THE STRUCTURAL BASIS OF THE POOR FIBRIN SPECIFICITY OF UROKINASE(Ⅰ)——KNOWLEDGE-BASED PREDICTION OF KRINGLE STRUCTURES OF UROKINASE AND ITS RELATED PROTEINS

The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional structure of Kringle-1 of prothrombin (PTK-1) at 2.8 resolution. The predicted three-dimensional structure of these Kringles shows that the binding site of PGK-1 is characterized by an apparent dipolar site, the polar parts of which are separated by a hydrophobic region. PAK-2 possesses the anionic center but has not a cationic binding center which might be provided by a guanidinium group from Arg-69 located adjacent to the Arg-71 position. UKK possesses neither the anionic binding center nor the cationic center which are probably the main reason for the poor fibrin specificity of urokinase.     

He—Ne激光血管内照射与尿激酶治疗脑梗塞对比研究及微观机理初探

将６２例脑梗塞患者随机分为两组,并分别用激光血管内照射（ＩＬＩＢ）及尿激酶进行治疗,继而对两组疗效进行对比性观察、测试及评估。文末对ＩＬＩＢ的作用机理进行了分析。     

尿激酶活性测定方法的比较

根据中国及日本药典,对测定尿激酶活性的两种方法的灵敏度和重复性进行了考察对比,对不同样品测定结果进行了比较。     

镧、铈对低分子量单链尿激酶基因在酵母中表达的影响

LaCl3能提高rscu-PA-32k在酵母中的表达效率，2和5mmol.L^-1LaCl3可以使表达产物活力提高13％和20％，从14．6U／ml分别增加到16．5和17．5U/ml，而CeCl3则使表达产物的活力降低，2和5mmol.L^-1 CeCl3分别使产物活力下降了21％和33％，从14＝6U／ml分别下降到11．5和9．8U/ml。     

THE STRUCTURE BASIS OF THE POOR FIBRIN SPECIFICITY OF UROKINASE(Ⅱ)——THE INHIBITION OF UROKINASE A CHAIN 149--157 ON THE FIBRIN STIMULATED ACTIVATION OF PLASMINOGEN BY TISSUE TYPE PLASMINOGEN ACTIVATOR

In view of the similarity of the charge distribution between fibrin A_α148--161 and Achain 149--157 of urokinase,the latter might compete with fibrin A_α148--161 when singlechain pro-urokinase is converted to double chain urokinase.To test this, the stretch of uro-kinase A chain 135--157 was separated from the low molecular weight urokinase, a competi-tive binding between this stretch and fibrin to tPA kringle-2 was shown by radio-bindingassay. The inhibition of the stretch on the fibrin stimulated activation of plasminogen wasdemonstrated in the caseinolytic system. The synthesized novapeptide urokinase A chain 149--157 (R-peptide) showed a significant inhibition on the activation of plasminogen in the pres-ence of fibrin. By contrasting finely with R-peptide, a synthesized novapeptide in which Arg154and Arg156 were replaced by Asp (D-peptide) did not show any inhibition effect on the fi-brin stimulated activation of plasminogen by tPA. These results suggest that the positivelycharged residues in the     

Is inhibition process better described with MD(QM/MM) simulations? The case of urokinase type plasminogen activator inhibitors

Urokinase plasminogen activator (uPA) is an enzyme involved in cancer growth and metastasis. Therefore, the design of inhibitors of uPA is of high therapeutic value, and several chemical families have been explored, even if none has still emerged, emphasizing the need of a rationalized approach. This work represents a complete computational study of uPA complexed with five inhibitors, which present weak similarities. Molecular dynamics simulations in explicit solvent were conducted, and structural analyses, along with molecular mechanics (MM)/Poisson-Boltzmann surface area free energies estimations, yield precious structure-activity relationships of these inhibitors. Besides, we realized supplemental QM/MM computations that improved drastically the quality of our models providing original information on the hydrogen bonds and charge transfer effects, which are, most often, neglected in other studies. We suggest that these simulations and analyses could be reproduced for other systems involving protein/ligand molecular recognitions.     

原发肾病综合征患儿超声颈动脉参数、血清sTREM-1、suPAR水平变化及与急性肾损伤的相关性

选取原发性肾病综合征(PNS)患儿96例作为研究组,选取同期96例健康体检儿童作为对照组,开展前瞻性队列研究,均行超声颈动脉参数、血清可溶性髓系细胞表达的触发受体-1(sTREM-1)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)水平检测,并进行对比分析.本研究发现,研究组患儿颈动脉内中膜厚度(cIMT)、平均管壁横...     

分离尿激酶的亲和色谱填料的制备

 合成了分别以 Sepharose和聚甲基丙烯酸环氧丙酯为基质、对氨基苯甲脒为配基的分离尿激酶的两种亲和色谱填料 ,并用于尿激酶粗品的直接纯化 ,活性回收率分别为 1 0 8.3 %和 43 .4% ,比活提高倍数分别为 9.0 6倍和 3 6.9倍。     

新型磁性葡聚糖亲和吸附剂的制备及在尿激酶纯化中的应用

 采用反相悬浮包埋技术合成多分散的粒径在 5 0目～ 30 0目的磁性葡聚糖微球 (MDMS)。MDMS经环氧氯丙烷活化后 ,分别键合氨基乙酸、6 氨基己酸和乙二胺作为间隔臂 ,以碳二亚胺为偶联剂 ,分别偶联L 精氨酸甲酯、对氨基苯甲脒和胍基己酸配体 ,制备了 5种磁性亲和吸附剂。研究了分散介质及其粘度和密度、有机相和水相的体积比、表面活性剂的用量、搅拌速度等因素对微球制备的影响。将所制备的磁性亲和吸附剂应用于尿激酶粗品的纯化 ,并讨论了偶联试剂和配体对尿激酶纯化效果的影响。     

Bridging a Century-Old Problem: The Pathophysiology and Molecular Mechanisms of HA Filler-Induced Vascular Occlusion (FIVO)—Implications for Therapeutic Interventions

Biocompatible hyaluronic acid (HA, hyaluronan) gel implants have altered the therapeutic landscape of surgery and medicine, fostering an array of innovative products that include viscosurgical aids, synovial supplements, and drug-eluting nanomaterials. However, it is perhaps the explosive growth in the cosmetic applications of injectable dermal fillers that has captured the brightest spotlight, emerging as the dominant modality in plastic surgery and aesthetic medicine. The popularity surge with which injectable HA fillers have risen to in vogue status has also brought a concomitant increase in the incidence of once-rare iatrogenic vaso-occlusive injuries ranging from disfiguring facial skin necrosis to disabling neuro-ophthalmological sequelae. As our understanding of the pathophysiology of these injuries has evolved, supplemented by more than a century of astute observations, the formulation of novel therapeutic and preventative strategies has permitted the amelioration of this burdensome complication. In this special issue article, we review the relevant mechanisms underlying HA filler-induced vascular occlusion (FIVO), with particular emphasis on the rheo-mechanical aspects of vascular blockade; the thromboembolic potential of HA mixtures; and the tissue-specific ischemic susceptibility of microvascular networks, which leads to underperfusion, hypoxia, and ultimate injury. In addition, recent therapeutic advances and novel considerations on the prevention and management of muco-cutaneous and neuro-ophthalmological complications are examined.