An inhibitor of murine stem cell proliferation produced by normal human bone marrow.
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Animals↗
Biomedical subjects
M A Moore
Publications and source records attributed to M A Moore.
Regulation of the plasminogen activator activity of macrophage tumor cell lines.
Four murine monocyte-macrophage cell lines, WEHI-3, J774, RAW 264.10 and PU5-1.8, synthesize and secrete the proteolytic enzyme, plasminogen activator. Lymphocyte conditioned medium, 12-0-tetradecanoyl-phorbol-13-acetate and Concanavalin A enhance the enzyme activity of these lines, while low concentrations of anti-inflammatory glucocorticoids and also cholera toxin reduce the enzyme activity. These observations are similar to those found for mouse peritoneal exudate macrophages. It is suggested, therefore, that these cell lines might be useful models to delineate the cellular mechanisms involved in the control of the synthesis and secretion of macrophage plasminogen activator and of other macrophage secretory products, particularly those resulting from lymphocyte-macrophage interaction.
Animals↗
Ultrastructural analysis of pancreatic carcinogenesis: morphological characterization of N-nitroso-bis(2-hydroxypropyl)amine-induced neoplasms in the Syrian hamster.
Tumours of the exocrine pancreas of the Syrian hamster, induced by lifetime weekly injections of N-nitroso-bis-(2-hydroxypropyl)amine(BHP), were studied by light and electron microscopy and their fine structure was characterized. The neoplasms were cystic and papillary adenomata and adenocarcinomata, whose development was preceded by that of cystic foci of flattened epithelial cells. The tumour epithelia consisted of flattened, cuboidal or columnar cells, the latter frequently showing mucous metaplasia. Although there was a considerable degree of ultrastructural pleomorphism within tumours, some of which was apparently related to maturation, all the neoplasms shared sufficient common cellular characteristics to indicate a common histogenesis. Although the neoplasms induced by BHP closely resembled human "ductal" pancreatic tumours, they did not appear to arise from the ducts.
Adenocarcinoma↗
Ultrastructural analysis of pancreatic carcinogenesis. II. Establishment and morphology of a transplantable hamster pancreatic adenocarcinoma, FCP.
Hamster pancreatic adenocarcinomas were induced by life-time treatment with N-nitroso-bis(2-hydroxypropyl)amine; two of these transplanted subcutaneously into adult hamster recipients. One tumour, designated FCP, continued to grow and has been maintained through 8 serial transplant generations. The morphology and ultrastructure of FCP are described. It is relatively slow-growing, well-differentiated tumour that exhibits a stable growth rate and fine structure and closely resembles both primary hamster pancreatic adenocarcinomas and the human disease, and thus appears to be suitable for use in further biochemical and chemotherapeutic studies.
Adenocarcinoma↗
Ultrastructural analysis of pancreatic carcinogenesis. III. Multifocal cystic lesions induced by N-nitroso-bis(2-hydroxypropyl)amine in the hamster exocrine pancreas.
Hamsters were given weekly injections of the pancreatic carcinogen N-nitroso-bis(2-hydroxypyropyl)-amine for up to 44 weeks. The cystic foci induced by this treatment, which are putative precursor lesions, were studied by high resolution light microscopy and electron microscopy. They were found to consist mainly of cells that closely resembled those of hamster pancreatic adenomas and adenocarcinomas, confirming their status as precursors of these tumors. However, they additionally contained cells that possessed acinar cell characteristics, raising the possibility that dedifferentiated acinar cells might be involved in the histogenesis of the foci and thus of the pancreatic tumors.
Adenocarcinoma↗
The acute monocytic leukemias: multidisciplinary studies in 45 patients.
The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.
Adolescent↗
Expression of DR antigens on early human progenitors of neutrophilic and eosinophilic colonies in diffusion chambers (CFUd).
Incubation of the non-adherent low density cells from normal human bone marrow with an antiserum to DR antigens markedly inhibited their capacity to form granulocytic colonies in fibrin clot diffusion chambers implanted intraperitoneally into irradiated mice. The inhibitory effect of antiserum was abrogated after absorption of antiserum with B cells. Inhibition was obtained both with and without complement treatment. Neutrophilic colony formation exhibited a higher sensitivity to diluted antiserum to DR antigens as compared with eosinophilic colony formation. These results suggest that DR determinants are expressed on the neutrophilic and eosinophilic progenitor cells (CFUd) which give rise to colonies in diffusion chambers.
Animals↗
Comparative study of diagnostic procedures for congenital cytomegalovirus infection.
In a prospective study the incidence of congenital cytomegalovirus (CMV) infection was 2.2% (31 OF 1,412) as evidenced by viruria during the first week of life. Among immunoserologic methods used to screen these neonates, the rheumatoid factor test, although non-specific, proved to be the most convenient; its sensitivity for identifying infants with CMV infection was 35% to 45% with no false-positives. The rates for correct and incorrect identification of neonates at risk was, respectively, 33% and 3.1% when testing for increased levels of IgM; 5% and 10% when testing for increased levels of IgA; 76% and 21% when testing for IgM anti-CMV (IgM immunofluorescent test) antibody, and 0% when testing for IgA anti-CMV antibody. Rapid virologic diagnosis was achieved by assessing urine specimens. Confirmation by electron microscopy was possible in less than one hour in 92% of cases. The detection of early induced CMV-specific nuclear antigens by anticomplement immunofluorescence was diagnostic in 91% of cases within one day of inoculation of specimens in tissue culture. Infectivity of CMV in urine was well preserved for a least seven days at 4 C. Thus, in order to achieve a rapid diagnosis of congenital CMV infection, in sick as well as asymptomatic neonates, urine specimens may, if necessary, be transported at 4 C to distant laboratories.
Child, Preschool↗
Abnormal responsiveness of granulocyte-macrophage committed colony-forming cells from patients with chronic myeloid leukemia to inhibition by prostaglandin E1.
The formation of myeloid colonies in soft-agar cultures of normal human marrow was markedly inhibited by prostaglandin E. Morphological characterization of colonies in the presence or absence of prostaglandin E1 showed that inhibition was restricted to monocytoid rather than neutrophil differentiation. Myeloid colony formation by granulocyte-macrophage-commited colony-forming cells from patients with chronic myeloid leukemia was not inhibited even by high concentrations of prostaglandin E and was independent of colony morphology. The altered sensitivity of leukemic colony-forming cells to prostaglandin E was observed at all stages of the disease and persisted following chemotherapy-induced reversion to a partial or complete Philadelphia chromosome-negative bone marrow status. This evidence suggests that altered myeloid stem cell sensitivity to a normal regulatory factor may play a role in the pathophysiology of chronic myeloid leukemia.
Bone Marrow↗
Continuous human bone marrow culture: Ia antigen characterization of probable pluripotential stem cells.
The presence of Ia-like antigens on human CFU-C and BFU-e is confirmed and a cell type that lacked immediate capacity for granulocytic colony formation but generated CFU-c after brief incubation in simple suspension culture is identified. This pre-CFU-c, and its immediate progeny, was extremely sensitive to killing by anti-Ia serum with complement. In contrast, anti-Ia serum plus complement treatment of human bone marrow, while eliminating 93%-97% of all CFU-c and BFU-e, did not prevent the rapid regeneration of these progenitor cells and their production for some weeks under the conditions of continuous marrow culture. These studies suggest that the human equivalent of the pluripotential stem cell can replicate for some weeks in culture and generate committed progenitors, such as CFU-c and BFU-e. Furthermore, it would appear that Ia-like antigen is absent on the pluripotential stem cell, is rapidly gained as commitment to the various progenitor cell types occur, and is subsequently lost as these latter undergo differentiation within the marrow.
Bone Marrow Cells↗
Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny.
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Animals↗
Hypertensive emergencies.
Sustained, severe hypertension increases the risk of stroke and renal insufficiency in all patients, and may lead to aortic dissection or accelerated ischemic heart disease in patients with underlying vascular disease. In many situations, such hypertension demands urgent, immediate blood pressure reduction. In some cases, a gradual lowering of blood pressure is not only preferable, but is essential in preventing damage from overzealous therapy. Effective treatment of mild to moderate hypertension would prevent the great majority of hypertensive crises.
Antihypertensive Agents↗
Electromyographic investigation of muscle stretching techniques.
Myotatic reflexes can be enhanced following brief static contractions. Since static contractions are often used as precursors to muscle stretch, rationale underlying these techniques were questioned and re-examined through electromyography (EMG). Twenty-one female gymnasts performed three methods to produce hamstring stretch: static (S), contract-relax (CR), and contract-relax with agonist (hip flexors) contraction (CRAC). Hip joint angles and intra-individual electromyograms were statistically compared across stretch conditions. In 12 subjects, the CRAC method elicited significantly greater hamstring EMG activity (P < 0.05) than the other techniques. A higher level of muscle activation was associated with the S method in only one subject. No significant differences in EMG activity across stretch conditions were found in eight subjects suggesting that the relative effectiveness of the stretch techniques varied across individuals. Involuntary paroxysmal tremor activity was occasionally visible in EMG records of most subjects at the low levels of muscle activation. While apparently contributing to increased muscle stiffness, the CRAC technique produced the largest gains in hip flextion. Rank orderings of minimum pain and maximum perceived stretch effectiveness were significantly related with one another, and with decreasing EMG activity, but not with range of motion.
Adolescent↗
The fate of fetal and adult B-cell progenitors grafted into immunodeficient CBA/N mice.
The relative ability of various precursors to generate functional B cells in vivo was assessed by transferring normal, chromosomally-marked CBA/H-T6T6 cells to irradiated or unirradiated immunodeficient CBA/N mice. Emergence of donor-derived B cells was monitored by means of a B-cell cloning assay (in which CBA/N cells are inactive), and by karyotpic analysis of lymphoid, myeloid, and stem cell metaphases. Grafts of lymph node, spleen, anti-mu surface immunoglobin suppressed bone marrow, sIg+ cell-depleted marrow, normal marrow, fetal liver, and yolk sac suggest: (a) there is little self-renewal of sIg+ B cells in these models; (b) pre-committed cells have extensive proliferative/differentiative potential and at least initially contribute most of the newly-formed B cells; (c) populations or pre-B cells obtained from various sources differ in their regenerative ability; (d) CBA/N mice are deficient in a category of pre-B cells which are found in fetal liver; and (e) selective B-cell chimerism results from grafting of unirradiated CBA/N mice.
Age Factors↗
Persistence of inhibitory activity against normal bone-marrow cells during remission of acute leukemia.
Bone-marrow cells from patients with acute leukemia in remission were tested for their capacity to produce a substance (leukemia-associated inhibitory activity, LIA) that inhibits the formation of granulocyte and macrophage colonies in cultures of normal, but not of leukemic, bone marrow. LIA was detected in extracts of whole marrow in only eight of 83 patients in remission. However, extracts of slowly sedimenting cells, separated by velocity sedimentation from the marrows of eight patients in remission whose whole marrow had produced no LIA, produced inhibitory material in all cases. Extracts of the more rapidly sedimenting cells from these marrows contained an inactivator of LIA. Three of six patients in remission whose unfractionated marrow was unresponsive to LIA had a subpopulation of colony-forming cells that was sensitive to the inhibitor. These observations suggest that certain cellular functions dot not completely return to normal during remission of acute leukemia.
Acute Disease↗
Regulation of macrophage and granulocyte proliferation. Specificities of prostaglandin E and lactoferrin.
Hemopoietic colony-forming cells committed to macrophage differentiation (M-CFC) are selectively and differentially inhibited by prostaglandin E (PGE). A hierarchy of sensitivity was observed among murine CFC stimulated by colony-stimulating factors (CSF) which differ in their ability to initiate proliferation of morphologically distinct colony types, or stimulated by CSF provided by macrophage feeder layers. Inhibition of macrophage colony formation to 50 percent levels occurred with PGE concentrations between 10(-8) and 10(-9) M, and was still evident at 10(-10) -10(-11) M PGE concentrations. The growth of mixed colonies containing both macrophages and neutrophils was less sensitive to the inhibitory effects of PGE, however, the monocytoid component of these colonies was reduced in the presence of PGE. Neutrophil progenitor cell proliferation was not influenced by PGE concentrations below 10(-6) M, regardless of time of addition of PGE, whereas clonal macrophage expansion, as well as clone size, was sensitive to inhibition by PGE when added as late as 3 d after culture initiation. Prostaglandin F(2alpha), was not inhibitory to colony formation. Experimental evidence for a selective role of macrophage PGE in the regulation of macrophage colony formation was directly provided by utilizing resident peritoneal macrophages as a source of CSF for bone marrow target cell overlays. Simultaneous morphological analysis of colonies proliferating in bilayer culture in response to increasing concentrations of macrophages, and direct measurements of PGE synthesized by an identical number of macrophages maintained in liquid culture demonstrate that a specific decline in macrophage colony formation occurs coincident with a linear increase in macrophage PGE synthesis. Inhibition of macrophage PGE synthesis by indomethacin results in the specific enhancement of macrophage colony formation. Furthermore, macrophage PGE synthesis is induced by CSF preparations with the selective capacity to differentially stimulate macrophage proliferation, but not by those which preferentially stimulate granulocyte colony formation. In comparison to the effects of PGE on M-CFC, polymorphonuclear granulocyte-derived lactoferrin (LF) reduces macrophage production of colony-stimulating activities for macrophage, mixed macrophage- neutrophil and neutrophil colony formation. The ability of LF to reduce macrophage PGE synthesis, presumably by decreasing CSF production, suggests that LF and PGE can interact in the control of macrophage and granulocyte proliferation.
Animals↗
Pluripotential stem cell replication in continuous human, prosimian, and murine bone marrow culture.
Prolonged replication of pluripotential stem cells and committed progenitor cells is sustained for prolonged periods in a murine marrow culture system. Alterations in stem cell replication and differentiation are observed after infection of the cultures with Friend virus and Kirsten sarcoma virus consistent with transformation of pluripotential stem cells in the first case and transformation of the macrophage component of the hemopoietic microenvironment in the second. Prolonged myelopoiesis and CFU-c proliferation was also observed in continuous human and prosimian marrow cultures, suggesting the applicability of this technique for analysis of stem cell control and in vitro leukemogenesis in species other than the mouse.
Animals↗
Correlation of biochemical and immunological markers with conventional morphology and clinical features in 120 patients with malignant lymphomas.
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B-Lymphocytes↗