Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

糖尿病小鼠小肠绒毛杯状细胞分泌黏原颗粒的变化

目的：观察糖尿病小鼠小肠绒毛杯状细胞分泌的黏原颗粒是否改变,为进一步研究糖尿病的消化系统并发症提供形态学基础。方法分别选取3,5,8,10月龄db/db糖尿病小鼠及相应年龄段的db/+m正常小鼠,每组6只,标本用4%多聚甲醛灌流固定后,从距Treitz韧带约10 cm处切下一段空肠,用PAS染色方法对小肠杯状细胞分泌的黏原颗粒进行观察。结果糖尿病组小肠绒毛易被破坏,糖尿病组中杯状细胞的分泌物比同月份正常对照组显著增加(P<0.05)；糖尿病组中3月龄的杯状细胞分泌物最多,8月龄最少,并且8月龄分别与3月龄、5月龄比较均存在着显著差异(P<0.05)；正常对照组随月龄增长无显著性差异(P>0.05)。结论糖尿病时杯状细胞分泌物增多可能对小肠绒毛有保护作用。     

P16INK4、PCNA在肺癌中表达的研究

目的 通过检测肺癌组织中p16、PCNA的表达，探讨其在肺癌发生发展中的作用及相互关系。方法 采用S—P免疫组化方法，检测83例肺癌标本及15例正常肺组织标本中P16^INK4和PCNA的表达。结果 P16^INK4和PCNA在正常肺组织和肺癌组织中表达的阳性率存在显著性差异。P16^INK4表达的阳性率在小细胞癌与非小细胞癌之间有显著性差异。PNTM分期高的肺癌标本P16^INK4及PCNA表达阳性率显著高于分期低的肺癌标本。不同分化程度的肺癌组织P16^INK4及PCNA表达阳性率有显著性差异。结论 肺癌的发生与P16^INK4的低表达和PCNA的高表达有关。而P16^INK4的表达与肺癌的组织学类型、分化程度、临床分期有关；PCNA的表达与肺癌的分化程度、临床分期有关。     

Morphological types of ganglion cells in the dog and wolf retina.

The morphological types of ganglion cells in the dog and wolf retina were studied by intracellular staining with Lucifer Yellow. These retinae contain a range of ganglion cell types that closely correspond to those found in cat retina: alpha cells with large somata and large, relatively densely branched dendritic trees; beta cells with medium-sized somata and small, densely branched dendritic trees; and a variety of other types with smaller somata and varying dendritic branching patterns and dendritic field sizes. The correspondence of canine and cat ganglion cell types strengthens the view that there is a common set of ganglion cell types in carnivores. Alpha and beta cell dendritic trees of dog and wolf are monostratified in either the inner or the outer part of the inner plexiform layer, suggesting an on/off dichotomy in the response to light. Dendritic field sizes of dog alpha and beta cells increase from the central area to peripheral retina: alpha cell fields from 160-200 microns to about 1,100 microns diameter, and beta cell fields from 25 microns to about 360 microns diameter. These sizes are quantitatively very similar to those found in cat retina. The close qualitative and quantitative morphological correspondence of cat and dog ganglion cells suggests that they are also functionally very similar. It is likely that dog alpha cells have brisk-transient (Y), and dog beta cells brisk-sustained (X) concentric receptive fields. From the smallest beta cell sizes it is concluded that the visual acuity of the dog may be as good as that of the cat.     

整合素β1在自身免疫性心肌炎小鼠心肌的表达

目的:观察整合素β1在自身免疫性心肌炎小鼠心肌的表达变化。方法:猪肌凝蛋白皮下注射免疫Balb/c小鼠,建立慢性自身免疫性心肌炎模型,于初次免疫后14、30和60d对心肌组织进行病理学检查,同时用激光共聚焦技术和间接免疫荧光法检测整合素β1在心肌的表达变化。结果:在初次免疫后14d,小鼠心脏有局部炎症出现,整合素β1在心脏血管周围的表达高于正常组（P<0.05）;在第30天,小鼠心脏炎性浸润更加明显,整合素β1在心肌的表达增强,显著高于正常组（P<0.05）;第60天,小鼠心脏炎症细胞减少,而纤维化则开始出现,整合素β1在心肌的表达最强（P<0.05）,且排列紊乱。结论:整合素β1在自身免疫性心肌炎的发生及发展过程中起着不同重要作用,整合素β可能参与自身免疫反应及心肌的重构。     

小鼠膜性肾小球肾炎复制方法及免疫荧光定量研究

目的：介绍实验性小鼠膜性肾小球肾炎(MGN)的复制方法，并探讨其免疫荧光定量分析在肾小球肾炎研究中的应用价值。方法：制备阳离子化牛血清白蛋白(GBSA)并复制小鼠MGN，对各组小鼠进行电镜及免疫荧光观察，并进行免疫荧光定量研究。结果：电镜、免疫荧光观察均显示病理Ⅰ组(PⅡ组)具有典型的MGN病变，病理Ⅱ组(PⅡ组)病变轻微且不典型。免疫荧光定量研究证实PⅠ、PⅡ组与对照组差异有显著性；PⅠ、PⅡ组间差异无显著性。结论：C—BSA可作为复制小鼠MGN的良好抗原，隔日2mg／只尾静脉注射4w即可复制出稳定的小鼠MGN模型。免疫荧光定量分析不仅能直接而准确地反映MGN病理变化，而且在MGN早期即具有诊断价值。     

颈前部皮神经构筑研究

目的　为研究皮肤疾病和损伤提供皮神经构筑资料。方法　用S 10 0蛋白免疫组化染色法研究正常成人颈前部胸锁乳突肌前、后缘皮肤各层内皮神经的数量、分布及构筑特点。结果　 ( 1)皮肤乳头层内皮神经的小分支多分布在皮突下和乳头内血管丛附近。 ( 2 )真皮网状层内神经多位于小血管附近和汗腺、皮脂腺以及毛囊周围 ,神经分支呈串珠状或波纹形。 ( 3 )皮下组织内神经干和神经网同时存在。结论　皮肤内感觉神经树的分布及构筑特点与血管树相似。     

D1S549等6个短串重复序列基因座在河南汉族群体的遗传多态性

目的　探讨河南汉族群体的D1S5 49、D3S175 4、D2 2S683和CSF1PO、TPOX、TH0 1基因座遗传多态性分布。方法　ACD抗凝血样采自 2 19名无血缘关系汉族个体 ,酚 氯仿法提取DNA ,应用复合扩增技术对D1S5 49等 6个短串重复序列 (STR)基因座进行扩增 ,采用高分辨率的聚丙烯酰胺凝胶电泳分离、银染法显影技术。统计各基因频率、计算杂合度、多态信息含量、个人识别概率及亲权否定概率。结果　 6个STR基因座基因频率的分布均符合Hardy Weinberg平衡 ,各基因座的杂合度分别为 0 .7964、0 .72 3 1、0 .815 9、0 .75 81、0 .65 2 3、0 .6816;非父排除概率为 0 .62 46、0 .4914、0 .65 0 1、0 .5 2 3 6、0 .40 98、0 .42 87;个人识别机率为 0 .8996、0 .8781、0 .92 3 1、0 .8896、0 .8167、0 .83 92 ;多态信息含量为 0 .72 16、0 .6994、0 .742 1、0 .7169、0 .65 17、0 .710 6。结论　D1S5 49等 6个STR基因座是一组高度多态性的遗传标记系统 ,在人类遗传学及法医学研究中具有重要意义     

多种底物在免疫金银染色检测抗核抗体试验中的联合应用

将多种底物联合应用于免疫金银染色检测ANA试验,与各底物单独应用比较,可明显改善检测的敏感性与核型显示。其中,两种鼠脏器印片联合应用的结果可与Hep-2细胞的结果相当,三种及四种鼠脏器印片联合应用的结果可与Hep-2细胞和一种鼠脏器印片联合应用的结果相当,且均不使正常人ANA阳性率明显升高。     

Intracytoplasmic Lumina in Human Oviduct Epithelium

Intracytoplasmic lumina (ICL) in human oviduct epithelium were investigated with transmission electron microscopy. ICL were found in 43 out of 60 cases examined. They were ultra-structurally characterized by microvilli lining the lumina, periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining-positive finely granular material in the lumina, and secretory vesicles in the cytoplasm surrounding the lumina. Although ICL were observed at various heights within the epithelium, they were mainly seen in basally located cells that did not face the oviduct lumen. Various stages of formation and development of ICL were observed in the basally located epithelial cells with secretory activities. Primary ICL were originated in the cytoplasm where the secretory granules were aggregated with smooth-surfaced tubular vesicles. Electron microscopic observations after PA-TCH-SP staining revealed that ICL were formed by fusion of the secretory granules with the tubular vesicles. ICL were enlarged into round profiles by further fusion of secretory granules and tubular vesicles, and subsequently opened to the oviduct lumen, or fused to each other to develop into large extracellular cysts within the epithelium.