Risk factors for capillary leakage syndrome after bone marrow transplantation

 Age, hematopoietic growth factors, cyclosporin A, mode of bone marrow transplantation (BMT) (autologous, allogeneic-related, unrelated), and underlying disease were assessed as potential risk factors for capillary leakage syndrome (CLS) in 96 patients after BMT. CLS was defined as unexplained weight gain of >3% within 24 h and nonresponsiveness to furosemide. CLS occurred in 9/21 patients after unrelated compared with 2/33 after allogeneic-related BMT (p=0.0017) for hematopoietic disorders (n=54) and in 6/7 patients after allogeneic-related compared with 3/35 after autologous BMT (p=0.0001) for solid tumors (n=42). Hematopoietic growth factors and cyclosporin A were no signficant risk factors on their own. We conclude that unrelated BMTs or high-intensity conditioning regimens used in combination with allogeneic-related BMT are the main risk factors for CLS. Received: 6 January 1997 / Accepted: 10 March 1997     

人外周血内皮祖细胞移植促裸鼠缺血组织血管新生的初步研究

目的观察人外周血内皮祖细胞移植对下肢缺血裸鼠血管新生的影响。方法从人自愿者外周血中分离单个核细胞 ,置于EBM -2培养基内培养7d后 ,获得内皮祖细胞。将1×106个内皮祖细胞通过尾静脉注入下肢缺血裸鼠体内 (8只 ) ,对照组 (8只 )通过尾静脉注入等量的PBS。移植后第28d ,处死动物 ,进行组织学和生理学评估。结果内皮祖细胞组毛细血管密度较对照组明显增加[(136.4±40.5)/视野 ,(53.65±14.02)/视野 (P<0.01)] ;内皮祖细胞组的肢体致残率 (25 % )较对照组 (50 % )减少。结论体外扩增的内皮祖细胞移植能够促进缺血组织的血管新生 ,并能减少肢体的致残率。     

体外丹参、藻酸双酯钠对脑血栓形成患者红细胞与内皮细胞粘附的影响

丹参、藻酸双酯钠是临床治疗脑血管病的常用药。本研究发现，在体外流场中用丹参、藻酸双酯钠分别处理脑血栓形成病人的红细胞后，此红细胞与培养的人脉静脉内皮细胞的粘附数目明显减少、粘附强度明显减弱；而且，在临床常用剂量下藻酸双酯钠的这种抗粘附作用优于丹参。认为丹参、藻酸双酯钠的这种抗粘附作用可能是临床用以治疗脑血栓形成的一个重要机理。     

Renin-producing renal cell carcinomas—clinical and experimental investigations on a special form of renal hypertension

Summary The pathogenetic relationship between tumour and hypertension was investigated in 129 patients with renal cell carcinoma, of whom 41 (31.8%) were hypertensive. Of these 41 patients with renal tumours and hypertension, 6 (14.6%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumour kidney to contralateral kidney ratio of between 4 and 7, and 2 patients also had secondary hyperaldosteronism. In the same 6 cases the renin content in the renal tumour tissue was significantly higher than that in tissue from the adjacent tumour-free renal cortex of the ipsilateral kidney. Immunohistochemical demonstration of renin in the tumour was only possible in these 6 cases. In 5 of these patients blood pressure returned to normal following nephrectomy; in the 6th case there was a drop in blood pressure after nephrectomy. In 3 renin-positive tumours examined, autonomous renin production was demonstrated in cell culture. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumour.     

复方丹参滴丸对急慢性高粘滞血症模型血管内皮细胞分泌功能的影响

目的：观察复方丹参滴丸对高粘滞血症血管内皮分泌功能的影响，探索其作用机制。方法：复合因素(高分子右旋糖酐、肾上腺素、牛血清白蛋白)、长时间(112天)造成高粘滞血症慢性模型；一次性静脉注射高分子右旋糖酐。皮下注射(sc)肾上腺素造成急性高粘滞血症模型，分别用复方丹参滴丸进行治疗，观察血管肉皮细胞分泌功能的变化。结果：慢性高粘滞血症模型血浆血栓素B2(TXB2)和内皮素(ET)浓度非常显升高，而6-酮-前列腺素F1x(6-酮)浓度非常显降低；急性高粘滞血症模型血管内皮分泌功能无显变化；长期使用复方丹参滴丸能调整、改善血管内皮分泌功能的异常状态；复方丹参滴丸改善血管内皮分泌功能的即时效应不显。     

HLA-DR expression in macaque neuroendothelial cells in vitro and during SIV encephalitis

HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system.     

Analysis of the mechanism of action of bradykinin on human basilar artery in vitro

Summary Bradykinin (BK) initially produced concentration-related relaxations of human basilar artery in vitro. Concentration-effect curves constructed at 2 h intervals to BK over an 8 h period were reproducible. The rank order of potency of three kinins on the human basilar artery was found to be BK > methionyl-lysyl-BK > des-Arg⁹-BK. The B₂-receptor antagonist Thi^5,8 d-Phe⁷-BK but not the B₁-receptor antagonist des-Arg⁹-Leu⁸-BK selectively blocked BK-induced relaxations of the human basilar artery.The relaxant effects of bradykinin and acetylcholine but not papaverine were attenuated after removal of the endothelium or treating the tissues with BW755C. Indomethacin was without effect. Concentration-effect curves to angiotensin I were markedly attenuated by captopril at a concentration which had no effect on BK, angiotensin II or 5-hydroxytryptamine responses. It is concluded that BK induced relaxations of the human basilar artery are mediated via activation of a B₂ receptor and the response is dependent upon the release of a factor present in the endothelium. Angiotensin converting enzyme is present in the human basilar artery and is important for the conversion of angiotensin I to angiotensin II but apparently not for the degradation of BK. It is likely that other kininases are present and active in the tissue. Send offprint requests to E. T. Whalley at the above address     

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

Nitric oxide synthesis in endothelial cytosol: Evidence for a calcium-dependent and a calcium-independent mechanism

Summary Release of nitric oxide (NO) from endothelial cells critically depends on a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells. Therefore, we studied whether the free cytosolic calcium concentration directly affects the activity of the NO-forming enzyme(s) present in the cytosol from freshly harvested porcine aortic endothelial cells. NO was quantified by activation of a purified soluble guanylate cyclase coincubated with the cytosol. In the presence of 1 mM L-arginine, 0.1 mM NADPH and 0.1 mM EGTA, endothelial cytosol (0.2 mg of cytosolic protein per ml) stimulated the activity of guanylate cyclase 5.0 + 0.5-fold (from 31 + 9 to 153 + 15 nmol cyclic GMP formed per min per mg guanylate cyclase). Calcium chloride increased this stimulation further in a concentration-dependent fashion by up to 136 + 15% (with 2 M free calcium; EC₅₀ 0.3 M). The calcium-dependent and -independent activation of guanylate cyclase was enhanced by superoxide dismutase (0.3 M) and was inhibited by the stereospecifically acting inhibitor of L-arginine-dependent NO formation N^G-nitro-L-arginine (1 mM) and by LY 83583 (1 M), a generator of superoxide anions. Our findings suggest a calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells. Send of fprint requests to A. Mülsch, at the above address     

人骨髓间质干细胞体外扩增和向内皮细胞定向诱导分化的研究

目的：体外分离、扩增成人骨髓间质干细胞（MSCs）和向内皮细胞（ECs）定向诱导分化，开辟心血管组织工程种子细胞的新来源。 方法： 采用Percoll(1 073 g/L)从正常成人骨髓中分离出MSCs，纯化和扩增后流式细胞仪鉴定其纯度；用血管内皮生长因子(VEGF)诱导MSCs向ECs分化，Ⅷ因子(vWF)免疫组化和透射电镜(TEM)鉴定细胞性质。 结果： 5.0×105个MSCs在体外扩增15代后，获得8.0×1012个MSCs，扩增了约1.6×107倍；MSCs在加入VEGF诱导培养大约14-21 d，80%-90%的诱导细胞对Ⅷ因子相关抗原呈阳性反应；TEM可观察到胞浆内有Weible-palade小体，证实为ECs。 结论： 成人骨髓MSCs在体外具有定向诱导分化为ECs的潜能，这为心脏组织工程瓣体外构建, 尤其是在小儿先天性心脏病组织工程研究中种子细胞的来源提供了可能性。