Characterization of malignant lymphomas in leukemic phase by multiple differentiation markers of mononuclear cells. Correlations with clinical features and conventional morphology.
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Biomedical subjects
Publications and source records attributed to R Mertelsmann.
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A case report is presented of a 79 year old patient with a bilateral brochopneumonia. Four days after beginning the therapy with cephalothin and furosemide an acute renal failure appeared and six days later a haemolytic anaemia was observed. The modificated Coombs test was positive. The post mortem histiological examination of the kidneys revealed cloudy swelling, necrosis of tubuli, containing protein cylinders ("chromoproteid kidney").
Two of seventy patients with Hodgkin's disease who had exploratory laparotomy with liver biopsy and splenectomy were found to have extensive epithelioid-cell granulomas in liver and spleen. The coincidence of malignant tumour and epithelioid-cell granulomas of liver and spleen without lymph-node involvement is unusual. Knowing of the coincidence of Hodgkin's disease and such granulomas is clinically important because extensive diagnostic measures, including biopsy, are necessary in the differential diagnosis, and the patient's prognosis will depend on the therapeutic measures taken.
Specific activities are determined of two functional fractions of alpha-amanitin sensitive DNA-dependent RNA polymerases in nucleic from human normal and chronic lymphocytic leukemia lymphocytes. Specific activity of "free" RNA polymerase in CLL corresponds ot 0.133 pmoles (3H)-UMP/10(6) cells as compared to 0.209 in normals. Activities of the "engaged" enzymes are 0.139 in CLL and 0.132 in normals. "Free" enzymes in NL and CLL are completely inhibited by 400 ng/ml Rifamycin AF/013, while the "engaged" enzymes exhibit 70% of their original activity. 1.0 ng/ml alpha-amanitin suppress 50% of the activity of the "free" enzyme in CLL. The "free" enzyme in NL and the "engaged" enzymes in NL and CLL do not show any residual activity in the presence of 1.0 ng/ml alpha-amanitin.
In order to judge differentiation of cells in soft agar colonies, cytological and cytochemical classification of single cells within these colonies is necessary. In this study, 1,026 colonies from 15 normal and 95 leukemic bone marrows have been evaluated using cytological, cytochemical, and immunocytochemical techniques. In 180 colonies from 15 normal controls no segmented neutrophils have been observed. The colonies mostly consisted of monocytes and macrophages, rarely pure eosinophil colonies were observed. The number of monocyte/macrophage colonies in untreated AML and the percentage of pure eosinophil colonies in AML and ALL in remission are reduced, as compared to normal controls. In 174 colonies from a total of 926 colonies derived from bone marrows of leukemic patients, plasma cells and in 20 colonies, blast cells have been observed. In contrast to normal colonies, growth of colonies containing blast cells does not depend upon the conditioned medium of the leukocyte feederlayer. This investigation has demonstrated the necessity of cytological and cytochemical classification in addition to quantiative evaluation of soft agar colonies when studying the effect of factors on proliferation and differentiation of normal and leukemic stem cells.
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Acridine dyes inhibit the incorporation of 3H-thymidine and 3H-uridine in intact cells to the same extent as Actinomycin D. In contrast to Actinomycin D, RNA synthesis by DNA - dependent RNA polymerase in a cell-free system is inhibited at lo2 higher concentrations of acridine dyes, only. Possible differential effects on the cell membrane resulting in decreased intracellular pools of uridine and thymidine are discussed.
Specific Activities of DNA-dependent RNA polymerases A and B have been determined in nuclei from leukocytes in acute and chronic leukemia. Enzyme activities, dependent on exogenous DNA template, were determined in homogenates of nuclei from isolated mononuclear cells or from isolated granulocytes. Activities of polymerases A and B have been found significantly elevated in homogenates of nuclei from mononuclear cells in acute myelocytic leukemia, while they were found subnormal in corresponding cell fractions from chronic myelocytic leukemia and chronic lymphatic leukemia. During cytostatic treatment polymerase activities were approaching normal values. The prognostic relevance of these data for the course of human leukemia is discussed.
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Dendritic cells (DC) are professional antigen-presenting cells that can be generated in vitro from CD34+ peripheral blood progenitor cells by recombinant cytokines. These cells have potential implications for immunotherapeutic approaches in the treatment of cancer and other diseases. Physiologically, immature DC in the periphery capture and process antigens, then mature to interdigitating DC and migrate to lymphoid organs, where they activate lymphocytes. However, it is not known if DC generated in vitro have the capacity to traffic in vivo to the lymphoid tissues, such as spleen and lymph nodes. We have investigated whether human radiolabeled DC differentiated in vitro migrate and localize to lymphoid tissues after intravenous and intralymphatic injection. The distribution and localization of the DC were evaluated in five patients with malignant melanoma using serial whole-body gamma camera imaging. Intravenously infused DC demonstrated transient lung uptake followed by localization in the spleen and liver for at least 7 days. DC injected into a lymphatic vessel at the dorsal foot were rapidly detected in the draining lymph nodes where they remained for more than 24 h. These data suggest that DC differentiated in vitro localize preferentially to lymphoid tissue, where they could induce specific immune responses.
Proliferation of acute myelogenous leukemia (AML) derived blast cells requires the presence in culture of one or more growth factors. In the majority of cases Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate clonogenicity of AML blasts, which can be synergised by Interleukin-6 (IL-6), Interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). In contrast, macrophage colony-stimulating factor (M-CSF) favors deterministic divisions. A substantial part of AML samples have clonogenic cells which, however, proliferate autonomously in vitro. The production by leukemic cells of a variety of growth or synergizing factors including GM-CSF, G-CSF, IL-1, IL-6, and Tumor Necrosis Factor (TNF) has been demonstrated and a fraction of cases will use these molecules to support clonogenic growth in an autocrine or paracrine fashion. However, unlike the situation with retrovirus-induced murine or avian leukemias, the role of production of CSFs and other cytokines by human leukemic cells in the transformational process remains uncertain.