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human
monocytes isolated from peripheral blood. Six of the seven extracts tested were
active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the
aqueous extract was inactive. Overall, the plant extracts and the purified compounds
displayed low toxicity in vitro. A nonsoluble extract fraction and one purified
alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56
and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The
structure, activity and low toxicity of isositsirikine in vitro are described here
for the first time in A. ramiflorum, but only the neutral and
precipitate plant fractions were tested for activity, which caused up to 53%
parasitaemia inhibition of Plasmodium berghei in mice with
blood-induced malaria. This plant species is likely to be useful in the further
development of an antimalarial drug, but its pharmacological evaluation is still
required. 相似文献
65.
Cell polarity is typically oriented by external cues such as cell-cell contacts, chemoattractants, or morphogen gradients. In the absence of such cues, however, many cells can spontaneously polarize in a random direction, suggesting the existence of an internal polarity-generating mechanism whose direction can be spatially biased by external cues. Spontaneous 'symmetry-breaking' polarization is likely to involve an autocatalytic process set off by small random fluctuations. Here we review recent work on the nature of the autocatalytic process in budding yeast and on the question of why polarized cells only develop a single 'front'. 相似文献
66.
An integrated UASB-sludge digester system for raw domestic wastewater treatment in temperate climates 总被引:1,自引:0,他引:1
To improve the performance of an upflow anaerobic sludge blanket (UASB) reactor treating raw domestic wastewater under temperate climates conditions, the addition of a sludge digester to the process was investigated. With the decrease in temperature, the COD removal decreased from 78% at 28 °C to 42% at 10 °C for the UASB reactor operating alone at a hydraulic retention time of 6 h. The decrease was attributed to low hydrolytic activity at lower temperatures that reduced suspended matter degradation and resulted in solids accumulation in the top of the sludge blanket. Solids removed from the upper part of the UASB sludge were treated in an anaerobic digester. Based on sludge degradation kinetics at 30 °C, a digester of 0.66 l per liter of UASB reactor was design operating at a 3.20 days retention time. Methane produced by the sludge digester is sufficient to maintain the temperature at 30 °C. 相似文献
67.
68.
Riera KM Rothfusz NE Wilusz RE Weinberg JB Guilak F McNulty AL 《Arthritis research & therapy》2011,13(6):R187
Introduction
Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair. 相似文献69.
Riquelme M Yarden O Bartnicki-Garcia S Bowman B Castro-Longoria E Free SJ Fleissner A Freitag M Lew RR Mouriño-Pérez R Plamann M Rasmussen C Richthammer C Roberson RW Sanchez-Leon E Seiler S Watters MK 《Fungal biology》2011,115(6):446-474
Neurospora crassa has been at the forefront of biological research from the early days of biochemical genetics to current progress being made in understanding gene and genetic network function. Here, we discuss recent developments in analysis of the fundamental form of fungal growth, development and proliferation -- the hypha. Understanding the establishment and maintenance of polarity, hyphal elongation, septation, branching and differentiation are at the core of current research. The advances in the identification and functional dissection of regulatory as well as structural components of the hypha provide an expanding basis for elucidation of fundamental attributes of the fungal cell. The availability and continuous development of various molecular and microscopic tools, as utilized by an active and co-supportive research community, promises to yield additional important new discoveries on the biology of fungi. 相似文献
70.
Couzinet S Yugueros J Barras C Visomblin N Francois P Lacroix B Vernet G Lew D Troesch A Schrenzel J Jay C 《Journal of microbiological methods》2005,60(2):275-279
Using high-density oligonucleotide array technology, 30 Staphylococcus aureus strains were studied for the presence of mutations in genes involved in fluoroquinolone resistance: grlA, gyrA, grlB and gyrB. For the two most important genes, gyrA and grlA, correlation with sequencing reached 95.1%. If all genes were considered, correlation was 88.8%. 相似文献