放射损伤后骨髓祖细胞变化的探讨

分析16例放射损伤患者的骨髓祖细胞变化,提示放射损伤后除骨髓粒、巨系祖细胞受损外,骨髓造血微环境也受到严重破坏,如何改善微环境以利造血恢复,是今后治疗的新课题。     

Transient bone marrow inhibition caused by aminoglutethimide

A 53-year-old woman with reversible bone marrow insufficiency caused by aminoglutethimide (AGT) treatment of metastatic breast carcinoma is described. The clinical picture included moderate thrombocytopenia and severe granulocytopenia complicated by Gram-positive septicaemia and skin infections, and by oral candidiasis. Withdrawal of AGT and antibiotic therapy resulted in clinical and haematological recovery, but the patient died suddenly, probably from a cardiac cause. Autopsy revealed widespread bone metastases, but no bone marrow infiltration of breast carcinoma. The haematological hazards caused by application of AGT are discussed.     

骨髓间充质干细胞促进异基因骨髓移植后造血恢复

目的探讨骨髓间充质干细胞(BMMSC)对异基因骨髓移植小鼠造血功能恢复的影响。方法将供鼠C57BL/6(H-2b)的骨髓细胞和体外培养的BMMSC联合输给致死量照射的受鼠BalB/c(H-2d)。在移植后第1、7、14天检测受鼠外周血红细胞(RBC)、白细胞(WBC)、血小板(BPC);移植后第7、14天检测受鼠骨髓中的脾集落形成单位(CFU-S)。结果联合移植组小鼠第7、14天的外周血红细胞、白细胞、血小板、CFU-S数均显著高于单纯移植组(P<0.01)。结论BMMSC能促进异基因骨髓移植后造血功能重建。     

Relationship between absolute and relative hematocrit changes and bone marrow response in rats

The object of the present study was to evaluate the physiologic mechanisms regulating erythropoiesis by monitoring the changes in reticulocyte count in the circulation and the formation of erythroblastic islands in the bone marrow following hypertransfusion and dehydration. Forty-eight male Wistar rats (110-130 grams) were transfused with 70% isogenic suspension of washed and packed red cells at a dose of 2.5 ml/100 g body weight intravenously on two consecutive days (absolute erythrocytosis) or deprived of water for three days to produce relative erythrocytosis and then injected i.v. with saline at a dose of 2.5 ml/100 g body weight with water provided at libitum. Hematocrit was measured using the microhematocrit method. Reticulocytes were enumerated using the new methylene blue stain. Plasma EPO levels were measured radioimmunologically and a bone marrow suspension was prepared for morphological examination and absolute erythroblastic islands determination. We observed a marked suppression of erythropoiesis following the transfusion as evidenced by the elevation in hematocrit values up to 0.64 +/- 0.04, a decrease in reticulocyte count and plasma EPO reduction--13.5 +/- 3.4 mU/ml (P < 0.05) and a suppression of EO formation in the bone marrow (P < 0.01). The hematocrit of the dehydrated rats was elevated during the first 24 hours (P < 0.001). Reticulocytes, as well as EO, decreased on day 3 down do 53.6 x 10(9)/l +/- 9.8 x 10(9)/l (P < 0.001) and 153.6 x 10(3) +/- 21.5 x 10(3)/femur (P < 0.001), respectively. The EPO level was measured simultaneously--16.3 +/- 4.2 mU/ml versus 24.6 +/- 5.3 mU/ml at day 1 (P < 0.001). Following rehydration, a fast increase in the hematocrit value with a concomitant increase in EO and the reticulocyte counts was observed. Our results show that the absolute and relative changes in hematocrit values are paramount in the feedback mechanism for erythroid homeostasis.     

The differential diagnosis of polycythaemia--a bone marrow study (the bone marrow in polycythaemia)

Bone marrow sections from posterior iliac crest aspiration and/or trephine specimens have been examined in 39 patients with true polycythaemia, along with a variety of other clinical and laboratory data. The emphasis has been on objective assessment of cellularity and megakaryocyte concentration in a prospective four year study. In patients with untreated primary polycythaemia mean cellularity was 87.0% and 86.4% for aspirate and trephine specimens compared with 55.5% and 48.7% for secondary cases and 48.3% and 45.5% for controls. Eighty per cent of primary polycythemia patients had moderate to marked megakaryocytic hyperplasia. We conclude that, in the presence of an elevated red cell volume, marrow cellularity of greater than 75%, particularly when accompanied by megakaryocytic hyperplasia, of iliac crest aspirate or trephine specimens is sufficient per se to establish a diagnosis of polycythaemia rubra vera.     

Drugs and the bone marrow

Some drugs have a predictable suppressive effect upon the bone marrow and are used in the treatment of malignant disease. Others are unpredictable and may cause unanticipated side effects to bone marrow during the treatment of non-malignant pathologies. In this article, bone marrow maturation is discussed and both the defined and potential effects of drugs upon the bone marrow are considered.     

葡多酚对骨髓细胞辐射损伤的保护作用

目的 研究葡多酚（GPC）对辐射诱发的小鼠骨髓细胞增殖活性损伤的保护作用。方法 体外实验：给予不同剂量GPC的小鼠骨髓细胞用60^Coγ射线进行一次性照射，用四甲基偶氮噻唑蓝（MTT）法检测各组细胞增殖活性。体内实验：将经口灌胃给予不同剂量GPC的小鼠用60^Coγ射线进行全身性亚急性照射，取骨髓细胞用MTT法检测各组增殖活性，用流式细胞仪检测各组细胞周期和凋亡率，用免疫组织化学方法检测各组Bcl—2表达。结果 体外实验：辐射对照组放高GPC剂量组细胞增殖活性和Bcl—2表达水平升高，G0／G1期细胞比例下降，S、G2＋M期细胞比例有不同程度升高，凋亡率明显降低，2组之间差异有统计学意义（P〈0．05）。结论 GPC对辐射损伤引发的骨髓细胞增殖活性改变和凋亡具有明显保护作用。     

克隆筛选法体外纯化骨髓间充质干细胞

目的尝试使用简单的克隆筛选法来纯化骨髓间充质干细胞（Bone marrow mesenchymal stem cells,BMSCs）并进行鉴定。方法对早期分离培养的BMSCs,采取低密度接种（10／cm^2）,待有单克隆形成,用细胞刮除去其他细胞,将克隆的细胞以低密度接种,待再次有单克隆形成时可重复以上操作,反复进行筛选。对筛选的BMSCs生物学特性进行观察,FACs鉴定BMSCs的标记物的表达,并进行成脂、成骨诱导试验。结果采用克隆筛选法培养BMSCs在传代筛选2—3代后即可获得形态均一的细胞群,FACs鉴定细胞高表达BMSCs的阳性标记物（CD2998．8％,CD9098．4％）,低表达BMSCs的阴性标记物（CD312．6％,CIM53％）。BMSCs能被高效地诱导向脂肪和骨分化。结论本实验采用的克隆筛选法可在短期内获得高纯度的BMSCs,方法简单易行而效率高。     

Modulation of bone marrow heme and protein synthesis by trace elements

We examined the effect of heavy metals and trace elements, such as Cu, Au, Cd, Zn, and Pb, on heme synthetic and degradatory enzymes in rat bone marrow suspensions. Cu, Cd, and Au, at a low concentration of 5 × 10^?6m, inhibited δ-aminolevulinic acid (δALA) dehydratase by 61, 47, and 47% respectively. A similar concentration of Zn did not inhibit the enzyme activity and, in fact, was able to protect against Au and Pb inhibition in the normal marrow. Cd was unable to recover any of the enzyme activity and, in fact, caused further inhibition. We determined the rate of cellular protein synthesis by measuring the rate of incorporation of radiolabeled precursor [¹⁴C]leucine. Cu and Au, at a concentration of 10^?5m, inhibited leucine incorporation into marrow globin and nonglobin protein by 26 and 34%, respectively. Substantially higher concentrations of Zn, as well as Fe, were required to inhibit leucine incorporation into protein. These studies led us to postulate that the inhibition of δALA dehydratase by heavy metals was directly related to the inhibition of heme and protein synthesis in the bone marrow cell suspensions. No evidence of a significant change in heme oxygenase activity in vitro was observed after treatment with any of the heavy metals or trace elements used. These results suggest that trace elements by themselves or in a combination reduce the capacity of the erythroid cell to synthesize heme, the prosthetic group of many hemoproteins. In addition, we have shown that in an iron-overloaded rat the bone marrow contains approximately 45% more heme oxygenase activity than that of the control. Administration of Au alone did not increase heme degradation, but the combination of Fe and Au resulted in a marked induction of heme oxygenase. Finally, for the first time we were able to demonstrate that excess iron and/or decreased Zn concentration may predispose δALA dehydratase to inhibition by an interaction with other metals, such as Pb, by an undefined mechanism(s).     

苯体外诱导小鼠骨髓细胞凋亡的研究

目的 观察苯对离体小鼠骨髓细胞的凋亡诱导作用。方法 荧光染色法检测细胞形态;DNA凝胶电泳法观察DNA裂解片段;流式细胞仪测细胞DNA含量法检测细胞凋亡率。结果 荧光染色法检测显示苯诱导小鼠骨髓细胞出现典型的凋亡特征形状;DNA凝胶电泳检测出苯诱导终浓度为15、25mmol/L,诱导时间为3h,电泳图谱呈现典型的DNA梯型条带;流式细胞仪检测DNA含量结果表明苯诱导小鼠骨髓细胞凋亡呈剂量－效应和时间－效应关系。结论 在体外培养条件下,苯是一种小鼠骨髓细胞凋亡诱导剂。     

骨髓活检在诊断骨髓转移瘤中的价值

目的探讨骨髓活组织检查在诊断骨髓转移瘤中的价值。方法骨髓转移瘤患者行一步法骨髓抽吸取材,活检塑料包埋切片行HGF、Gomori染色,骨髓涂片行瑞特氏染色。结果骨髓活检检出率为97.1%,骨髓涂片检出率为60.9%,骨髓活检与骨髓涂片诊断相符率为57.9%;骨髓活检检出率明显高于骨髓涂片(P<0.01)。结论骨髓活检可作为诊断骨髓转移瘤的常规检测手段。     

苯致骨髓造血功能损伤的研究进展

苯的代谢产物醌类和酚类化合物引起骨髓造血损伤的可能机制包括氧化应激损伤、细胞间信息传递异常、p53基因失活、代谢酶基因多态性、免疫因素等.本文就上述内容以及一些苯接触水平检测指标的最新进展加以阐述.