Biomedical subjects

M A Moore

Publications and source records attributed to M A Moore.

At least 325 records · Page 18Linked to original sources

PubMed1985

Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor.

Pluripotent hematopoietic colony-stimulating factor (pluripotent CSF), a protein that is constitutively produced by the human bladder carcinoma cell line 5637, has been purified from low serum (0.2% fetal calf serum)-containing conditioned medium. The purification involved sequential ammonium sulfate precipitation, ion-exchange chromatography, gel filtration, and reversed-phase high-performance liquid chromatography. The purified protein has a molecular weight of 18,000 in NaDodSO4/polyacrylamide gel electrophoresis, both by the silver staining technique and by elution of biological activity from a corresponding gel slice, and has an isoelectric point of 5.5. Pluripotent CSF supports the growth of human mixed colonies, granulocyte-macrophage colonies, and early erythroid colonies and induces differentiation of the human promyelocytic leukemic cell line HL-60 and the murine myelomonocytic leukemic cell line WEHI-3B (D+). The specific activity of the purified pluripotent CSF in the granulocyte-macrophage colony assay is 1.5 X 10(8) units/mg of protein.

Biological Assay↗

PubMed1985

Specific expression of the human cellular fps/fes-encoded protein NCP92 in normal and leukemic myeloid cells.

We have found that both an antibody directed against a synthetic peptide representing an amino acid sequence of the conserved kinase domain of transforming protein P140 of Fujinami sarcoma virus and a regressing tumor antiserum recognized the products of the c-fps/fes genes of both avian and mammalian cells. The anti-peptide antibody also recognized a 94-kilodalton protein that was related to but distinct from the c-fps/fes product in structure and in tissue distribution. A 92-kilodalton protein, NCP92, was found to be the mammalian counterpart of the previously identified avian c-fps/fes protein NCP98 by its structural similarity to NCP98, its associated tyrosine kinase activity, and its similar tissue distribution. The highest levels of NCP92 were found in tissue macrophages and in bone marrow. In bone marrow NCP92 expression was restricted to cells of the monocyte/macrophage and granulocyte lineages. That the expression of NCP92 is limited to these cell types was confirmed by the analysis of murine and human hematopoietic tumors representing different cell lineages: NCP92 was positive in leukemic cells of granulocytic and monocytic origin but not in B-lymphocytic, T-lymphocytic, or erythroid tumor cells. The expression of NCP92 seems to be related to the capacity of myeloid cells to differentiate and to respond to certain colony-stimulating factors.

Animals↗

PubMed1985

Unilateral adrenal hemorrhage: an unusual presentation.

An asymptomatic adrenal mass was discovered in an elderly patient during evaluation of an abnormal urinary sediment. Exploratory laparotomy revealed an adrenal hematoma as the cause of the mass. No clear cause of the adrenal hemorrhage was identified, and postoperatively there was no evidence of adrenal insufficiency. Though rare, signs of adrenal hemorrhage may include an asymptomatic adrenal mass, and should be considered in the differential diagnosis of this problem.

Adrenal Gland Diseases↗

PubMed1985

13-cis-Retinoic acid does not increase the true remission rate and the duration of true remission (induced by cytotoxic chemotherapy) in patients with chronic phase chronic myelogenous leukemia.

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Adolescent↗

PubMed1985

Current management of hypertension.

Treatment of hypertension is best accomplished in stepwise fashion, beginning with nondrug therapy followed by a knowledgeable selection of antihypertensive drugs. Consideration must be given to the side effect profile as well as the cost of the medication. Diuretics are still useful, both as first-step drugs and as second-step and third-step drugs to overcome the sodium retention associated with many antihypertensive agents.

Adrenergic beta-Antagonists↗

PubMed1985

Comparison of the various forms of glutathione S-transferase with glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase as markers of preneoplastic and neoplastic lesions in rat kidney induced by N-ethyl-N-hydroxyethylnitrosamine.

Alterations in gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase (ALP) activities and binding of specific antibodies to glucose-6-phosphate dehydrogenase (G6PDH), gamma-GT and the A, B, C, D, and P forms of glutathione S-transferase (GST-A, -B, -C, -D, and -P, respectively) in preneoplastic and neoplastic lesions induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the rat kidney were investigated. Morphologically the lesions were of basophilic type and were classified either as altered tubules or adenomas, the latter being further subdivided into microadenomas and adenomas depending on size and the presence of compression. The fact that all lesions demonstrated only weak (or negative) gamma-GT, ALP and GST-B stainings, all of which are normally evident in proximal tubules, and also the occasional finding of cells bearing a periodic acid-Schiff-positive apical brush border within altered tubules strongly positive for GST-A, indicated their histogenesis from the proximal segment of the nephron. Thus a directed shift to a phenotype opposite to that observed in the cells of origin was demonstrated. Comparison of phenotype within the range of EHEN-induced lesions strongly suggested putative preneoplastic character for the altered tubules. Transition to adenomas appeared to be correlated with progressive loss of GST-A and moderate to slight increase of G6PDH.

Adenoma↗

PubMed1985

Distinct activities of interferon-gamma, lymphokine and cytokine differentiation-inducing factors acting on the human monoblastic leukemia cell line U937.

The human monoblast leukemia line U937 is growth inhibited and induced to express various characteristics of mature monocytes by lymphokines (LK) and other cytokines. Previous experiments have shown that interferon-gamma (IFN-gamma) is responsible for some but not all of the differentiation-inducing effects on U937. To determine the variety and specificity of activity, the following factors were studied: phytohemagglutinin-induced LK that contained IFN-gamma (100 units/ml); purified IFN-gamma; human colony-stimulating factor 1 (CSF-1); and conditioned medium(a) (CM) from the human bladder carcinoma cell line 5637 and the hepatoma cell line SK-HEP. LK preparations contained no colony-stimulating activity, whereas CM from 5637 and SK-HEP both contained granulocyte-macrophage CSF (3000 to 4000 units/ml) but no IFN activity. IFN-gamma is the major immunoglobulin G Fc receptor-inducing species within lymphokine, since anti-interferon-gamma antibody inhibited most of this activity. Other sources of Fc receptor-inducing activity were CM from SK-HEP and 5637 cell lines. Human CSF-1 when tested up to 800 units/ml was inactive for Fc receptor induction. LK induced the chemotactic peptide receptor, but this induction was due to factors other than IFN-gamma as anti-IFN-gamma antibody did not inhibit the induction, and purified IFN-gamma at a dose equivalent to that found in LK (100 units/ml) had no activity in the assay. SK-HEP and 5637 CM had strong chemotactic peptide receptor-inducing activity, but human CSF-1 was inactive up to 800 units/ml. Peroxide production after stimulation with phorbol myristic acid could be induced by LK, LK with anti-IFN-gamma antibody, 5637, and SK-HEP treatment. IFN-gamma (100 units/ml) and CSF-1 (800 units/ml) were ineffective. Peroxide production was induced by IFN-gamma at concentrations above 1000 units/ml. The inducibility of several enzymatic activities was determined as additional measures of maturation. N-Acetylglucuronidase was induced, for example, by LK, IFN-gamma, 5637 CM, and phorbol myristic acid. Alkaline phosphatase was induced by LK, IFN-gamma, dexamethasone, and phorbol myristic acid. 1,25-Dihydroxycholecalciferol was also examined and could induce most of the maturational markers examined. The results demonstrate that non-IFN cytokines from several sources have profound differentiation-inducing effects on monoblast leukemia cells in a pattern different from that of IFN-gamma.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies↗

PubMed1985

Distinct differentiation-inducing activities of gamma-interferon and cytokine factors acting on the human promyelocytic leukemia cell line HL-60.

The human promyelocytic leukemia cell line HL-60 and monoblastic leukemia cell line U937 undergo differentiation when induced by lymphokine and cytokine preparations. Growth inhibition, acquisition of immunoglobulin Fc receptors, increased expression of monocyte-related surface antigens, and an increase in lysosomal enzyme contents accompany maturation induced by gamma-interferon and other cytokine factors tested. Additionally, increased receptors for chemotactic peptide (fMLPR), increased hydrogen peroxide release in response to phorbol myristic acetate stimulation, and the release of prostaglandins (PGE2 and 6-keto-PGF1a) follow exposure to lymphokine and cell line sources of myeloid colony-stimulating activity (CSA). Gamma-Interferon (gamma-IFN) induced fMLPR in HL-60 (only at 1000 units/ml) but not in U937. Additionally, gamma-IFN did not induce prostaglandin release in either cell line. These myeloid colony-stimulating activity-associated differentiation-inducing factors were obtained from the human hepatoma++ cell line SK-Hep and bladder carcinoma cell line 5637, which were free of interferon activity. The 2-day phytohemagglutinin-induced lymphokine contained no detectable CSA and was a good source of differentiation activity. A simple, rapid assay for a new human CSA with pluripotent hematopoietic stimulating activity (pluripoietin) is described based on stimulation of [3H]glucosamine incorporation. Cell line conditioned media containing pluripoietin, purified pluripoietin, and gamma-IFN are active in this assay. These myeloid leukemia cell line differentiation factors are thus different from interferon and conventional CSA. These results suggest that endogenous human cytokines may have a role in the differentiation of leukemic as well as normal myeloid cells.

Antibodies, Monoclonal↗

PubMed1985

Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor.

Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.

Animals↗

PubMed1985

Action of 1,25-(OH)2D3 in nude mice bearing transplantable human myelogenous leukemic cell lines.

After cyclophosphamide priming, subcutaneously (s.c.) transplanted cells from established human leukemia cell lines U937, K562, or HL-60 consistently yielded single, nonmetastatic tumors. Tumorigenesis with KG-1 cells was inconstant. Within each cell line, cytologic, electron-microscopic, cytogenetic, isoenzyme, immunochemical, and enzyme cytochemical studies confirmed identity of cultured and tumor cells. Adenosine triphosphatase reactivity was limited to leukemic cells in vivo. Isoenzyme electrophoretic patterns, distinct for each cell line, provided a reliable criterion to establish clonality and to verify tumor cell origin. Antitumor activity of the active vitamin-D3 metabolite 1,25-(OH)2D3 was assessed in vivo against U937, K562, and HL-60 cells by cell transplantation and concurrent s.c. contralateral implantation of miniosmotic pumps containing the 1,25-(OH)2D3 in a propylene glycol vehicle. Tumors developed in all treated U937 mice, 50% with K562 and 25% bearing HL-60 transplants. All transplants proliferated in mice either with pumps containing only vehicle or no pumps. Coincidence of tumor and vehicle decreased survival time. No differences in cytoreactivities or morphology were apparent between cultured cells and tumor cells in treated or untreated mice. This nude mouse system is useful for in vivo studies of human myelogenous leukemia cells. Implanted miniosmotic pumps provide controlled delivery of antineoplastic agents and their vehicles for in vivo studies. 1,25-(OH)2D3 may be a valuable adjunctive therapeutic for control of human myelogenous leukemias.

Animals↗

PubMed1985

Abnormalities in myelopoietic regulatory interactions with acidic isoferritins and lactoferrin in mice infected with Friend virus complex: association with altered expression of Ia antigens on effector and responding cells.

The regulation of myelopoiesis was evaluated in B6D2F1 mice inoculated with Friend virus complex (spleen focus-forming virus plus helper virus) or helper virus alone by analyzing acidic isoferritin (AIF) and lactoferrin (LF) interactions with target cells. Under normal conditions, AIF suppresses colony and cluster formation by an Ia-antigen-positive cycling subpopulation of mouse granulocyte-macrophage progenitor cells (CFU-GM). Under the same conditions, the release of AIF-inhibitory activity and granulocyte-macrophage colony stimulatory factors (GM-CSF) from an Ia-antigen-positive subpopulation of monocytes and macrophages is suppressed by LF. Within one to two days after inoculation in vivo with Friend virus complex or helper virus, mouse CFU-GM become insensitive in vitro to suppression by purified human AIF as well as crude mouse AIF, and by four days, bone marrow, spleen, and thymus cells of these mice release much greater quantities of AIF-inhibitory activity than the cells from mice injected with control medium. The Friend virus complex itself has no influence in vitro on CFU-GM from normal mice. In addition, the release of AIF-inhibitory activity from bone marrow, spleen, and resident peritoneal cells and the release of GM-CSF from resident peritoneal cells of mice infected with Friend virus complex are not suppressed by LF. The inability of AIF to suppress colony formation by bone marrow and spleen CFU-GM from mice infected with Friend virus complex is associated with the loss of Ia (I-A subregion) antigens from CFU-GM, even though CFU-GM are in cycle. The nonresponsiveness of bone marrow, spleen, and peritoneal cells from these mice to LF suppression of AIF release and the inability of LF to influence GM-CSF release from peritoneal cells is associated with loss of Ia antigens from these cells. The above abnormalities are similar to the defects noted using cells from patients with leukemia. These results suggest that mice infected with Friend virus complex can serve as a model for investigating abnormalities in cell regulation and their relationships to disease progression.

Animals↗

PubMed1985

Biological characterization of a granulomonopoietic enhancing activity derived from cultured human lipid-containing macrophages.

We describe the biologic characteristics of an activity produced by human monocyte-derived lipid-containing cells (MDLCCs) that enhances the colony-forming capacity of granulocyte-macrophage progenitors (CFU-GM). Medium conditioned by well-developed MDLCCs (at day 21 to day 28 of cultivation) was added to bone marrow cultures containing GCT cell line-conditioned medium (GCT-CM) or other material as a source of granulocyte-macrophage colony-stimulating factors (GM-CSFs). MDLCC-conditioned medium (CM) had no detectable granulocyte-macrophage colony-stimulating activity (GM-CSA), but it contained an activity that enhanced the colony number in both day 7 and day 14 CFU-GM cultures. Dose-response curves for GCT-CM in the presence of MDLCC-CM demonstrated that this enhancing effect occurred at concentrations of GM-CSFs that stimulate maximal CFU-GM growth. This enhancing effect was seen with both granulocytic and monocytic progenitor cells. It was titratible and required the continuous presence of MDLCC-CM from initiation of culture. No enhancement was noted when MDLCC-CM was added 48 hours after plating. The enhancement still occurred when marrow cells were first incubated with MDLCC-CM and GCT-CM was added at later times. Neither the enhancing activity nor its production was dependent on horse serum contained in MDLCC culture medium. The enhancing effect was also seen when other sources of GM-CSA were used: medium conditioned by 5637 cell line, phytohemagglutinin-stimulated lymphocytes (PHAL), or placenta tissue. Furthermore, this enhancing activity appeared to be specific for CFU-GM. Addition of MDLCC-CM to mixed and erythroid cultures, stimulated by suboptimal and optimal concentrations of PHAL-CM did not modify the number of mixed colonies or erythroid bursts. This granulomonopoietic enhancing activity contained in MDLCC-CM was heat stable (56 degrees C and 75 degrees C for 30 minutes) and nondialyzable (3,500 and 14,000 molecular weight cut off tubing). Its production was increased by treating MDLCC with lipopolysaccharide (5 micrograms/mL) or zymosan (60 micrograms/mL) and inhibited by lactoferrin (10(-7) mol/L). The production of a granulomonopoietic enhancing activity by MDLCCs represents the demonstration of another positive feedback regulator of myelopoiesis involving the monocyte-macrophage system.

Cells, Cultured↗

PubMed1985

Depletion of stromal cell elements in human marrow grafts separated by soybean agglutinin.

We report studies demonstrating the presence on human marrow stromal cells of binding sites for the soybean lectin (SBA). Marrow cells were separated by agglutination with SBA into an agglutinated cell (SBA+) fraction containing most mature hemic cells including T lymphocytes, and an unagglutinated cell (SBA-) fraction containing the hematopoietic stem cells. The vast majority of fibroblast colony-forming units (CFU-F) (97.2% +/- 1.1%) were in the SBA+ fraction. Mixing experiments using SBA+ and SBA- cells excluded the possibility that these results were caused by an unequal distribution of accessory cells having a regulatory effect on CFU-F growth. In the heterogeneous adherent layers of long-term marrow cultures derived from SBA+ and SBA- cells, endothelial cells, and adipocytes were found almost exclusively in cultures of SBA+ marrow cells. Immunofluorescence studies with fluorescein-labeled SBA revealed the staining of cultured marrow fibroblasts. This staining was inhibited by D-galactose, which is the sugar that specifically binds to SBA. Staining of marrow-derived heterogeneous adherent layers with fluorescein-labeled SBA demonstrated that cultured endothelial cells (identified by rhodamine-labeled antibodies against factor VIII-associated protein) and early adipocytes also had surface glycoproteins binding SBA, although its density on the latter cells was much less important. Thus, our data indicate that human marrow grafts processed with soybean lectin to remove T cells are also depleted of the cellular components of the marrow stroma.

Adipose Tissue↗

PubMed1985

Long-term culture of human bone marrow macrophages: macrophage development is associated with the production of granulomonopoietic enhancing activity (GM-EA).

We describe a liquid culture system allowing the long-term maintenance and differentiation of human marrow monocytes into well-developed, lipid-containing macrophages, and we show that these cells produce a regulating activity that enhances the colony formation induced by granulocyte-macrophage colony-stimulating factors (GM-CSF). Adherent, low density (less than 1.074 g/cm3) human marrow cells were used as a source of monocytic cells. Of 12 different culture conditions tested, alpha-medium supplemented with 20% horse serum and incubation at 37 degrees C provided the best conditions for macrophage development, adipogenesis, and long-term culture. Neither insulin (1 to 10 micrograms/ml) nor hydrocortisone (10(-6) M) improved the lipid accumulation in cultures containing horse serum. Trypsin was employed to remove fibroblasts without detaching monocytic cells from the marrow-derived adherent cell layers. Marked structural and functional changes characterized the transformation of monocytes into lipid-containing macrophages. Cell enlargement up to seven or eight times by 21 to 28 days of culture was associated with an increase in small and medium-sized lipid granules, as well as in acid phosphatase and nonspecific esterase activities. Ultrastructurally, there was an increase in the number of mitochondria, Golgi apparatus, lysosomes, rough endoplasmic reticulum, and lipid inclusions, which remained of small size and did not coalesce to form larger inclusions. The absolute quantity of Fc receptors, Ia antigens, and antigens recognized by monoclonal antibodies 61D3 and 63D3 also increased as a function of cell size. As marrow monocyte-macrophage differentiation proceeded, a rapid decline in GM-CSF production was accompanied by an increase in an activity that by itself had no capacity to stimulate colony formation in CFU-GM cultures devoid of GM-CSF, but did enhance the colony formation induced by optimal concentrations of GM-CSF. Neither the enhancing activity nor its production was related to the horse serum present in the culture supernatants. The morphology of colonies enhanced by this activity was different from the morphologic spectrum in non-enhanced cultures. This granulomonopoietic enhancing activity (GM-EA) represents another positive feedback regulator of hematopoiesis derived from cells of the monocyte-macrophage system.

Adult↗

PubMed1985

Lymphokine-activated killer cells are generated before classical cytotoxic T lymphocytes after bone marrow transplantation in mice.

Lymphokine-activated killer (LAK) cells are demonstrable within 2 wk after syngeneic or allogeneic (H-2-compatible) bone marrow transplantation in mice. Classical cytotoxic T lymphocytes (CTL) are not active until at least 4 wk after transplant. Both LAK cells and CTL bear the Thy-1 marker and do not possess the murine natural killer cell marker asialo GM.

Animals↗

PubMed1985

OKT3 monoclonal antibody induces production of colony-stimulating factor(s) for granulocytes and macrophages in cultures of human T lymphocytes and adherent cells.

OKT3 monoclonal antibody (mab) recognizes a membrane antigen associated with the T cell antigen recognition receptor, and is known to be mitogenic and to induce lymphokine production. Our studies demonstrate the ability of OKT3 mab to induce from cultures of human T lymphocytes supplemented with adherent cells the production of colony-stimulating factor(s) for granulocytes and macrophages (GM-CSF) and interferon-gamma (IFN-gamma), an inhibitor of clonal growth of hematopoietic progenitor cells. As has been shown for the mitogenic and IFN-gamma-inducing activity of OKT3 mab, the induction of GM-CSF release in cultures of T cells is strictly dependent on the presence of adherent cells. However, the concentrations of OKT3 mab required for optimal GM-CSF production (50 ng/ml) were found to be 80-fold higher than those sufficient for maximal IFN-gamma production, proliferation, and interleukin 2 production. IFN-gamma activity induced by OKT3 mab partially inhibited colony and cluster formation from progenitor cells of granulocytes and macrophages in vitro. Therefore, neutralization of the IFN-gamma by monoclonal anti-human-IFN-gamma antibody before assay of conditioned medium in bone marrow cultures significantly enhanced the detection of GM-CSF. Kinetic studies demonstrated maximal cumulative GM-CSF production in response to optimal OKT3 mab concentrations on days 4 through 6 in cultures of T cells supplemented with 15% adherent cells. Highly enriched OKT4+ and OKT8+ T cell subsets co-cultured with adherent cells in the presence of OKT3 mab both produced GM-CSF and IFN-gamma and showed similar dose-response curves to OKT3 mab. The requirement for the presence of adherent cells could not be overcome by the addition of purified interleukin 1 or macrophage supernatants. Studies using irreversible inhibitors of DNA (mitomycin C) or protein biosynthesis (emetine-HCl) revealed the necessity of intact DNA synthesis and translation in mononuclear cells to produce GM-CSF in response to OKT3 mab. Loss of GM-CSF production was observed when either adherent cells or T lymphocytes were treated with emetine before co-culture with untreated cells of the other population in the presence of OKT3 mab. In contrast, mitomycin C reduced GM-CSF production significantly when T cells, but not adherent cells, were pretreated. These results suggest that T lymphocytes and adherent cells closely cooperate in the production of GM-CSF induced by OKT3 mab.

Antibiotics, Antineoplastic↗

PubMed1985

A protein cross-reacting immunohistochemically with rat glutathione S-transferase placental form as a marker for preneoplasia in Syrian hamster pancreatic and hepatocarcinogenesis.

Immunohistochemical staining using antirat glutathione S-transferase placental form (GST-P) rabbit antibody demonstrated marked binding to cells of putative preneoplastic lesions induced in both the liver and pancreas of Syrian hamsters by dihydroxy-di-n-propylnitrosamine treatment, whereas background normal-appearing tissue was negative. Thus, a protein showing immunological cross-reaction with rat GST-P is also elevated during pancreatic carcinogenesis and hepatocarcinogenesis in the hamster, suggesting its usefulness as a marker with potential relevance to the mechanisms underlying the neoplastic process.

Animals↗

PubMed1985

Generation of natural killer cell lines from murine long-term bone marrow cultures.

Functionally active natural killer (NK) cells with the ability to lyse 51Cr-labeled YAC-1 lymphoma target cells are no longer detectable by 1 wk of culture in cultured marrow cells harvested from Dexter-type long-term marrow cultures (LMC). Interferon, which enhances NK cell-mediated target cell lysis, fails to induce NK activity from LMC cells even at high effector to target cell ratios. However, such LMC cells, when placed in secondary cultures in the presence of Con A-splenic leukocyte-conditioned medium (spleen-CM) generated a population of cells with NK activity within 1 wk. Kinetic studies showed that the generation of NK activity was not due simply to proliferation of a few surviving NK cells, but suggested derivation from NK precursors through clonal expansion and functional maturation. This NK activity was further shown to be associated with a subpopulation of cells bearing surface Thy-1, Ly-5, and NK-1 as well as asialo-GM1 antigens but lacking Ly-1 antigen. The expression of Ly-2 antigen, however, was variable. Electron microscopy studies of isolated asialo-GM1-positive cells showed a uniform lymphoblastoid morphology with large cytoplasmic to nuclear ratios and prominent electron dense cytoplasmic granules characteristic of large granular lymphocytes. In support of the NK nature of such cultured cells was the ability of anti-asialo-GM1 and complement to abrogate, and of interferon to augment, target cell lysis. Isolated cell lines also showed target selectivity similar to NK cells. The implications of the studies on further analysis of the nature of NK precursors is discussed.

Animals↗