Association of furunculosis and familial deficiency of mannose-binding lectin

BACKGROUND: Polymorphisms in the mannose-binding lectin gene reduce serum mannose-binding lectin levels and are associated with enhanced risk of infection. In a family with recurrent staphylococcal disease presenting as furunculosis or carbuncles, an association with mannose-binding lectin deficiency was investigated. MATERIALS AND METHODS: Levels of functional mannose-binding lectin were estimated and the genotypes of the mannose-binding lectin gene were analysed on blood samples, collected from the members of one particular family with a high prevalence of furunculosis. RESULTS: Functional mannose-binding lectin levels in sera of 13 of the 28 members of one family showed deficiency. Furunculosis or carbuncles appeared to be present in nine of the 28 family members, seven of which showing the pBly allele and mannose-binding lectin deficiency. Four young family members of the second generation were pBly positive and mannose-binding lectin deficient, but had not shown furunculosis yet. CONCLUSION: Members of a particular family suffering from furunculosis differ from their 'healthy' relatives as to mannose-binding lectin genotypes, indicating the relevance of normal mannose-binding lectin levels in the defence against staphylococcal disease.     

甘露糖结合凝集素水平的调节与肺结核易感性关系的研究

目的研究甘露糖结合凝集素(MBL)水平的调节与肺结核易感性的关系。方法对142例肺结核患者和120例健康对照者血清中MBL水平进行测定。同时采用限制性片段长度多态性分析方法对MBL2基因多态性进行测定。结果采用单因素方差分析不同基因型组的MBL水平,YA/YA组,XA/YA组和XA/XA、YA/YB、XA/YB、YB/YB组,发现3组之间和任何两组之间的MBL水平差异均有统计学意义(P0.01)。肺结核患者MBL水平显著高于健康对照(P0.01)。健康对照者中携带YA/YA基因的个体中有93.2%(55/59)的MBL水平大于1 000ng/mL。而携带XA/XA或B等位基因的个体100%(26/26)的MBL水平小于或等于1 000ng/mL。结论 MBL水平可能与肺结核易感性有关,而决定高水平MBL的YA/YA基因可能是一种保护性基因。     

甘露糖结合凝集素基因多态性与妊娠糖尿病的关系

摘要:目的：探讨甘露糖结合凝集素(MBL)基因外显子上的52、54、57密码子以及其启动子区域 550位点多态性与妊娠糖尿病(GDM)发病的关系。 方法：选取GDM患者、正常妊娠对照各75例,检测血糖、血压、血清MBL水平,并用基因测序法检测并分析MBL基因外显子上的52、54、57密码子以及启动子区域 550位点的序列特征。 结果：GDM组和正常妊娠对照组MBL基因外显子上的54位密码子和启动子区550位点存在多态性,并且其对应的等位基因频率存在统计学差异（χ²分别为5.811和6.475,P<0.05）,Logistic回归分析显示其突变型为GDM的危险因素。正常妊娠对照组血清MBL水平高于GDM组（t=3.10,P<0.05）。54位密码子位点的野生型、杂合型、纯合突变型血清MBL水平差异有统计学意义（F=81.939,P<0.05）。 结论: MBL基因外显子上的54密码子及启动子区 550位点多态性位点与南京地区汉族GDM有关。     

Strategies developed by bacteria and virus for protection from the human complement system

The complement system is an important part of innate immunity providing immediate protection against pathogens without a need for previous exposure. Its importance is clearly shown by the fact that patients lacking complement components suffer from fulminant and recurring infections. Complement is an explosive cascade, and in order to control it there are inhibitors present on every human cell and also circulating in blood. However, many infectious agents have developed strategies to prevent clearance and destruction by complement. Some pathogens simply hijack the host's complement inhibitors, while others are able to produce their own homologues of human inhibitors. Knowledge of these mechanisms on a molecular level may aid development of vaccines and novel therapeutic strategies that would be more specific than the use of antibiotics that, apart from causing resistance problems, also affect the normal flora, the outcome of which could be devastating. In this study the structural requirements and functional consequences of interactions between the major soluble inhibitor of complement C4b‐binding protein and Neisseria gonorrhoeae, Bordetella pertussis, Streptococcus pyogenes, Escherichia coli K1, Moraxella catarrhalis and Candida albicans are described. Furthermore, a novel inhibitor produced by Kaposi's sarcoma‐associated herpesvirus is identified and characterized in detail: KCP. It is shown that KCP inhibits classical C3‐convertase and presents activated complement factors C4b and C3b for destruction by a serine proteinase, factor I. Using molecular modelling and site‐directed mutagenesis, it was possible to localize sites on the surface of KCP required for complement inhibition and it is concluded that KCP uses molecular mechanisms identical to human inhibitors.     

20%甘露醇致静脉损伤的防护

对１２０例接受２０％甘露醇静脉滴注的病人进行了静脉损伤防护的实验研究。观察组６０例，采用严格选择和使用静脉，局部持续热敷以及提高２０％甘露醇静滴时温度和穿刺的成功率，与对照组６０例传统方法滴注的病人进行了对照比较，结果表明：两组间静脉的刺激程度、静脉炎的发生率及静脉的使用次数有显著性差异（Ｐ＜０．０１），说明２０％甘露醇静滴时采取综合性防护措施对减轻静脉刺激、减少损伤和提高静脉的使用率有显著效果。     

Allosteric modifiers of neuronal nicotinic acetylcholine receptors: new methods, new opportunities

Allosteric, non-competitive inhibitors (NCIs) of neuronal nicotinic acetylcholine receptors (nAChRs) have been shown to produce a wide variety of clinically relevant responses. Many of the observed effects are desired as the nAChR is the therapeutic target, while others are undesired consequences due to off-target binding at the nAChR. Thus, the determination of whether or not a lead drug candidate is an NCI should play an important role in drug discovery programs. However, the current experimental techniques used to identify NCIs are challenging, expensive, and time consuming. This review focuses on an alternative approach to the investigation of interactions between test compounds and nAChRs based upon liquid chromatographic stationary phases containing cellular fragments from cell lines expressing nAChRs. The development and validation of these phases as well as their use in drug discovery and pharmacophore modeling are discussed.     

Three odorant binding proteins may regulate the behavioural response of Chrysopa pallens to plant volatiles and the aphid alarm pheromone (E)‐β‐farnesene

Artificial Chrysopa pallens release is a well‐known method for suppressing aphids, but it is difficult to establish lacewing populations in the field. Understanding the functions of C. pallens odorant‐binding proteins (CpalOBPs) and behavioural responses of C. pallens to plant volatiles and aphid alarm pheromone (E)‐ß‐farnesene has important implications for population establishment after lacewing release. Based on our previous study, five antennae‐enriched CpalOBPs were selected. Sequence alignment and phylogenetic analysis revealed that these five CpalOBPs were Classic OBPs and separated into different clades. Of them, CpalOBP10 clustered in the same clade with aphid OBP7, which mediates the perception of green leaf volatiles and (E)‐ß‐farnesene. Ligand‐binding assays showed 31 compounds, including plant‐derived compounds, pest‐induced volatiles and (E)‐ß‐farnesene, had high binding affinities for at least one of these five CpalOBPs. Of the 31 compounds, the pest‐induced volatiles (Z)?3‐hexenyl hexanoate and 2‐hexyl‐1‐decanol, used in host location by the black bean aphid, elicited significant attractive behavioural responses from C. pallens. Conversely, (E)‐ß‐farnesene elicited strongly repellent behavioural responses. It is conceivable that C. pallens utilizes plant‐derived compounds, pest‐induced volatiles and (E)‐ß‐farnesene as foraging cues. Our studies provide new insights into the interrelationships amongst C. pallens, its prey and the host plants. Compounds that elicited significant behavioural responses from C. pallens were also identified.     

Drugs that target dynamic microtubules: a new molecular perspective

Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These "biological vectors" can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.     

Specific involvement of two amino acid residues in cis‐nerolidol binding to odorant‐binding protein 5 AlinOBP5 in the alfalfa plant bug,Adelphocoris lineolatus (Goeze)

Olfaction plays an important role in insects' survival and reproduction. Odorant‐binding proteins (OBPs) are considered to be one of the crucial proteins in the insect olfactory pathway. In this study, an antenna‐specific OBP of the alfalfa plant bug, Adelphocoris lineolatus AlinOBP5, was expressed and purified in vitro. The binding affinities of AlinOBP5 with sex pheromone analogues of the Miridae and cotton volatiles were investigated by fluorescence competitive binding assays. The binding sites of AlinOBP5 were predicted by three‐dimensional structure modelling and molecular docking, and site‐directed mutagenesis. AlinOBP5 could not effectively bind with sex pheromone analogues of Miridae but showed high binding abilities with specific cotton volatiles, such as cis‐nerolidol, ethyl laurate, β‐ionone, β‐caryophyllene, 2,3‐dimethylbenzoic acid and (E)‐farnesol. The strongest binding affinity was to cis‐nerolidol, suggesting a role of AlinOBP5 in general odorant chemoreception. Based on the relatively strong binding affinity and the reported physiological activity of cis‐nerolidol in other insects, we chose cis‐nerolidol for further homology modelling and ligand docking. The results of molecular simulation and site‐directed mutagenesis indicated that two amino acids, Lys74 and Pro121, in the protein binding pocket are the key amino acids involved in the binding of cis‐nerolidol. The Lys74 residue may participate in specific recognition of ligands, and the Pro121 residue plays a crucial role in ligand binding and release by changing the binding pocket environment and stabilizing the conformation of the C‐terminus of AlinOBP5.     

Serine‐ and mannose‐modified liposomal contrast agent for computed tomography: evaluation of the enhancement in rabbit liver VX‐2 tumor model

Kupffer cell imaging is a powerful tool for the detection of liver cancer. This diagnostic procedure depends on the faculty of the reticuloendothelial system (RES) which takes up foreign bodies, including small particles. The current study aimed to develop a novel RES targeting liposomal contrast agent that functionalized with serine or mannose, the moiety specifically binding to a corresponding receptor on phagocytic cells. Liposomes loaded with non‐ionic X‐ray contrast media, Iohexol, were prepared by supercritical carbon dioxide reverse‐phase evaporation method and were intravenously injected to healthy rabbits in order to evaluate the liver parenchymal enhancement in X‐ray computed tomography (CT). From 10 to 40 min after injection, the mean enhancement value of the liver parenchyma approached 45 and 34 Hounsfield units (HU) when serine‐modified iodinated liposomal contrast agent (ILCA) and mannose‐modified ILCA were applied, respectively. The tumor‐to‐liver contrast values were also evaluated after the administration of the prepared ILCA to rabbits with VX‐2 carcinoma. For serine‐modified ILCA, tumor‐to‐liver contrast was 82 HU at 1 min and >24 HU at 10–40 min; for mannose‐modified ILCA, the values were 58 HU at 0.5 min and >21 HU at 10–40 min. These vales estimated from the region of intrest and the imaging figures of liver indicate the potential of ILCA for clinical use. Copyright © 2010 John Wiley & Sons, Ltd.     

芦荟多糖的提取与含量测定

目的：研究芦荟多糖的提取和含量测定方法。方法：采用水提醇沉法提取芦荟多糖，以甘露糖标准液绘制标准曲线，用苯酚-硫酸、紫外分光光度法于490nm波长处测定芦荟多糖的含量。结果：芦荟多糖含量为8．796mg/ml。结论：该测定方法准确，重复性好，对芦荟多糖含量的测定获得满意结果。     

Association between urine retinol‐binding protein levels and nonalcoholic fatty liver disease: A cross‐sectional study in Chinese population

Objective

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increased, becoming a public health problem worldwide. Our objective was to investigate the association between urine retinol‐binding protein (RBP) and NAFLD in a Chinese population and develop a multivariate logistic regression model for NAFLD prediction.

Methods

A total of 317 NAFLD patients and 391 healthy controls were enrolled in this cross‐sectional study based on inclusion and exclusion criteria, from whom fasting urine and blood were collected for further study. Urine RBP level and other parameters were measured and compared between NAFLD subjects and controls.

Results

Urine RBP levels (expressed by RBP/creatinine ratio) in NAFLD patients were significantly higher than controls (median 133.1 mg/g vs 110.7 mg/g; P < .001). Urine RBP/creatinine ratio was verified as an independent factor for NAFLD prediction after adjustment in multivariate logistic regression. The area under curve (AUC) of receiver operating characteristic (ROC) was 0.889 with the 95% confidence interval from 0.867 to 0.912.With a cutoff point of 0.215, the sensitivity and specificity of urine RBP/creatinine ratio in NAFLD prediction were 81.1% and 84.5%, respectively.

Conclusion

Our results demonstrated that urine RBP/creatinine ratio was an independent risk factor for NAFLD while the predictive model for NAFLD diagnosis is noninvasive with high sensitivity and specificity.

     

Antibody-independent complement activation by myelin via the classical complement pathway

Murine or rabbit whole brain homogenates were shown to activate human complement via the classical pathway by an antibody-independent reaction. This activity required Ca++ ions. Anticomplementary activity in fractionated murine brain was found to reside in the myelin fraction and in purified myelin. It was absent, however, both from highly purified myelin basic protein (MBP) and from the MBP-free residue. Because purified MBP is a monomer and this protein exists in brain tissue largely as a dimer, the ability of the cross-linked form of MBP to activate complement was investigated. MBP, dimerized with difluorodinitrobenzene, was highly anticomplementary. The murine brain, inactive when taken from the newborn mouse, was shown to first acquire the capacity to activate complement at 7 d after birth. This finding is consistent with the report that the synthesis of myelin protein has been shown to be initiated in murine brain 8 d after birth. Complement activation by MBP could play an important role in the pathological changes observed in neurological disorders.     

Age‐specific differences in binding of heparin to plasma proteins

Summary. Background: Clinically significant age‐related differences in the anticoagulation effect of heparin have previously been established in vitro as well as in different clinical settings in vivo. These differences were hypothesized to be due to the age‐specific differences in binding of heparin to plasma proteins. Objectives: The aim of this project was to investigate global age‐related differences in heparin binding to plasma proteins. Patients/Methods: Heparin‐binding proteins were identified by incubating heparin‐coated magnetic beads with plasma samples from neonates, children and adults, and purifying the proteins that were bound to the beads in this reaction system. Results: These results provide the first preliminary evidence of age‐related differences in the total number and concentration of proteins bound to heparin. The results also suggest, for the first time, that there are age‐related differences of heparin binding to antithrombin and thrombin. Conclusions: The results of this study, although preliminary, support and contribute to the explanation of the mechanism of age‐related differences in the effect of heparin observed previously in vitro and in vivo.