The suppression of mitogen- and alloantigen-stimulated peripheral blood lymphocytes by cultured human T lymphocytes.
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Biomedical subjects
Publications and source records attributed to R D Maca.
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Lymph nodes were examined from 41 cases of typical chronic lymphocytic leukemia (CLL). Degree of immaturity was graded as absent to minimal (Grade I), moderate (Grade II) and marked (Grade III). A moderate degree of immaturity was found in the lymph node in 14 of 41 cases even though the cells seen on the initial bone marrow and peripheral blood smears obtained from these patients were essentially all mature. The morphology of these nodes could be confused with poorly differentiated lymphocytic or mixed lymphocytic-histiocytic lymphoma in terms of the degree of immaturity present. A marked degree of immaturity present. A marked degree of immaturity was found in 5 cases; the morphology of these cases resembled histiocytic lymphoma. In the remaining 22 cases immaturity was essentially absent. The morphology of these cases was similar to that of diffuse well differentiated lymphocytic lymphoma. Our studies suggest that a moderate degree of immaturity in the lymph node of patients with CLL does not indicate that these patients will have a marked shortening of their survival.
A patient who developed an immunoblastic leukemia of T-cell type two and one half years after initial diagnosis of mixed cellularity Hodgkin's disease, stage IIIB, is described. The patient's course was characterized by an initial 15-months remission following radiation therapy. A relapse of Hodgkin's disease was treated with intensive chemotherapy. Thirteen months later the patient entered a rapid terminal course with multiple organ infiltrates and a leukemic peripheral blood. The leukemic phase was characterized by a 55,000 WGC with 48% immunoblasts, greater than 90% of which marked as T-cells. Although acute myelogenous leukemia, acute lymphocytic leukemia, lymphosarcoma cell leukemia and other tumors have been described in Hodgkin's disease after intensive therapy, this is the first report of the unusual association of a T-cell immunoblastic leukemia with Hodgkin's disease.
The effects of hydrocortisone, dexamethasone and prednisone on the morphology, replication, DNA synthesis, cell protein content and protein synthesis of cultured, human endothelial cells were evaluated. After culturing the cells with these glucocorticoids for 24-48 h, the cells covered a greater portion of the culture surface area. The mean surface area of the individual endothelial cell treated with glucocorticoids was 1.53 times greater than that of the untreated control endothelial cell. When compared with controls, the endothelial cover provided by the cells treated with glucocorticoids was more extensive and in many instances covered the entire culture surface. The change in morphology was associated with an increase in protein synthesis and protein content of the cells without an increase in DNA synthesis or cellular replication. Dexamethasone was approximately 10-fold more effective than hydrocortisone, while prednisone was the least effective. Aldosterone, DOCA, testosterone, progesterone, oestradiol and oestriol were ineffective. These studies indicate that glucocorticoids can alter the morphology and biochemistry of cultured endothelial cells and may have implications for the effects of steroids in the treatment of thrombocytopenic states and vascular disorders in man.
The adhesive characteristics of cultured acute lymphocytic leukemia cells (CCRF-CEM), lymphoma cells (Raji), and freshly isolated acute lymphocytic leukemia cells to human cultured endothelial cells were studied. An assay system was used whereby these neoplastic cells were allowed to interact with endothelial cells while being continuously agitated on a rocking platform. All cell lines adhered significantly to the endothelium monolayers. This process appeared not to be dependent upon intact microtubular or microfilament function. Likewise, removing surface sialic acid from either cell type did not alter this process. In contrast incubating the endothelial cells for 24 or 48 hr with dexamethasone decreased adhesiveness of either CCRF-CEM or Raji cells to the endothelial cells by approximately 40%. Incubating these cells with hydrocortisone instead of dexamethasone for 48 hr was equally as effective in altering the endothelial cell adhesiveness. The decreased adhesiveness could be blocked by cycloheximide, indicating that this altered adhesiveness of the endothelial cells involves protein synthesis, presumably of a surface protein. We suggest that this assay system may provide a means to evaluate other agents that can alter the surface characteristics of endothelial cells, which may have important implications in various disease states such as inflammation, thrombogenesis, and metastatic disease.
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Sialyl transferase activity was demonstrated on the surfaces of intact, cultured lymphoblastoid cells (RAJI) derived from a Burkitt's lymphoma. Pretreatment of the cells with neuraminidase increased the labeled sialoprotein by severalfold. A nunber of nucleotides were effective in decreasing the amount of sialoprotein assembly. CMP was the most effective inhibitor. UMP, AMP, and GMP were also inhibitory, but to a lesser degree. The diphosphate derivatives were similarly inhibitory, but generally less active than their monophosphate counterparts. The cyclic nucleotides were the least effective of all nucleotides tested; cCMP and cAMP showed a small degree of activity, whereas cUMP and cGMP were without effect. These studies indicated that a number of noncyclic and cyclic nucleotides can influence the activity of the sialyl transferase system.
With a newly developed turbidometric method, concanavalin A was shown to agglutinate normal lymphocytes, lymphoma cells, and leukemic cells from chronic lymphocytic leukemia and from acute myelocytic and lymphocytic leukemia. However, there was a marked difference in the kinetics of this agglutination process. Leukemic blast cells and cells from a patient with convoluted lymphoma agglutinated poorly in this system. Conversely, the degree of agglutination for chronic lymphocytic leukemia cells was greater than that for the blast cells and also slightly greater than that for normal lymphocytes. Cultured cells from a Burkitt's lymphoma (Raji) and from a patient with poorly differentiated lymphoma agglutinated very rapidly with concanavalin A. Prior incubation of all cell types with neuraminidase markedly enhanced the agglutination process similar to that of trypsinization. Thus, these studies illustrate the usefulness of this method in quantitating the kinetics of agglutination of various human neoplastic cell types by concanavalin A.