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1.
《Vaccine》2021,39(30):4099-4107
The fungal genus Candida includes common commensals of the human mucosal membranes, and the most prevalently isolated species, C. albicans, poses a threat of candidemia and disseminated infection associated with an unacceptably high mortality rate and an immense $4 billion burden (US) yearly. Nevertheless, the demand for a vaccine remains wholly unfulfilled and increasingly pressing. We developed a double-peptide construct that is feasible for use in humans with the intention of preventing morbid infection by targeting epitopes derived from fructose bisphosphate aldolase (Fba) and methionine synthase (Met6) which are expressed on the C. albicans cell surface. To test the applicability of the design, we vaccinated mice via the intramuscular (IM) route with the conjugate denoted Fba-Met6 MP12 and showed that the vaccine enhanced survival against a lethal challenge. Because overall endpoint IgG1 and IgG2a antibody titers were robust and these mouse subclasses are associated with protective functionality, we investigated the potential of Fba and Met6 specific antibodies to facilitate the well-defined anti-Candida response by complement, which opsonizes fungi for degradation by primary effectors. Notably, reductions in the fungal burdens and enhanced survival were both abrogated in MP12-vaccinated mice that were pre-challenge dosed with cobra venom factor (CVF), a complement depleting factor. Altogether, we demonstrated that complement is relevant to MP12-based protection against disseminated C. albicans, delineating that a novel, multivalent targeted vaccine against proteins on the surface of C. albicans can enhance the natural response to infection. 相似文献
2.
PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular
mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of
G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling
pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system.
PTH was administered intermittently (4 min/h, 10−7 M) or continuously at an equivalent cumulative dose (6.6 × 10−9 M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein
levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to
continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor.
In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH
for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13
and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation
of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling. 相似文献
3.
Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (IK,Ca) were investigated in ramified murine brain macrophages. In order to induce IK,Ca the intracellular concentration of nominal free Ca2+ was adjusted to 1μM. The Ca2+-activated K+ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change
in extracellular K+ concentration shifted the reversal potential of IK,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect IK,Ca. Ca2+-activated K+ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal
effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit
IK,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of IK,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested
at a concentration of 2mM for their ability to block IK,Ca. La3+ reduced IK,Ca by 72.8%, whereas Cd2+ decreased IK,Ca by 17.4%; in contrast, Ni2+ did not have any effect on IK,Ca. Ba2+ applied at a concentration of 1mM reduced IK,Ca voltage-dependently at hyperpolarizing potentials.
Received: 17 January / Accepted: 5 May 1997 相似文献
4.
Emilie Balasse Gregory Gatouillat Dominique Patigny Marie Christine Andry Claudie Madoulet 《Vaccine》2009
Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth. 相似文献
5.
具有骨诱导活性的仿生骨基质材料的制备 总被引:9,自引:2,他引:7
目的将一种具有与骨形态发生蛋白2相似骨诱导活性的多肽p24共价结合于改性聚(丙交酯-co-乙交酯)基质材料上,以制备出具有骨诱导活性的仿生骨基质材料。方法将活性多肽p24通过交联剂共价结合于改性PLGA材料上作为实验组;以未加交联剂多肽溶液和材料简单混合反应为对照组,通过X射线光电子光谱法和扫描电镜检测交联情况;同时对两组材料进行钙离子吸附实验,初步评价其仿生矿化能力。结果XPS检测结果表明,实验组及对照组材料表面均已结合硫元素,两者含有硫元素含量分别为1.50%及0.09%;钙离子吸附实验结果表明,12h及24h时实验组材料的钙离子吸附量分别为0,126mg及0.231mg;12h及24h时对照组材料的钙离子吸附量分别为0.053、0.102mg。多肽交联之材料较混合之材料的钙离子吸附能力显著增强。结论在改性PLGA三嵌段材料上固定了BMP2活性多肽,为以后发挥其骨诱导活性修复骨缺损奠定了良好基础。 相似文献
6.
高效液相色谱法测定脑活素注射液中的氨基酸含量及肽图分析 总被引:9,自引:2,他引:7
本文采用高效液相色谱法分析研究了进口药品脑活素注射液中的氨基酸含量及其低分子肽的肽图。试验结果反映了该药品的内在质量,同时提出控制质量的可靠方法. 相似文献
7.
8.
Thomas Wlfel Aline Van Pel Vincent Brichard Jrg Schneider Barbara Seliger Karl-Hermann Meyer Zum Büschenfelde Thierry Boon 《European journal of immunology》1994,24(3):759-764
A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368–376. Both peptides contain consensus motifs of HLA-A2 binding peptides. 相似文献
9.
抗性家蝇蛹期多肽的双向电泳分析 总被引:5,自引:0,他引:5
分析抗性家蝇蛹期多肽,以了解蛋白质变化情况。方法:对家蝇的抗性株、对照株和敏感株蛹体内的多肽进行了聚丙烯酸胺凝胶电泳分析。结果:抗性株具有一特异的多肽点,且有3个多肽点在量上明显多于对照株。结论:杀虫剂的作用可使抗性家蝇体内的蛋白在质和量上发生改变。 相似文献
10.
Dengjel J Decker P Schoor O Altenberend F Weinschenk T Rammensee HG Stevanovic S 《European journal of immunology》2004,34(12):3644-3651
T-helper (Th) cells play an important role in orchestrating the effector function of CTL in anti-tumor immunity. However, only a limited number of Th cell epitopes has been characterized. Here we describe a novel approach for identifying naturally processed and presented peptides derived from chosen antigens. This method combines a transfection step of antigen-presenting cells with a vector encoding a fusion protein between the Ii chain and the antigen of interest, elution of the HLA-bound peptides and identification of the antigen-derived peptides by mass spectrometric comparison to the non-transfected cells. In vitro-stimulated Th cells against the identified peptide of interest specifically recognize transfectants overexpressing the cognate antigen. Using this approach, we were able to identify the HLA-DR4-restricted Th cell epitope NPPSMVAAGSVVAAV derived from cyclin D1, which is frequently overexpressed in tumors. This method will help in identifying peptide candidates for vaccination studies for tumor immunotherapy. 相似文献