空肠弯曲菌HSP43诱导自身免疫机理──分子模拟和抗原优势

我们曾发现空肠弯曲菌４３ｋＤ热休克蛋白（ＨＳＰ４３）能诱导小鼠产生自身免疫应答，本文则进一步分析了这种诱导作用的机理。二株针对ＨＳＰ６０保守区序列的单克隆抗体ＩＩＨ９和ＭＬ－３０不但能结合人及小鼠细胞中ＨＳＰ６０家族成员，而且也能结合ＨＳＰ４３，表明ＨＳＰ４３、人及小鼠ＨＳＰ６０三者均属同一家族成员，具有序列上的高度同源性。小鼠用空肠弯曲菌免疫后出现了针对１０种菌体蛋白的抗体，其中最早被诱导的抗体是针对ＨＳＰ４３的，并且该种抗体在随后８０ｄ观察期间内保持了较高活性，表明ＨＳＰ４３是优势抗原。本文结果提示，ＨＳＰ４３较易被免疫系统识别而产生应答，通过和宿主ＨＳＰ６０高度序列同源性而可能呈现分子模拟，从而诱导自身免疫损伤。     

Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases

Preimplantation genetic diagnosis was performed in 61 day 3 embryos obtained by in-vitro fertilization from seven patient carriers of haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa, and FG syndrome, which is characterized by mental retardation and hypotonia. After multiplex polymerase chain reaction, 16 embryos were diagnosed as being unaffected, and these were transferred to the uterus on the following day (day 4). Of these embryos, six (37.5%) implanted, resulting in the delivery of a singleton and a twin pregnancy, a late second trimester miscarriage (twins at week 20) and a first trimester miscarriage at week 8. All the diagnoses were confirmed by amniocentesis. We report for the first time a late day 4 transfer of biopsied human embryos undergoing preimplantation genetic diagnosis. This transfer schedule allows an extra day to perform genetic analyses on single blastomeres and to monitor any adverse effect of the biopsy procedure.      

拇指背动脉岛状皮瓣再造拇指的解剖学研究

作者在18只尸体手标本上,对拇指背动脉进行了显微解剖研究,发现该动脉出现率较恒定,起始部血管外径平均为0.63mm,动脉可解剖长度为7.2cm,血管分布范围包括第一掌骨背侧、部份鱼际区及拇指近节背桡侧5×10cm 的皮肤。以拇指背动脉及与其相连的桡动脉远段为蒂,可以游离成一个理想的岛状皮瓣,适用于拇指再造及邻近的组织缺损修复。     

Approaches to functional genomics: potential of matrix-assisted laser desorption ionization--time of flight mass spectrometry combined with separation methods for the analysis of DNA in biological samples

MALDI-TOF MS has potential as a valuable technique in DNA mapping studies and may well be complementary to other approaches to DNA analysis such as gel electrophoresis and sequencing. This study used 2,6-dihydroxyacetophenone (DHAP) mixed with diammonium hydrogen citrate (DAHC) as the matrix. In addition, recent technical advances such as time lag focussing (TLF) and better selection of matrices (such as 3-hydroxypicolinic acid (3 HPA) and picolinic acid (PA)) extended the range of DNA fragments that can be studied by this approach. The following samples were investigated: Poly-T mixture (dT 15, 19, 20, 25, 74 and 75), plasmid pBR322 derived oligonucleotides (10, 11, 12, 13, 14, 15, 19, 20 and 50 nucleotides long) and DNA fragments of 25, 36 and 37 base pairs corresponding to a fragment in the restriction map for the gene corresponding to the hexon protein of Adenovirus 2 and 5. The results were contrasted with similar analyses performed by ion-paired reversed-phase HPLC coupled to on-line electrospray mass spectrometry.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

单克隆抗体2A7亲和层析法纯化红细胞膜表面的CD59分子

用抗ＣＤ５９单抗２Ａ７与ＣＮＢｒ－Ｓｅｐｈａｒｏｓｅ４Ｂ偶联制备亲和层析柱，从正常人红细胞膜蛋白抽提物中分离纯化出ＣＤ５９分子。本法纯化的ＣＤ５９分子量为１８－２０ＫＤａ对还原剂敏感，与ＭｃＡｂｓｓＭＥＭ４３和１Ｆ５有高亲和性，再掺入豚鼠红细胞后，能够抑制人体补体的反应性溶血，本文还对三株抗ＣＤ５９单抗２Ａ７，ＭＥＭ４３及１Ｆ５的抗原特异性进行了初步分析。     

Regulation of the association between PSTPIP and CD2 in murine T cells

Prominent in T cells and natural killer cells, CD2 binding protein 1 (CD2BP1) plays an important role in CD2-mediated adhesion and signal transduction. In the current study, we investigated CD2 and PSTPIP (proline, serine, threonine phosphatase interacting protein, murine homologue of CD2BP1) interactions in purified mouse splenic T cells. PSTPIP associated with CD2 in both resting and activated T cells. Following various stimuli, such as concanavalin A, anti-TCRbeta, anti-CD3epsilon, anti-CD3epsilon/phorbol myristate acetate (PMA), IL-2, or PMA/ionomycin, PSTPIP and CD2 expression, as well as their association, increased in a time-dependent fashion. While PSTPIP expression and CD2 expression were comparable across most groups, the PSTPIP-CD2 association stimulated by anti-CD3epsilon alone was significantly greater than with other stimuli. Stimulation by anti-CD3epsilon plus anti-CD28 induced even greater PSTPIP-CD2 association than anti-CD3epsilon treatment alone, indicating that CD28 initiated signals are involved in regulating this interaction. There was no direct association between CD3epsilon or CD28 and PSTPIP. Tyrosine phosphorylated PSTPIP bound poorly to CD2 compared to dephosphorylated PSTPIP, and protein tyrosine phosphatase was shown to affect both phosphorylation of PSTPIP and the CD2-PSTPIP association. In addition to CD2, PSTPIP associated with CD4, CD8, CD54, and CD62L. CD2 and CD4 ligation reciprocally regulated their association with PSTPIP. These findings indicate that T cell activation, particularly through the CD3 and CD28 signal transduction pathways, regulates PSTPIP-CD2 interactions. PSTPIP likely has additional broader effects through interactions with CD4, CD8, CD54, and CD62L, and this may influence T cell responses to antigen.     

Antibodies to HIV-1 gp41 recognize synthetic peptides of human IFN-alpha and IFN-beta

Based on our finding that a common epitope exists between HIV-1 gp41 and human type I interferons (IFN-alpha and IFN-beta), and increased levels of antibodies against human IFN-alpha and IFN-beta were observed in HIV-1-infected individuals, we tried to explain the mechanism of increased levels of antibodies. Mouse antisera recognizing HIV-1 recombinant soluble (rs) gp41 (aa 539-684) interacted with two synthetic peptides sequence-corresponding to the IFN-alpha/beta receptor binding site on human IFN-alpha and IFN-beta, while normal mouse serum (pooled normal sera) did not. The anti-rspg41 antisera after adsorption by IFN-beta sepharose column lost the activity of interaction with both synthetic peptides. In another experiment, rsgp41 could bind to sepharose column conjugated with anti-IFN-beta polyclonal antibodies (IgG). These results indicate that the common epitope on gp41 and type I interferons could induce antibodies recognizing the receptor binding site on IFN-alpha and IFN-beta, suggesting that increased levels of antibodies against IFN-alpha and IFN-beta in HIV-1-infected individuals could be induced by gp41.     

GPR34-mediated sensing of lysophosphatidylserine released by apoptotic neutrophils activates type 3 innate lymphoid cells to mediate tissue repair

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