Thrombospondin from activated platelets promotes sickle erythrocyte adherence to human microvascular endothelium under physiologic flow: a potential role for platelet activation in sickle cell vaso-occlusion

Adherence of erythrocytes to vascular endothelium likely contributes to the pathophysiology of episodic vascular occlusion in patients with sickle cell disease (SCD). In addition, coagulation activation has been reported in sickle patients during complications such as pain episodes. To test the hypothesis that platelet activation contributes to sickle erythrocyte binding, we investigated whether factors released from activated sickle platelets promote adherence of sickle erythrocytes to human microvascular endothelial cells (MEC) under flow conditions. Activated sickle platelet supernatant (ASPS) promoted high levels of sickle erythrocyte adherence to MEC (55.4 +/- 3.9 erythrocytes/mm2) but only moderate adherence of normal erythrocytes to MEC (14.1 +/- 0.7 erythrocytes/mm2). When MEC were incubated with an antibody (OKM5) against CD36 (a thrombospondin [TSP] receptor), platelet supernatant mediated sickle erythrocyte adherence was inhibited 86%, suggesting that TSP participated in the adherence. To further define the role of TSP in adherence, additional studies using purified TSP were performed. At a concentration of 0.2 micrograms/mL TSP in serum-free media (SFM), sickle erythrocyte adherence to MEC was 33.9 +/- 2.7 erythrocytes/mm2 and sixfold greater than either sickle erythrocyte adherence in the absence of TSP or normal erythrocyte adherence in the presence of TSP. Doubling the concentration of TSP to 0.4 micrograms/mL proportionally increased adherence of sickle erythrocytes. Incubation of MEC with OKM5 or anti-alpha v monoclonal antibodies inhibited TSP-mediated sickle erythrocyte adherence more than 95%. These data suggest that activated platelet release factors, including alpha-granule TSP, which promote receptor-mediated sickle erythrocyte adherence to microvascular endothelium. Such factors released during in vivo platelet activation could contribute to vaso-occlusive complications by promoting erythrocyte adherence and microvascular occlusion.     

Hepatic falciform artery: anatomy, angiographic appearance, and clinical significance

Three patients developed supraumbilical skin rashes during hepatic artery infusion chemotherapy by a surgically placed perfusion catheter and drug-infusion pump. In one patient, hepatic arterial scintigraphy with technetium-99m macroaggregated serum albumin showed increased uptake corresponding to the rash, and a hepatic arteriogram showed a dilated falciform branch of the left hepatic artery. Surgical ligation of the falciform artery permitted further treatment without recurrent rash. Based on a review of 100 celiac arteriograms, the incidence of the falciform artery on angiographic studies is approximately 2%. The angiographic appearance of this artery is presented, and its potential clinical significance in hepatic artery perfusion chemotherapy is discussed.     

进展期结肠癌MSCT分期诊断与病理对照研究

目的评估结肠充气多层螺旋CT(MSCT)扫描在结肠疾病及大肠癌术前分期的诊断价值。方法对37例临床怀疑结肠疾病的患者,进行MSCT检查,并利用工作站进行后处理以获取CT仿真内镜(CTVE)、多平面重建(MPR)、表面阴影成像(SSD)和透明显示(Raysum)图像,并结合横断面图像,分析其图像特征,并与纤维内窥镜、手术病理对照分析,探讨多层螺旋CT在结肠疾病中的应用价值;并对手术病理证实的结肠癌进行术前Dukes分期评价。结果MSCT显示大肠癌部位的敏感性达100%;对大肠癌Duke分期的准确率为92.30%,对浆膜面浸润诊断的灵敏度90.90%,特异度为90%。4种后处理对结肠癌的浆膜面浸润情况及病理对照符合率依次为:MPR(92.3%),CTVE(84.6%),Raysum(69.2%),SSD(50%)。结论MSCT扫描对大肠癌的术前分期很有价值,尤其对判断局部浸润和远处转移的情况更为准确,对评估大肠癌术前分期有较高的临床应用价值。     

BUB1与APC蛋白在不同乳腺组织中的表达及临床意义

背景与目的：乳腺癌的发展涉及多个染色体的改变，且与肿瘤的形态和进展相关。本研究探讨乳腺正常、增生及癌组织中BUB1、APC蛋白的表达及其临床意义。方法：收集辽宁医学院附属第一医院2005年24--2008年2月乳腺存档蜡块87份，其中乳腺癌67例，乳腺增生20例，另收集正常乳腺蜡块15例（取自距癌组织边缘≥5cm处）。所有标本均取自女性患者，年龄30-78岁，平均年龄49岁。用免疫组化方法检测乳腺正常、增生及癌组织中BUB1与APC蛋白的表达。结果：正常乳腺组织BUB1蛋白阳性表达率为86．7％，增生组织中为80．0％，癌组织中为46．O％，三者间差异有显著性（P〈0．01）。BUB1表达与淋巴结转移、远处脏器转移，肿瘤分化程度有关（P〈0．05）。正常乳腺组织APC蛋白阳性表达率为93．3％，增生组织中为75．0％，癌组织中为55．3％，三者间差异有显著性（P〈0．05），APC蛋白表达与乳腺癌的TNM分期、远处脏器转移有关（P〈0．05）。结论：BUB1蛋白和APC蛋白表达异常是乳腺癌产生的机制之一，与乳腺癌的发生发展、转移有关，两者在乳腺癌的发生过程中具有协同性。     

长期酒精摄入对大鼠骨骼肌组织IR、IRS-1和PI-3K基因表达的影响

目的研究酒精长期作用下对大鼠骨骼肌胰岛素受体(IR)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇3-激酶p85亚单位(PI-3K)mRNA表达的影响,探讨酒精与胰岛素抵抗的关系及相关分子机制。方法清洁级Wistar大鼠80只(雌雄各半),按体重随机分为对照组和低、中、高剂量组,分别给予蒸馏水以及10%、20%和33%酒精溶液,灌胃剂量为每天10ml/kgbw。第19周末,断头处死大鼠,测定空腹血糖和血胰岛素,计算HOMA胰岛素抵抗指数(HOMA-IR)。提取骨骼肌总RNA,通过RT-PCR测定IR、IRS-1、PI-3K(p85)mRNA表达水平。结果雄性大鼠,与对照组比较高剂量组空腹血糖,低、中剂量组空腹胰岛素水平升高,各酒精剂量组HOMA-IR指数均升高。IRmRNA的表达在中、高剂量组降低,而IRS-1、PI-3K(p85)mRNA表达水平表现为随着酒精剂量的增加先升高后降低,与对照组比较差异有显著性(P<0.05);与对照组比较,雌性大鼠高剂量组空腹血糖升高、空腹血胰岛素下降,IR、IRS-1、PI-3K(p85)mRNA的表达在中、高剂量组降低(P<0.05)。各剂量组HOMA-IR指数与对照组比较差异无显著性。结论长期摄入过量酒精可以造成骨骼肌组织IR、IRS-1、PI-3K(p85)mRNA表达的降低,这可能是酒精降低胰岛素敏感性,引起胰岛素抵抗的分子机制。