Homing receptors on human and rodent lymphocytes--evidence for a conserved carbohydrate-binding specificity

Lymphocyte recirculation begins with the attachment of circulating cells to the structurally distinctive postcapillary venules of lymphoid organs termed high-endothelial venules (HEVs). In both rodents and humans, the attachment of lymphocytes to the HEVs of peripheral lymph nodes (PNs) on the one hand and gut-associated lymphoid tissues (GALTs) on the other appears to involve discrete adhesive structures on the surfaces of the interacting cells. In rodents, we previously showed that a carbohydrate-binding receptor at the lymphocyte surface participates in the attachment to the HEV of peripheral nodes. The studies reported herein document the involvement of a similar receptor in the selective attachment of human peripheral blood lymphocytes to the HEVs of PNs. We argue that the close functional relationship between the human and rodent receptors indicates that this component of the adhesive interaction has been conserved through evolution.     

Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria

The purpose of these studies was to determine the molecular basis of the phenotypic mosaicism that is a defining feature of paroxysmal nocturnal hemoglobinuria (PNH). Analysis of T cell clones from a female patient revealed four distinct phenotypes based on surface expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that is mutant in PNH) from these clones was analyzed, four discrete somatic mutations were identified. Analysis of X chromosomal inactivation among the abnormal T cell clones was consistent with polyclonality. Together, these studies demonstrate that the phenotypic mosaicism that is characteristic of PNH is a consequence of genotypic mosaicism and that, at least in this case, PNH is a polyclonal rather than a monoclonal disease. That four distinct somatic mutations were present in a single patient suggests that in conditions that predispose to PNH PIG-A may be hypermutable.     

A granulocyte reactive monoclonal antibody, 1G10, identifies the Gal beta 1-4 (Fuc alpha 1-3)GlcNAc (X determinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules

1G10, a monoclonal IgM antibody that identifies a differentiation antigen on human granulocytes and a subpopulation of monocytes, was found to react specifically with glycosphingolipids bearing the Gal beta 1-4(Fuc alpha 1-3)GlcNAc hapten (X determinant). This carbohydrate determinant was found on both glycolipid and glycoprotein molecules isolated from HL-60 cells (a promyelocytic leukemia cell line). Thus, this highly conserved carbohydrate-defined determinant previously described on mouse embryonic and mouse and human carcinoma cells is also expressed as a tissue-specific differentiation antigen on normal human granulocytes.     

三维电解剖系统指导房性心律失常射频导管消融的价值

目的探讨电解剖系统指导在房性心律失常射频导管消融中的作用和优势。方法对25例心房颤动（阵发性15例、持续性10例）在电解剖系统指导下进行重建左心房后行线性消融，7例持续性房性心动过速（右心房性4例、左心房性3例）在电解剖系统指导下重建左／右心房标测激动顺序后行消融。结果25例心房颤动均完成预定的线性消融，其中14例阵发性者在窦性心律下电学隔离成功，10例持续性和1例阵发性者在心房颤动时电学隔离成功。7例持续性房性心动过速均在消融过程中转为窦性心律。电解剖系统指导下平均手术时间心房颤动为220min，房性心动过速为86min；平均X线透视时间心房颤动为48min，房性心动过速为20min。所有患者手术过程中均无并发症。结论在电解剖系统指引下，环肺静脉电隔离治疗心房颤动安全有效；有助于设计房性心动过速消融径线，缩短手术时间，提高成功率。     

Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study

To determine whether cytomegalovirus (CMV) antigenemiaguided ganciclovir treatment may be as effective, may require less treatment, and thus may cause less marrow toxicity than ganciclovir administered at engraftment, 226 marrow transplant recipients were randomized at engraftment to receive placebo (antigenemia-ganciclovir group) or ganciclovir (ganciclovir group) until day 100 in a double-blind study. In patients with antigenemia of 3 or more positive cells in 2 slides and/or viremia, study drug was discontinued and ganciclovir was started for at least 3 weeks or until negative CMV antigenemia and resumed only if antigenemia recurred. More patients in the antigenemia-ganciclovir group developed CMV disease before day 100 after transplantation compared with the ganciclovir group (14% v 2.7%, P = .002). Of the 16 patients with CMV disease before day 100 in the antigenemia-ganciclovir group, 10 (8.8%) had disease before or during the first episode of antigenemia and 6 (5.3%) developed disease after discontinuation of ganciclovir. Untreated low-grade antigenemia progressed to CMV disease in 19% of patients with grade 3-4 compared with 0% of patients with grade 0-2 acute graft-versus-host disease (P = .04). There was no significant difference in CMV disease by day 180 after transplantation and thereafter. CMV-related death, transplant survival, and neutropenia were not significantly different between the groups. In the ganciclovir group, more invasive fungal infections occurred (P = .03) and more ganciclovir was used (P < .0001). Thus, delaying the start of ganciclovir until highgrade antigenemia and discontinuing ganciclovir based on negative antigenemia results in more CMV disease by day 100 than ganciclovir administered at engraftment. However, ganciclovir at engraftment is associated with more early invasive fungal infections and more late CMV disease resulting in similar survival rates.     

Prolonged Atrium Electromechanical Interval Is Associated with Stroke in Patients with Atrial Fibrillation After Catheter Ablation

Electromechanical Interval and Strokes After Ablations of AF . Introduction: Atrial fibrillation (AF) is associated with increased risk of embolic stroke. Catheter ablation of AF provides an effective therapy for patients with symptomatic and drug‐refractory AF. The aim of this study was to evaluate whether the atrial electromechanical interval is useful in identifying patients at risk of stroke after successful catheter ablation. Methods and Results: A total of 279 AF patients who received catheter ablation and showed no evidence of recurrences were enrolled. Electromechanical interval (PA–PDI) was determined as the time interval from the initiation of P wave deflection to the peak of mitral inflow A wave on pulse wave Doppler imaging. The PA–PDI interval was measured for each patient after the 3‐month blanking period of catheter ablation. The clinical endpoint was the occurrence of ischemic stroke. During the follow‐up of 46.5 ± 17.2 months, 6 patients suffered from ischemic strokes. Patients with strokes had higher CHA₂DS₂–VASc scores and longer PA–PDI intervals (138.7 ± 12.4 ms vs 161.2 ± 7.7 ms, P value < 0.001) compared to those without strokes. At a cutoff point of 150 ms identified by ROC curve, the positive and negative predictive values of the PA–PDI interval to predict stroke were 86.7% and 100%, respectively. The PA–PDI interval improved the predictive performance of the CHA₂DS₂–VASc score, and the area under the ROC curve increased from 0.75 to 0.85. Conclusions: Our results suggest that the PA–PDI interval is a useful tool to identify patients with high risk of stroke after successful catheter ablation of AF. (J Cardiovasc Electrophysiol, Vol. 24, pp. 375‐380, April 2013)     

PCI-32765和Bortezomib对B细胞肿瘤细胞系细胞增殖、凋亡的影响及其机制的研究

本研究旨在探讨Btk抑制剂PCI-32765和蛋白酶体抑制剂bortezomib对Raji、Ramos细胞的增殖、凋亡的影响及其作用机制.PCI-32765和bortezomib单药及联合用药处理Raji和Ramos细胞后,分别运用CCK-8法及流式细胞术检测细胞的增殖与凋亡,Western blot法检测Btk、NFκB、c-IAP1、Bcl-xL、caspase-3等蛋白的表达.结果表明：①PCI-32765（0.5、1.0、2.0、3.0、4.0、5.0、6.0μmol/L）和bortezomib（10、20、30、40、50、60、80 nmol/L）处理Raji和Ramos细胞48 h,均可抑制细胞增殖,抑制率呈剂量依赖性,且两药具有协同作用;②PCI-32765（2.0μmol/L）、bortezomib（20 nmol/L）单药及联合用药处理Raji和Ramos细胞不同时间（8、12、24、36、48、72 h）,均可抑制细胞存活率,抑制率呈时间依赖性,且两药具有协同作用;③PCI-32765（2μmol/L）和bortezomib（20 nmol/L）单药及联合用药处理Raji和Ramos细胞48 h,可明显促进Raji及Ramos细胞的凋亡.Raji细胞实验结果,空白对照组、PCI-32765和bonezomib单药组、联合用药组的细胞凋亡率分别为10.34±0.53％、24.26±0.91％、43.66±1.08％与74.06±0.72％,各组间有统计学差异（P＜0.05）;Ramos细胞实验结果,空白对照组、PCI-32765和bortezomib单药组、联合用药组的细胞凋亡率分别为15.16±1.49％、71.36±0.82％、75.32±2.36％与84.30±0.91％,各组间有统计学差异（P＜0.05）;④PCI-32765和bonezomib单药处理Raji、Ramos细胞后,细胞内Btk、NFκB、Bcl-xl及c-.IAP1的表达水平较对照组降低,Caspase-3的表达水平升高,两药联用后,作用增强.结论：PCI-32765和bonezomib可以协同抑制Raji与Ramos细胞的增殖,促进其凋亡,其机制可能与抑制Btk、NFκB的活性,下调Bcl-xl及c-IAP1等抗凋亡蛋白,同时上调Caspase-3等凋亡蛋白的表达而发挥作用.     

妊娠晚期孕妇抑郁与睡眠质量的相关性研究

目的 了解妊娠晚期孕妇抑郁和睡眠质量的现况及其影响因素,探讨妊娠晚期孕妇抑郁与睡眠质量的相关性。方法 选择中卫市2所医院535名符合调查要求的孕妇进行问卷调查,采用匹兹堡睡眠质量指数量表（pittsburgh sleep quality index,PSQI）和抑郁自评量表（self-rating depression scale,SDS）评定孕妇睡眠质量及抑郁。结果 535名孕妇抑郁检出率为34.2%,睡眠障碍的检出率为20.6%。有抑郁的孕妇睡眠障碍检出率（29.0%）高于无抑郁的孕妇（16.2%）,差异有统计学意义（χ²=12.018,P=0.001）。PSQI总分和SDS得分呈正相关（r=0.680,P<0.001）。文化程度低、夫妻关系差、有孕期并发症、睡眠障碍是妊娠晚期孕妇抑郁的危险因素。有孕期并发症、担忧孩子健康、抑郁是妊娠晚期孕妇睡眠障碍的危险因素。结论 妊娠晚期孕妇睡眠质量与抑郁呈正相关,应采取综合性干预措施改善妊娠晚期孕妇的抑郁情绪和睡眠质量。     

不同剂量链脲佐菌素建立妊娠期糖尿病大鼠模型稳定性的比较

目的：探讨链脲佐菌素（STZ）建立妊娠期糖尿病（GDM）大鼠模型中不同给药剂量对模型稳定性的影响,研究GDM对母体及胎儿的影响率、转阴率和死亡率.方法：将46只SD孕鼠随机分为STZ低、中、高不同剂量组,分别一次性腹腔注射STZ35,45,60mg/kg;对照组腹腔注射等量的柠檬酸缓冲液.于妊娠第3,9,14,19d时测空腹血糖,并观察成模孕鼠在妊娠中体质量、饮水量、摄食量和尿量变化,比较孕鼠成模情况.结果：STZ45mg/kg组孕鼠在用药后出现明显的“三多一少”症状,其成模率83.3%为最高,转阴率最低.空腹血糖值STZ45mg/kg组（21.8±3.0）mmol/L与对照组（5.9±1.2）mmol/L相比较,其高血糖状态持续时间长,最稳定,且体质量也明显降低,差异具有统计学意义（P〈0.05）.结论：STZ45mg/kg腹腔注射给药是建立GDM大鼠模型的最佳剂量,具有较好的稳定性.