pp60c-src encoded by the proto-oncogene c-src is a product of sensory neurons

The advent of recombinant DNA technology has led to the identification in the DNA of normal animal cells of over 30 proto-oncogenes that are homologous to retroviral transforming genes. One of these encodes a protein kinase (pp60c-src) of unknown function, that is preferentially synthesized in brain and neural retina. Here the expression of pp60c-src in the peripheral nervous system was examined in sensory neurons from chick dorsal root ganglia with antisera raised against the transforming protein of Rous sarcoma virus (pp60v-src) expressed in Escherichia coli carrying the cloned v-src gene. This antiserum recognizes pp60c-src specifically in normal chicken cells. Western immunoblotting showed that dorsal root ganglia of stage 30 (day 6.5) chick embryos contained elevated levels of pp60c-src. Immunoperoxidase staining of neuron-enriched cultures prepared from chick dorsal root ganglia showed pp60c-src immunoreactivity in cells with neuronal morphology; flat, fibroblastic cells contained no detectable immunoreactivity. Indirect double immunofluorescence with pp60src antibodies and monoclonal antibodies against the 200-kD subunit of neurofilament protein confirmed that the cells expressing pp60c-src were neurons. Ninety-six percent of the neurofilament-positive cells were immunoreactive with pp60src antibodies, and conversely, all pp60c-src-positive cells were immunoreactive with neurofilament antibodies. pp60c-src immunofluorescence appeared to be distributed over the cell body, processes, and growth cones. These results clearly demonstrate that pp60c-src is a product of neurons and is expressed in sensory neurons in culture.     

Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10–45 years

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B^®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.     

风疹易感人群婚前风疹疫苗接种预防先天性风疹综合征

目的探讨婚前风疹易感人群风疹疫苗接种在提高孕妇对风疹的免疫力,预防先天性风疹综合征中的作用.方法对10 913例婚前风疹病毒抗体IgG阴性者给予国产风疹减毒活疫苗注射.3个月随防671例,比较风疹疫苗接种前后该地区孕妇近期风疹感染的发病率.结果818例风疹病毒抗体IgG阴性者接种后抗体转阳率为99.8%.风疹疫苗接种前后3年孕妇近期风疹感染率分别为0.37%及0.08%,有明显下降,有非常显著差异(P＜0.001).结论应用国产风疹减毒活疫苗对婚前易感人群作预防接种可提高育龄妇女对风疹的免疫力,降低孕期风疹感染的发生率,是预防先天性风疹综合征及风疹致畸的有效、安全措施.     

2008年连云港市“手足口病”流行特征及病原学分型

目的分析连云港市2008年手足口病的流行特征及病原学分型情况。方法应用流行病学方法对2008年该市的手足口病流行资料进行分析。结果依据疫情报告,实验室诊断病例45例,其中CoxA1638例,EV71型7例,其他肠道病毒0例。2008年该市临床报告手足口病例1067例,报告发病率为23.19/10万,比2007年上升442.34%,男女发病比为3.1∶1。发病年龄最小的为0岁组,最大的为8岁;0～5岁组,共计发病976例,占总发数的91.47%。发病数的构成以散居儿童最多,占76.66%。地区分布:全市各个区县均有手足口病病例报告,但城区的总体发病率高于县。结论连云港市手足口病发病率有上升趋势;控制传染源是有效防止该病流行的关键。     

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.     

Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

Recombinant glycoprotein based vaccine for Chandipura virus infection

Chandipura virus (CHPV) has emerged as an important pediatric encephalitis-causing pathogen with very high mortality in India. No specific vaccine or treatment is available till date. We attempted to prepare a candidate vaccine employing recombinant CHPV Glycoprotein (rGp). The Glycoprotein gene (G-gene) of CHPV was expressed using Baculovirus expression system. The rGp was purified by HPLC and used for mice immunization, 3 doses, and 4 weeks apart. One microgram rGp was found to be optimum. Sero-conversion was observed as early as 2nd week by detecting anti-CHPV IgG antibodies. Antibody titres were immunogen-concentration dependent. Intracerebral challenge of the immunized mice with 100 LD₅₀ of the homologous strain demonstrated 90% protection. In in vitro neutralization, antibodies from the immunized mice were able to neutralize heterologous viruses. There was 60% T cell proliferation observed against rGp in immunized mice. The study shows that rGp induces both arms of immune response and represents an ideal vaccine candidate for further evaluations.     

Acute encephalopathy associated with influenza and other viral infections

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.     

小儿腮腺炎并发中枢神经系统感染52例临床分析

目的:探讨小儿腮腺炎并发中枢神经系统感染的临床特点.方法:对52例小儿腮腺炎并发中枢神经系统感染的临床资料进行回顾性总结分析.结果:3～7月份为小儿腮腺炎并发中枢神经系统感染的发病高峰季节(92.31%).发病年龄以6～12岁为主(82.69%),多发生于腮腺肿痛3天以上伴有持续发热者(78.85%),少数患者同时有其它脏器的损害,一般治疗疗效较好.结论:腮腺炎极易并发中枢神经系统感染,年长儿发生率高,应推广接种流腮活疫苗降低发病率.