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《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
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静脉预注H1,H2受体阻滞药对减轻鱼精蛋白副作用的研究 总被引:3,自引:0,他引:3
将30例ASD、VSD患者随机分为对照与预防用药两组,对比观察H1、H2受体阻滞药苯海拉明、西米替丁对减轻鱼精蛋白副作用的效果和应用鱼精蛋白后补体C3、C4、CH50浓度变化。结果发现预防用药组血液动力学变化明显小于对照组,两组之间差异显著(P<0.01)。应用鱼精蛋白后C3、C4、CH50均下降,与用药前相比差异显著(P<0.01)。提示鱼精蛋白中和肝素可引起补体激活、组胺释放,H1、H2受体阻滞药能够减轻鱼精蛋白引起的血压下降。 相似文献
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Dario Roccatello Marco Formica Guido Cavalli Maria C. Amprimo Maria G. Pignatelli Paolo Costa Ruggero de Paulis Giacomo Quattrocchio rea Molino Gianbeppe Giordano 《Artificial organs》1990,14(1):69-72
Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated. 相似文献
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Neutrophil Oxygen Radical Production by Dialysis Membranes 总被引:1,自引:0,他引:1
The ability of different dialysis membranes to activate polymorphonuclearneutrophil oxygen radical production was investigated with chemiluminescence.All the six membranes, namely cuprophan, cellulose acetate,polycarbonate, polysulphone, polyacrilonitrile and polymethylmethacrylatewere able to interact with neutrophils and stimulate their oxygenradical production, the highest responses being seen with polyacrilonitrile,polymethylmethacrylate and polycarbonate. To analyse the roleof complement in this interaction, fresh plasma, heat inactivatedand zymosan-activated plasma were added: with fresh plasma oxygenradical production was stimulated on cuprophan, cellulose acetateand polysulphone, not modified on polycarbonate, and decreasedon polyacrilonitrile and polymethylmethacrylate. With heat-inactivatedplasma, the responses were decreased or abrogated on all themembranes except polycarbonate and polymethylmethacrylate, whereaswith zymosanactivated plasma similar responses to fresh plasmawere observed. In addition, when plasma was used to precoatthe membrane, cuprophan, cellulose acetate and polysulphonedisclosed an enhanced neutrophil oxidative burst, while precoatedpolyacrilonitrile and polymethylmethacrylate were less stimulatorythan uncoated membranes. In contrast the precoating of polycarbonatedid not modify oxygen radical production. These data suggestthat neutrophil activation occurs by direct membrane neutrophilinteraction. Plasmatic factors modulate this interaction butcomplement seems involved on cellulosic and polysulphone membranesonly. Therefore, it appears that oxygen radicals produced fromcontact of neutrophils with the dialysis membrane might playan initial and/or additional role in the events occurring atthe initiation of haemodialysis. 相似文献
7.
O. F. M. SELLEVOLD T. M. BERG K. A. REIN O. W. LEVANG O–J. IVERSEN K. BERGH 《Acta anaesthesiologica Scandinavica》1994,38(4):372-379
A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml-1±1.2 to 27.5 ng ml-1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml-1 ± 1.2 to 35.6 ng ml-1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated. 相似文献
8.
中华眼镜蛇蛇毒对大鼠异种心脏移植超急性排斥反应的影响 总被引:6,自引:1,他引:5
试用中华眼镜蛇蛇毒消耗补体,观察其对豚鼠到SD大鼠异种心脏移植超急性排斥反应的影响。一次性给予小剂量CCV腹腔注射后可明显降低大鼠血清补体溶血活性,4-24小时后渐降至给药前1/2以下水平。CCV可明显延长异种移植心脏4 存活时间达2.5-36小时,对照组仅为25分钟;CCV与脾切除,前列腺素E1联用可进一步延长移植心的存活时间,最长1例达40小时。 相似文献
9.
Effects of zymosan-activated plasma and phorbol myristate acetate on isolated, perfused rabbit lungs
The effects of complement activation on pulmonary vascular permeability are disputed. In rabbit lungs perfused with autologous blood, zymosan activated plasma (ZAP) induced a moderate increase in pulmonary vascular resistance (PVR), but did not detectably change the vascular permeability within 2 h. The stronger neutrophil granulocyte (PMN) activator, phorbol myristate acetate (PMA), usually gave larger PVR increases and also increased pulmonary vascular permeability. Lungs from neutropenic animals, similarly perfused and given PMA, showed unchanged PVR reactions but had no apparent increase in vascular permeability. Lungs perfused with cell-free medium and given PMA displayed modest PVR increases, and no measurable permeability change. The lung preparatory procedure itself markedly influenced leukocyte circulation. Exsanguination of lung donors decreased the concentration of circulating PMN significantly, and they virtually disappeared from the perfusate within minutes after start of lung perfusion. PMN-mediated effects must therefore have been caused by cells already sequestered in the lungs. We conclude that ZAP does not induce an increased pulmonary vascular permeability in isolated, perfused rabbit lungs, in contrast to PMA. The permeability effects of PMA appear to be PMN dependent. 相似文献
10.
中国人不同C4基因型时血中C4浓度的定量检测 总被引:1,自引:0,他引:1
用神经氨酸酶及羧肽酶B处理血浆,依次经C4高压琼脂糖电泳、免疫固定、薄层激光扫描等步骤,并结合血浆免疫火箭电泳定量法对我国武汉地区随机人群的血浆C4总量及C4两种同种型,主要别型,单、双QO,重复座位等时的血浆C4含量进行了检测与分析。结果发现:遗传因素明显影响血浆C4水平,因而在群体中表现宽广的C4浓度范围,特别在有C4QO与C4重复基因座位时差异特别明显。这一研究提示,不同的C4基因型,循环C4含量表现明显差异。临床上检测C4含量时应该考虑患者的C4基因型别。 相似文献