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
Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of t...Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of this study was to evaluate the frequency and distribution of the intron 22-inversion mutation in the patients and in the family members in the region.Methods 29 hemophilia A patients from Jammu and Kashmir(20 severe,8 moderate and 1 mild) were analyzed for intron 22-inversion mutation.Results 11(38%) were positive for the distal type of inversion mutation.The mutation was found in 9/20(45%) patients with severe factor Ⅷ deficiency and 2/8(25%) with moderate severity hemophilia A,whereas the patient with mild hemophilia A was found to be negative for inversion mutation.Evaluation of twenty-six female relatives from 11 families of inversion mutation positive patients identified one mother and one sister from one family to be the carrier,suggesting its origin in the mother. Conclusion The present study confirms the intron-22 inversion mutation in F8C gene as the major cause of hemophilia A in the population from Jammu and Kashmir with a higher frequency of inversion mutation in sporadic cases compared to the familial cases.展开更多
目的观察不同储存温度对于全血中Ⅷ因子含量的影响,评价不同时间Ⅷ因子含量的符合性。方法随机采集200 m L全血,每袋全血均分为2份,设冷藏组(4±2)℃和室温组(22±2)℃,分别于全血采集后不同时间点取样检测Ⅷ因子含量。结果冷...目的观察不同储存温度对于全血中Ⅷ因子含量的影响,评价不同时间Ⅷ因子含量的符合性。方法随机采集200 m L全血,每袋全血均分为2份,设冷藏组(4±2)℃和室温组(22±2)℃,分别于全血采集后不同时间点取样检测Ⅷ因子含量。结果冷藏组和室温组在全血采集后0、3、6、9、12、15、18 h时血浆中Ⅷ因子含量的差异均无统计学意义(P>0.05)。冷藏组和室温组在全血采集后15 h其血浆中的Ⅷ因子含量为0.76±0.14和0.87±0.21,合格率为75%(15/20)和80%(16/20),均符合我国血站技术操作规程(2012版)和英国指南中新鲜冰冻血浆质量控制要求。结论全血采集后储存于冷藏环境和室温环境中对于血浆中Ⅷ因子的含量无显著差异。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.
文摘Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of this study was to evaluate the frequency and distribution of the intron 22-inversion mutation in the patients and in the family members in the region.Methods 29 hemophilia A patients from Jammu and Kashmir(20 severe,8 moderate and 1 mild) were analyzed for intron 22-inversion mutation.Results 11(38%) were positive for the distal type of inversion mutation.The mutation was found in 9/20(45%) patients with severe factor Ⅷ deficiency and 2/8(25%) with moderate severity hemophilia A,whereas the patient with mild hemophilia A was found to be negative for inversion mutation.Evaluation of twenty-six female relatives from 11 families of inversion mutation positive patients identified one mother and one sister from one family to be the carrier,suggesting its origin in the mother. Conclusion The present study confirms the intron-22 inversion mutation in F8C gene as the major cause of hemophilia A in the population from Jammu and Kashmir with a higher frequency of inversion mutation in sporadic cases compared to the familial cases.
文摘目的观察不同储存温度对于全血中Ⅷ因子含量的影响,评价不同时间Ⅷ因子含量的符合性。方法随机采集200 m L全血,每袋全血均分为2份,设冷藏组(4±2)℃和室温组(22±2)℃,分别于全血采集后不同时间点取样检测Ⅷ因子含量。结果冷藏组和室温组在全血采集后0、3、6、9、12、15、18 h时血浆中Ⅷ因子含量的差异均无统计学意义(P>0.05)。冷藏组和室温组在全血采集后15 h其血浆中的Ⅷ因子含量为0.76±0.14和0.87±0.21,合格率为75%(15/20)和80%(16/20),均符合我国血站技术操作规程(2012版)和英国指南中新鲜冰冻血浆质量控制要求。结论全血采集后储存于冷藏环境和室温环境中对于血浆中Ⅷ因子的含量无显著差异。
