Characterization of an immunologic polymorphism (D79H) in the heavy chain of factor V.

BACKGROUND: During the study of a family with hereditary factor (F)V deficiency (FV Amersfoort, 1102 A > T in exon 7) we identified an individual with 5% FV heavy chain antigen (FV(HC)) and 50% FV light chain antigen (FV(LC)). Further testing revealed that apart from the FV Amersfoort allele a second variant FV allele was segregating in this family, which encodes for a FV molecule with a reduced affinity for mAb V-23 used in the FV heavy chain ELISA (ELISA(HC)). OBJECTIVE: Identification and characterization of the molecular basis responsible for the reduced affinity of the variant FV for mAb V-23. METHODS: Family members of the proband were screened for mutations in the exons coding for the heavy chain of FV, after which the recombinant variant FV could be generated and characterized. Next, the cases and controls of the Leiden Thrombophilia Study (LETS) were genotyped for carriership of the variant FV. RESULTS: In the variant FV allele a polymorphism in exon 3 (409G > C) was identified, which predicts the replacement of aspartic acid 79 by histidin (D79H). Introduction of this mutation in recombinant FV confirmed that it reduces the affinity for binding to mAb V-23. The substitution has no effect on FV(a) stability and Xa-cofactor activity. In Caucasians the frequency of the FV-79H allele is approximately 5%. Analysis of the LETS revealed that the FV-79H allele is not associated with FV levels (FV(LC)), activated protein C sensitivity (using an activated partial thromboplastin time-based test) or risk of venous thrombosis (OR 1.07, CI 95: 0.7-1.7). CONCLUSION: The D79H substitution in FV should be considered as a neutral polymorphism. The monoclonal antibody V-23, which has a strongly reduced affinity for FV-79H, is not suitable for application in diagnostic tests.     

Von Willebrand factor, platelets and endothelial cell interactions

Summary.  The adhesive protein von Willebrand factor (VWF) contributes to platelet function by mediating the initiation and progression of thrombus formation at sites of vascular injury. In recent years there has been considerable progress in explaining the biological properties of VWF, including the structural and functional characteristics of specific domains. The mechanism of interaction between the VWF A1 domain and glycoprotein Ibα has been elucidated in detail, bringing us closer to understanding how this adhesive bond can oppose the fluid dynamic effects of rapidly flowing blood contributing to platelet adhesion and activation. Moreover, novel findings have been obtained on the link between regulation of VWF multimer size and microvascular thrombosis. This progress in basic research has provided critical information to define with greater precision the role of VWF in vascular biology and pathology, including its possible involvement in the onset of atherosclerosis and its acute thrombotic complications.     

CCR1趋化因子受体在人肝癌组织中表达及其临床意义

目的了解CCRl趋化因子受体在人肝癌组织中表达分布情况，探讨其表达水平与临床病理特性的关系。方法采用RT-PCR、免疫组化、Western blot技术检测45例肝癌组织及相应癌旁肝组织CCRl趋化因子受体表达及分布情况，并分析其表达水平与临床病理特性的关系。结果RT-PCR、Western blot在肝癌组织及相应癌旁肝组织中均可以检测到CCR1趋化因子受体mRNA及蛋白，肝癌组织表达水平高于癌旁肝组织。免疫组化显示CCR1趋化因子受体主要表达于肝癌细胞膜。CCR1mRNA表达水平与病人性别、年龄、血清AFP水平、肿瘤大小、分期无明显相关性，而与肿瘤是否有包膜（t=2．305，P〈0．05）、门静脉浸润显著相关（t=3．004，P〈0．01）。无门静脉浸润的肝癌组织中，47．4％免疫组化染色强度为＋＋～＋＋＋，而有门静脉浸润的肝癌组织中，80．8％染色强度为＋＋～＋＋＋，两者比较差异具有显著意义（X^2=5．511，P〈0．05）。结论肝癌细胞表达CCR1趋化因子受体，其表达水平与肝癌侵袭性尤其是门静脉浸润相关，有望成为判断肝癌侵袭性及预后的指标。     

Decreased Risk of Renal Allograft Thrombosis Associated With Interleukin-2 Receptor Antagonists: A Report of the NAPRTCS

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.     

103Pd放射性核素支架抑制损伤血管平滑肌细胞增殖的实验研究

[目的]采用兔腹主动脉损伤致再狭窄的动物模型,探讨钯-103(103Pd)放射性核素支架对损伤血管中膜平滑肌细胞增殖的影响。[方法]选用雄性新西兰兔50只,随机分为普通支架组及核素支架组,设正常对照。分别于术后3、7、14、28及56 d取材,进行病理形态学、透射电镜、免疫组化(增殖细胞核抗原PCNA、细胞周期素蛋白Cy-clin E)及原位杂交(C-myc mRNA)实验观察。[结果]①光镜下发现,核素支架组管腔狭窄程度明显低于普通支架组,术后第56天最显著(P<0.01);②透射电镜显示,术后3~28 d,核素支架组中膜血管平滑肌细胞增殖明显低于普通支架组,7d时达峰,为13.78％±0.64％vs19.53％±0.44％(P<0.01);③免疫组化显示,术后3~28 d核素支架组PCNA及Cyclin E表达均低于普通支架组,7 d为表达高峰,PCNA为16.35％±0.79％vs24.36±0.55％,Cy-clin E为14.78％±1.07％ vs 22.65％±1.00％(P<0.01)。④对c-myc mRNA进行原位杂交显示,术后3~28 d核素支架组的表达明显低于普通支架组,7 d达峰值,为17.48％±0.53％ vs 25.34％±0.87％(P<0.01);⑤C-mycmRNA与PCNA相关性分析提示二者呈明显正相关(P<0.01)。[结论]103Pd放射性核素支架通过抑制损伤血管中膜平滑肌细胞的增殖,降低再狭窄的程度,从而减少再狭窄的发生率。     

颈动脉狭窄在脑保护装置下的支架置入治疗

目的探讨颈动脉狭窄患者支架治疗中的脑保护装置的有效性和安全性及治疗意义。方法对14例颈动脉狭窄患者进行血管内支架治疗。全部应用了脑保护装置(滤网型)。结果14例患者成功地释放了18枚自膨式支架。其中2例发生微栓子脱落轻度卒中,治疗1～3d完全恢复,颈动脉狭窄6例出现短暂性心率减慢和低血压。随访期所有患者均未发生脑梗死。结论在支架治疗中,脑保护装置的应用可减少治疗中的神经并发症,是一种有效和安全的治疗方法。     

蘑菇状覆膜内支架的设计和在食管胃吻合口-胸腔瘘中的应用

目的 设计封堵食管胃吻合口-胸腔瘘的覆膜内支架。方法 根据食管胃吻合口区的特殊解剖结构和吻合口胸腔瘘的病变特点，设计蘑菇状覆膜内支架。透视下，5例吻合口巨大胸腔瘘患者置入6枚蘑菇状覆膜内支架。结果 蘑菇状覆膜内支架能有效封堵食管胃吻合口巨大胸腔瘘，解决了进食问题，改善了营养状况。结论 蘑菇状覆膜内支架结构设计合理，操作简单、安全，近期疗效明显，是一项值得推广的新技术。     

X线、超声联合导向介入治疗布-加氏综合征

目的:探讨X线、超声联合导向下对布 加氏综合征的介入治疗方法和临床应用价值。方法:本组病人 30例,采用X线和超声联合导向。穿刺下腔静脉闭塞或狭窄部位,经球囊扩张后在X线、超声联合定位置入支架 成形。结果:28例成功,占93%。无严重并发症。术后患者症状明显缓解,下腔静脉压基本恢复正常(治疗前 2.8±0.51kPa,治疗后0.7±0.2kPa)。结论:采用X线、超声联合导向介入治疗布 加氏综合征是一种成功率高、 损伤小、效果可靠的治疗方法。     

前列腺切除术后深静脉血栓形成26例分析

目的：预防前列腺切除术后深静脉血栓形成，减少肺栓塞等严重并发症。方法：通过对26例下肢深静脉血栓形成患者的分析，讨论前列腺切除术后深静脉血栓形成因素，提出预防措施。结果：保守治疗18例，15例痊愈，3例好转；行髂股静脉取栓术2例痊愈；表现为肺栓塞6例，4例死亡，2例治愈。结论：前列腺切除术后患者是高血凝状态和血管收缩是形成深静脉血栓的内因，而围手术期处理不当是促使血栓形成的外因。围手术期采用抗高血凝和血管收缩措施，进行正确的围手术期处理可较好预防深静脉血栓形成。     

腹部手术后并发下肢深静脉血栓16例分析

目的　探讨腹部手术后并发下肢深静脉血栓形成 (DVT)的原因、诊治要点和预防措施。方法　回顾性分析 1 6例腹部手术后并发DVT病人的临床特点及诊断、治疗方法。结果　发生DVT的高危因素是复合创伤、恶性肿瘤、血粘度增高、老年病人、合并高血压病、糖尿病及术后常规应用止血药等。本组 1 6例均治愈 ,无一例发生肺栓塞等严重后果。结论　腹部手术后并发DVT者要积极早期治疗 ,对发生DVT的高危人群术前、术后应采取预防措施