骨唾液酸蛋白在体外培养人骨髓间充质干细胞向成骨细胞分化中的角色

目的：骨唾液酸蛋白在骨矿化形成方面扮演重要角色，实验观察其是否能诱导体外培养的人骨髓间充质干细胞向成骨细胞分化。方法：实验于2005—10／2006—12在解放军广州军区广州总医院医学实验科完成。①材料来源：选取在本院体检的健康志愿者2人，对本实验均知情同意。采用Ni-NTA亲和纯化技术，从本室构建的毕赤酵母GS115／pPICZaA-hbsp发酵上清中纯化重组人骨唾液酸蛋白。②实验方法：对健康志愿者进行髂骨穿刺抽取骨髓液，采用贴壁法培养得到骨髓间充质干细胞。设立4组：骨唾液酸蛋白组添加0．1nmol／L骨唾液酸蛋白；成骨诱导液组添加10nmol／L地塞米松、10mmol／L磷酸甘油、50mg／L抗坏血酸；联合组添加上述两组的所有试剂；空白对照组不添加任何处理因素；各组均处理细胞12d。⑧实验评估：光镜及电镜观察培养的细胞形态；以细胞计数法测定生长曲线，应用流式细胞仪分析细胞周期，采用免疫荧光细胞化学法和流式细胞分析检测干细胞标志物STRO-1的表达；生化试剂盒测定碱性磷酸酶活性；von Kossa染色法检测钙沉积。结果：①单个骨髓间充质干细胞为长梭形，经骨唾液酸蛋白处理后细胞大而扁平，原来密集的克隆分散开。②与空白对照组比较，骨唾液酸蛋白组引起细胞生长曲线右移，细胞Go／G，期比例平均增加12．09％（P〈0．01），S期比例减少65．92％（P〈0．01），STRO-1阳性细胞百分率下降26．54％（P〈0．01）。⑧与空白对照组比较，骨唾液酸蛋白组细胞碱性磷酸酶活性增加50．0％，成骨诱导液组增加59．5％，联合组增加71．43％，并且随着处理时间的延长，活性增加越显著。④空白对照组细胞vonKossa染色呈阴性，其余各组均呈阳性。其中联合组的黑色矿化结节体积最大、数目最多；骨唾液酸蛋白组的结节体积较小、数目较少；成骨诱导液组居中。结论：骨唾液酸蛋白对人骨髓间充质干细胞有促进成骨分化和矿化作用，且与成骨诱导液联用效果更佳。     

Pilotprojekt „Telenotfallmedizin Niedersachsen“

Notfall + Rettungsmedizin - Der Einsatz von Telemedizin im Rettungsdienst wird in Deutschland seit einigen Jahren erprobt und eingesetzt. Dies ist eine bedeutsame Entwicklung zur Aufrechterhaltung...     

Is troponin I useful for predicting in-hospital risk for unstable angina patients in a community hospital? Results of a prospective study

INTRODUCTION AND OBJECTIVES: Before including troponin I detection in the daily practice of our hospital we performed a prospective study to determine its real usefulness and to establish the best cut-off point. METHODS: We studied 82 consecutive patients admitted with unstable angina to a community hospital. Troponin I was determined (> 10 h after chest pain). Patients were referred to a tertiary hospital for catheterization/revascularization if clinical events developed. RESULTS: Twenty-five patients (31%) suffered events during admission: recurrent angina in 23 cases (28%); heart failure in 5 (6%); exitus in 3 (4%); myocardial infarction in 1 (1%). The cut-off point for troponin I that best predicted events was 0.1 ng/ml. Patients with troponin I > 0.1 (34 patients, 42%) experienced more events [47 vs. 19%; OR = 3.8 (1.4-10.4); p = 0.01] and had higher rates of recurrent angina (42 vs. 19%), heart failure (12 vs. 2%) and exitus (9 vs 0%). Patients with ECG changes and troponin I > 0.1 showed a significantly higher percentage of events (63%) than those with ECG changes alone (23%) or troponin I > 0.1 alone (15%) or those without ECG changes and troponin I < 0.1 (17%) (p < 0.0001). CONCLUSIONS: Troponin I elevation is useful for predicting in-hospital risk for unstable angina patients admitted to a community hospital. A low cut-off value (0.1 ng/ml) predicts events. The association of ECG changes and high troponin I identifies a population at very high risk; however, the absence of both variables in patients with a diagnosis of unstable angina does not preclude the development of events.     

Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, accounting for an estimated 600,000 deaths annually. Aberrant methylation, consisting of DNA hypomethylation and/or promoter gene CpG hypermethylation, is implicated in the development of a variety of solid tumors, including HCC. We analyzed the global levels of DNA methylation as well as the methylation status of 105 putative tumor suppressor genes and found that the extent of genome-wide hypomethylation and CpG hypermethylation correlates with biological features and clinical outcome of HCC patients. We identified activation of Ras and downstream Ras effectors (ERK, AKT, and RAL) due to epigenetic silencing of inhibitors of the Ras pathway in all HCC. Further, selective inactivation of SPRY1 and -2, DAB2, and SOCS4 and -5 genes and inhibitors of angiogenesis (BNIP3, BNIP3L, IGFBP3, and EGLN2) was associated with poor prognosis. Importantly, several epigenetically silenced putative tumor suppressor genes found in HCC were also inactivated in the nontumorous liver. Our results assign both therapeutic and chemopreventive significance to methylation patterns in human HCC and open the possibility of using molecular targets, including those identified in this study, to effectively inhibit HCC development and progression.     

Relationship of C-reactive protein levels with angiographic findings and markers of necrosis in non-ST-segment elevation acute coronary syndrome

INTRODUCTION AND OBJECTIVES: The mechanism responsible for elevated C-reactive protein levels (inflammation of the ruptured atherosclerotic plaque or myocardial necrosis) in acute coronary syndromes is controversial. The aim of this study was to investigate the relationship between C-reactive protein levels and angiographic complexity of the culprit lesion and troponin elevation in patients with non-ST elevation acute coronary syndromes. PATIENTS AND METHOD: The study group consisted of 125 patients with single-vessel disease. Troponin-I and C-reactive protein were measured, and the complexity of the culprit lesion was analyzed (TIMI flow and thrombus). Information on age, sex, smoking habit, hypertension, hypercholesterolemia and diabetes was obtained from the medical record. RESULTS: The quartile distribution of C-reactive protein showed more patients with TIMI flow < 3 (31%, 28%, 18%, and 55%; P=.02), thrombus (3%, 6%, 7%, and 28%; P=.007) and troponin-I elevation (19%, 44%, 50%, and 66%; P=.003) in the fourth quartile. Multivariate analysis showed both thrombus (OR = 4.1; 95% CI, 1.2-14.3; P=.03) and troponin elevation (OR = 2.6; 95% CI, 1.1-6.3; P=.03) to be associated with C-reactive protein > 18 mg/L (fourth quartile cut-off). When treated as a continuous variable, higher levels of C-reactive protein were also associated with thrombus (P=.02) and troponin elevation (P=.003). No other clinical variables were related with C-reactive protein levels. CONCLUSIONS: Both angiographic complexity of the culprit lesion and elevated troponin level are related with increased C-reactive protein levels in non-ST elevation acute coronary syndromes.     

Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study

Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs.