完全性葡萄胎和正常胎盘组织中p21的表达

目的研究p21表达与葡萄胎发生的关系。方法取完全性葡萄胎和正常早孕流产标本各30例,用SABC免疫组织化学染色方法,检测p21癌基因在两种组织中的表达,并采用图像分析技术,对正常早孕绒毛组和葡萄胎组织p21癌基因的表达情况进行对比分析。结果与正常绒毛相比,p21癌基因在葡萄胎组织中的表达量没有显著性差异,表达部位有明显不同。结论p21癌基因与完全性葡萄胎的发生密切相关。     

血清胎盘生长因子、血管生成素-2联合应激诱导蛋白2预测重度子痫前期患者胎盘早剥的临床研究

摘要 目的：探讨重度子痫前期（SPE）患者胎盘早剥的危影响因素,并探讨胎盘生长因子（PLGF）、血管生成素-2（Ang2）联合应激诱导蛋白2（Sestrin2）对重度子痫前期并发胎盘早剥的预测价值。方法：选取2019年4月至2022年4月长沙市第四医院收治的SPE患者348例。根据患者是否发生胎盘早剥分组,分为胎盘早剥组（n=75）和无胎盘早剥组（n=273）。检测并对比两组血清PLGF、Ang2及Sestrin2水平。采用单因素及多因素Logistic回归模型分析SPE患者并发胎盘早剥的影响因素;采用受试者工作特征（ROC）曲线分析PLGF、Ang2联合Sestrin2对SPE患者并发胎盘早剥的预测价值。结果：胎盘早剥组的PLGF、Ang2低于无胎盘早剥组,Sestrin2高于无胎盘早剥组（P<0.05）。SPE并发胎盘早剥与剖宫产史、收缩压（SBP）、舒张压（DBP）、血小板、尿素氮、纤维蛋白原、血肌酐有关（P<0.05）。多因素Logistic回归模型分析结果显示：SBP偏高、DBP偏高、纤维蛋白原偏低、血肌酐偏高是SPE并发胎盘早剥的危险因素。Sestrin2水平下降,PLGF、Ang2水平升高则是SPE并发胎盘早剥的保护因素（P<0.05）。血清PLGF、Ang2联合Sestrin2检测对SPE并发胎盘早剥的预测价值优于各指标单独检测（P<0.05）。结论：SPE并发胎盘早剥患者中Sestrin2水平升高,PLGF、Ang2水平下降,联合检测可以辅助预测SPE并发胎盘早剥的发生。SBP偏高、DBP偏高、纤维蛋白原偏低、血肌酐偏高是SPE并发胎盘早剥的危险因素。Sestrin2水平下降,PLGF、Ang2水平升高是SPE患者并发胎盘早剥的保护因素。     

Trinucleate cells and the ultrastructural localisation of bovine placental lactogen

Summary Bovine placental lactogen activity is shown by immunogold electron microscopy to be restricted to (a) the granules and the Golgi body from which they form in the bovine fetal trophectodermal binucleate cell, and (b) granules of similar size and staining reaction in trinucleate giant cells found in the maternal uterine epithelium throughout pregnancy. These results support the hypothesis that a fetal binucleate cell forms a maternal giant cell by migration to and fusion with a uterine epithelial cell.     

Chondroitin sulphate A (CSA)-binding of single recombinant Duffy-binding-like domains is not restricted to Plasmodium falciparum Erythrocyte Membrane Protein 1 expressed by CSA-binding parasites

Individuals living in areas with high Plasmodium falciparum transmission acquire immunity to malaria over time and adults have a markedly reduced risk of contracting severe disease. However, pregnant women constitute an important exception. Pregnancy-associated malaria is a major cause of mother and offspring morbidity, such as severe maternal anaemia and low birth-weight, and is characterised by selective accumulation of parasite-infected erythrocytes (IE) in the placenta. A P. falciparum protein named VAR2CSA, which belongs to the large P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family, enables the IE to bind chondroitin sulphate A (CSA) in the placenta. Knock-out studies have demonstrated the exclusive capacity of VAR2CSA to mediate IE binding to CSA, and it has been shown that four of the six Duffy-binding-like (DBL) domains of VAR2CSA have the ability to bind CSA in vitro. In this study, we confirm the CSA-binding of these DBL domains, however, the analysis of a number of DBL domains of a non-VAR2CSA origin shows that CSA-binding is not exclusively restricted to VAR2CSA DBL domains. Furthermore, we show that the VAR2CSA DBL domains as well as other DBL domains also bind heparan sulphate. These data explain a number of publications describing CSA-binding domains derived from PfEMP1 antigens not involved in placental adhesion. The data suggest that the ability of single domains to bind CSA does not predict the functional capacity of the whole PfEMP1 and raises doubt whether the CSA-binding domains of native VAR2CSA have been correctly identified.     

Do indicators of maternal iron status reflect placental iron status at delivery?

Indicators of maternal iron (Fe) status were studied in relation to placental Fe (Pl-Fe) status. Placental (Pl) and maternal (M) venous blood samples were obtained from primiparous women ($n=38$), with normal delivery at Paroissien Hospital, Argentina. Maternal hemoglobin (M Hb), soluble transferrin receptor (M sTfR) (ELISA) and serum ferritin (M S-Ft) were studied in relation to Pl-Fe, ferritin (Pl-Ft) and transferrin receptor (Pl-TfR). Pl-TfR was measured by dot blot assay, Pl-Ft and M S-Ft by immunoassay (IRMA) and Pl-Fe by atomic absorption spectrometry. Fe status indicators were, respectively, (mean±SD): M Hb 113±16 g/L; M S-Ft 36±42 μg/L; M sTfR 6.3±3.1 mg/L; Pl-Fe 170±56 μg/g placenta; Pl-Ft 33±18 μg/g placenta; Pl-TfR 18±18 (range 0–58) μg/g placenta. Pl-Fe, Pl-Ft and Pl-TfR did not correlate to M Hb, M S-Ft and M sTfR. Women with Pl- Fe, Pl-Ft and Pl-TfR above or below the corresponding median values did not show any statistical significant difference in M Hb, M sTfR or M S-Ft values. Pl-Ft concentration was lower in women with Hb<110 g/L than in women with normal values: 26±13 vs. 38±20 μg/g, respectively ($p=0.021$). When Pl-TfR, Pl-Ft and Pl-Fe were compared in women with M S-Ft above or below the cut-off point of 10 or 20 μg/L, no significant difference was found for Pl-TfR neither for Pl-Ft nor Pl-Fe. These results suggest that maternal indicators of Fe status, particularly M sTfR and M S-Ft, do not reflect Fe status of the placenta at delivery.     

Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria

Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria is caused by parasites capable of sequestering in the placenta. This is mediated by VAR2CSA, a parasite antigen that interacts with chondroitin sulfate A (CSA). One vaccine strategy is to block this interaction with VAR2CSA-specific antibodies. It is a priority to define a small VAR2CSA fragment that can be used in an adhesion blocking vaccine. In this, the obvious approach is to define regions of VAR2CSA involved in receptor binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with nanomolar affinity, and that the CSA-binding site lies in the N-terminal part of the protein. In this study we define the minimal binding region by truncating VAR2CSA and analyzing CSA binding using biosensor technology. We show that the core CSA-binding site lies within the DBL2X domain and parts of the flanking interdomain regions. This is in contrast to the idea that single domains do not possess the structural requirements for specific CSA binding. Small-angle x-ray scattering measurements enabled modeling of VAR2CSA and showed that the CSA-binding DBL2X domain is situated in the center of the structure. Mutating classic sulfate-binding sites in VAR2CSA, along with testing dependence of ionic interactions, suggest that the CSA binding is not solely dependent on the sulfated CSA structure. Based on these novel PfEMP1 structure-function studies, we have constructed a small VAR2CSA antigen that has the capacity to induce highly adhesion-blocking antibodies.     

Obligate Ordered Binding of Human Lactogenic Cytokines

Class 1 cytokines bind two receptors to create an active heterotrimeric complex. It has been argued that ligand binding to their receptors is an ordered process, but a structural mechanism describing this process has not been determined. We have previously described an obligate ordered binding mechanism for the human prolactin/prolactin receptor heterotrimeric complex. In this work we expand this conceptual understanding of ordered binding to include three human lactogenic hormones: prolactin, growth hormone, and placental lactogen. We independently blocked either of the two receptor binding sites of each hormone and used surface plasmon resonance to measure human prolactin receptor binding kinetics and stoichiometries to the remaining binding surface. When site 1 of any of the three hormones was blocked, site 2 could not bind the receptor. But blocking site 2 did not affect receptor binding at site 1, indicating a requirement for receptor binding to site 1 before site 2 binding. In addition we noted variable responses to the presence of zinc in hormone-receptor interaction. Finally, we performed Förster resonance energy transfer (FRET) analyses where receptor binding at subsaturating stoichiometries induced changes in FRET signaling, indicative of binding-induced changes in hormone conformation, whereas at receptor:hormone ratios in excess of 2:1 no additional changes in FRET signaling were observed. These results strongly support a conformationally mediated obligate-ordered receptor binding for each of the three lactogenic hormones.     

先天性佝偻病与纳米细菌关系研究的现状与展望

先天性佝偻病是胎儿出生后就发生的特殊阶段的佝偻病,病因并不十分清楚,迁延不愈会影响小儿骨骼发育和免疫功能。纳米细菌导致的胎盘钙化与小儿佝偻病有关,推测纳米细菌与先天性佝偻病有关。因此诊断和防治纳米细菌感染可能对于先天性佝偻病的预防有一定临床意义。     

纳米细菌的分离培养和保存方法探讨

目的 以钙化的胎盘组织为例,寻求在钙化组织中分离纳米细菌的最佳方法,以便更多疑似与纳米细菌感染有关的疾病得以准确分离出纳米细菌菌株,并探讨培养和保存纳米细菌的最适宜的条件.方法 (Ⅰ)胎盘钙化组织标本分别用盐酸脱矿与超声振荡脱矿的方法分离纳米细菌,计算其分离阳性率.(2)分离出的纳米细菌分别用细胞培养箱与细菌培养箱培养1个月,利用分光光度计记录两种条件下纳米细菌浓度的变化,并描绘生长曲线.(3)分别用4、- 20与- 80℃冰箱保存钙化组织和纳米细菌,记录纳米细菌分离和复苏的生长状况并绘制生长曲线.结果 (1)钙化组织用盐酸脱矿更易分离得到纳米细菌.(2)细胞与细菌培养环境下纳米细菌的生长速度并无明显差别.(3)4℃保存钙化组织和纳米细菌对于其分离和复苏都要优于- 20℃和- 80℃.结论 对钙化组织进行盐酸脱矿可以更好的分离出纳米细菌,并且可以在细菌培养箱内培养纳米细菌,新鲜钙化组织标本和纳米细菌可以短时间保存在4℃.