BONE-BONE MARROW INTERACTION

这项研究的长期目标是增加我们对 造血组织和骨组织之间的生理相互作用， 寻找造血细胞在骨调节中的可能作用 周转 在这种工作机制的过度骨弹性骨 在肿瘤诱导的嗜中性粒细胞动物模型中的吸收， 将探索高钙血症。 可能的体液骨吸收剂或造血干细胞刺激剂 将通过体外骨吸收检测来自肿瘤组织的试剂 测定和造血干细胞集落测定。 肿瘤源性骨 再吸收活性和肿瘤衍生的促有丝分裂活性， 将表征成骨细胞和粒细胞祖细胞， 他们之间的关系将被审查。 体液免疫和 体内骨吸收和造血模拟的细胞机制 将通过对荷瘤小鼠血清的研究进行， 骨吸收活性，通过植入扩散室， 通过输注荷瘤小鼠的小鼠颅骨， 小鼠血清注入骨硬化小鼠，并通过抑制造血 使用抑制性药物。 研究血流在 造血细胞和骨转换将通过血流进行 使用微球进行测量。 淋巴因子在活化淋巴细胞中的作用 造血干细胞和破骨细胞在荷瘤小鼠将 通过体内淋巴细胞耗竭小鼠和体外淋巴细胞培养研究 实验 这项研究将增加我们对这两种机制的理解， 嗜盐性贫血和高钙血症是结合在一起的， 可能相关或无关。 我们相信这些 调查将为我们提供有用的信息， 某些肿瘤相关性高钙血症和嗜钙症的病理生理学 在人身上。（男）

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)