Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen

Platelet thrombospondin interacts with plasminogen in a specific and saturable manner. Thrombospondin was found to specifically bind to plasminogen and the nonenzyme chain of plasmin. Preincubation of 125I- labeled thrombospondin with 30 mmol/L lysine was without effect in the binding of thrombospondin to immobilized plasminogen; preincubation of 125I-labeled plasminogen with 30 mmol/L lysine, on the other hand, significantly reduced the binding of plasminogen to immobilized thrombospondin, suggesting that the interaction of thrombospondin with plasminogen is not the direct result of the lysine binding sites of plasminogen. Arginine and benzamidine, ligands known to specifically bind to the kringle 5 domain of plasminogen, blocked the binding of thrombospondin to plasminogen. Limited elastase proteolysis of plasminogen and plasmin resulted in the generation of two distinct thrombospondin binding domains, one of which was retained on lysine- agarose. The isolation and amino-terminal analysis of these domains following elastase proteolysis of plasminogen identified them, respectively, as a domain containing kringle structures 4 and 5 and plasmin and the other domain consisting of kringle 5-plasmin. A 16- residue synthetic peptide, which represents the amino acids linking kringle 4 to kringle 5 (residues 435-450 of native plasminogen), was without effect in either binding to thrombospondin or blocking the binding of thrombospondin to plasminogen. Plasminogen, therefore, possesses a single thrombospondin interactive site that is independent of, but influenced by, the lysine binding site containing kringle structures and most likely is located within the kringle 5 domain.     

Naratriptan: biological profile in animal models relevant to migraine

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT_1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT_1B and 5HT_1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC₅₀ values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC₅₀ value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD₅₀ dose = 193 g kg⁻¹) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID₅₀ = 4.1 g kg⁻¹). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT_1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2-3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.     

Effectiveness of a prospective physician self-audit transfusion- monitoring system

BACKGROUND: The purpose of this study was to search for a more effective transfusion-monitoring system than the existing system of retrospective peer review. STUDY DESIGN AND METHODS: This research used a study-control, preintervention and postintervention design, to evaluate the effectiveness of a prospective physician self-audit transfusion-monitoring system that functioned without the direct involvement of transfusion service physicians. This research also evaluated the effectiveness of issuing to physicians a memo with transfusion guidelines. Three process indicators were used to assess physician behavior at various stages of the blood-ordering process: 1) the number of crossmatches ordered per admission, 2) the transfusion-to- crossmatch ratio, and 3) the number of blood units returned to the laboratory after physician self-auditing. The study used two outcome indicators to reflect overall blood utilization: 1) the percentage of patients who received red cell transfusions and 2) the number of blood units transfused per recipient each month. RESULTS: The prospective physician self-audit system implemented at the study hospital did not reverse physician transfusion decisions, and the process of issuing to physicians a memo with transfusion guidelines at the control hospital failed to reduce blood usage. However, a transient reduction in blood utilization was observed at the study hospital. CONCLUSION: The reduction was hypothesized to be due to a Hawthorne effect, in which observed behavior is affected by the subject's awareness of the research study.     

Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A

In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD.     

胃肠混合性腺神经内分泌癌的回顾性病例分析

背景：近年来,胃肠腺神经内分泌肿瘤发病率不断上升,为推动疾病的防治,我国制定了中国胃肠胰神经内分泌肿瘤病理学诊断共识。目的：探讨胃肠混合性腺神经内分泌癌（MANEC）的临床病理特点。方法：选取2002年4月-2009年1月天津大港油田总医院确诊的胃肠腺癌患者100例,对患者肿瘤组织标本进行免疫组化染色,检测突触素（Syn）、嗜铬粒素A（CgA）、癌胚抗原（CEA）、细胞角蛋白8/18（CK8/18）、Ki-67的表达。分析MANEC患者的临床资料,包括性别、年龄、临床症状、病理特征以及预后。结果：100例胃肠腺癌患者中,MANEC 6例,发生率为6%。MANEC临床表现以腹痛、腹胀、便血常见。MANEC发生于胃小弯2例、回盲部1例、升结肠1例、直肠2例。镜下可见MANEC由腺癌和神经内分泌癌两种成分构成。6例患者均接受手术治疗,5例在短时间内复发和（或）腹腔转移。结论：MANEC形态学上与低分化腺癌不易区别,确诊主要依赖于组织学证据和免疫组化标记,预后较普通腺癌差。     

化疗联合G-CSF动员的骨髓及外周血CD34+细胞表达粘附分子的变化

探讨化疗合G－CSF动员前，后患骺髓及外周血CD34^ 细胞表达CD44，CD49d，CD62L及趋化因子CXCR4的动态变化，用免疫荧光直接三角标记和流式细胞术测定G－CSF动员前，后骨髓及外周血CD34^ 细胞的CD44，CD49d，CD62L及趋化因子CXCR4的表达，观察输注各表达亚群细胞数与移植后造血重建的关系。结果发现，动员后骨髓中CD34^ CD44^ 和CD34^＋CD49d^ 细胞的百分比较动员前明显降低, 而外周血中二的比例则显升高；动员前，后骨髓中CD34^＋CD62L^＋和CD34^＋CXCR4^ 细胞的变化并不明显，而外周血中前明显增加，后则显减少。输入CD44^＋，CD49d^ ，CD62L^ 及CXCR4^ 的CD34^＋细胞的量与移植后血中中性粒细胞和血小板恢复的时间未表明有显的相关，结论：G－CSF动员可下调骨髓CD34^＋细胞的CD44，CD49d，CD62L及CXCR4的表达，从而进入外周血循环，输注这些细胞的临床意义有待累积更多病例的分析。     

西藏某驻军医院护士心理健康调查与分析

目的 探讨高原环境中部队医院护士心理健康状况及其影响因素。方法 对驻藏部队某医院43名护士进行症状自评量表（SCL－90）测评，并与军人常模、中国成人常模以及以往高原边防军人相应调查结果进行比较。结果 本组受试焦虑、恐怖因子显高于军人常模，除阳性均分、敌对无显差异外的各项分值均显高于中国成人常模，总分、躯体化、抑郁、焦虑、敌对五项分值显低于高原边防军人。结论 高原部队医院护士心理健康状况接近军人常模，但也表现出一定焦虑倾向。     

早期肠内高营养名期胃癌术后患者白细胞介素—2系统水平的影响

目的：探讨术后早期应用肠内高营养治疗对晚期胃癌患者白细胞介素（ＩＬ）－２系统水平的影响。方法：９８例晚期胃癌术后患者随机分成早期肠内高营养组和常规输液对照组,采用酶联免疫吸附测定（ＥＬＩＳＡ）等方法检测两组患者治疗一的外周血清ＩＬ－２、ＩＬ－２受体（ＩＬ－２Ｒ）α及可溶性ＩＬ－２Ｒ（ｓＩＬ－２Ｒ）水平。结果：早期肠内高营养组患者治疗１周后,机体ＩＬ－２和ＩＬ－２Ｒα水平较治疗前显著上升,ｓＩＬ－２     

泡状棘球蚴病宿主淋巴细胞的变化及意义

目的　为探讨泡状棘球蚴病宿主体内淋巴细胞在免疫调节和发病中的作用。方法　对泡球蚴感染BALB/c小鼠观察至 2 5周 ,在不同时间取脾制备细胞悬液 ,检测CD+ 4 ,CD+ 8细胞数量。对 2 5例泡球蚴病患者和 18例健康人群 ,用FCM分析了CD+ 3 ,CD+ 4 ,CD+ 8,CD+ 19,CD+ 3 8,CD+ 56和HLA -DR+ 细胞的变化。结果　泡球蚴感染BALB/c小鼠后 ,1～ 8周以CD+ 4 细胞为主 ,随后CD+ 4 细胞减少 ,CD+ 8细胞增加 ,2 0周后改变显著 (P <0 0 5 ) ,CD+ 4 /CD+ 8比值迅速倒置。泡状棘球蚴病患者CD+ 3细胞未发生改变 ,CD+ 4 细胞较正常对照组下降 (P <0 0 5 ) ,CD+ 8细胞上升 (P <0 0 5 ) ,使CD+ 4 /CD+ 8比值降低 (P <0 0 5 )。CD+ 56细胞较正常对照组显著性降低 (P <0 0 1) ,CD+ 19,CD+ 3 8和HLA -DR+ 细胞未发生改变 (P >0 0 5 )。结论　泡球蚴感染小鼠前 8周 ,以CD+ 4 细胞反应为主 ,具有保护性免疫。感染后期逐渐以CD+ 8细胞为主 ,使机体呈免疫抑制状态 ,有利于泡球蚴生存。泡状棘球蚴病患者机体呈免疫抑制状态 ,有利于泡状棘球蚴在体内的生长