BONE-BONE MARROW INTERACTION

这项研究的长期目标是增加我们对 造血组织与骨组织的生理相互作用， 探讨造血细胞在骨调节中的可能作用 营业额。在这项工作中，过度的骨弹性骨的机制 肿瘤诱导性中性粒细胞减少症动物模型的吸收 高血钙症将被研究。 可能的体液骨吸收药物或造血干细胞刺激 通过体外骨吸收检测来自肿瘤组织的药剂 造血干细胞集落检测。肿瘤来源的骨 骨吸收活性和肿瘤来源的有丝分裂活性 成骨细胞和粒细胞前体细胞将被鉴定和 他们的关系将被审查。体液和体液的调查 骨吸收的细胞机制与体内造血模拟 将通过对荷瘤小鼠血清的研究来进行 骨吸收活性，通过植入含有以下物质的扩散室 小鼠颅骨在荷瘤小鼠体内的输注荷瘤 小鼠血清进入骨质疏松症小鼠，并通过抑制造血 使用抑制性药物。血流在脑出血中的作用研究 造血细胞和骨的转换将通过血液流动来实现 使用微球进行测量。淋巴因子在淋巴因子活化中的作用 荷瘤小鼠的造血干细胞和破骨细胞将 体内淋巴细胞耗竭小鼠和体外淋巴细胞培养的研究 实验。 这项研究将增加我们对两者机制的理解 中性粒细胞增多和高钙血症一起出现，以及它们是否 可能与这种荷瘤动物有关，也可能不相关。我们相信这些 调查将为我们提供有用的信息，帮助我们了解 某些肿瘤相关性高钙血症和中性粒细胞增多的病理生理学 在人类身上。(M)

The long-term objective of this research is to increase our knowledge about physiological interactions between hemopoietic tissue and bone tissue, seeking a possible role of hemopoietic cells in regulation of bone turnover. In this work mechanisms of excessive osteoelastic bone resorption in an animal model with tumor-induced neutrophilia and hypercalcemia will be explored. Possible humoral bone-resorbing agents or hemopoietic stem cell stimulating agent from the tumor tissue will be detected by in vitro bone resorption assays and hemopoietic stem-cell colony assays. The tumor-derived bone resorbing activity and the tumor-derived mitogenic activities for osteogenic cells and granulocyte progenitors will be characterized and their relationships will be examined. Investigations of humoral and cellular mechanisms of bone resorption and hemopoietic simulation in vivo will be carried out by studies of tumor-bearing mouse serum for bone-resorbing activities, by implantation of diffusion chambers containing mouse calvaria in tumor-bearing mice, by transfusions of tumor-bearing mouse serum into osteopetrotic mice, and by suppression of hemopoiesis using suppressive drugs. Investigations of the role of blood flow in hemopoietic cellularity and bone turnover will be carried out by blood flow measurements using microspheres. The role of lymphokines in activation of hemopoietic stem cells and osteoclasts in tumor-bearing mice will be studied by in vivo lymphocyte-depleted mice and in vitro lymphocyte culture experiments. This research will increase our understanding of the mechanisms of how both neutrophilia and hypercalcemia are brought together and whether they are possibly related or not in this tumor-bearing animal. We believe these investigations will provide us with useful information in understanding the pathophysiology of certain tumor-associated hypercalcemia and neutrophilia in man. (M)