Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progre...Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.展开更多
Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd ...Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank stored blood can be used to replenish antithrombin Ⅲ, while bank stored blood in one day can be used to replenish FⅧ.展开更多
BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated w...BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must improve.CASE SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 days.CONCLUSION AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.展开更多
目的:分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果,提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。方法:收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37℃孵育2 h APTT纠正试验,选取15份样本进行即刻...目的:分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果,提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。方法:收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37℃孵育2 h APTT纠正试验,选取15份样本进行即刻和常温孵育15 min、30 min、1和2 h及37℃孵育30 min、1和2 h APTT纠正试验。结果:APTT纠正试验结果与凝血因子Ⅷ抑制物滴度呈明显的相关性,ROC曲线下37℃孵育2 h APTT纠正试验判断有无凝血因子Ⅷ抑制物最佳诊断界点是43.8 s(敏感度85.90%,特异度100%),区分高滴度与低滴度Ⅷ抑制物的最佳诊断界点为52.4 s(敏感度98.18%,特异度95.65%)。即刻APTT无法纠正的临界凝血因子Ⅷ抑制物滴度为5.14 BU/ml,37℃孵育2 h APTT不能纠正对应的凝血因子Ⅷ抑制物的滴度为1.31 BU/ml。对不同时间和温度下APTT纠正试验结果进行配对t检验,差异有统计学意义(P<0.05)。结论:APTT纠正试验结果可作为凝血因子Ⅷ抑制物的筛查指标,较低Ⅷ抑制物滴度时呈明显的对温度-时间的依赖性,血友病患者即刻APTT无法纠正则应警惕较高滴度凝血因子Ⅷ抑制物存在的可能。展开更多
目的探讨第三代全长链重组凝血因子Ⅷ(third-generation full length recombinant human coagulation factorⅧ,fLFⅧ)预防治疗中间型、重型血友病A对患儿出血的影响。方法回顾性分析78例中间型、重型血友病A患儿的临床资料,所有患儿均...目的探讨第三代全长链重组凝血因子Ⅷ(third-generation full length recombinant human coagulation factorⅧ,fLFⅧ)预防治疗中间型、重型血友病A对患儿出血的影响。方法回顾性分析78例中间型、重型血友病A患儿的临床资料,所有患儿均采用fLFⅧ进行预防治疗,统计预防治疗12个月后的中间型、重型血友病A患儿年出血次数、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、血友病关节健康评分(HJHS)总分、血友病功能独立性评分量表(FISH)总分、凝血因子Ⅷ(FⅧ)抑制物的出现情况及fLFⅧ不良反应发生情况。结果应用fLFⅧ25 U/kg、每周3次进行预防治疗1年,中间型重型血友病A的年出血次数均较预防治疗前显著下降,差异有统计学意义(P<0.01);预防治疗后中间型、重型血友病A患儿APTT水平均较预防治疗前显著下降,差异有统计学意义(P<0.01);预防治疗12个月后中间型、重型血友病A患儿HJHS评分较预防治疗前显著下降,FISH评分较预防治疗前显著升高(P<0.01)。78例患儿中1例患儿报告了抑制物产生,分析其原因为患儿在治疗中使用了极少的其他凝血因子药物,全部病例未见药物相关不良反应及不良事件的发生。结论 fLFⅧ预防治疗中间型、重型血友病A可有效减少患儿年出血次数及APTT水平,改善患儿关节功能,安全性好,抑制物产生率低,长期用药耐受性好。展开更多
基金Supported by a grant from Medical Technology Research Center for Health Development of China National Health and Family Planning Commission(No.W2012FZ007)
文摘Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.
文摘Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank stored blood can be used to replenish antithrombin Ⅲ, while bank stored blood in one day can be used to replenish FⅧ.
基金Supported by Traditional Chinese Medicine Research Program of Hebei Provincial Administration of Traditional Chinese Medicine,No.2025313 and No.2025448.
文摘BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must improve.CASE SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 days.CONCLUSION AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.
文摘目的:分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果,提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。方法:收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37℃孵育2 h APTT纠正试验,选取15份样本进行即刻和常温孵育15 min、30 min、1和2 h及37℃孵育30 min、1和2 h APTT纠正试验。结果:APTT纠正试验结果与凝血因子Ⅷ抑制物滴度呈明显的相关性,ROC曲线下37℃孵育2 h APTT纠正试验判断有无凝血因子Ⅷ抑制物最佳诊断界点是43.8 s(敏感度85.90%,特异度100%),区分高滴度与低滴度Ⅷ抑制物的最佳诊断界点为52.4 s(敏感度98.18%,特异度95.65%)。即刻APTT无法纠正的临界凝血因子Ⅷ抑制物滴度为5.14 BU/ml,37℃孵育2 h APTT不能纠正对应的凝血因子Ⅷ抑制物的滴度为1.31 BU/ml。对不同时间和温度下APTT纠正试验结果进行配对t检验,差异有统计学意义(P<0.05)。结论:APTT纠正试验结果可作为凝血因子Ⅷ抑制物的筛查指标,较低Ⅷ抑制物滴度时呈明显的对温度-时间的依赖性,血友病患者即刻APTT无法纠正则应警惕较高滴度凝血因子Ⅷ抑制物存在的可能。
