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Biomedical subjects

M A Moore

Publications and source records attributed to M A Moore.

At least 397 records · Page 22Linked to original sources
PubMed1981

Ultrastructural analysis of pancreatic carcinogenesis. IV. Pseudoductular transformation of acini in the hamster pancreas during N-nitroso-bis(2-hydroxypropyl)amine carcinogenesis.

Electron and high resolution light microscope studies were made of the pseudoductular structures that develop in the pancreas of the Syrian hamster during chronic treatment with the pancreatocarcinogen, N-nitroso-bis(2-hydroxypropyl)amine (BHP). These pseudoductules, which precede the development of tumours, arise from acini, whose cells undergo dedifferentiation by selective autophagy of their zymogen granules and granular endoplasmic reticulum. It is proposed that the pseudoductules develop into the ultrastructurally similar cystic foci that appear to be the immediate precursors of pancreatic tumours in this experimental model. The possibility is discussed that the acinar cells are the primary target for BHP carcinogenesis.

Animals↗
PubMed1981

Detection of luxol-fast-blue positive cells in human promyelocytic leukemia cell line HL-60.

Differentiation of HL-60 cells toward the eosinophilic series has not been reported previously. Eosinophil granule specific staining with Luxol-fast-blue was used to determine if HL-60 cells could differentiate into the eosinophilic lineage. The specificity of the Luxol-fast-blue stain for cells of the eosinophilic series was substantiated by comparison of the staining of cells from a patient with an eosinophilic syndrome by Wright-Giemsa and Luxol-fast-blue. Luxol-fast-blue positivity was most notable in cells found in colonies formed from HL-60 clonogenic cells in semisolid agar medium. Colony and cluster formation was spontaneous but in the presence of medium conditioned by either human placental cells or the human monocyte-like cell line, GCT, Luxol-fast-blue positive colonies and clusters were detected at a higher frequency.

Cell Line↗
PubMed1981

Long-term in vitro culture of murine mast cells. II. Purification of a mast cell growth factor and its dissociation from TCGF.

Procedures are described for the isolation of a mast cell growth factor (MCGF) from medium conditioned by mitogen-activated splenic leukocytes (CM). Although optimal conditions for the production of MCGF in CM are identical to those for the production of T cell growth factor (TCGF), MCGF can be dissociated from TCGF after the first stage of purification on a DEAE-cellulose column. MCGF elutes from the column in the breakthrough fraction, whereas TCGF binds avidly to DEAE and is eluted only at high salt concentration. MCGF also differs from TCGF with respect to m.w. (as estimated by Sephadex G-150 chromatography) and sensitivity to trypsin. In addition, MCGF is produced by the murine myelomonocytic leukemia WEHI-3 and the radiation induced thymic lymphoma LBRM-33 cells, whereas TCGF is produced only by the latter in the presence of a mitogen. Another hemopoietically active factor, granulocyte colony-stimulating factor (G-CSF) present in media conditioned by WEHI-3 and LBRM-33 cells, however, shares a number of properties with MCGF. Although studies with purified or partially purified MCGF have thus far failed to reveal a correlation between MCGF and G-CSF, further biochemical analyses are necessary to dissociate MCGF from G-CSF.

Animals↗
PubMed1981

Phenotypic evaluation of chronic myeloid leukemia.

Marrow culture studies revealed a spectrum of qualitative and quantitative defects in granulocyte-macrophage progenitors (GM-CFC) of patients with chronic myeloid leukemia in chronic phase and blastic crisis. Parallel culture studies and terminal transferase determinations revealed that a significant proportion of patients in blastic crisis possess two coexisting acute phase clones, one lymphoblastic and one myeloblastic. Measurement of response to and production of T cell growth factor showed that the leukemic blast cells from patients with TdT-positive blastic crisis produced the factor, but did not exhibit a proliferative response to exogenous factor. This phenotype was identical to that observed in TdT-positive acute lymphoblastic leukemia. Additional regulatory defects were identified in CML, since leukemic GM-CFC proliferation was resistant to inhibition by concentrations of prostaglandin E, which are markedly inhibitory for normal GM-CFC. The self-renewal or recloning capacity of GM-CFC was also identified as a unique feature of some patients with CML. The addition of retinoic acid to primary cultures of leukemic GM-CFC completely abolished this recloning capacity.

Bone Marrow↗
PubMed1981

Diagnostic and prognostic significance of the CFU-c assay in acute nonlymphoblastic leukemia.

A simplified system for classification of aggregate incidence and growth pattern in the CFU-c (colony-forming units in culture) assay, allowing simple and reproducible interpretation of test results, was developed and applied to 552 bone marrow samples from 202 patients with acute leukemia. Ninety-six consecutive patients with acute nonlymphoblastic leukemia were studied at diagnosis. The microcluster growth pattern ("acute myeloid leukemia-type") found in 57% of the patients was significantly associated with higher remission induction rates on both protocols (p = 0.004). No relationship between growth pattern at diagnosis and remission duration was observed. The acute myeloid leukemia-type growth pattern was found to be more frequent in leukemias exhibiting morphological evidence for partial myeloid or monocytic differentiation. The favorable prognostic significance of Auer rods previously described was recognized in two CFU-c growth pattern categories. Of patients exhibiting an acute myeloid leukemia-growth pattern and Auer rods, 89% obtained complete remissions compared to 38% in the Auer rod-negative group showing other growth pattern variants. The CFU-c assays performed during complete remission on 354 samples of 48 patients with acute nonlymphoblastic leukemia and, as a control, on 85 samples of 43 patients with acute lymphoblastic leukemia revealed marked spontaneous as well as chemotherapy-related fluctuations of aggregate incidence and growth pattern. These and similar observations obtained with other assay systems are probably of major pathophysiological significance but preclude clinical application of the CFU-c assay to the monitoring of remission status in patients with acute nonlymphoblastic leukemia.

Acute Disease↗
PubMed1981

Ultrastructural demonstration of terminal deoxynucleotidyl transferase (TdT).

Using an electronmicroscopic peroxidase-antiperoxidase technique in combination with a three-step fixation procedure according to Willingham, the ultrastructural site of terminal deoxynucleotidyl transferase (TdT) could be shown in cells of a human lymphoblastic leukemia cell line (MOLT 4). TdT appeared in the cytoplasm of the cells associated with large membrane bound granules from 150 to 600 nm in diameter usually arranged in aggregates. TdT-positive spaces were completely segregated form the rest of the cytoplasm and seemed to be interconnected by a tubular system. No TdT was detected in the nuclei.

Cell Compartmentation↗
PubMed1981

Long-term in vitro culture of murine mast cells. I. Description of a growth factor-dependent culture technique.

A feeder layer independent long-term in vitro culture system for murine mast cells is described. Concanavalin A-activated murine splenic leukocyte-conditioned medium, prepared under conditions optimal for T cell growth factor production, has been found also to contain a growth-promotion activity for murine mast cells identified by their morphology, characteristic ultrastructure of the granules, positive reactions with toluidine blue and alcian blue, presence of receptors for IgG and IgE, as well as presence of histamine, serotonin, L-Dopa, 5-hydroxytryptophan, and sulfated products within the cytoplasm. After 2 to 3 wk of culture in the presence of the conditioned medium, mast cell lines were established from various sources initially devoid of matured mast cells. Such sources included spleen and bone marrow of athymic nude mice, long-term cultured marrow cells as well as T cell-depleted normal marrow. Cultured mast cells are absolutely dependent upon the conditioned medium-derived growth factor(s) for growth and viability. Death ensues within 24 hr in the absence of the factor(s). Established mast cell lines have been maintained in exponential growth for over 1 yr by passaging in the conditioned medium every 3 to 7 days.

Animals↗
PubMed1981

Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts.

Human marrow cells were processed sequentially by density centrifugation and by velocity sedimentation in serum-free Percoll gradients in order to purify megakaryocytes and to determine if these cells are the source of the growth factor derived from platelets. Cell homogenates were made from the resulting fractions and tested for growth-promoting activity(ies) in 3T3 cells and in well characterized human marrow fibroblasts. Growth was evaluated by 3H-TdR incorporation and changes in DNA cell content, as measured by flow microfluorometry. The highest mitogenic activity was derived from homogenates of low density (less than 1.050 g/cu cm), rapidly sedimenting cells. This fraction contained the highest percentage of megakaryocytes. The assessment of growth-promoting activity(ies) derived from various megakaryocyte-enriched marrow cell homogenates containing different proportions of megakaryocytes demonstrated a positive correlation between the number of megakaryocytes and their stimulatory capacity as determined by 3H-TdR uptake. The growth-promoting activities elicited from homogenates of platelets and marrow fractions enriched for megakaryocytes were similar. The dose--response curves for both were parallel, and they were both temperature resistant and trypsin sensitive. These findings implicate megakaryocytes as a source of the growth factor derived from platelets and suggest that megakaryocytes may play a role in the pathogenesis of the marrow fibrosis observed in myeloproliferative disorders by stimulating fibroblast proliferation and collagen secretion.

Blood Platelets↗
PubMed1980

[Production of a mastocyte growth factor in lymphocyte cultures stimulated by a mitogen or by allogenic cells].

Supernatants from mouse spleen leukocytes stimulated by concanavalin A or from a secondary MLC between donor and recipient of a skin allograft can induce in bone marrow cells an exponential growth of mononuclear cells with cytoplasmic basophilic granules. These cells can be maintained in liquid suspension culture for up to 6 months. They lack the properties of T or b lymphocytes, monocytes or macrophages. They have the morphological features of mast cells or basophils; the cytoplasmic granules are metachromatic for toluidine blue, alcian blue-positive at pH 0.3 and contain histamine. In addition, these cells bind monoclonal mouse IgE. They may be considered as cells of the basophil-mast cell lineage.

Animals↗
PubMed1980

Analysis of multiple cell markers in acute leukemia complicating Hodgkin's disease.

A multidisciplinary methodology was applied to study 6 patients with acute leukemia (AL) following treatment for Hodgkin's disease. All 6 patients developed acute monocytic leukemia according to cytochemical criteria; morphologically, 3 cases were undifferentiated monoblastic leukemia; 3 cases were partially differentiated monocytic leukemia. In 3 of the 6 cases, cell suspensions from peripheral blood and/or bone marrow bore predominantly surface receptors for the Fc fragment of IgG and/or C-3 fraction of complement and exhibited variable degrees of phagocytosis. Two cases lacked any recognizable membrane markers or phagocytic activity. Terminal transferase enzymatic activity was not diagnostically elevated. Soft agar bone marrow culture studies revealed no growth or a characteristic leukemic cluster pattern. Chromosome analysis done in 1 of the 2 patients studied revealed hypodiploidy and structural rearrangement. Prospective studies, done serially, will help determine whether development of AL in patients with Hodgkin's disease results from the influence of intensive and potentially oncogenic therapy or represents progression from a preleukemic stage inherent to the original tumor.

Adult↗
PubMed1980

Synthesis and release of erythroid colony- and burst-potentiating activities by purified populations of murine peritoneal macrophages.

We investigated the effects of murine resident peritoneal macrophages on the in vitro proliferation of erythropoietin (Ep)-sensitive committed precursors colony-forming unit-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) with a two-layer cloning system of methylcellulose and semisolid agar. The addition of increasing numbers of macrophages to the agar underlayer resulted in a progressive increase in the numbers of both CFU-E and BFU-E that proliferated in the presence of Ep. CFU-E, but not BFU-E, proliferated to form colonies in the absence Qf exogenously added Ep, and this proliferation was enhanced in a dose-dependent fashion by the presence of macrophages in the underlayer. The enhancing effects of a given number of macrophages and a given concentration of Ep were greater than the sum of the individual effects of macrophages and Ep alone. This erythropoietic syngerism was more evident with BFU-E because burst formation was not seen in the absence of exogenously added Ep. Macrophage underlayers stimulated three to five times the number of erythroid bursts seen with Ep alone. Cell-free agar underlayers or agar underlayers prepared with nonadherent peritoneal cells or unseparated cells from thymus, lymph node, or spleen failed to augment Ep- dependent erythroid colony formation. No enhancement of CFU-E or BFU-E was demonstrable after depletion ofadherent cells from peritoneal cell suspensions by passage over columns of Sephadex G-10. Analysis by sedimentation velocity of peritoneal cells confirmed that the cells responsible for elaborating the erythroid-enhancing activity were macrophages on the basis of morphologic, histochemical, and functional criteria. Serum- free media conditioned by macrophages in the absence of Ep contained the erythroid-enhancing activities, which indicated that Ep was not required for the elaboration of these diffusible substances. These studies indicate that although macrophages are not obligate for the growth of erythroid precursors, they serve as an important source of diffusible factors that reduce the in vitro requirement for Ep.

Animals↗
PubMed1980

Induction and long-term maintenance of Thy-1 positive T lymphocytes: derivation from continuous bone marrow cultures.

In the present study we investigated the presence of T-lymphocyte progenitors in the long-term murine bone marrow culture system described by Dexter: mature Thy-1 antigen-bearing T lymphocytes are lost in these cultures after a few days. By culturing nonadherent cells from such cultures in the presence of a supernatant of concanavalin A-stimulated spleen cells, a source of T-cell growth factor, we found that Thy-1 positive blast cells proliferated together with a second population of Thy-1 negative cells. These two populations of cells have been maintained in long-term in vitro cultures by passaging the cells in fresh conditioned medium at regular intervals. Moreover, we have been able to establish pure cultures of the Thy-1 bearing blast cells after separating them from the non-T cells using their adherence property to plastic surfaces. Long-term cultures of T lymphocytes can thus be established from long-term marrow cultures as well as from the spleen, thymus or fresh bone marrow.

Animals↗
PubMed1980

A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias.

A micromethod for the determination of TdT in peripheral leukocytes and bone marrow cells has been developed that allows unequivocal identification and quantitation of TdT in less than 1 X 10(6) leukocytes from ALL patients, i.e., in 1 ml of peripheral blood and/or 0.5 ml of bone marrow obtained during routine clinical sampling. The method involves disruption of cell pellet with high salt and detergent followed by centrifugation of extracts at 12,000 X g and partial purification on phosphocellulose matrix by a batch elution technique using a standard laboratory microcentrifuge. Using this microassay, TdT activities have been determined in 500 samples of peripheral blood and bone marrow of 240 adult patients with acute leukemias (86 ALL, 108 ANLL, 44 blastic CML, two acute leukemias following P. vera). From an analysis of our data based on TdT activity, cell surface markers and growth patterns in soft agar and observations published in the literature, it can be concluded that the frequencies of TdT + phenotypes in the various clinical-morphological diagnostic groups are approximately 95% in ALL, 10% in ANLL, 50% in AUL, and 35% in blastic CML. Since the presence of high TdT activity is clearly associated with clinical response to specific forms of chemotherapy in blastic CML and most probably, also in ANLL, the determination of TdT should be considered in all cases of acute leukemias to objectively define prognostically important subgroups which can not be diagnosed by conventional means.

Acute Disease↗