Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated α-synuclein

Background  

The pathogenesis of idiopathic Parkinson's disease (PD) remains elusive, although evidence has suggested that neuroinflammation characterized by activation of resident microglia in the brain may contribute significantly to neurodegeneration in PD. It has been demonstrated that aggregated α-synuclein potently activates microglia and causes neurotoxicity. However, the mechanisms by which aggregated α-synuclein activates microglia are not understood fully.     

下肢皮神经-浅静脉营养血管远端蒂复合瓣的解剖学基础

小腿和踝足部的损伤临床十分多见,尽管目前有多种修复方法,但与传统修复方法相比,皮神经营养血管远端蒂组织瓣能将近侧的供区组织带蒂转移至远侧受区,极大地改变了踝足创伤的修复重建模式[1～3].     

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.     

人胚胎大脑海马发育过程中凋亡神经元超微结构观察

本文借助电子显微镜技术对 4月胎龄组及 6月胎龄组水囊引产胎儿海马中段部位的凋亡神经元超微结构进行观察、拍照 ,并对结果进行了分析讨论。结果显示 :两组对象中均可见凋亡神经元 ,所见的凋亡神经元的超微结构变化基本相同 ,即细胞核内有明显的染色质边集和凝结成块的现象 ,并可见核膜皱缩和扭曲。另外 ,6月组凋亡细胞的结构变化较 4月组更为明显。在 6月组细胞质内和核内均有小体出现 ,其他细胞器无显著变化。从而更进一步说明在胚胎海马发育中存在着神经元不同性质的死亡现象 -即正常死亡和凋亡。而且提出 6月组显现出更为明显的凋亡神经元形态变化     

PENA方法的建立及与ELISA IgM检测CMV的比较

目的　介绍一种敏感、稳定、快速、简便的实验室检测CMV的方法 ,同时探讨该种新方法与ELISA检测CMV方法的优、缺点。方法　对 5 5 2例病人应用间接荧光免疫法测定细胞核中的特异病毒早期抗体 (PENA)和ELISA法测定IgM抗体。结果　PENA方法 :强阳性 88例 ,阳性率 15 4 9% ,弱阳性 2 73例 ,阳性率 5 9 4 6 % ;ELISA -IgM方法 :阳性 34例 ,阳性率6 16 %。结论　PENA方法操作简便 ,与ELISA方法相比较 ,可对CMV感染进行早期测定及诊断 ,并可区分既往感染和即时感染 ,具有敏感性和稳定性 ,是测定小儿CMV感染的一种较好的方法     

Characterization of a novel HLA-DQB1 allele, DQB1*020102

A novel human leukocyte antigen (HLA)-DQB1 allele, DQB1*020102, was detected in a 28-year-old woman of Han ethnic in Guangzhou, China. Compared with HLA-DQB1*020101 and HLA-DQB1*0202, they differed in only one nucleotide at the position 167 (C to T) of exon 2, which was a highly conserved position. This is a synonymous mutation, which does not cause any change in the amino acid sequence of mature protein.     

Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival

Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise, we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.Abbreviations APC Antigen-presenting cells - CTL Cytotoxic T lymphocytes - DC Dendritic cells - DC-IL-10 IL-10 gene-modified immature dendritic cells - iDC Immature dendritic cells - IL-10 Interleukin-10 - MLR Mixed leukocyte reaction - MOI Multiplicity of infection     

Corticothalamic inhibition in the thalamic reticular nucleus

Mutual inhibition between the GABAergic cells of the thalamic reticular nucleus (RTN) is important in regulating oscillations in the thalamocortical network, promoting those in the spindle range of frequencies over those at lower frequencies. Excitatory inputs to the RTN from the cerebral cortex are numerically large and particularly powerful in inducing spindles. However, the extent to which corticothalamic influences can engage the inhibitory network of the RTN has not been fully explored. Focal electrical stimulation of layer VI in the barrel cortex of the mouse thalamocortical slice in vitro resulted in prominent di- or polysynaptic inhibitory postsynaptic currents (IPSCs) in RTN cells under the experimental conditions used. The majority of cortically induced responses consisted of mixed PSCs in which the inhibitory component predominated or of large IPSCs alone, implying inhibition of neighboring cells by other, cortically excited RTN cells. Within the mixed PSCs, fixed and variable latency components could commonly be identified. IPSCs could be blocked by application of ionotropic glutamate receptor antagonists or of GABA(A) receptor antagonists, also indicating their dependence on corticothalamic excitation triggering disynaptic or polysynaptic inhibition. Spontaneous GABA(A) receptor-dependent IPSCs were routinely observed in the RTN and, taken together with the results of cortical stimulation, indicate the existence of a substantial network of intrareticular inhibitory connections that can be effectively recruited by the corticothalamic system. These results suggest activation of cortical excitatory inputs triggers the propagation of inhibitory currents within the RTN and support the view that activation of the RTN from the somatosensory cortex, although focused by the topography of the corticothalamic projection, is capable of disynaptically engaging the whole inhibitory network of the RTN, by local and probably by reentrant GABA(A) receptor-based synapses, thus spreading the corticothalamic influence throughout the RTN.     

Genotyping of Mycobacterium leprae on the basis of the polymorphism of TTC repeats for analysis of leprosy transmission

The polymorphism of TTC repeats in Mycobacterium leprae was examined using the bacilli obtained from residents in villages at North Maluku where M. leprae infections are highly endemic (as well as from patients at North Sulawesi of Indonesia) to elucidate the possible mode of leprosy transmission. TTC genotypes are stable for several generations of passages in nude mice footpads and, hence, are feasible for the genotyping of isolates and epidemiological analysis of leprosy transmission. It was found that bacilli with different TTC genotypes were distributed among residents at the same dwelling in villages in which leprosy is endemic and that some household contacts harbored bacilli with a different genotype from that harbored by the patient. Investigations of a father-and-son pair of patients indicated that infections of bacilli with 10 and 18 copies, respectively, had occurred. Genotypes of TTC repeats were found to differ between a son under treatment and two brothers. These results reveal the possibility that in addition to exposure via the presence of a leprosy patient with a multibacillary infection who was living with family members, there might have been some infectious sources to which the residents had been commonly exposed outside the dwellings. A limited discriminative capacity of the TTC polymorphism in the epidemiological analysis implies the need of searching other useful polymorphic loci for detailed subdivision of clinical isolates.     

Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics

We generated a high-growth H5N1/PR8 virus by plasmid-based reverse genetics. The virulence associated multiple basic amino acids of the HA gene were removed, and the resulting virus is attenuated for chickens and chicken eggs. A formalin-inactivated oil-emulsion vaccine was prepared from this virus. When SPF chickens were inoculated with 0.3 ml of the vaccine, the hemagglutinin-inhibition (HI) antibody became detectable at 1 week post-vaccination (p.v.) and reached a peak of 10log2 at 6 weeks p.v. then slowly declined to 4log2 at 43 weeks p.v. Challenge studies performed at 2, 3 and 43 weeks p.v. indicated that all of the chickens were completely protected from disease signs and death. Ducks and geese were completely protected from highly pathogenic H5N1 virus challenge 3 weeks p.v. The duration of protective immunity in ducks and geese was investigated by detecting the HI antibody of the field vaccinated birds, and the results indicated that 3 doses of the vaccine inoculation in geese could induce a 34 weeks protection, while 2 doses induced more than 52 weeks protection in ducks. We first reported that an oil-emulsion inactivated vaccine derived from a high-growth H5N1 vaccine induced approximately 10 months of protective immunity in chickens and demonstrated that the oil-emulsion inactivated avian influenza vaccine is immunogenic for geese and ducks. These results provide useful information for the application of vaccines to the control of H5N1 avian influenza in poultry, including chickens and domestic waterfowl.