An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

Clinical influence of vagotomy on postoperative acute phase response

BACKGROUND: Although there is increasing evidence suggesting that the vagus nerve functions as a connector between the nervous and immune systems in animals, little is known about the role of the vagus nerve in postoperative acute phase response in humans. MATERIALS AND METHODS: The extent of fever and acute phase protein response and the production of inflammatory cytokine during the early postoperative period were compared among the patients who had undergone total gastrectomy including truncal vagotomy (n = 13), those having distal gastrectomy with division of vagal branches (n = 14), and the patients with vagal nerve preserving gastrectomy (n = 12). RESULTS: There was no significant difference in serum levels of C-reactive protein, alpha-1-antirypsin, and interleukin-6 among the three groups. Also, postoperative maximum body temperature was similar. CONCLUSIONS: Vagotomy did not influence acute phase response after gastric cancer surgery. A multipathway mechanism for acute phase response including the induction of fever is suggested.     

肾综合征出血热病毒气溶胶的物理稳定性实验研究

本文采用荧光素钠正常鼠脑悬液做模拟示踪物质，对肾综合征出血热病毒气溶胶在空气中的物理稳定性进行了测定，并与其生物稳定性做了比较。结果表明：病毒气溶胶的粒子大小在１ｕｍ左右，它随气溶胶的胶龄增长而减少，且其分散度变窄。初始气溶胶的物理回收率及其各胶龄的物理存留率均明显地高于它的生物回收率和生物存活率。本文还就肾综合征出血热病毒气溶胶的物理稳定性和生物稳定性，对本病空气传播的影响进行了讨论。     

呼和浩特市农区首次发现流行性出血热报告

呼和浩特市历史上未曾发现流行性出血热自然疫源地，也未见到流行性出血热疫情报告。1995年3月，本市中文齐镇发生1例临床表现典型并经血清学证实的流行性出血热病例。病家及其周围居民区家鼠密度为3.61％，以褐家鼠为优势种。送检捕获鼠鼠肺51份，阳性率21.57％。病家周围健康人群流行性出血热隐性感染调查，阳性率2.71％（1/37）。流行病学调查表明，病人病前1周－2个月内无外出史，故病人系本地感染。动物流行病学调查证实，呼和浩特农区存在流行性出血热自然疫源地。     

不对称PCR制备单链探针检测登革Ⅱ型病毒复制型RNA和复制中间体RNA

登革病毒是具包膜的单股正链RNA虫媒病毒 ,病毒的复制过程发生在感染细胞胞浆 ,复制型 (RF)RNA是病毒半保留复制的循环模板 ,复制中间体 (RI)RNA的合成则是病毒复制所必需的。经RT PCR获得的DNA模板进行不对称PCR扩增 ,当限制性引物终浓度为 2 5 0nmol L ,两引物比例为 1 0 0∶1时 ,即得到不对称PCR的预计单链和双链DNA产物。此单链产物用于标记探针进行核酸杂交。结果表明不对称PCR制备单链探针进行核酸杂交可用于检测病毒复制型RNA和复制中间体RNA的合成     

The effects of ambient and hypothalamic temperatures on the hyperthermic responses to prostaglandins E1 and E2

Summary The effects of ambient and hypothalamic temperatures were studied on the hyperthermic responses to prostaglandins E₁ and E₂ (PGE₁ and PGE₂) injected intraventricularly in the unanesthetized rabbit. Hyperthermic responses to PGE₁ observed at different thermal environments were approximately equal in magnitude and time course. However, the prevailing ambient temperature influenced the thermoregulatory mechanisms by which the hyperthermia was achieved. In a hot environment, PGE₁-hyperthermia was brought about by suppression of heat loss mechanism with little change in heat production. During cold exposure body temperature was raised mainly by an increase in heat production without a significant change in heat loss. PGEs-hyperthermias were attenuated by warming and enhanced by cooling the anterior hypothalamus. These changes in the hyperthermic responses to PGE₁ and PGE₂ are in contrast to those obtained with intraventricular injection of noradrenaline at different ambient temperatures and during hypothalamic heating and cooling. It is therefore unlikely that noradrenaline is involved in the hyperthermic responses to PGEs. On the other hand, the results support the view that prostaglandins may be mediators of pyrogen-induced fever.     

A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Delta30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host.     

Large left atrial myxoma presented as fever of unknown origin: a challenging diagnosis and a review of the literature

Myxoma is the most common type of primary tumors of the heart in adults. The majority of patients with myxomas may experience symptoms due to central or peripheral embolism or intracardiac obstruction, while in some cases, they may be completely asymptomatic. Rarely, patients develop unusual symptoms that complicate the diagnostic evaluation. Herein, we describe the case of a 70-year-old patient with a long-lasting low-grade fever due to a large left atrial myxoma revealed during a transthoracic echocardiography.     

Response of body temperature and serum iron concentration to repeated pyrogen injection in rabbits

We measured body temperature and serum iron concentration after five daily consecutive injections of febrile doses of Salmonella typhosa lipopolysaccharide (0.1 g/kg) and two doses of Staphylococcus aureus cell walls (1×10⁷ and 5×10⁷ cells) in rabbits. Tolerance to endotoxin injection, as manifest by a significant attenuation in the body temperature elevation, developed after the first injection of endotoxin. The endotoxin-induced fall in serum iron concentration was attenuated significantly by the 5th day of endotoxin injection. In contrast, no tolerance developed in either the body temperature or serum iron response following repeated daily injections of S. aureus. Rabbits rendered tolerant to endotoxin showed normal febrile and serum iron responses to subsequent S. aureus injection. Rabbits given serial injections of S. aureus, although not tolerant to S. aureus itself, exhibited attenuated body temperature responses but not serum iron responses to endotoxin injection. We suggest that repeated injection of endotoxin diminishes the ability of endotoxin to stimulate endogenous pyrogen (EP) synthesis and/or release, a property not shared by the gram-positive pyrogen S. aureus. However, repeated injection of S. aureus weakens the central endotoxin-EP pathway.     

登革3型病毒prM-E和NS1多基因重组质粒DNA免疫原性增强效果观察

目的　观察登革 3型病毒的prM E和NS1基因重组质粒DNA混合免疫对免疫原性的增强作用 ,为登革DNA疫苗混合免疫提供实验依据。方法　将登革 3型病毒的prM E和NS1基因重组质粒DNA分别混合及单独免疫BALB/c小鼠 ,采用中和试验及MTT法检测免疫小鼠血清中和抗体及脾细胞特异性CTL(cytotoxicT lymphocytes)杀伤率。结果　混合重组质粒DNA免疫组与单一prM E基因重组质粒DNA免疫组均在末次免疫后第 14天检测到中和抗体 ,在第 33天达到高峰 ,为 1∶32。在末次免疫后第 4 1天 ,当效靶比为 4 0∶1时 ,混合重组质粒DNA免疫组的特异性CTL杀伤率为 15 % ,而 2个单质粒DNA组分别为 10 .9%和 12 .4 %。结论　重组质粒DNA混合免疫可同时诱发小鼠产生体液免疫和细胞免疫 ,而且细胞免疫应答具有一定的增强作用 ,但没有出现特异性CTL杀伤率的协同增强效果。