Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways

Plasma fibronectin binds in a specific and saturable manner to thrombin- stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin- stimulated cells. Second, formaldehyde-fixed cells with surface- associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.     

Developing Empirically Based, Culturally Grounded Drug Prevention Interventions for Indigenous Youth Populations

This article describes the relevance of a culturally grounded approach toward drug prevention development for indigenous youth populations. This approach builds drug prevention from the “ground up” (i.e., from the values, beliefs, and worldviews of the youth that are the intended consumers of the program) and is contrasted with efforts that focus on adapting existing drug prevention interventions to fit the norms of different youth ethnocultural groups. The development of an empirically based drug prevention program focused on rural Native Hawaiian youth is described as a case example of culturally grounded drug prevention development for indigenous youth; the impact of this effort on the validity of the intervention and on community engagement and investment in the development of the program are discussed. Finally, implications of this approach for behavioral health services and the development of an indigenous prevention science are discussed.     

Primärversorgung penetrierender Verletzungen

Blast injuries may result from a variety of causes but the biomechanical impact and pathophysiological consequences do not differ between domestic or industrial accidents or even terrorist attacks. However, this differentiation relevantly affects the tactical procedures of the rescue teams. Focusing on further detonations, top priority is given to the personal safety of all rescue workers. The rareness of blast injuries in a civilian setting results in a lack of experience on the one hand but on the other hand the complexity of blast injuries to the human body places high demands on the knowledge and skills of the entire rescue team for competent treatment. The purpose of this article is to explain the physicochemical principles of explosions and to convey tactical and medical knowledge to emergency medical services.     

A gene for nonspecific X-linked mental retardation (MRX41) is located in the distal segment of Xq28

We report on a family in which non-syndromal mild to moderate mental retardation segregates as an X-linked trait (MRX41). Two point linkage analysis demonstrated linkage between the disorder and marker DXS3 in Xq21.33 with a lod score of 2.56 at θ = 0.0 and marker DXS1108 in Xq28 with a lod score of 3.82 at θ = 0.0. Multipoint linkage analysis showed that the odds for a location of the gene in Xq28 vs Xq21.33 are 100:1. This is the fourth family with non-specific X-linked mental retardation with Xq28-qter as the most likely gene localization. © 1996 Wiley-Liss, Inc.     

Characterization of a virus-specific proteolytic activity processing the gag precursor of the simian sarcoma-associated virus

The proteolytic processing of the gag precursor polypeptide pr65gag of simian sarcoma-associated virus (SSAV) has been studied in vivo and in vitro. In SSAV-infected cells (i.e., in vivo) proteins of 52 and 38 kDa and the viral protein p30 could be immunoprecipitated with anti-p30 serum. This cleavage pattern is only in part imitated by in vitro cleavage of the isolated pr65gag with avian myeloblastosis virus (AMV) protease p15. However, in vitro incubation of isolated pr65gag with detergent-disrupted SSAV particles generated products identical in size to those found in vivo, i.e., proteins of 52 and 38 kDa and p30. The extent of cleavage is dependent on the concentration of the disrupted virions added to the incubation mixture. Studies with protease inhibitors suggest that the SSAV enzyme is a serine-type protease like that of other mammalian retroviruses and unlike the protease of avian viruses. The SSAV protease activity eluted from a molecular sieve column in a range of about 10-15 kDa reflecting the molecular weight of the murine leukemia virus (MuLV) protease (Mr = 13.5K). Thus, it appears that there is a close similarity between the proteolytic enzymes present in different mammalian retroviruses such as MuLV and SSAV.     

红景天抑制人脐静脉内皮细胞生长的初步研究

目的:利用体外培养人脐静脉内皮细胞,观察中药红景天对细胞生长的影响,初步探讨急、慢性高原病患者服用中药红景天防治高原病及改善症状等的作用机制。方法:培养人脐静脉内皮细胞EVC-304,设对照组与加药组,加药组分别加入不同浓度的红景天,培养3d后计数。加药组及对照组细胞用瑞氏染料染色并拍照。收集细胞以流式细胞术检测细胞周期。结果:对照组细胞形态正常,成梭形,排列紧密,分散均匀。加药组细胞数量明显减少,细胞皱缩,聚集成团,形态各异。流式细胞术检测显示加药组G1期细胞含量增多,S期细胞减少。结论:红景天具有抑制血管内皮细胞生长的作用,可能是通过抑制细胞的增殖来抑制内皮细胞生长。抑制血管内皮细胞生长对于阻止血管内膜增生,防止形成肺动脉高压,降低慢性高原病发病率具有实际应用意义。     

PCT、CRP动力学评估脓毒血症预后及诊断意义的研究

目的 观察血清降钙素原(PCT)、C反应蛋白(CRP)及其动力学变化,评估其在严重脓毒症/感染性休克患者的诊断及预后价值.方法 本研究采用回顾性分析方法,2014年9月1日至2016年4月30日选择184例ICU中被诊断为严重脓毒症/感染性休克疾病患者,检测入院时血清PCT、CRP水平和治疗后第2,第3和第5天的PCT、CRP水平.结果 通过△PCT、△CRP评估PCT、CRP的动力学在存活者与死亡组中有显著性统计学意(△PCT2/0,P=0.0001;△PCT3/0,P=0.0001;△PCT5/0,P=0.0001;△CRP2/0,P=0.0069;△CRP3/0,P=0.0001;△CRP5/0,P=0.0001),在严重脓毒症和感染性休克组中也存在显著差异(PCT5,P=0.007;△PCT5/0,P=0.007).受试者工作特征曲线(ROC)模型显示,△PCT3/0(AUC=0.721)、△PCT5/0(AUC=0.77)、△CRP5/0(AUC=0.766)水平判断严重脓毒症/感染性休克患者预后有较好的临床意义.△PCT5/0 (0.619)对严重脓毒症或感染性休克有一定的辅助诊断效果,其在ROC曲线上灵敏度、特异性均较高的临界点为0.624,所以,以第5天的血清△PCT5/0水平＞0.624可作为预测感染性休克的临界点.结论 血清中PCT、CRP对严重脓毒症/感染性休克早期有较好的临床诊断及预后价值,其动力学研究可以提高对严重脓毒症/感染性休克诊断及预后评估的敏感性及准确性.     

不同抗生素用药方案在预防腹膜透析置管术后腹膜炎中的比较

目的比较不同预防性用药方案在新置腹膜透析导管患者的使用情况,探讨抗生素用药在预防新置腹膜透析导管患者术后发生腹膜炎的重要性。方法回顾性分析2008年10月至2012年10月在北京大学深圳医院肾内科腹膜透析中心接受腹膜透析置管术开始行腹膜透析治疗的患者173例。按照预防性使用抗生素方法分为3组,A组:患者在腹膜透析置管术后3天内使用含有头孢唑啉0.25g/L的腹透液,共计101例次;B组:患者在腹膜透析置管术前3h静脉滴注头孢唑林0.5g,共计48例次;C组:患者术前及术后3天均未使用抗生素,共计24例次。比较3组患者术后14天内腹膜炎的发生率。结果 A组101例患者中1例出现腹膜炎,发生在术后第11天,占0.99%;B组48例患者中2例出现腹膜炎,均发生在术后第1天,占4.17%;C组24例患者中4例出现腹膜炎,3例发生在术后第1天,1例发生在术后第2天,占16.67%。对3组患者腹膜炎发生率进行两两比较,A组与C组比较,P=0.005,P<0.01,差异有统计学意义;B组与C组比较,P>0.05,差异无统计学意义;A组与B组比较,P>0.05,差异无统计学意义。结论腹膜透析置管术围手术期预防性抗生素用药十分有必要,术后腹腔内给药或术前一次静脉用药能有效预防术后腹膜炎发生。