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Pharmacokinetics and biodistribution of a monoclonal antibody to Cryptococcus neoformans capsular polysaccharide antigen in a rat model of cryptococcal meningitis: implications for passive immunotherapy. 新型隐球菌荚膜多糖抗原单克隆抗体在隐球菌脑膜炎大鼠模型中的药代动力学和生物分布:对被动免疫治疗的影响。
D L Goldman, A Casadevall, L S Zuckier

Several investigators have developed monoclonal antibodies against the capsular polysaccharide of Cryptococcus neoformans which have potential therapeutic applications. Using a rat model of C. neoformans meningitis, we studied the biodistribution and pharmacokinetics of a murine anticryptococcal capsular monoclonal antibody (mAb 2H1) after intravenous and intracisternal administration. After intravenous administration of 125I-labelled 2H1 to infected rats, there was no detectable localization of 125I in the brain or cerebrospinal fluid by either gamma-camera imaging of the whole animal or organ scintillation counting. In contrast, direct intracisternal instillation of 2H1 to infected rats resulted in persistent intracranial activity. In addition, the whole body half-life of intravenously administered radio labelled mAb 2H1 was significantly reduced in infected rats compared with uninfected rats. Our observations suggest that if high central nervous system (CNS) levels of mAb are needed to achieve a therapeutic effect in human C. neoformans meningoencephalitis, direct administration of mAb into the cerebrospinal fluid or modification of the mAb to increase penetration into the CNS may be required. Furthermore, higher or more frequent dosing of mAb may be required to maintain therapeutic levels in the presence of infection. This study demonstrates the usefulness of the rat as an experimental system for studying issues related to cryptococcosis.

一些研究人员已经开发出针对新型隐球菌荚膜多糖的单克隆抗体,具有潜在的治疗应用价值。采用大鼠新生球菌脑膜炎模型,研究了小鼠抗隐球菌荚膜单克隆抗体(mAb 2H1)在静脉注射和腹腔注射后的生物分布和药代动力学。在给感染大鼠静脉注射125I标记的2H1后,通过对整个动物的伽马相机成像或器官闪烁计数,都没有在脑或脑脊液中检测到125I的定位。相反,直接向感染大鼠注入2H1可导致持续的颅内活动。此外,与未感染的大鼠相比,经静脉注射放射性标记mAb 2H1的感染大鼠的全身半衰期显著缩短。我们的观察结果表明,如果需要在中枢神经系统(CNS)中使用高水平的单抗来达到治疗人类新生c型脑膜脑炎的效果,则可能需要将单抗直接注入脑脊液或对单抗进行修饰以增加对中枢神经系统的渗透。此外,在存在感染的情况下,可能需要更高或更频繁的单抗剂量来维持治疗水平。这项研究表明,大鼠作为研究隐球菌病相关问题的实验系统是有用的。
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引用次数: 11
Identification of a 105 kilodalton Cryptococcus neoformans mannoprotein involved in human cell-mediated immune response. 一种105千道尔顿的新型隐球菌甘露蛋白的鉴定与人细胞介导的免疫反应有关。
L Pitzurra, A Vecchiarelli, R Peducci, A Cardinali, F Bistoni

In the present study, using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot techniques, the patterns of proteins extracted from C. neoformans yeast cells were analysed. A major 105 kilodalton (kDa) antigen that binds to Concanavalin A and cross-reacts with anti-mannan antibodies was identified. The 105 kDa mannoprotein, highly expressed in the acapsular mutant of C. neoformans with respect to the encapsulated strain, is involved in the lymphoproliferative response of T lymphocytes to Cryptococcus-sensitized monocytes.

本研究采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和Western blot技术,对从新生酵母细胞中提取的蛋白质进行了分析。鉴定了一种主要的105千道尔顿(kDa)抗原,该抗原与豆豆蛋白A结合并与抗甘露聚糖抗体交叉反应。105kda甘露糖蛋白在新生隐球菌的荚膜突变株中高度表达,参与T淋巴细胞对隐球菌致敏单核细胞的淋巴增生性反应。
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引用次数: 0
In vitro growth-inhibitory activity of pneumocandins L-733,560 and L-743,872 against putatively amphotericin B- and fluconazole-resistant Candida isolates: influence of assay conditions. 肺假丝菌L-733,560和L-743,872对两性霉素B和氟康唑耐药假丝菌的体外生长抑制活性:测定条件的影响
P. W. Nelson, M. Lozano-Chiu, J. Rex
L-733,560 and L-743,872 are water-soluble pneumocandins with potent antifungal activity. By beginning with the NCCLS M27-T method and varying test format (microdilution vs macrodilution), time of reading (24 h vs 48 h), and test medium (RPMI 1640 vs Antibiotic Medium 3), we have demonstrated that the MICs for these compounds can be altered significantly: the microdilution format, reading after 24 h and use of Antibiotic Medium 3 all reduced the measured MIC. No cross-resistance was demonstrated with either fluconazole or amphotericin B.
L-733,560和L-743,872是水溶性肺菌素,具有较强的抗真菌活性。从ncls M27-T方法和不同的测试格式(微稀释vs大稀释)、读取时间(24 h vs 48 h)和测试介质(RPMI 1640 vs抗生素培养基3)开始,我们已经证明,这些化合物的MIC可以显著改变:微稀释格式、24小时后读取和抗生素培养基3的使用都降低了测量的MIC。氟康唑和两性霉素B均未出现交叉耐药。
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引用次数: 59
Interaction between Cryptococcus neoformans and alveolar macrophages. 新型隐球菌与肺泡巨噬细胞的相互作用。
N. Gross, K. Nessa, P. Camner, M. Chinchilla, C. Jarstrand
Phagocytosis, oxidative metabolism and phagolysosomal pH of rat alveolar macrophages (AM) were studied at different points of time after challenge with Cryptococcus neoformans. Phagocytosis was evaluated using a fluorescent quenching technique which distinguishes between attached and ingested organisms. The nitroblue tetrazolium (NBT) test was used as an indirect measurement of the oxidative metabolism of the phagocytes. The pH of the phagolysosomes was measured using a cytofluorometric technique. Both the attachment and ingestion of serum opsonized C. neoformans by AM were slow during the first hours of incubation, but were considerable after 24 h. The oxidative metabolism of Am challenged with the yeast was insignificant during the first hour, but reached high levels after 24 h. Most phagolysosomes in AM with ingested cryptococci had a pH < 5.5. Our results indicate that these AM defence mechanisms, although poor during the first hours after exposure to the yeast, are of significance after 24 h. Thus, in the immunocompetent host the AM should prevent the dissemination of C. neoformans from the lungs.
研究了大鼠肺泡巨噬细胞(AM)在不同时间点的吞噬作用、氧化代谢和吞噬溶酶体pH。使用荧光猝灭技术来评估吞噬作用,该技术可以区分附着的和摄入的生物体。硝基蓝四氮唑(NBT)试验用于间接测量吞噬细胞的氧化代谢。利用细胞荧光技术测定吞噬溶酶体的pH值。AM对血清活化的新生隐球菌的附着和摄取在孵育的最初几个小时内都是缓慢的,但在24小时后就相当大了。酵母攻毒的AM在第一个小时内氧化代谢不明显,但在24小时后就达到了很高的水平。我们的研究结果表明,这些AM防御机制,虽然在暴露于酵母后的第一个小时内很差,但在24小时后是重要的。因此,在免疫能力强的宿主中,AM应该阻止新生梭状菌从肺部传播。
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引用次数: 18
Contact-sensing by hyphae of dermatophytic and saprophytic fungi. 皮生和腐生真菌菌丝的接触感应。
T H Perera, D W Gregory, D Marshall, N A Gow

Contact-sensing or thigmotropism is the directional growth response of cells in relation to topographical guidance cues. Thigmotropism is thought to play a major role in the location of infectable sites on plants by phytopathogenic fungi and has recently been shown to be a property of hyphae in the human pathogenic fungus Candida albicans. Here we show that hyphae of the dermatophytes Epidermophyton floccosum, Microsporum canis and Trichophyton mentagrophytes reorientate their direction of growth in response to grooves and pores of membrane substrata as did hyphae of the saprophytes Mucor mucedo and Neurospora crassa. This suggests that the thigmotropic behaviour of hyphae is not a specific property of pathogens, but rather a general feature of the growth of fungal hyphae that must forage for nutrients on surfaces and within solid materials.

接触感应或向肌性是细胞对地形引导线索的定向生长反应。嗜血性被认为在植物病原真菌对植物感染部位的定位中起主要作用,最近已被证明是人类病原真菌白色念珠菌菌丝的一种特性。本研究表明,与腐生植物Mucor mucedo和Neurospora crassa的菌丝一样,皮生植物、絮状表皮植物、犬小孢子菌和毛霉的菌丝也会根据膜底的沟槽和孔重新调整其生长方向。这表明,菌丝的趋近性行为不是病原体的特定特性,而是真菌菌丝生长的一般特征,菌丝必须在表面和固体材料中觅食营养物质。
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引用次数: 32
Infection caused by Cryptococcus neoformans var. gattii serotype B in an AIDS patient in India. 印度一名艾滋病患者感染由乙型血清型加蒂型新型隐球菌引起。
M. Abraham, V. Mathews, A. Ganesh, T. John, M. Mathews
Cryptococcus neoformans is an opportunistic pathogen infecting AIDS patients. However, infection caused by C. neoformans var. gattii in AIDS patients is reportedly rare. We report herein the first culture proven C. neoformans var. gattii serotype B infection in an AIDS patient in India.
新型隐球菌是感染艾滋病患者的机会致病菌。然而,据报道,艾滋病患者中由新生卡氏弧菌引起的感染是罕见的。我们在此报告在印度的艾滋病患者的第一个培养证实新生C.加蒂变种血清B型感染。
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引用次数: 16
Prevalence and characterization of Microsporum canis carriage in cats. 猫携带犬小孢子虫的流行和特征。
B. Mignon, B. Losson
In order to determine the prevalence and to characterize the carriage of Microsporum canis in cats, different mycological examinations (including a culture obtained by hair brushing and Wood's light examination) were performed on 632 animals of different origins. Group 1 comprised 467 healthy pet cats belonging to veterinary students. In this group, prevalence of carriage was 2.1%: eight cats were asymptomatic transient carriers and one cat was an asymptomatic infected animal presenting discrete Wood's-positive lesions disseminated on the whole body that were visible after sedation and clipping. The carriage prevalence was higher (15.7%) in group 2 comprising 134 European cats destroyed in a pound and kept together. In two additional groups of cats, it was shown that an infected cat was responsible for the dissemination of fungal material into its environment including the other in-contact animals. When the active source of fungus was removed, the dissemination stopped, resulting in a decrease in the amount of infective material recovered from both the animal carriers and the environmental surfaces. This was also observed in two experimental groups of guinea pigs. No association between feline immunodeficiency virus infection and the M. canis carriage was observed in a retrospective case-control study performed on group 2. None of these cats was feline leukaemia virus positive.
为了确定犬小孢子菌在猫中的流行程度和携带特征,对632只不同来源的动物进行了不同的真菌学检查(包括通过刷毛获得的培养和伍德氏光检查)。第一组由兽医学生的467只健康宠物猫组成。在该组中,携带率为2.1%:8只猫是无症状的短暂携带者,1只猫是无症状的感染动物,在镇静和夹夹后,可以看到全身散布的离散伍德氏阳性病变。第2组的携带率较高(15.7%),该组由134只欧洲猫组成,在一磅中被销毁并放在一起。在另外两组猫中,研究表明,受感染的猫负责将真菌物质传播到其环境中,包括其他接触的动物。当真菌的活性来源被去除时,传播停止,导致从动物载体和环境表面回收的感染物质数量减少。在两个实验组的豚鼠中也观察到这一点。在对第2组进行的回顾性病例对照研究中,未观察到猫免疫缺陷病毒感染与犬支原体携带之间的关联。这些猫都没有猫白血病病毒阳性。
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引用次数: 78
Identification of a concanavalin A-binding antigen of the cell surface of Sporothrix schenckii. 申氏孢子丝菌细胞表面豆蛋白a结合抗原的鉴定。
O C Lima, L M Bezerra

Sporothrix schenckii (1099-18) cell wall peptido-rhamnomannan (CWPR) was fractionated by affinity chromatography with Concanavalin A. The Con A-bound and Con A-unbound fractions were probed with an anti-S. schenckii rabbit serum. We identified within the Con A-bound fraction three main antigens with approximate molecular weights of 84, 70 and 58 kDa. Glycopeptide beta-elimination reduced rabbit antiserum reactivity for the 84 kDa antigen (gp84) with concomittant enhanced reactivity for the 70 kDa antigen (gp70). By Western blot with Con A-HRP conjugate we demonstrated that gp84 strongly reacted with this lectin and this was the predominant antigen identified. The gp84 antigen was also demonstrated to be present on other S. schenckii strains.

用Concanavalin a亲和层析法分离申克孢子菌(1099-18)细胞壁肽-鼠李甘露聚糖(CWPR),用抗s检测Con a结合和Con a未结合部分。申氏兔血清。我们在Con a结合片段中鉴定出三种主要抗原,分子量分别为84、70和58 kDa。糖肽β消除降低了兔对84 kDa抗原(gp84)的抗血清反应性,同时增强了对70 kDa抗原(gp70)的反应性。通过Western blot与Con A-HRP偶联,我们证实gp84与该凝集素强烈反应,这是鉴定的优势抗原。gp84抗原也被证实存在于其他申克沙门氏菌株上。
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引用次数: 29
Unusual mould infection of the human stratum corneum. 罕见的人类角质层霉菌感染。
J E Arrese, C Piérard-Franchimont, G E Piérard

Two atopic siblings presented with unilateral chronic scaly plantar lesions. Histology revealed the presence of fungi with unusual morphological aspects. Scopulariopsis brevicaulis and Phoma spp., respectively, grew on repeated cultures. Dermatophytes were absent. Such opportunistic fungal infections of the stratum corneum are extremely rare.

两个异位兄弟姐妹表现为单侧慢性足底鳞状病变。组织学显示真菌的存在与不寻常的形态方面。分别在重复培养上生长的短杆状opsis和Phoma spp。无皮生菌。这种角质层的机会性真菌感染极为罕见。
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引用次数: 18
Protein synthesis patterns of Paracoccidiodes brasiliensis isolates in stage-specific forms and during cellular differentiation. 巴西副球虫分离株在特定阶段和细胞分化过程中的蛋白质合成模式。
S. M. Salem-Izacc, R. S. Jesuíno, W. A. Brito, M. Pereira, M. Felipe, C. M. Soares
In this paper we compared the protein synthesis patterns of Paracoccidioides brasiliensis isolates. The protein profiles were compared for both yeast and mycelial forms and similarity analysis among them was performed by calculating similarity matrices and grouping the isolates in dendrograms. The examined isolates exhibited highly variable cellular morphology at 36 degrees C, when typical yeast cells were expected. On the other hand, at 26 degrees C all the isolates showed mycelial morphology. The analysis of protein synthesis profiles made it possible to cluster the P. brasiliensis isolates into groups that correlated with the morphological data. Interestingly, growth at 36 degrees C strongly decreased the heterogeneity of protein synthesis patterns seen in mycelial isolates. It was possible to cluster the isolates grown at 36 degrees C in three groups based on their two-dimensional protein synthesis analysis. The similarity index observed among the mycelial isolates was lower than that obtained with yeast cells, suggesting a more homogenous gene expression pattern in the host-adapted form than in the saprobic phase.
本文比较了巴西副球虫分离株的蛋白质合成模式。比较了酵母和菌丝体的蛋白质谱,并通过计算相似矩阵和将分离物按树状图分组进行了相似性分析。检测的分离株在36℃时表现出高度可变的细胞形态,而典型的酵母细胞是预期的。另一方面,在26℃时,所有分离株都表现出菌丝形态。蛋白质合成谱分析使得将巴西疟原虫分离物聚类成与形态学数据相关的群成为可能。有趣的是,生长在36摄氏度强烈降低蛋白质合成模式的异质性,在菌丝分离物中看到。根据二维蛋白质合成分析,可以将在36℃下生长的分离株聚类为三组。与酵母细胞相比,菌丝分离物的相似性指数较低,表明在宿主适应形态中,基因表达模式比在腐殖质期更为均匀。
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引用次数: 23
期刊
Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology
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