Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression

Yellow fever (YF) is a zoonotic infection with more than 200,000 cases reported annually. Relatively little is known about YF pathogenesis in humans. In this study, we demonstrate that human vascular endothelial cells are susceptible to infection with wild-type and vaccine strains of the YFV and that these infections lead to a differential cellular response to infection. The infection of endothelial cells with either virus resulted in a significant induction of interferon-inducible genes p 78 and Cig 5 while wild-type virus induced a much more pronounced IL 6 and Bc l2 response than did the vaccine strain. Both viruses induced RANTES gene expression, but only the wild-type virus had corresponding increases in RANTES protein expression. The results demonstrate that the wild-type and vaccine strains of YFV elicit significantly different responses to infection in endothelial cells, despite being nearly identical genetically. These differences may account for the attenuated phenotype of the YFV vaccine strain, though the mechanism remains unclear. These data also point to a role for vascular endothelial cells in YF hemorrhagic fever and also suggest that IL 6 may play a role in increased viral pathogenesis, perhaps by influencing coagulation via release of coagulation co-factors such as fibrin or fibrinogen.     

Effect of antipyretics on the formation of leukocytic pyrogen by granulocytes

The effect of sodium salicylate, acetylsalicyclic acid, aminopyrine, and phenazone on the ability of granulocytes to produce endogenous pyrogen was studied. Experiments in vitro with verification of the viability of the leukocytes showed that of these antipyretics only sodium salicylate inhibited pyrogen formation.Department of General Pathology, Scientific-Research Institute of Experimental Medicine, Academy of MedicalSciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 166–168, August, 1979.     

新疆出血热病毒核蛋白基因的高效表达及其在诊断中的初步应用

目的　克隆并测定了克里米亚 刚果出血热病毒 (CCHFV)中国分离株 (新疆出血热病毒 ,XHFV)BA8816 6株核蛋白 (NP)基因的序列并实现其在细菌中的高效表达与临床诊断的应用。方法　病毒RNA经RT PCR扩增出完整的NP基因。将扩增产物进行序列分析并克隆至融合表达载体pET32a ,使重组质粒在大肠杆菌BL 2 1中高效表达。将融合蛋白经初步纯化后包被ELISA板用于抗体检测。结果　XHFVBA8816 6株NP基因序列以及推导的氨基酸序列与其它XHFV的NP基因和蛋白序列同源性较高 ,在进化树上形成独立的分支。BA8816 6株NP基因编码 4 82个氨基酸的核蛋白 ,推测的相对分子质量 (Mr)约为 5 4× 10 3。在细菌中表达的融合蛋白经印迹试验证明具有良好的抗原性。以所建立的ELISA方法检测疫区人和动物血清的结果与IFA一致 ,并与临床诊断有很好的符合率。结论　BA8816 6株与其它XHFVBA6 6 0 19、BA84 0 2的NP基因在进化上关系密切 ,综合M基因的序列分析结果 ,人源分离株BA8816 6可能是来自蜱的BA84 0 2变异株。表达于细菌中的核蛋白可作为安全的诊断性抗原用于临床检测及流行病学调查 ,所建立的方法准确、特异、简便、快速     

Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract

The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy.     

The RNA helicase, nucleotide 5'-triphosphatase, and RNA 5'-triphosphatase activities of Dengue virus protein NS3 are Mg2+-dependent and require a functional Walker B motif in the helicase catalytic core

The nonstructural protein 3 (NS3) of Dengue virus (DV) is a multifunctional enzyme carrying activities involved in viral RNA replication and capping: helicase, nucleoside 5'-triphosphatase (NTPase), and RNA 5'-triphosphatase (RTPase). Here, a 54-kDa C-terminal domain of NS3 (DeltaNS3) bearing all three activities was expressed as a recombinant protein. Structure-based sequence analysis in comparison with Hepatitis C virus (HCV) helicase indicates the presence of a HCV-helicase-like catalytic core domain in the N-terminal part of DeltaNS3, whereas the C-terminal part seems to be different. In this report, we show that the RTPase activity of DeltaNS3 is Mg2+-dependent as are both helicase and NTPase activities. Mutational analysis shows that the RTPase activity requires an intact NTPase/helicase Walker B motif in the helicase core, consistent with the fact that such motifs are involved in the coordination of Mg2+. The R513A substitution in the C-terminal domain of DeltaNS3 abrogates helicase activity and strongly diminishes RTPase activity, indicating that both activities are functionally coupled. DV RTPase seems to belong to a new class of Mg2+-dependent RTPases, which use the active center of the helicase/NTPase catalytic core in conjunction with elements in the C-terminal domain.     

Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid

BACKGROUND: The clinical efficacy and safety of a six-grass pollen allergoid has been studied. The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this reappraisal. METHODS: A 2-year double-blind multicentre placebo-controlled phase 3 clinical trial was undertaken in 154 patients suffering symptoms of rhinoconjunctivitis with or without asthma (GINA I or II). Therapy comprised two consecutive preseasonal short-courses of subcutaneous injections using a grass pollen allergoid adsorbed to aluminium hydroxide. RESULTS: A combined symptom and medication score (SMS) was used as the primary end-point for clinical efficacy. SMS from the first year showed a significant difference of 26.6% between the two study groups (P=0.026) and this was improved after the second year when there was a 48.4% difference in SMS between active and placebo treatment in favour of the allergoid (P = 0.018). Highly significant increases in grass pollen allergen-specific IgG1 and IgG4 antibody concentrations were measured in association with active treatment. Allergen tolerance was increased as judged by a conjunctival provocation test and significant improvements in quality of life were documented using a standardized questionnaire. The allergoid was well tolerated. CONCLUSIONS: The grass pollen allergoid was shown to be safe and clinically efficacious in the management of hay fever with or without asthma (GINA I or II).     

Blood Lymphocyte Proliferation Response to Pollen Extract as a Monitor of Immunotherapy

In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self-evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self-evaluation or conjunctival provocation test changes in the individual patients. The results indicate the lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity.     

Replication of alcelaphine herpesviruses in various cell culture systems and subsequent purification of virus

Summary Cultures of fetal aoudad sheep kidney (FAK), bovine embryonic lung (BEL), and African green monkey kidney (Vero) cells were compared for differential replication of alcelaphine herpesviruses. Cell-free virus appears more rapidly when infected cells are incubated at 33° C rather than at 37° C. Events in the replication and morphologic development of several alcelaphine herpesvirus isolates have been documented using light and electron microscopy. Techniques for indirect immunofluorescence and serum virus neutralization are described. When virus free of host-cell contaminants is desired for biochemical analysis, virus isolates are initially purified on sucrose gradients and then further purified by density gradient centrifugation in Percoll.     

Atypical respiratory pathogens

The main atypical pathogens in respiratory tract infections are classified on the basis of their ability to cause atypical pneumonia. This is not a well-defined clinical entity, and it is evident that atypical pathogens can sometimes cause 'typical' pneumonias and vice versa. This emphasizes the need for microbiological diagnosis, since it affects the selection of proper treatment, in which β-lactam antibiotics and aminoglycosides are not effective. Moreover, mixed infections caused by atypical and typical pathogens together are common. At this moment rapid and sensitive diagnostic methods are lacking. Besides numerous viruses, the main bacterial pathogens causing atypical pneumonias are Mycoplasma pneumoniae , two chlamydia species. Chlamydia pneumoniae and C. psittaci , one rickettsia, Coxiella burnetti , and several Legionella species. The majority of these pathogens cause upper respiratory tract infections more often than overt pneumonias. An atypical agent, Chlamydia pneumoniae , has also been associated with chronic inflammatory conditions in the cardiovascular system. The most recently discovered pathogen in atypical pneumonias is a hantavirus causing hantavirus pulmonary syndrome.     

广州市一起登革热家族聚集性暴发事件的调查与分析

目的探讨登革热家庭聚集性发病的流行病学特点及传播效率，为今后进行有效的预防和控制登革热暴发提供参考。方法采用现场流行病学调查方法对广州市一起登革热家庭聚集性暴发事件进行调查和分析；采用ELISA、RT-PCR和病毒分离的方法对标本进行检测。结果2006年8月广州市荔湾区发生一起登革热家庭聚集性暴发事件，该家族15名家庭成员先后共有6人发病，罹患率40．0％，其中6例患者登革热抗体IgM或IgG阳性3例，病毒分离阳性3例，荧光PCR检测阳性者1例，基因序列测序和病毒分离结果最终确定为登革I型病毒。结论根据临床表现、实验室检测结果以及流行病学调查．虽然该家族部分患者登革热抗体为阴性，但病例发病均在一个最长潜伏期内，因此可以确定该家族发生了登革热聚集性暴发，荔湾区龙津中路龙兴里最有可能是共同感染地．感染来源不明，感染时间为家庭聚会日可能性大。