A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease

The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele.     

涎腺癌肉瘤临床及病理分析

目的：探讨涎腺癌肉瘤的临床病理学特点及其鉴别诊断。方法：对3例涎腺癌肉瘤患者的临床资料进行回顾性研究并复习相关文献，对全部病例的组织学标本重新进行镜下观察。结果：涎腺癌肉瘤临床表现常为迅速增大的颜面部肿物并伴疼豢。光匀下组织学观察常可见肉瘤和癌两种成分并存，癌多为鳞状细胞癌和腺癌，肉瘤以骨或软骨肉瘤为主。结论：涎腺癌肉瘤的临床特点与涎腺其他恶性肿瘤较难区别，但涎腺癌肉瘤的恶性程度极高。     

Building a mouse model hallmarking the congenital human cytomegalovirus infection in central nervous system

To investigate the mechanisms that human cytomegalovirus (HCMV) can vertically transmit from the placenta of mice to infect their offspring in the central nervous system (CNS) and cause congenital anomalies, and in order to provide basic research for preparing HCMV vaccine, we have developed a new type of mouse model of HCMV congenital CNS infection. Pure strain mice were propagated after being infected with HCMV. Then the degree of infection by HCMV to offspring was determined. The experiment shows that in the infection groups the mortality of fetal mice and the fatality of neonatal mice in one week are higher than that of the control groups (P < or = 0.05). At the same time we investigated the CNS of fetus's mice whose mothers were infected by HCMV. Our results showed: 1. The virus was successfully isolated from their cerebral cortex. 2. The signal of HCMV hybridization print was found in their nervous cell through in situ hybridization. 3. Especially human herpes virus-like particles and inclusion bodies in the plasm of nerve cell were found in the tissue of their brain under the electron microscope. This new type of mouse model of HCMV inherent CNS infection will help prepare HCMV vaccine and research HCMV congenital infection in CNS.     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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Use of PCR to study epidemiology of Serratia marcescens isolates in nosocomial infection.

A method to characterize strains of Serratia marcescens based on the PCR amplification of enterobacterial repetitive intergenic consensus sequences has been developed. The PCR fingerprints were generated from boiled supernatants prepared directly from bacterial colonies without the need for DNA extraction. The technique was applied to isolates obtained during an outbreak of pneumonia from seven mechanically ventilated patients, and its result indicated that the outbreak was due to the spread of two epidemic strains. This technique was validated by comparison with rRNA gene restriction analysis. There was complete concordance between these two techniques in discriminating the outbreak-related strains from epidemiologically unrelated isolates. Typing with both biochemical profile and antibiogram profile, though simple, was found to be less reliable than genotyping. The results show that this enterobacterial repetitive intergenic consensus PCR provides a rapid and simple means of typing S. marcescens isolates for epidemiologic studies.     

Immunologic cross-reactivity between structural proteins of human T-cell lymphotropic virus type I and the blood stage of Plasmodium falciparum.

To determine the serologic cross-reactivity between human T-cell lymphotropic virus type I (HTLV-I) and parasite antigens, we measured antibody responses against HTLV-I, Plasmodium falciparum, Plasmodium vivax, and Brugia malayi in serum specimens obtained from regions where malaria (n = 482) and filariasis (n = 101) are endemic. Analysis of immune reactivity to HTLV-I antigens showed that specimens from regions where malaria is endemic had significantly higher rates of enzyme immunoassay (EIA) reactivity (76 of 482 [15.8%] than those from regions where filariasis is endemic (0 of 101 [0%]). Western blot (immunoblot) analysis of the HTLV-I EIA-reactive specimens demonstrated predominant Gag reactivity (HTLV-Iind). Only two specimens each from Indonesia and Brazil and four specimens from Papua New Guinea had Env reactivity by radioimmunoprecipitation analysis. Furthermore, a positive correlation between HTLV-EIA and titers of antibody to the blood stage of P. falciparum (rs = 0.24, P < 0.005) was discerned; no correlation was observed between antibodies to the blood stage or the circumsporozoite protein of P. vivax and the circumsporozoite protein of P. falciparum. In addition, P. falciparum-infected erythrocyte lysate specifically abrogated binding of Gag-specific antibodies in HTLV-Iind specimens from regions where malaria is endemic without affecting binding in HTLV-I-seropositive specimens, suggesting that the immunologic cross-reactivity between HTLV Gag proteins and malaria parasites is restricted to the blood-stage antigens of plasmodia in specimens from regions where malaria is endemic. However, HTLV-seroindeterminate specimens from the United States did not demonstrate serologic cross-reactivity, suggesting that antigenic mimicry of HTLV proteins extends to other nonplasmodial antigens as well.     

Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.      

大鼠延髓网状背侧亚核下行投射终末在脊髓灰质的分布

本研究应用PHA－L顺行追踪技术研究了大风延髓网状背测亚核（SRD）至脊髓灰质下行投射的终止部位。结果表明：SRD发出的下行纤维走行于脊髓的背外侧京中，从高位至低位，脊髓灰质中的PHA－L顺标终末的密度逐渐降低。SRD的下行投射终未在脊髓中具有明显的同侧分布优势，主要终止在同侧脊历灰质的Ⅳ～Ⅶ层和X层，Ⅰ、Ⅱ层中只有少量的标记终末，对侧脊髓灰质中除了在Ⅳ层和X层中有中等密度的颁标终末分布外，其余各层中几乎无标记终未、PHA－L顺标终未与BSI-B4标记的初级传入C纤维终末在Ⅰ．Ⅱ层内重叠公布．本研究为SRD在调控脊髓的伤害性信息传递方面也起重要作用这一论点提供了直接的形态学依据．     

胎牛血清外泌体对成骨细胞增殖的作用

背景:研究表明外泌体具有促进骨再生的能力,但从胎牛血清中提取的外泌体是否可以促进骨形成仍存在争议。目的:观察胎牛血清外泌体对成骨细胞增殖能力的影响,从而为临床治疗骨破坏提供新思路。方法:通过超速离心法从胎牛血清中提取外泌体,采用透射电子显微镜和Western blot法验证外泌体是否提取成功;然后用10 mg/L胎牛血清外泌体干预成骨前体细胞MC3T3-E1,通过CCK-8实验检测外泌体对成骨细胞增殖能力的影响,Western blot检测外泌体对成骨细胞骨形态发生蛋白2和骨桥蛋白表达的影响。以不含外泌体的胎牛血清培养的MC3T3-E1细胞为对照组。结果与结论:①胎牛血清外泌体具有典型的脂质双层膜结构,大小在30-150 nm之间,外泌体表面标记因子CD81表达呈阳性,而微囊表面标记物CD40表达呈阴性;②外泌体组的增殖能力明显高于对照组,差异有显著性意义(P<0.05);外泌体组成骨标志性因子骨形态发生蛋白2和骨桥蛋白的表达水平明显高于对照组,差异有显著性意义(P<0.05);③结果表明,胎牛血清外泌体对成骨细胞的增殖起促进作用,可为临床治疗骨破坏提供新思路。