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M J Cline

Publications and source records attributed to M J Cline.

At least 109 records · Page 6Linked to original sources
PubMed1979

Splenic irradiation in myelofibrosis: effect on circulating myeloid progenitor cells.

We have investigated the mechanism of splenic irradiation-induced granulocytopenia in two patients with myelofibrosis and marked splenomegaly. Serial assays were performed for circulating granulocyte-monocyte progenitors capable of colony formation in vitro (CFU-C). For comparison, similar studies were performed on two patients receiving whole brain irradiation for glioma. Splenic irradiation caused a significant decrease in circulating CFU-C in the myelofibrosis patients. There was no decrease in circulating CFU-C in the brain-irradiated patients. No radiation-induced humoral inhibitor of granulopoiesis and no increased CFU-C radiosensitivity could be demonstrated in the myelofibrosis patients. These observations, taken together with previous data on splenic blood flow and pooling, suggest that the major mechanism of irradiation-induced granulocytopenia in myelofibrosis is destruction of proliferating precursor cells in the splenic tissue and sinusoids.

Aged↗
PubMed1979

Growth of mouse and human bone marrow in diffusion chambers in mice. Development of myeloid and erythroid colonies and proliferation of myeloid stem cells in cyclophosphamide- and erythropoietin-treated mice.

Both murine and human bone marrow cells were cultured in plasma clots which were formed inside diffusion chambers implanted into cyclophosphamide- and saline-treated mice. After an initial fall, the number of mouse bone marrow cells and numbers of mouse myeloid stem cells (CFU-C) and agar cluster-forming units rose faster in the cyclophosphamide-treated animals. These hosts also favored formation of myeloid (CFU-D-G) and erythroid (CFR-D-E) colonies and myeloid higher than those of CFU-C from the same marrow population. These observations suggest the existence of humoral factors stimulating granulocyte progenitor cell replication and differentiation. At its best the increment of CFU-D-E number was equivalent to that caused by a single 0.1 unit erythropoietin dose. Culture of normal human marrow cells resulted in colonies in the plasma clot containing only granulocytes and macrophages. Cyclophosphamide-treated host animals were essential for human CFU-D-G development. Plating efficiency for human marrow myeloid colonies was better in the conventional in vitro agar cultures than in diffusion chambers.

Animals↗
PubMed1979

Controlling the production of blood cells.

The development since 1966 of a technology for growing stem cells in vitro has provided new insights into the controls of blood cell production. Hematopoietic hormones have been purified and important cellular interactions in hematopoiesis have been defined.

Anemia, Aplastic↗
PubMed1979

Autotransplantation after in vitro immunotherapy of lymphoblastic leukemia.

We have used in vitro immunotherapy before autologous bone marrow transplantation for three patients with acute lymphoblastic leukemia (ALL). Bone marrow was removed during remission, and mononuclear cells were separated by density-step centrifugation on Ficoll-Hypaque. The cells from each patient were treated with a heteroantiserum and complement to eliminate leukemic cells and were cryopreserved. Following chemotherapy and total body irradiation, the treated marrows were thawed and infused. All the patients showed positive evidence of returning marrow function before death. One patient who survived 4 months showed no evidence of leukemia at post mortem, and marrow sections demonstrated active hematopoiesis of all cell lines.

Bone Marrow Transplantation↗
PubMed1979

Antigenic characteristics of normal and malignant human hematopoietic cells. Potential use of antigenic differences in cell separation and marrow transplantation.

Recent studies using cytotoxic and cell separation techniques have identified differentiation-related antigens on human hematopoietic cells. These results, combined with bone marrow transplantation studies, have yielded a picture of antigenic modulation from the pluripotent hematopoietic stem cell through the differentiated end cells.

Antigens, Surface↗
PubMed1979

Autologous bone marrow transplantation in patients with cancer.

Ten patients with non-leukemic neoplasms received intensive, marrow-lethal doses of drugs and radiation followed by rescue with autologous cryopreserved bone marrow (nine) or marrow from an identical twin as part of a phase 1-2 study. Nine patients had extensive disease that was unresponsive to conventional therapy. Marrow engraftment was documented in all evaluable cases and most patients had a substantial anti-tumor response. Three patients are alive from 4 to 10 months following transplantation without evidence of disease.

Bone Marrow Transplantation↗
PubMed1979

Human myeloid progenitor cells expressing HLA antigens.

Marrow cells of known HLA type were incubated with HLA antiserum plus complement and then plated in soft agar. Colony formation was consistently inhibited by appropriate HLA antisera. Mixing experiments excluded an indirect effect on CFU-C by lysis of mature leukocytes. We conclude that human CFU-C express HLA antigens.

Antibody Specificity↗
PubMed1979

Isolation, cryopreservation, and autotransplantation of human stem cells.

We have used cryopreserved autologous hematopoietic cells to repopulate bone marrow of patients receiving intensive chemotherapy and radiation. We employed the technique of density step centrifugation to concentrate stem cells from whole bone marrow. The concentrate of cells was frozen in vials using dimethyl sulphoxide (DMSO) as a cryo-protective agent and was stored in the vapor phase of liquid nitrogen. Test vials were thawed and assayed for myeloid stem cells (CFU-C) to determine the potential of the larger marrow aliquot. These test values were compared to the recovery of cells and CFU-C when the marrow was used for autotransplantation. The return of hematopoietic function after autotransplantation was evaluated and correlated with the dosage of cells and CFU-C infused.

Bone Marrow Cells↗
PubMed1978

Pretransplant lymphocytotoxins and bone-marrow graft rejection.

A correlation was demonstrated between bone-marrow graft rejection and pretransplant lymphocytotoxins. This finding might prove useful as a test for identification of patients at high risk of rejection who might benefit from more intensive immunosuppression.

Adolescent↗
PubMed1978

Production of bone resorbing activity in poorly differentiated monocytic malignancy.

A patient with poorly differentiated monocytic malignancy had extensive lytic lesions of bone and hypercalcemia. The patient's bone margins showed little evidence of osteoclast activity. Serum parathormone concentrations were slightly increased relative to the degree of hypercalcemia, consistent with impaired renal function. Serum concentrations of the relevant prostaglandins were normal. Supernatant medium from cultured tumor cells caused prominent bone resorption in vitro. The studies on this patient provide evidence that malignant cells of the monocyte-macrophage line are capable of direct bone resorption.

Adult↗
PubMed1978

Recent developments in understanding the pathogenesis of aplastic anemia.

Bone marrow failure in aplastic anemia (AA) could result from abnormalities of hematopoietic stem cells, abnormal control of hematopoiesis, or abnormalities of the hematopoietic environment. Bone marrow transplantation, in vitro marrow culture techniques, and studies in animal models of marrow failure have provided insights on the possible pathogenetic mechanisms underlying AA. Studies in man and in murine models suggest that most often AA results from injuries to hematopoietic stem cells. Despite the intriguing report of abnormal regulatory cells in congenitally anemic mice, instances of marrow failure due to defective humoral or cellular control of hematopoiesis have not been identified in man. In vitro studies employing allogeneic marrow targets have suggested that immune suppression of hematopoiesis may occasionally mediate AA in man. Marrow failure due to abnormalities of the hematopoietic microenvironment has been suggested by experience with bone marrow transplantation, but no direct study of this possibility has been reported. Based on available evidence, it seems likely that AA will prove to be many diseases that share common clinical and morphologic features.

Anemia, Aplastic↗
PubMed1978

Immune suppression of hematopoiesis.

Recent evidence suggests that immune mechanisms can injure proliferating hematopoietic precursor cells in the bone marrow. These may involve either humoral antibody or cell-mediated cytotoxic mechanisms. Immune injury can result in a variety of bone marrow failure syndromes. Immunologically induced abnormalities or blood cell production may be restricted to a single series, such as erythrocyte or granulocyte precursors, or may involve several hematopoietic lines; clinical manifestations reflect the cell line or lines that are injured. Immune suppression of hematopoiesis has now been described in pure red cell aplasia, immune panleukopenia, systemic lupus erythematosus, atypical cases of aplastic anemia and miscellaneous other hematologic diseases.

Agranulocytosis↗
PubMed1978

Monocytes, macrophages, and their diseases in man.

Mononuclear phagocytes are a widely distributed system of cells involved in host defense functions, immunologic reactions, disposal of unwanted organic and inorganic materials, and synthesis of biologically active compounds such as complement components and prostaglandins. The system includes early precursor cells in the bone marrow, blood monocytes, alveolar and peritoneal macrophages, sinusoidal lining cells in the spleen, and Kupffer cells in the liver. We have recently come to understand the biology of these interesting cells and the diseases they produce.

Antigen-Antibody Reactions↗
PubMed1978

UCLA Conference. Monocytes and macrophages: functions and diseases.

The mononuclear phagocyte complex is a widespread system of cells originating in the bone marrow monoblast and promonocyte, passing through the intermediate monocyte stage in the blood, and culminating in the tissue macrophages of the lung, liver, spleen, and pleural and peritoneal spaces. The cells are prominently phagocytic and have a well-developed lysosomal system. They function in host defense reactions against micro-organisms, in interactions with lymphoid cells in immunity, in disposal of cell debris, and possible in the regulation of granulopoiesis. Monocytes and the alveolar macrophage are the most accessible cells of this system for study. Several diseases of mononuclear phagocytes have been identified and characterized. These include microbicidal defects associated with increased susceptibility to infection, enzyme defects leading to storage diseases, and neoplastic diseases in which both cell proliferation and biologically active cell products contribute to the clinical disorder.

Animals↗