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Biomedical subjects

P Ralph

Publications and source records attributed to P Ralph.

At least 91 records · Page 5Linked to original sources
PubMed1982

Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro.

The recent identification of a leukemia-associated inhibitory activity (LIA) against granulocyte-macrophage progenitor cells (CFU-GM) as acidic isoferritins has now led to detection of this activity in normal bone marrow and blood cells. Detection of this activity depends on stimulation of CFU-GM by granulocyte-macrophage colony stimulatory factors (GM-CSF), and some conditioned media (CM) sources of GM-CSF (human placental and monocyte, mouse macrophage and WEHI-3) contained low levels of acidic isoferritin that lowered colony formation. Inactivation or removal of this activity increased the stimulatory capacity of the CM. CM depleted of acidic isoferritins or CM originally devoid of this activity (human GCT, 5637, Mo, lymphocytes: mouse L cells or pokeweed-mitogen-stimulated spleen cells) increased the sensitivity of the assay to detect acidic isoferritin inhibitory activity. This activity was selectively contained and released from normal monocytes and macrophages. Restriction of this activity to mononuclear phagocytes was substantiated, as only continuous cell lines of monocytes and macrophages or lines capable of induction to this lineage contained and released acidic isoferritin inhibitory activity. The cells of origin and target cells of action suggest that acidic isoferritin-inhibitory activity can be considered as a negative feedback regulator, at least in vitro.

Animals↗
PubMed1981

T-cell growth factor (interleukin 2) and terminal transferase activity in human leukemias and lymphoblastic cell lines.

Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.

Acute Disease↗
PubMed1981

Synergistic effects of human B and T lymphocyte mitogens induce uniform, high levels of immunoglobulin secretion among normal donors.

Synergistic effects of B-cell mitogen Staphylococcus bacteria strain Cowan I (Cowan I) plus T-cell activator pokeweed mitogen (PWM) in generating immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (MNC) were investigated. ISC were assayed by reverse plaque-forming cells uing protein A-coated red blood cells. Low concentrations of PWM plus Cowan I gave superadditive effects on ISI induction, generating 3-20 times as many ISC as optimal amounts of either mitogen alone. The mitogens together and separately showed similar kinetics of ISC; synergy was observed at every day tested. IgM ISC represented 10% of initial MNC from all cell donors tested even if the donors were low responders to either mitogen alone. The numbers of ISC obtained are higher than previous reports and more uniform among donors, making this a superlative method for studies on normal human immunoglobulin secretion.

Antibody-Producing Cells↗
PubMed1981

Tumor promoter phorbol myristic acetate stimulates immunoglobulin secretion correlated with growth cessation in human B lymphocyte cell lines.

Immunoglobulin production by lymphoblast cell lines was studies using protein A-red blood cell plaque formation to detect individual secreting cells. Immunoglobulin (Ig) secretion by 6 of 12 human B-cell lines tested could be stimulated up to twentyfold by phorbol myristic acetate (PMA) at subtoxic concentrations of 10-1000 ng/ml depending on the line. Stimulation was found with both IgM and IgG cell lines. No switch of Ig class synthesis was found in the cell lines as a result of PMA incubation. Increase in Ig secretion was closely associated with cessation of growth resembling induction of terminal differentiation in the cells. PMA induction of Ig secretion in B lymphocytes from normal peripheral blood requires the cooperation of T cells. PMA stimulation of certain cell lines reported here suggests that the lines are late in the differentiation pathway to plasmacyte and can be easily triggered to secrete Ig by membrane-altering agents.

Antibody Formation↗
PubMed1981

Cell interactions influencing murine marrow megakaryocytes: nature of the potentiator cell in bone marrow.

Auxiliary bone marrow cells are required for optimal murine megakaryocyte colony formation in addition to progenitor cells and a colony stimulating activity (CSA) present in WEHI-3 cell conditioned medium. These auxiliary cells are adherent, with a sedimentation rate of 5.8 mm hr-1 and buoyant density of 1.065-1.078 gcm-3. The activity from bone marrow cells is loss at irradiation doses above 900 rad. Bone marrow cells with these characteristics, and supernatants from lung, bone shafts, and peritoneal exudate cells were all active in enhancing megakaryocyte colony incidences in mouse bone marrow cultures above those stimulated by an obligatory activity in WEHI-3 cell conditioned medium. Certain macrophage cell lines (J774, P388D1) could elaborate the activity. This study confirms that a potentiation activity enhances CSA stimulation of megakaryocyte colony formation. The potentiator is elaborated by bone marrow cells in limiting amounts requiring either high cell concentrations or an exogenous source of the activity for optimal colony growth.

Animals↗
PubMed1981

Differences in antibody-dependent cellular cytotoxicity and activated killing of tumor cells by macrophage cell lines.

A series of murine macrophage cell lines was assayed for killing of B and T lymphocytic and myeloid tumor targets by radiolabel release at effector:target ratios of 20:1. One group of lines was inactive in all assays. Another group of lines showed moderate spontaneous cytotoxicity to lymphoid tumors that was greatly enhanced by inclusion of antibody, lipopolysaccharide, or phorbol myristate acetate in the 22-hr assays. Addition of lymphokine to the assays induced only moderate killing. Pretreatment of cell lines with lipopolysaccharide, phorbol myristate acetate, lymphokine, or nonlymphocyte sources of macrophage colony-stimulating factors did not activate "angry" or nonspecific killing. However, such pretreatment greatly stimulated antibody-dependent cellular cytotoxicity. Cytotoxicity was not due to crowding or poor culture conditions: macrophage line supernatants were not toxic; rapidly growing lymphoid lines used in place of macrophages did not kill; and high macrophage concentrations (10(6)/ml) had reduced cytotoxic activity. These experiments show that the same cell type can mediate both activated killing and antibody-dependent cellular cytotoxicity of tumor targets. The active macrophage lines appear to be qualitatively similar to each other and to peritoneal exudate populations in tumoricidal activity. We showed previously that these macrophage lines could also phagocytose and lyse antibody-coated red blood cells. The pretreatment experiments suggest that the antibody-dependent cellular cytotoxicity state can be regulated independently of macrophage nonspecific tumoricidal capacity. These culture line models of macrophages offer several advantages in the analysis of cytotoxicity.

Animals↗
PubMed1981

Induction of human immunoglobulin secretion. I. Synergistic effect of B cell mitogen Cowan I plus T cell mitogens or factors.

Synergistic effects of B cell mitogen Staphylococcus bacteria strain Cowan I (Cowan I) plus T cell mitogens in generating immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (MNC) were investigated. ISC were assayed by reverse plaque-forming cells with protein A-coated red blood cells. Low concentrations of pokeweed mitogen (PWM) plus Cowan I gave superadditive effects on ISC induction, generating 3 to 10 times as many ISC as optimal amounts of either mitogen alone. The mitogens together and separately showed similar kinetics of ISC; synergy was observed at every day tested. Plaque-forming cells of IgM, IgG, and IgA classes all showed strong synergy, together routinely representing 20% of initial MNC. At day 7 of culture, over 80% of non-E-rosetting cells were ISC. Cell donors tested gave these strong responses even if they were low responders to either mitogen alone. Cowan I plus other T cell mitogens, PHA, Con A, and protein A, also provided good signals for B cell activation. Cowan I induced marked proliferation of purified B cells, but T cell-helper signals were required for differentiation to ISC. T cell-helper factor, induced by PWM or PHA, also showed synergistic effects with Cowan I in induction of ISC. Purified B cells did not respond to T cell-helper factor(s) alone to proliferate or differentiate to ISC. These results indicate that optimal ISC induction occurs with a B cell mitogen plus T cell signals acting synergistically.

Antibody-Producing Cells↗
PubMed1980

Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.

Cell Line↗
PubMed1980

Specific inhibitory activity against granulocyte-progenitor cells produced by non-T lymphocytes from patients with neutropenia.

Bone marrow and peripheral blood cells of patients with non-leukemic neutropenia contain and elaborate a granulocyte-progenitor cell inhibitory activity. The inhibitory activity is common to the neutropenias of the various etiologies studied, which included congenital, idiopathic, autoimmune, cyclical, common variable immuno-deficiency with hypogammaglobulinemia and drug induced states. It derives from non-adherent, low density, slowly sedimenting and non-E-rosetting cells and appears to require RNA and protein synthesis, but not cell division, for its production. The material is not species specific, inhibits autologous and allogeneic normal CFUgm and leukemic CFUgm, is not cell-cycle specific in action and is most effective against granulocyte colony forming cells (CFUg), less effective against mixed granulocyte-macrophage colony forming cells (CFUgm) and least or non-effective against macrophage colony forming cells (CFUm). This inhibitory activity has no influence on cells which generate CFUc in suspension culture or on the erythroid colony forming (CFUe) and burst forming (BFUe) units. It is different from other known inhibitory activities such as lactoferrin, leukemia inhibitory activity, E type prostaglandins, interferon and immunoglobulins. This inhibitory activity, while at present an in vitro phenomenon, may be produced as a secondary response within a compromised host.

Agranulocytosis↗
PubMed1980

Induction of leukemia-associated inhibitory activity and bone marrow granulocyte-macrophage progenitor cell alterations during infection with Abelson virus.

Neonatal and adult BALB/c mice were investigated in a longitudinal study for the acquisition of leukemia-associated inhibitory activity (LIA) interactions after inoculation with Abelson virus in vivo. Within 2 to 4 days after virus infection, the granulocyte-macrophage colony-forming cells from the bone marrow and spleen of the infected mice became insensitive to inhibition by LIA, even though colony morphology appeared normal. Shortly after, or simultaneously with, the detection of the colony-forming cell resistance phenomenon, LIA was found in bone marrow, spleen, and thymus cells. The abnormal interactions appeared to be related to induction of lymphoma in BALB/c neonates and to a lymphoproliferative disease in adult BALB/c mice. In contrast, normal cellular interactions were noted in adult C57BL/6 mice which were not susceptible to the Abelson disease after virus inoculation and in untreated neonatal and adult BALB/c and adult C57BL/6 mice. Their colony-forming cells were sensitive to inhibition by LIA, and no LIA was detected in their bone marrow, spleen, and thymus cells. The abnormal cellular interactions are similar to those noted in human leukemia, lymphoma, and "preleukemia." This suggests that Abelson virus-infected mice can serve as a model for the study of LIA interactions.

Abelson murine leukemia virus↗
PubMed1980

A subpopulation of human polymorphonuclear neutrophils contains an active form of lactoferrin capable of binding to human monocytes and inhibiting production of granulocyte-macrophage colony stimulatory activities.

Subpopulations of human peripheral blood polymorphonuclear neutrophils (PMN) differing in functional capacity were separated by a rosetting procedure by using rabbit IgG antibody-coated sheep erythrocytes (EA). EA+ and EA- populations of PMN both contained lactoferrin (LF) as determined by radioimmunoassay. However, only LF (10(-16) to 10(-6) M) obtained from EA+ (= FC receptor (FcR)+) PMN was able to suppress the production of granulocyte-macrophage colony stimulatory activity derived from human monocytes. LF from EA- PMN was inactive at concentrations as high as 10(-5) M. Extracts of EA- PMN contained proteolytic enzymes, not apparent in FcR+ PMN, that inactivated the inhibitory activity of LF obtained from FcR+ PMN. These results were substantiated by immunofluorescence studies. LF from FcR+ PMN bound to monocytes whereas LF from EA- PMN demonstrated negligible binding to the monocytes and extracts from EA- PMN drastically decreased the capability of LF obtained from FcR+ PMN to bind to monocytes. These studies demonstrate functional heterogeneity of peripheral blood PMN and suggest a role for PMN subpopulations in the regulation of myelopoiesis.

Animals↗