IL-12p40-overexpressing immature dendritic cells induce T cell hyporesponsiveness in vitro but accelerate allograft rejection in vivo: role of NK cell activation and interferon-gamma production

Infusion of genetically modified dendritic cells (DC) expressing immunosuppressive molecules is a potential therapy for organ rejection. IL-12p70, a cytokine produced mainly by DC and macrophages, consists of two subunits, p40 and p35. IL-12p70 is an activator of T cells, while the IL-12p40 subunit serves as a natural antagonist for IL-12p70 action. The primary aim of this study was to evaluate the effect of IL-12p40 gene-modification on both the T-cell stimulatory activity of immature DC (imDC) and their ability to prolong cardiac allograft survival. IL-12p40 gene-modified imDC (DC-p40) exhibited a phenotype characteristic of imDC and displayed impaired T-cell allostimulatory ability in vitro. However, to our surprise, for murine vascularized heterotopic heart transplantation (HHT), administration of donor-derived DC-p40 7 days prior to transplantation did not prolong allograft survival but instead significantly exacerbated cardiac allograft rejection. Further study showed that DC-p40 augmented NK cell activity both in vitro and in vivo and enhanced interferon-gamma (IFN-gamma) production in vivo, which might be due to the increased IL-23 production by DC-p40. Our data suggested that although IL-12p40 gene-modified immature DC can induce T cell hyporesponsiveness in vitro, their ability to activate NK cells and induce IFN-gamma production counterbalances this, exacerbating cardiac allograft rejection. The unexpected effects of DC-p40 limit their value in promoting allograft survival in vivo and likely reflect the complexity of IL-12p40 biology.     

Pseudosubstrate inhibition of protein kinase PKR by swine pox virus C8L gene product

The interferon-induced protein kinase PKR is activated upon binding double-stranded RNA and phosphorylates the translation initiation factor eIF2alpha on Ser-51 to inhibit protein synthesis in virally infected cells. Swinepox virus C8L and vaccinia virus K3L gene products structurally resemble the amino-terminal third of eIF2alpha. We demonstrate that the C8L protein, like the K3L protein, can reverse the toxic effects caused by high level expression of human PKR in yeast cells. In addition, expression of either the K3L or C8L gene product was found to reverse the inhibition of reporter gene translation caused by PKR expression in mammalian cells. The inhibitory function of the K3L and C8L gene products in these assays was found to be critically dependent on residues near the carboxyl-termini of the proteins including a sequence motif shared among eIF2alpha and the C8L and K3L gene products. Thus, despite significant sequence differences both the C8L and K3L proteins function as pseudosubstrate inhibitors of PKR.     

海藻酸钙/聚组氨酸微胶囊的毒性试验研究

为了考察海藻酸钙/聚组氨酸微胶囊的毒性特征,我们利用MTT比色法和小鼠尾静脉注射法,分别考察了该微胶囊的细胞毒性和急性全身毒性。结果表明：微胶囊浓度≤1.0mg/mL时,材料对L929细胞生长无明显抑制作用;微胶囊浸提液即使在高浸提比（10.0mg/mL）下,浸提产物也无细胞毒性作用。急性全身毒性试验结果显示：微胶囊浸提液不引起急性全身毒性反应,表明微胶囊浸提液无有毒的沥滤物和降解产物产生。说明海藻酸钙/聚组氨酸微胶囊无明显毒性。     

Peroxisomal proliferator activated receptor-γ deficiency in a Canadian kindred with familial partial lipodystrophy type 3 (FPLD3)

Background  

Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-γ. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition.     

Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development

FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.     

重复电刺激前肢神经引起成年大鼠运动皮层的可塑性改变

为了了解成年大鼠运动皮层的功能可塑性，利用皮层内微刺激方法测定ＭＩ代表区并观察重复电刺激前肢神经对ＭＩ代表区的影响。实验组大鼠（９例）持续１．２－２小时的前肢神经电刺激导致前肢运动区与面部触须运动区边界向ＶＩ方向，移动２６３．３±９０．９μｍ并同时伴有运动阈值的改变；ＦＬ内ＭＴ降低５．０±１３．３μＡ，而在ＶＩ内ＭＴ升高９．６±１１．６μＡ对照组大鼠间隔１．５－２小时的两次测定结果，ＦＬ－ＶＩ边界     

单侧外周伤害性刺激诱发大鼠脊髓中转录因子CREB的双侧磷酸化(英文)

c AMP反应成分结合蛋白 (c AMP response elem ent-binding protein,CREB)是一种转录因子 ,它在磷酸化之后可调节靶基因的转录。 CREB在 13 3位置的丝氨酸的磷酸化 ,与脊髓中伤害性传入的处理有关 ,本文作者等用特殊抗体对此进行了免疫细胞化学研究。在正常大鼠 ,虽然几乎所有脊髓神经元的核中都可见 CREB的轻度着色 ,但磷酸化的 CREB仅见于双侧腰段脊髓的 ～ 层 (75± 15 vs60± 18)和 层 (9± 3 )。用福尔马林注射引起一侧后脚掌出现炎症时 ,可在双侧腰段脊髓看到磷酸化CREB细胞核的快速 (小于 5 min)和节段性的显著增多 ;它们主要分布在双侧背角表层 ～ 层 (2 5 4± 2 0 vs 2 62± 2 3 )、 层(115± 13 )和双侧 ～ 层 (3 46± 2 0 vs3 2 8± 2 6) ;而在对照和炎症组大鼠的胸段脊髓中均未见磷酸化 CREB的增加。在注射CFA诱发一侧炎症或切断一侧坐骨神经的实验组大鼠 ,也可看到至少延续到第三天的强而双侧性的 CREB的磷酸化。这种由一侧后肢伤害性传入引致腰段脊髓中镜像式双侧 CREB磷酸化的出现 ,与一般看到的损伤传入只在同侧脊髓背角引起某些神经化学改变的结果不同 ,可能是人神经损伤后或在实验动物中出现对侧镜像式疼痛过敏现象的基础     

吻合器痔上黏膜环切术与传统外剥内扎术的对比研究

目的 探讨吻合器痔上黏膜环切术(procedure for proplapse and hemorrhoids,PPH)的适应证、方法、临床应用价值.方法 总结41例PPH手术(Ⅰ组)和62例传统外剥内扎术(Milligan-Morgan手术)(Ⅱ组)临床资料,对手术时间、术后止痛次数、住院时间、术后并发症及住院费用等进行对比研究.结果 总的症状改善满意率分别为95%(Ⅰ组)及82%(Ⅱ组),除住院费用外,Ⅰ组其手术时间、术后止痛次数、住院时间明显优于Ⅱ组,并发症发生率除术后便血、早期大便失禁、早期排尿困难外,余无统计学意义.结论 PPH治疗Ⅲ°～Ⅳ°痔的近期疗效优于Milligan-Morgan手术,且具有安全、有效、手术时间短、住院时间少、恢复快等优点.     

膀胱抗菌机制—粘膜抗菌蛋白初步研究

本文报道以１％乙酸冲洗雌性Ｗｉｓｔａｒ大鼠膀胱和雌性新西兰白兔膀胱，分别获得其膀胱酸溶性提取物。ＡＵ－ＰＡＧＥ分析表明，两种膀胱粘膜酸溶性提取物都有十余条主蛋白带，而不含常见的杀菌物质溶菌酶和防御素样分子。琼脂糖弥散法杀菌试验显示，两种膀胱粘膜酸溶性提取物对致病性大肠杆菌ＭＬ－３５ｐ耐药株都有杀菌活性。进一步采用电泳凝胶琼脂糖弥散法杀菌试验分析，结果表明大鼠膀胱粘膜酸溶性提取物中有两条蛋白带具明显的杀菌活性，我们称这两条蛋白带为ＲａｔＢＰ－１和ＲａｔＢＰ－２。而兔膀胱粘膜酸溶性提取物的杀菌活性亦与两条被称为ＲａｂＢＰ－１和ＲａｂＢＰ－２的蛋白带相关。本文首次提示，在膀胱粘膜内存在抗菌蛋白，可能是膀胱粘膜杀菌作用的分子基础。