Search PubMed⌕ Search

Biomedical subjects

M A Moore

Publications and source records attributed to M A Moore.

At least 307 records · Page 17Linked to original sources
PubMed1986

Human pluripotent hemopoietic colony stimulating factor: activities on human and murine cells.

Human pluripotent colony stimulating factor (Pluripoietin) was shown to act synergistically with human pluripotent alpha-like colony-stimulating activity (Pluripoietin-alpha) supporting the proliferation and differentiation of human CFU-GM progenitor cells in vitro, increasing colony size and numbers. In addition, Pluripoietin enhanced cytotoxic activity of mature human neutrophil granulocytes in an antibody-dependent cellular cytotoxicity assay. Biological activities of Pluripoietin known so far suggest great potentials for clinical use. Preclinical in vivo studies of Pluripoietin in different disease situations may be feasible in mice, because Pluripoietin is active on granulocyte precursors and on a variety of other murine cells.

Animals↗
PubMed1986

Pluripoietin alpha: a second human hematopoietic colony-stimulating factor produced by the human bladder carcinoma cell line 5637.

We have identified a factor constitutively produced by the human bladder carcinoma cell line 5637, which has the following capacities: to induce the differentiation of the human promyelocytic leukemic cell line HL-60; to induce the expression of chemotactic peptide receptors in leukemic cells as well as in normal peripheral blood granulocytes; to function as a chemoattractant for neutrophils as well as, under certain conditions, inhibiting their migration; to support the growth of eosinophil and granulocyte/macrophage progenitors, which is maximal when scored at day 14; and to support the growth of human mixed pluripotent progenitors and erythroid bursts from normal human bone marrow. This factor has a molecular size of 32 kDa by gel filtration and 16.5 kDa by NaDodSO4/PAGE. We have termed this factor pluripoietin alpha.

Bone Marrow Cells↗
PubMed1986

Modifying influence of dehydroepiandrosterone on the development of dihydroxy-di-n-propylnitrosamine-initiated lesions in the thyroid, lung and liver of F344 rats.

Following initial treatment of F344 rats with dihydroxy-di-n-propylnitrosamine, exposure to dehydroepiandrosterone (DHEA) administered in the diet at a concentration of 0.6% brought about significant decrease in weight gain, independent of food consumption, and inhibited the development of thyroid tumors and hepatocyte-altered enzyme foci. In addition to inducing a diffuse increase in glucose-6-phosphatase dehydrogenase (G6PD) and gammaglutamyl transpeptidase in the liver. DHEA treatment was associated with development of small numbers of basophilic hepatocellular foci which differed markedly in enzyme phenotype from the clear cell (glycogen storing) lesions predominating in the carcinogen-treated animals maintained on basal diet. The results are consistent with the concept that DHEA-modification of neoplastic development, as reported earlier in a number of different organs and here in the liver and thyroid, may be in some way partly mediated by changed expression of the key enzyme of the pentose phosphate pathway, G6PD, and related metabolic systems. Heterogeneity in the quality of initiated hepatocytes with regard to capacity for inhibition or promotion indicated by the present data point to the existence of more than one pathway to tumour development in the rat liver.

Animals↗
PubMed1986

Dehydrogenase histochemistry of N-ethyl-N-hydroxyethylnitrosamine-induced focal liver lesions in the rat--increase in NADPH-generating capacity.

Histochemical investigation of altered dehydrogenase enzyme activity in putative pre-neoplastic lesions induced by N-ethyl-N-hydroxyethylnitrosamine in the rat liver revealed a clear increase in NADPH-generating potential, most markedly within nodules. Glucose-6-phosphate dehydrogenase, malic enzyme and isocitrate dehydrogenase all showed elevated activity while the activities of succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase were reduced. Alteration in enzyme activity suggested an adaptive shift in metabolism, the increase in levels of enzymes responsible for generation of reduced NADP possibly conferring enhanced drug detoxifying or cholesterogenic potential.

Animals↗
PubMed1986

Comparative histochemical investigation of the glutathione S-transferase placental form and gamma-glutamyltranspeptidase during N-nitrosobis(2-hydroxypropyl)amine-induced pancreatic carcinogenesis in hamsters.

Immunohistochemical staining using anti-rat glutathione S-transferase placental form (GST-P) rabbit antibody and enzyme histochemical staining for gamma-glutamyltranspeptidase (gamma-GT) were investigated in putative preneoplastic lesions and adenocarcinomas in the pancreas of Syrian golden hamsters treated with N-nitrosobis(2-hydroxypropyl)amine (BHP). Areas with ductular proliferation, ductal hyperplasia, and intraductal carcinoma were strongly positive for GST-P binding and negative for gamma-GT. Cystic adenoma, microcarcinoma, and carcinomas were constantly positively stained by GST-P and partially positive for gamma-GT. GST-P appears to be useful as a positive marker for putative preneoplastic lesions in pancreatic carcinogenesis. Since normal acinar cells are strongly positive for gamma-GT, the findings might suggest that acinar cells contribute to the development of cystic adenoma, microcarcinoma, and carcinomas.

Animals↗
PubMed1986

Influence of dehydroepiandrosterone, diaminopropane and butylated hydroxyanisole treatment during the induction phase of rat liver nodular lesions in a short-term system.

The effects of concomitant treatment with dehydroepiandrosterone, an inhibitor of glucose-6-phosphate dehydrogenase (G6PD), diaminopropane (DAP), an inhibitor of ornithine decarboxylase or the microsomal drug detoxifying enzyme inducer butylated hydroxyanisole (BHA) during the induction phase of rat liver nodular lesion development were investigated. Clear reductions in both number and size of foci and nodules as assayed quantitatively with the aid of marker enzymes G6PD, glutathione S-transferase P form or gamma-glutamyl transpeptidase were established for treatment with either DHEA or BHA. DAP in contrast did not exert influence on the number of lesions, but brought about a significant reduction in size. The quantitative data taken together with the finding that increased labelling of tritiated thymidine occurred in extrafocal hepatocyte populations in BHA-treated animals, give direct support to the view that alteration in enzyme phenotype within putative pre-neoplastic lesions plays a central role in their generation with this short-term model. In particular, a physiological adaptive significance of G6PD elevation is suggested.

Animals↗
PubMed1986

Immunohistochemically demonstrated suppressed expression of tryptophan oxygenase, a marker for liver differentiation, within putative preneoplastic rat liver lesions.

The behaviour of rat liver putative preneoplastic lesions with respect to the enzyme tryptophan oxygenase (TO), a liver-specific differentiation marker, and a possible growth-related marker, glucose-6-phosphate dehydrogenase (G6PD) was investigated during and after their induction by diethylnitrosamine initiation and subsequent 'selection pressure'. Using specific antibodies to rat liver TO and G6PD and the avidin-biotin complex method for immunohistochemical staining it was demonstrated that all of the nodular lesions showing increased expression of G6PD during the induction phase were also negative or deficient in TO enzyme protein. With the onset of 'phenotypic instability' or loss of marker enzymes, a gradual return to normal expression of TO activity was evident. Administration of dexamethasone and L-tryptophan 11 weeks after cessation of carcinogen treatment allowed differentiation between morphologically altered, apparently persisting lesions in which no, or little, enzyme induction was apparent and instable lesions showing a strong increase in levels of TO protein. Thus, persisting nodular lesions share a common lack of response to normal homeostatic physiological control.

Animals↗
PubMed1986

Immunohistochemically demonstrated glucose-6-phosphate dehydrogenase, gamma-glutamyl transpeptidase, ornithine decarboxylase and glutathione S-transferase enzymes: absence of direct correlation with cell proliferation in rat liver putative pre-neoplastic lesions.

Comparison of binding of specific antibodies to glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl transpeptidase (GT), ornithine decarboxylase (ODC) and the glutathione S-transferase B and P forms (GST-B, P) was made in putative pre-neoplastic lesions during their induction and subsequent development using the Solt-Farber model. The earliest focal hepatocellular lesions were evident as single, or small groups of GST-P-positive hepatocytes in tissue taken at partial hepatectomy 3 weeks after initial application of diethylnitrosamine (DEN). With the onset of proliferation and increase in size the majority of the lesions expressed elevated levels of all of the enzyme proteins investigated with a correlation between strength of binding and morphology being apparent. While [3H]thymidine incorporation was limited during the period of acetylaminofluorene administration, to the hepatocytes demonstrating altered enzyme phenotype no direct link between proliferation rate within individual foci and level of G6PD expression could be discerned. Similarly, the elevated level of labelling characteristic of persisting nodular lesions at later stages also did not correlate with degree of G6PD alteration in individual cells. The results indicate that while changed enzyme phenotype appears as an ordered pattern suggestive of physiological adaptive nature, the degree of alteration is not directly related to proliferation kinetics under the rapid induction conditions characteristic of the Solt-Farber model.

Animals↗
PubMed1986

Immunohistochemical demonstration of increased glucose-6-phosphate dehydrogenase in preneoplastic and neoplastic lesions induced by propylnitrosamines in F344 rats and Syrian hamsters.

Changes in the level of expression of glucose-6-phosphate dehydrogenase (G6PD) within propyl nitrosamine-induced preneoplastic and neoplastic lesions in F344 rats and Syrian golden hamsters were investigated using an immunohistochemical approach. Previously demonstrated increases in G6PD activity in rat liver and hamster pancreatic foci of altered cells were revealed as being due to elevation in the quantity of enzyme protein, suggesting an underlying change in gene expression. Furthermore, strong positive binding of G6PD antibody in thyroid, lung, urinary bladder and kidney lesions indicated that increase in this enzyme protein might be a common marker for neoplastic alteration, regardless of organ. While the function of elevated G6PD may be related to growth requirements, the finding that preneoplastic lesions in some cases bind more strongly than more malignant populations suggests additional involvement of the enzyme in other biochemical pathway(s) relevant to tumorigenesis.

Animals↗
PubMed1986

Enhancement of the proliferation of human marrow erythroid (BFU-E) progenitor cells by prostaglandin E requires the participation of OKT8-positive T lymphocytes and is associated with the density expression of major histocompatibility complex class II antigens on BFU-E.

The relationship between major histocompatibility complex class II antigens (MHC class II, eg, HLA-DR, Ia), T lymphocytes, and the enhancement of erythroid colony formation from BFU-E by prostaglandin E was analyzed using normal bone marrow cells. In primary methylcellulose culture, the addition of prostaglandin E1 (PGE1) to unseparated buffy coat, low-density, or nonadherent low-density (NAL) marrow cells resulted in an enhancement of the total number of erythroid (BFU-E) colonies observed. Treatment of bone marrow cells with a monoclonal antihuman MHC class II antibody plus complement (C') resulted in a reduction of the total number of colonies by approximately 50% and abrogation of the enhancing effect of PGE1. Analysis of accessory cell requirements by depletion of both adherent cells and sheep erythrocyte rosetting lymphocytes (E+ cells) and reconstitution using C' or anti-MHC class II antibody plus C'-treated T cell-depleted NAL (NALT-) marrow cells and E+ cell populations treated with C' or anti-MHC class II antibody plus C' demonstrated a requirement for MHC class II antigen-T cells, but not adherent cells, and a requirement for MHC class II antigen + BFU-E in order to observe the enhancing effect of PGE1 on erythroid colony formation. Positive selection of BFU-E in NALT- bone marrow expressing differing density distributions of MHC class II antigens was accomplished with monoclonal anti-MHC class II antibodies and sorting with a fluorescence-activated cell sorter (FACS). Addition of E+ cells to the different populations of MHC class II antigen+ NALT- cells demonstrated that the PGE-enhancing effects on erythroid colony formation were directly related to increasing density distributions of MHC class II antigens on BFU-E. Colony formation by BFU-E expressing a low density distribution of MHC class II antigens or having no detectable MHC class II antigens, as determined by FACS analysis, was not enhanced by PGE1 in the presence of MHC class II antigen-positive or -negative T cells.

Alprostadil↗
PubMed1986

Monocyte-conditioned medium and interleukin 1 induce granulocyte-macrophage colony-stimulating factor production in the adherent cell layer of murine bone marrow cultures.

We have studied how production of colony-stimulating factors (CSF) can be induced in murine long-term bone marrow cultures (LTBMC). We found that the adherent cells, but not the nonadherent cells, of LTBMC synthesized and secreted large amounts of CSF upon stimulation with monocyte-conditioned medium (MCM) from the early phase of monocyte culturing. This CSF induced both granulocyte- and macrophage-containing colonies. Interleukin 1 (IL-1) also induced CSF production by the adherent cells, although not to the same extent as MCM. Medium conditioned by E-rosette-positive lymphocytes could not substitute for MCM. CSF production varied in long-term bone marrow cultures less than two weeks old, but thereafter the amount of CSF obtained was relatively independent of the age of the cultures (2-26 weeks). No correlation was found between the content of granulocyte-macrophage colony-forming cells (GM-CFC) in the nonadherent cell fraction of LTBMC and the ability of the adherent cell layer to produce CSF. These results suggest a two-stage process for CSF synthesis. Monocytes produce a factor(s) that, in a second step, leads to bioassayable levels of CSF in the supernatant of adherent cells in LTBMC.

Animals↗
PubMed1985

Biological activities of a human pluripotent hemopoietic colony stimulating factor on normal and leukemic cells.

We studied the biological effects of pluripoietin, a human pluripotent hemopoietic colony-stimulating factor (CSF) purified from the 5637 bladder carcinoma cell line. We found that this human CSF appears to be a unique hemopoietic growth factor, differing from interleukin 3 (IL-3) by virtue of its leukemia differentiating activity in mouse and man, and from mouse granulocyte CSF, which does have differentiation-inducing activity, but lacks pluripoietic activity. In addition, differences from IL-3 were observed in cross-species activity on normal and leukemic cells.

Animals↗
PubMed1985

A nitrocellulose-filter assay for the binary complex of 5-fluorodeoxyuridylate and Lactobacillus casei thymidylate synthetase.

The interaction of 5-fluorodeoxyuridylate (FdUMP) with thymidylate synthetase to form a binary complex has been widely reported, yet previous attempts to detect this complex by nitrocellulose filtration have failed. In contrast, a nitrocellulose-filter-binding assay utilizing [6-3H]FdUMP which measures the interaction of the enzyme with the nucleotide is reported. Extensive washing of the nitrocellulose-filtered complex between FdUMP and the enzyme resulted in no loss of bound ligand. Following denaturation with trichloroacetic acid, intact complex was detected by nitrocellulose filtration. No binding was observed between 5-fluorodeoxyuridine and the enzyme or between FdUMP and the N-ethylmaleimide-modified enzyme. As measured by the nitrocellulose filtration method, at least a 600-fold excess of FdUMP to enzyme was required to achieve saturation. The stoichiometry of FdUMP bound to the enzyme detected at saturation was 0.5-0.6 for native samples. When identical samples were subjected to denaturation prior to filtration, the stoichiometry of nucleotide binding was 0.3-0.4.

Chemical Phenomena↗