Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives

The SIR (susceptible-infectious-resistant) and SIS (susceptible-infectious-susceptible) frameworks for infectious disease have been extensively studied and successfully applied. They implicitly assume the upper and lower limits of the range of possibilities for host immune response. However, the majority of infections do not fall into either of these extreme categories. We combine two general avenues that straddle this range: temporary immune protection (immunity wanes over time since infection), and partial immune protection (immunity is not fully protective but reduces the risk of reinfection). We present a systematic analysis of the dynamics and equilibrium properties of these models in comparison to SIR and SIS, and analyse the outcome of vaccination programmes. We describe how the waning of immunity shortens inter-epidemic periods, and poses major difficulties to disease eradication. We identify a "reinfection threshold" in transmission when partial immunity is included. Below the reinfection threshold primary infection dominates, levels of infection are low, and vaccination is highly effective (approximately an SIR model). Above the reinfection threshold reinfection dominates, levels of infection are high, and vaccination fails to protect (approximately an SIS situation). This association between high prevalence of infection and vaccine failure emphasizes the problems of controlling recurrent infections in high-burden regions. However, vaccines that induce a better protection than natural infection have the potential to increase the reinfection threshold, and therefore constitute interventions with a surprisingly high capacity to reduce infection where reduction is most needed.     

The role of virus infection in a simple phytoplankton zooplankton system

Many planktonic species show spectacular bursts ("blooms") in population density. Though viral infections are known to cause behavioural and other changes in phytoplankton and other aquatic species, yet their role in regulating the phytoplankton population is still far from being understood. To study the role of viral diseases in the planktonic species, we model the phytoplankton-zooplankton system as a prey-predator system. Here the prey (phytoplankton) species is infected with a viral disease that divides the prey population into susceptible and infected classes, with the infected prey being more vulnerable to predation by the predator (zooplankton). The dynamical behaviour of the system is investigated from the point of view of stability and persistence both analytically and numerically. The model shows that infection can be sustained only above a threshold of force of infection, and, there exists a range in the infection rate where this system shows "bloom"-like stable limit cycle oscillations. The time series of natural "blooms" with different types of irregular oscillations can arise in this model simply from a biologically realistic feature, i.e., by the random variation of the epidemiological parameter (rate of infection) in the infected prey population. The difference in mean strength of infection alone can lead to the different types of patterns observed in natural planktonic blooms.     

Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors

Over-expression of matrix metalloproteinases by lung fibroblasts has been blamed for much of the tissue destruction associated with airway inflammation. Because cyclic AMP is known to regulate fibroblast proliferation, as well as cytokine and extracellular matrix protein production, the current study was designed to evaluate the ability of three selective phosphodiesterase (PDE) type 4 inhibitors, rolipram, cilomilast and CI-1044, to inhibit extracellular matrix degradation. Using zymography and ELISA, we found that pro-MMP-2 release was enhanced following 24 h treatment of human lung fibroblast (MRC-5) with TGF-beta1 (10 ng/ml) or TNF-alpha (10 ng/ml), whereas PMA (0.02 microM) had no effect. One hour of pre-incubation with PDE4 inhibitors (10 microM) induced an inhibition of TNF-alpha-stimulated pro-MMP-2 release. Zymography and immunoblotting revealed that fibroblasts cultured with PMA or TNF-alpha released increased amounts of pro-MMP-1, whereas TGF-beta1 had no effect. Incubation with CI-1044 or cilomilast significantly prevented the TNF-alpha increase in pro-MMP-1. These results suggest that PDE4 inhibitors are effective in inhibiting the pro-MMP-2 and pro-MMP-1 secretion induced by TNF-alpha and might underline a potential therapeutic benefit of selective PDE4 inhibitors in lung diseases associated with abnormal tissue remodelling.     

肿瘤患者痰培养中细菌谱及耐药性的研究

目的评价肿瘤患者治疗过程中细菌感染的病原种类分布及其耐药情况,从而达到为肿瘤患者的抗感染治疗提供依据。方法对321例肿瘤患者痰标本培养及药敏结果进行分析。结果321例肿瘤患者痰标本检出致病菌（含条件致病菌）435株,革兰阴性杆菌占69．7％,革兰阳性球菌占26．2％,念珠菌占4．1％．5种主要致病菌对常用的抗生素存在不同程度耐药．产超广谱β-内酰胺酶细菌18株,耐甲氧西林葡萄球菌9株。结论对于肿瘤患者的抗感染治疗．临床上应重视细菌的种类分布,细菌的耐药问题,合理使用抗生素。     

慢性重型肝炎患者股静脉双腔导管细菌培养分析

目的分析慢性重型肝炎患者股静脉双腔导管培养的菌群分布、药敏试验,与留置时间的相关性,探讨有效的防范措施。方法对慢性重型肝炎患者行股静脉双腔导管尖端增菌培养,并同时进行外周血培养。结果双腔导管细菌培养阳性25例,64％的病原菌为葡萄球菌属。留置时间10d以上细菌培养阳性率明显增加。结论慢性重型肝炎患者导管相关性感染发生率高,严格的无菌操作和精心护理是防治导管感染的关键。     

以儿童呼吸道感染为主的非典型EBV感染报道

目的报道儿童EBV感染所致的临床疾病谱与年龄特点,以进一步提高对EBV感染诊治水平.方法回顾性分析了EBV-VCA-IgM或EBV-DNA-PCR诊断的690例儿童EBV感染的疾病分布和年龄分布特点.结果EBV感染儿童非典型传染性单核细胞增多症患儿422例,占61.16%,非典型EBV感染268例,占38.84%.非典型EBV感染中以呼吸道感染最为多见,为191例,占非典型EBV感染的71.27%.其他为皮炎或口炎、血小板减少性紫癜、腹泻病、川畸病、肠系膜或颈淋巴结炎、肾炎或肾病和CNS感染等.EBV感染致传染性单核细胞增多症和呼吸道感染在各年龄组的分布差异无显著性,EBV感染男女比为1.79：1.结论儿童EBV感染所致疾病多样,累及系统多,非典型表现以呼吸道感染为主.传染性单核细胞增多症和呼吸道感染在各年龄组间差异无显著性.     

光学相干层析成像技术用于裸鼠皮肤霉菌感染研究

利用中心波长为850 nm的宽带光源SLD实现了纵向分辨率为8μm的光学相干层析成像系统。系统采用傅里叶域光学延迟线实现了深度扫描速度为160 mm/s,成像深度为3 mm。获得了裸鼠皮肤霉菌感染部位和健康皮肤的光学相干层析(optical coherence tom ography,OCT)图像,皮肤病变前后的内部结构信息清晰可见。     

血管内皮生长因子与肺癌治疗

肺癌是世界上主要癌症杀手之一,大部分肺癌病人都死于肿瘤转移所引起的并发症.由于现在大部分的肺癌病人预后不佳,因此寻找新方法、新途径治疗尤为重要.抗血管生成是目前的肿瘤治疗研究热点之一.对目前以抗血管内皮生成因子为手段的肺癌治疗方面的研究作一综述.     

双链RNA和植物对病毒的抗性

双链RNA能诱导转录后的基因沉默,是生物抵御病毒入侵、维持自身基因稳定的一种自我保护机制.把源自病毒的基因构建成反向重复结构转入植物体内,其转录出的RNA会通过分子内序列互补形成双链,将入侵病毒的同源序列降解,使转基因植株获得对病毒的高抗性.RNA干扰型抗病毒转基因植株中,转病毒基因的mRNA不存在或存在量很少,也不会翻译成有功能的病毒蛋白,因此不存在病毒RNA重组、异源包装及协生作用的潜在风险,具有较高的生物安全性.双链RNA抗病毒转基因正在成为一种高效、安全的植物抗病毒策略.     

Efficient adenoviral-mediated gene delivery into porcine mesenchymal stem cells

Mesenchymal stem cell (MSC) mediated gene therapy research has been conducted predominantly on rodents. Appropriate large animal models may provide additional safety and efficacy information prior to human clinical trials. The objectives of this study were: (a) to optimize adenoviral transduction efficiency of porcine bone marrow MSCs using a commercial polyamine-based transfection reagent (GeneJammer, Stratagene, La Jolla, CA), and (b) to determine whether transduced MSCs retain the ability to differentiate into mesodermal lineages. Porcine MSCs (pMSCs) were infected under varying conditions, with replication-defective adenoviral vectors carrying the GFP gene and GFP expression analyzed. Transduced cells were induced to differentiate in vitro into adipogenic, chondrogenic, and osteogenic lineages. We observed a 5.5-fold increase in the percentage of GFP-expressing pMSCs when adenovirus type 5 carrying the adenovirus type 35 fiber (Ad5F35eGFP) was used in conjunction with GeneJammer. Transduction of pMSCs at 10.3-13.8 MOI (1,500-2,000 vp/cell) in the presence of Gene Jammer yielded the highest percentage of GFP-expressing cells ( approximately 90%) without affecting cell viability. A similar positive effect was detected when pMSCs were infected with an Ad5eGFP vector. Presence of fetal bovine serum (FBS) during adenoviral transduction enhanced vector-encoded transgene expression in both GeneJammer-treated and control groups. pMSCs transduced with adenovirus vector in the presence of GeneJammer underwent lipogenic, chondrogenic, and osteogenic differentiation. Addition of GeneJammer during adenoviral infection of pMSCs can revert the poor transduction efficiency of pMSCs while retaining their pluripotent differentiation capacity. GeneJammer-enhanced transduction will facilitate the use of adenoviral vectors in MSC-mediated gene therapy models and therapies.