Precipitins to an aflatoxin-producing strain of aspergillus flavus in patients with malignancy

Summary Serum samples from 121 patients in whom malignant disease had been diagnosed, were assayed for precipitins to fungal isolates from leukemia-associated environments. Control sera were from age-, sex-, and race-matched patients with no history of malignant disease. Sera from 36 (30%) malignancy patients and seven (6%) controls yielded a precipitin band to an aflatoxin-producing Aspergillus flavus isolate from a leukemia-associated house ², p<0.05%). No significant numbers of precipitins were obtained to either of the other fungal isolates from that and another such house.Although A. fumigatus has frequently been incriminated as a source of infection in patients with malignancy, only 9% of malignancy patients had a precipitin response to it, as did 1.6% of controls. Also, the presence of the precipitins to A. flavus was not connected with past radiation or imunosuppressive therapy. However, among patients with precipitins to A. fumigatus there was a higher death rate in the year following the study. Precipitins to A. flavus may be related to heavy environmental exposure possibly leading to aflatoxin exposure which may contribute to development of malignancy through immunosuppressive effects.     

The Genomic Regions That Contain Ochratoxin A Biosynthetic Genes Widely Differ in Aspergillus Section Circumdati Species

Aspergillus section Circumdati includes 27 species, some of which are considered ochratoxin A (OTA) producers. However, there is considerable controversy about their potential OTA synthesis ability. In this work, the complete genomes of 13 species of Aspergillus section Circumdati were analyzed in order to study the cluster of OTA biosynthetic genes and the region was compared to those previously reported in A. steynii and A. westerdijkiae. The results obtained reveal that the genomes of some species in this section, including A. affinis, A. cretensis, A. elegans, A. muricatus, A. pulvericola, A. roseoglobulosus, and A. subramanianii, contain a potentially functional OTA biosynthetic cluster. Therefore, they might be able to synthesize the toxin. On the contrary, A. melleus, A. ochraceus, A. ostianus, A. persii, A. sclerotiorum, A. sesamicola, and A. westlandensis contain a truncated version of the cluster that lacks many of the genes involved in OTA biosynthesis, which might be related to their inability to produce OTA. The gain/loss pattern is different in all species, which suggests that the genetic evolution of this region might be due to independent events.     

Protection of immunocompromised mice from fungal infection with a thymus growth-stimulatory component from Selaginella involvens,a fern

Context:?Recent studies have shown that the water extract of Selaginella involvens (Sw.) Spring, a wild fern, exhibits thymus growth-stimulatory activity in adult mice (reversal of involution of thymus) and remarkable anti-lipid peroxidation activity. Follow-up studies were carried out in the present study.

Materials and Methods:?Activity-guided isolation of the active component (AC) was carried out. The effect of AC on immune function was studied using fungal (Aspergillus fumigatus) challenge in cortisone-treated mice. The in vitro antifungal activity of AC was assayed using disc diffusion assay. In vitro and in vivo effect of AC on DNA synthesis in thymus was studied using ³H-thymidine incorporation. In in vitro anti-lipid peroxidation, hydroxyl radical scavenging and inhibition of superoxide production were assayed.

Results:?The active principle/component (AC) was isolated in a chromatographically pure form from the water extract of S. involvens. AC showed positive reaction to glycosides. AC possessed both thymus growth-stimulatory and antioxidant properties. It protected cortisone-treated mice from A. fumigatus challenge. It did not exhibit in vitro antifungal activity. Increased ³H-thymidine incorporation was observed in the reticuloepithelium of thymus obtained from AC-treated mice. However, in vitro AC treatment to thymus for 5?h did not result in an increase in ³H-thymidine incorporation.

Discussion and conclusion:?AC (named as Selagin), from S. involvens, could reverse involution of thymus to a large extent, exhibit remarkable antioxidant activity, and protect immunocompromised mice from fungal infection. Therefore, it is very promising for the development of a drug to ameliorate old age-related health problems and prolong lifespan.     

Clinical utility of antifungal susceptibility testing in patients with fungal rhinosinusitis

PurposeTo determine the association between antifungal susceptibility test (AFST) results and in vivo therapeutic response in Indian patients with fungal rhinosinusitis.MethodsThe clinicoradiological, fungal culture, AFST, histopathology results and outcomes of 48 patients with fungal rhinosinusitis seen between 20132015 were analysed. Minimum inhibitory concentration (MIC) determination was performed for amphotericin B, itraconazole, voriconazole and posaconazole.ResultsForty patients had invasive and 8 had non-invasive fungal sinusitis. Rhizopus and Aspergillus species which comprised 46.9% each of isolates were mostly associated with acute invasive fungal rhinosinusitis and chronic granulomatous fungal rhinosinusitis respectively. All patients with non-invasive fungal rhinosinusitis had Aspergillus isolates.The Geometric Mean (GM) MIC for R. arrhizus of amphotericin B and posaconazole was 0.51 mcg/mL and 3.08 mcg/mL respectively and for A. flavus species for amphotericin B and voriconazole values were 1.41mcg/mL and 0.35 mcg/mL respectively.In patients with Aspergillus infections, while there was no association of MICs for azoles and outcome (p = 1), a strong association was noted between azole therapy and a good outcome (p = 0.003). In patients with Rhizopus infections, no association was found between MICs for amphotericin B and outcome (p = 1) and because of therapeutic complications, no association was found between amphotericin B therapy and outcome (p = 1).ConclusionNo significant association exists between in vitro (AFST) and in vivo responses despite low GM MICs for the drugs used in Aspergillus and Rhizopus infections. Therapeutic complications following conventional amphotericin B therapy confounds analysis. Clinical responses suggest that azoles are the drug of choice for Aspergillus infections.     

TLR2对曲霉感染支气管上皮细胞时Dectin-1表达的影响

目的 探讨烟曲霉感染人支气管上皮（HBE）细胞时Toll样受体2（TLR2）对树突状细胞植物血凝素-1 （Dectin-1）表达的影响.方法 建立烟曲霉感染HBE细胞模型,通过PCR、Western blot方法分别在mRNA、蛋白水平检测Dectin-1和TLR2的表达情况;沉默TLR2,复制感染模型,应用Western blot及流式细胞技术评价Dectin-1的表达变化.结果 ①烟曲霉感染后HBE细胞TLR2表达水平虽然有所升高,并在感染18h达到峰值,但与静息状态表达水平的差异无统计学意义（P＞0.05）.②沉默TLR2,在烟曲霉感染HBE细胞后18 h时Dectiin1的蛋白表达受到显著抑制（P＜0.05）.结论 HBE细胞静息状态下能够表达TLR2,在烟曲霉感染早期,随着时间的延长其表达有逐步增高的趋势;HBE细胞启动Dectin-1的表达可能是建立在TLR2对烟曲霉早期识别的基础上,通过下游信号通路的激活来实现的。     

烟曲霉致病相关因子的研究进展

毒力因子是在病原体适应生存环境的过程中产生.烟曲霉毒力是多因素相关的,包括微小的孢子结构使之能够吸入到达宿主的肺泡,耐热特征,疏水性,快速的繁殖速度以及抵抗氧化应激反应的能力.此外,烟曲霉适应环境及代谢相关的蛋白、通路信号分子、脂类代谢产物、毒素等均可看作毒力因子.     

Severe cutaneous aspergillosis in a premature neonate linked to nonsterile disposable glove contamination?

After having eliminated a dysfunction of the hospital's ventilation system and any other possible environmental reservoir, the investigation of a fatal case of primary cutaneous aspergillosis in a neonate with extremely low birth weight led to the conclusion that nonsterile disposable gloves kept stored in their native packages were the likely source of contamination.     

Antibody to Aspergillus fumigatus Antigens in Normal Sera: Influence on Positive-Negative Discrimination in ELISA

The response of precipitin-negative sera from non-selected asthmatic patients against a range of somatic and culture filtrate antigens of Aspergillus fumigatus in ELISA for anti-A. fumigatus IgG is described. Antibody to the various antigens was widely distributed but the precise distribution was dependent upon antigen type. To determine how the selection of negative reference sera from precipitin-negative sera can influence the discrimination between precipitin-positive and -negative sera in ELISA, panels of 10 sera were chosen from the extremes of the frequency distribution and by random selection. The closest agreement between precipitin testing and ELISA was seen when randomly-selected negative reference sera were incorporated in the assay, although the degree of correlation was dependent upon the detector antigen. These findings demonstrate the requirement for careful selection of sera included as negative reference sera in ELISA for anti-A. fumigatus IgG.