Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis

Human lymphoproliferative diseases can be hypothesized to invade locally and to metastatize via mechanisms similar to those developed by a variety of solid tumors, i.e., the secretion of extracellular matrix-degrading enzymes and stimulation of angiogenesis. To assess this hypothesis, Namalwa, Raji, and Daudi cell lines (Burkitt’s lymphoma), LIK and SB cell lines (B-cell lymphoblastic leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266 cell line (multiple myeloma) were evaluated for their capacity to produce matrix metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell lines were also assessed for their ability: (1) to produce the angiogenic basic fibroblast growth factor and vascular endothelial growth factor; (2) to induce an angiogenic phenotype in cultured endothelial cells, represented by cell proliferation, chemotaxis, and morphogensis; (3) to stimulate angiogenesis in different in vivo experimental models. All cell lines expressed the mRNA for one or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the active form of both metalloproteinases, while Daudi, CEM, and Jurkat cells produced metalloproteinase-2 but not -9. In contrast, urokinase-type plasminogen activator was secreted only by SB cells. While Raji, LIK, SB, CEM, and Jurkat cells secreted both basic fibroblast growth factor and vascular endothelial growth factor, Daudi and U266 cells produced only the former, and Namalwa cells only the latter. Accordingly, the conditioned medium of all cell lines stimulated cell proliferation and/or chemotaxis in cultured endothelial cells, with the exception of that of Namalwa cells which was ineffective. The conditioned medium of CEM and Jurkat cells induced morphogenesis in cultured endothelial cells grown on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB, U266, CEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment in the murine Matrigel sponge model and in a chick embryo chorioallantoic membrane assay. The extent of angiogenesis in both models was strictly correlated with the density of the mononuclear cell infiltrate. The results indicate that human lymphoproliferative disease cells possess both local and remote invasive ability via the secretion of matrix-degrading enzymes and the induction of angiogenesis which is fostered by host inflammatory cells and by an intervening ensemble of angiogenic factors.     

明胶酶在大鼠心肌缺血-再灌注损伤中的作用

目的：探讨明胶酶A（MMP-2）及明胶酶B（MMP-9）在大鼠心肌缺血-再灌注损伤（I/R）中的作用。方法：采用大鼠心肌缺血再灌注损伤模型，大鼠分7组：对照组（n=5），单纯缺血30 min组，缺血30 min再灌注1 min、5 min、10 min、20 min和30 min组（各组n=6）。利用Gelatin-PAGE观察外周血中MMP-2及MMP-9表达，并用免疫组织化学法观察MMP-2及MMP-9在心肌中表达情况。结果：单纯30 min缺血组（I_{30 min}）的MMP-2及MMP-9表达高于对照组（P<0.05）；在再灌注不同时间内，MMP-2表达不一：再灌注1 min（R_{1 min}）开始升高，再灌注5 min（R_{5 min}）达高峰，随后开始下降，再灌注30 min（R_{30 min}）为基线，其中R_{5 min}、R_{10 min}的MMP-2高于对照组及I_{30 min}组（P<0.05），而MMP-9在再灌注组间表达上则无显著差异（P>0.05）。免疫组织化学法显示明胶酶主要在细胞浆及细胞间质中表达，而且实验组强于对照组。结论：明胶酶的异常表达可能参与心肌缺血过程，其中MMP-2可能参与了大鼠心肌再灌注损伤的早期过程。     

Wnt-frizzled信号通路与心血管疾病关系的研究进展

Many researches have focused on the wnt- frizzled cascade in the recent years, while much work has been done in neoplastic diseases and embryology, the role of the wnt- frizzled signal transduction pathway in cardiovascular diseases has only recently begun to be explored. It plays a very important role in many physiological and pathophysiological processes, such as its transduction pathway, the healing after myocardial infarction, the proliferation, differentiation and orientation of cardiomyocytes, angiogenesis/neovascularization, cardiac hypertrophy and heart failure, the deposition of the extracellular matrix and so on. This article is aimed at its relation with myocardial infarction and the role of this pathway in cardiovascular diseases.     

Patency of the infarct-related coronary artery — a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarctrelated coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-¹²³I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (<70% of maximum) fatty acid uptake was initially 20.2±4.7 (mean±SD) and was reduced to 11.3±6.1 during the follow-up (95% confidence interval of the decrease 16.0–1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7±13.1, initial test, and 21.3±13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency. This finding emphasizes the need for further study to establish whether a direct link exists between myocardial metabolic state and patient survival after infarction.     

镁对急性心肌梗塞的治疗作用

本文报道了镁剂治疗急性心肌梗塞的疗效，结果表明：镁能有效地控制急性心肌梗塞病人的心律失常，能明显改善心功能不全的临床表现，缓解胸痛发作及减少再梗塞的发生，镁剂治疗急性心肌梗塞疗效显著。     

心率变异性与心肌梗塞范围关系的研究

报道７２例急性心肌梗塞患者的心率变异性（ＨＲＶ）值与心肌梗塞范围的关系，并与１２０例正常人的ＨＲＶ值进行对比，结果发现，心肌梗塞急性期ＨＲＶ值明显降低，与正常组对比有显著统计学意义，但ＨＲＶ值降低与心肌梗塞部位、范围无关，可能主要为心肌梗塞引起的应激反应所造成的体液及神经调节改变所致。     

MICROCOMPUTER DATA PROCESSING OF HEMODYNAMIC EFFECTS OF A CARDIOTOXIC FRACTION(Fr.19-2) FROM THE SOUTHERN CHINESE COBRA(NAJA NAJA ATRA CANTOR)IN ANESTHETIZED CATS

A new program of microcomputer data processing was developed on AppleIIe computer on-line with 8-ch polygraph in the study of hemodynamic effects of a cardiotoxic fraction (Fr. 19-2) from the southern Chinese cobra (Naja naja atra Cantor). In anesthetized open-chest cats, Fr. 19-2 caused a dose-related decrease in various indices of myocardial contractility and pumping function such as dp/dt_(max), V_(CE-DP40), V_(CE-CPIP),V_(pm), CO, CI, SV, SI, LVW, LVWI, LVSW and LVSWI. It reduced the heart rate without other cardiac arrhythmias. A marked decrease in -dp/dt_(max) (219.7±23.5 vs 110.5±29.1kPa/s, P<0.01) and an increase in time constant of the fall of left ventricular pressure during isovolumetric relaxation (T) was induced. LVEDP rised till the dose of Fr. 19-2 reached 0.4mg/kg. It is concluded that this cardiotoxic fraction predominantly inhibits the hemodynamic indices and myocardial performance. With the new microcomputer data real-time processing system, 33 elaborated hemodynamic indices were ca     

L-肉毒碱对阿霉素性心肌损伤保护作用的研究——心肌线粒体膜流动性测定

阿霉素可导致剂量累积性心肌细胞损伤。L-肉毒碱已确认能减轻心肌细胞形态学改变。本实验测定了心肌细胞线粒体膜流动性,目的是从生物化学角度观察L-肉毒碱对阿霉素性心肌损伤的作用。实验结果表明:阿霉素可引起线粒体膜流动性的明显改变。而补充外源肉毒碱可改善这种状态。     

Lack of correlation between coronary artery calcium and myocardial perfusion imaging

BACKGROUND: Coronary artery calcium (CAC) provides evidence of coronary atherosclerosis and has significant prognostic power. Although prior studies have documented a relationship between CAC and hemodynamically significant coronary artery stenosis, the results have not been conclusive. METHODS AND RESULTS: We evaluated 126 consecutive patients who underwent electron beam computed tomography CAC scoring by use of the Agatston method and stress myocardial perfusion imaging (MPI) within 3 months of each other. The analysis revealed no correlation between absolute CAC score and age- and gender-adjusted CAC scores with MPI. Overall, 18% of patients had abnormal MPI results irrespective of their CAC. CONCLUSION: CAC scoring and stress MPI should be thus considered complementary approaches rather than exclusionary in the evaluation of the patient at risk for coronary artery disease.     

血尿酸对急性心肌梗死预后的影响

目的 探讨血尿酸水平对急性心肌梗死(AMI)预后的影响.方法 对198例急性心肌梗死患者的血尿酸水平及其肌酸激酶同工酶(CK-MB)峰值,梗死后心绞痛、心律失常、心源性休克、心力衰竭的发生率和病死率的相关关系进行分析比较.结果 198例中正常血尿酸133例,高血尿酸65例.高血尿酸组CK-MB峰值较高,梗死后心绞痛、心律失常、心力衰竭的发生率和病死率均高于正常血尿酸组(P＜0.01或P＜0.05).结论 高血尿酸与AMI预后不良有关.