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P Badenoch-Jones

Publications and source records attributed to P Badenoch-Jones.

At least 19 recordsLinked to original sources
PubMed1987

Lectin-binding characteristics of related high- and low-metastatic rat mammary adenocarcinoma cell lines.

Lectin-binding characteristics of a previously described highly metastatic variant (clone 4), derived in vivo from a poorly metastatic rat mammary adenocarcinoma (DMBA-8), have been investigated. of the lectins studied clone 4 cells, unlike the parent cells, bound Ulex europaeus agglutinin (UEA-1; specificity alpha-L-fucose) and peanut agglutinin (PNA; specificity D-galactose). These differences may be related to the greatly enhanced ability of clone 4 cells to form lung foci after intravenous injection. After neuraminidase treatment the differential binding of PNA, as shown by flow cytofluorography, was abrogated whereas that of UEA was unchanged. After separation by SDS-PAGE, four proteins in total cell extracts of clone 4 cells bound 125I-UEA applied to the gels. These had subunit molecular weights greater than 100,000 daltons and were also found in cellular extracts of another highly metastatic rat mammary adenocarcinoma (MAT 13762-B), but were missing from DMBA-8 cell extracts. In clone 4 and MAT 13762-B cells exogenous 3H-fucose was mainly incorporated into four fucoproteins of similar molecular weights to those which bound 125I-UEA. DMBA-8 cells, which incorporated slightly less exogenous fucose, showed a different pattern of fucoprotein labelling, which would seem to explain why DMBA-8 cells failed to bind UEA. Differences in cell surface protein iodination patterns were also noted between DMBA-8 and clone 4 cells.

Adenocarcinoma↗
PubMed1986

Cellular and secreted tumor plasminogen activator: the effects of NaCl.

Plasminogen activator, secreted by metastatic tumor cells, was strongly inhibited in buffer or tissue culture medium containing physiological concentrations of NaCl. Intact cells, however, expressed strong activity under similar conditions. Thus, if plasminogen activator is involved in invasion and metastasis, the cellular activity, acting as an ectoenzyme, may be more important than secreted enzyme under physiological conditions.

Animals↗
PubMed1986

Purification and characterization of an inhibitor of plasminogen activator released by rat mammary adenocarcinoma cells.

An inhibitor of plasminogen activator (PA) secreted by a tumorigenic, but non-metastatic, rat mammary adenocarcinoma cell line has been purified to apparent homogeneity and characterized. It strongly inhibited human urokinase, but was 100 times less potent in inhibiting bovine trypsin and had no effect on plasmin or thrombin. A secreted, urokinase-type PA (Mr 48 000) and a cell-associated PA from a metastatic rat adenocarcinoma cell line were also strongly inhibited. In contrast, a tissue-type PA (Mr 66 000), secreted by human melanoma cells, was only slightly inhibited. Purified inhibitor showed a band of Mr 66 000 in sodium dodecyl sulphate/polyacrylamide gel electrophoresis and an isoelectric point of 4.5 after chromatofocusing. The inhibition of human urokinase was non-competitive.

Adenocarcinoma↗
PubMed1986

Enhanced plasminogen activator production by highly metastatic variant cell lines of a rat mammary adenocarcinoma.

Highly metastatic cell lines have been isolated from lung foci formed by the intravenous injection of large numbers (5 X 10(6)) of cells of a poorly metastatic rat mammary adenocarcinoma (DMBA-8). The metastatic variant lines were phenotypically different and, unlike the parent line, produced high levels of plasminogen activator (PA) separable into three major bands (MW 30,000, 48,000 and 83,000) on SDS-PAGE. It is suggested that PA may play a role in the enhanced metastatic ability of these cells. Using parallel DMBA-8 clones the rate of generation of the metastatic variant cells was estimated, by fluctuation analysis, to be approximately 1.85 X 10(-6) per cell generation.

Adenocarcinoma↗
PubMed1985

Studies on rat mammary adenocarcinomas: a model for metastasis.

Studies carried out by the authors on the rat mammary adenocarcinoma cell lines MAT 13762 and DMBA-8 are summarized. A series of variants and somatic cell hybrids have been prepared and partially characterized in terms of phenotypic properties which may correlate with metastatic potential. These include measurement of in vitro migration, lectin binding properties, expression of procoagulant activity and shedding of cell surface components. Particular emphasis has been placed on the production of enzymically-active plasminogen activator, as this seems to correlate with the ability of cells to metastasize. The finding has also been made that several of the cell types studied produce, in vitro, an inhibitor of plasminogen activator which may influence the metastatic behaviour of tumor cells. Results obtained are discussed in the context of the usefulness of these tumor systems for the study of spontaneous and experimental metastasis and the factors involved in these processes. Preliminary results of cloning and fluctuation analysis of metastatic potential together with discussion of the role of the metastatic heterogeneity and the formation of metastatic variants by mutation events are included.

Adenocarcinoma↗
PubMed1985

Characterisation of rat tumour cell hybrids: procoagulant and fibrinolytic activities.

The formation of lung colonies after i.v. injection of highly metastatic rat mammary adenocarcinoma cells (MAT 13762) was greatly reduced by concurrent treatment of rats with heparin. The procoagulant activity (PCA) of these cells, and of a non-metastatic adenocarcinoma (DMBA-8) has therefore been measured. These have been compared with PCA expressed by MAT 13762 cell derivatives including a non-metastatic hybrid clone (MAT 13762 X DMBA-8), its metastatic revertant, and clones selected in vivo from lung metastases. Potent PCA was expressed on intact MAT 13762 cells and in their spent culture media, the latter being sedimentable and associated with shed membrane vesicles. Cell-derived PCA, unlike thromboplastin, was equally effective in factor VII-deficient and normal bovine plasma. There were, however, no major differences in the expression of PCA (either cell-associated or shed) between the metastatic and non-metastatic cell types studied. Plasminogen activator (PA) production by these cells has also been measured. The results are discussed in the context of the possible role of fibrin formation and fibrinolysis in the metastatic process.

Adenocarcinoma↗
PubMed1985

An inhibitor of plasminogen activator produced by tumour cell fusion hybrids.

Expression of plasminogen activator (PA) activity may be an important factor in the ability of tumour cells to metastasize; however, not all metastatic cells produce detectable PA activity. Conditioned culture media from revertant metastatic clones of cells derived by fusion of metastatic and non-metastatic rat mammary adenocarcinoma cells were found to contain a potent inhibitor of PA. This inhibited thrombin, human urokinase (UK) and tumour-derived PA, but not plasmin or trypsin. Inhibition was still obtained after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE) of mixtures of PA and inhibitor, followed by development of PA activity on fibrin overlays. The PA inhibitor eluted from Sephadex G-200 over a broad M.wt. range (35,000-80,000) and was inactivated by heating to 70 degrees for 30 min. The appearance of inhibitory activity in the culture media was time-dependent and could be reduced by incubation of cells with cycloheximide. Because of these findings, the possible presence of inhibitors should be considered in investigations into the role of PA in the metastatic process.

Adenocarcinoma↗
PubMed1984

Studies on migration inhibitory factors of non-lymphoid origin.

A large number of mouse fibrosarcoma and adult guinea pig fibroblast cultures were examined for their ability to produce migration inhibitory activity. In most cases culture supernatants were found to inhibit macrophage migration, in a dose-dependent manner. Toxicity of the tested material could be excluded by: a) experiments using colchicine as a stimulator of macrophage migration and, b) examination of the effect of test materials on macrophage monolayer cultures. Additionally, migration inhibitory activity was found in fibroblast, but not fibrosarcoma frozen and thawed extracts. Furthermore, incubation of cells with puromycin could only inhibit production by fibrosarcoma, thus suggesting that the fibroblast activity was due to preformed cellular constituents. Fractionation of concentrated culture supernatants by Sephadex G-200 gel filtration showed that the activity derived from fibrosarcoma cells could be eluted in a narrow molecular weight fraction (18,000-22,500), whereas the fibroblast activity was heterogenously distributed over a wide range. Migration inhibitory activity in fibroblast extracts was mainly associated with higher molecular weight material. Differences could be demonstrated between these activities and lymphocyte migration inhibitory factor, including inhibition by methyl-pentoses and the presence of macrophage aggregating activity.

Animals↗
PubMed1984

Effect of an iron-chelating agent on lymphocyte proliferation.

The effect of the iron-chelating agent desferrioxamine on lymphocyte proliferation has been studied. Desferrioxamine at concentrations of 15 microM totally inhibited the proliferation of Concanavalin A-stimulated lymphocytes, whereas iron-saturated desferrioxamine was ineffective. Other metal salts, however, had little or no effect on the inhibition induced by this drug. Desferrioxamine was more effective at suppressing proliferation of T lymphocytes than B lymphocytes and additionally suppressed mixed lymphocyte cultures and the generation of cytotoxic T cells.

Animals↗
PubMed1984

Spontaneous capillary tube migration of metastatic rat mammary adenocarcinoma cells.

The spontaneous capillary tube migration of metastatic MAT 13762 rat mammary adenocarcinoma cells has been measured and compared with that of a non-metastatic variant, TGR. MAT 13762 cells migrated to a greater extent in the presence than in the absence of serum, and in both cases migration areas were considerably greater than for TGR cells. Different clones of hybrids, formed by fusing metastatic and non-metastatic variants, showed migration areas ranging from those of the metastatic to those of the non-metastatic parent cells. Despite their differing migrations, all of these clones were either non or only slightly metastatic. Treatment of TGR cells with trypsin enhanced their migration to that of MAT 13762 cells, whereas trypsin-treated MAT 13762 cells showed a slightly decreased migration. Although MAT 13762 cells, unlike TGR cells, produced large amounts of plasminogen activator (PA), no evidence was obtained for the direct involvement of PA in the high migration rate of MAT 13762 cells.

Adenocarcinoma↗
PubMed1983

The use of cell fusion to analyse factors involved in tumour cell metastasis.

Cell fusion has been used to study some of the factors involved in the process of metastasis. Highly metastatic rat mammary adenocarcinoma cells were fused with various non-metastatic cells and the hybrid clones isolated. These were then tested for their metastatic potential either by injecting the cells intravenously and measuring lung colony formation or by injecting the cells subcutaneously and measuring their ability to form lymphatic metastases. With most hybrid clones tested, the metastatic potential was either inhibited or greatly suppressed; thus this phenotype is a recessive characteristic. We also monitored the hybrid cells' ability to produce plasminogen activator (PA) a serine proteinase thought to be involved in the formation of metastatic lung foci. Whilst the highly metastatic parent cells produced large quantities of PA, none could be detected in the non-metastatic lines. Although the hybrid clones produced little PA activity this could not be correlated with their decreased metastatic potential in that one clone, after extensive in vitro culture, reverted to a more metastatic line without a concomitant increase in PA activity. The suppressed PA activity may be due to the presence of an inhibitor that is spontaneously produced by the hybrid cells.

Adenocarcinoma↗
PubMed1983

Diagnosis of penicillin allergy. An evaluation of the leucocyte aggregation test in man.

A study was made to establish the value of the leucocyte aggregation test (LAT) in drug allergy using penicillin antigen. The antigen-induced human peripheral blood leucocyte aggregation was measured quantitatively. The results obtained have been compared with the leucocyte migration inhibition test (LMIT) in patients with or without delayed penicillin allergy. Among forty-four penicillin-allergic subjects and thirty-six control subjects, LAT was found positive in respectively 70.5 and 30.5% (P less than 0.001) whereas LMIT was found positive in respectively 56.8 and 50% of the patients. These results were confirmed by multiple correspondence analysis (MCA), using a computer. Furthermore, this method, enables a more comprehensive and reliable interpretation of the tests, by the help of various quantitative and qualitative criteria. It is concluded that LAT shows more discrimination than the LMIT in distinguishing a penicillin-allergic population from a non-allergic one. In addition, LAT offers great technical advantages over the LMIT for the diagnosis of drug allergy.

Adult↗
PubMed1983

Phorbol myristate acetate-induced macrophage aggregation.

Phorbol myristate acetate (PMA) at nanomole concentrations induces a rapid aggregation of guinea pig macrophages. This aggregation is dependent on extracellular Mg2+ (but not Ca2+) for its development. Additionally, it is inhibited by some agents which also inhibit aggregation induced by lymphokines and the ionophore A23187. Although the mechanism of aggregation has not been determined, it does not appear to be related to either arachidonic acid metabolites or products of the respiratory burst. In this respect, it resembles the PMA-induced aggregation of neutrophils.

Animals↗
PubMed1982

Comparison of mycobacterial granulomas in guinea-pig lymph nodes.

A study was made of mycobacterial-induced granulomas in guinea-pig lymph nodes. Live BCG (Pasteur) induced a granuloma containing epithelioid cells while Cobalt irradiated Mycobacterium leprae induced a granuloma comprised of phagocytic macrophages. The granulomas were quantitated by measurement of lymph node weight and the areas of infiltration in histological sections. The time course of granuloma formation induced by Co-irradiated M. leprae was veary different from the time course of the granuloma formation induced by BCG. Collagen synthesis assessed by incorporation of 14C-proline into collagenase sensitive protein was greater in lymph nodes draining the site of injection of Co-irradiated BCG than those draining the site of injection of Co-irradiated M. leprae during the first 10 weeks. Collagen synthesis was delayed in the nodes from animals injected with live BCG for at least 10 weeks. Single cell suspensions of draining lymph nodes containing granulomas consisted of lymphocytes and large cells (epithelioid cells and macrophages). A high proportion of the large cells were found to be non-adherent in the live BCG-induced epithelioid cell granuloma. In contrast, M. leprae-induced granulomas contained a high percentage of adherent large cells. In both the granulomas, the majority of large cells were esterase positive and showed the presence of fibronectin. Most of the large cells in the granulomas did not carry receptors for the Fc component of IgG or the C3 component of complement and did not exhibit peroxidase activity.

Animals↗
PubMed1982

Lymphokine-induced macrophage aggregation: studies on the involvement of Mg2+.

The divalent cation requirements of lymphokine (LK)-induced macrophage aggregation have been investigated using a quantitative assay. It has been shown that LK-induced aggregation is dependent on exogenous Mg2+ but not Ca2+. By contrast, aggregation induced ty the ionophore A23187 is dependent on exogenous Ca2+ and Mg2+. Furthermore, exogenous Mg2+, at 0.5-5.0 mmol, both mimics the aggregation effects of LK and stimulates LK-induced aggregation. Additionally, both chlorpromazine and trifluoperazine inhibited aggregation indiced by LK, A23187, and exogenous Mg2+. Similarly, prostaglandin (PG)E2 inhibited, and indomethacin (10 micro M) stimulated, aggregation induced by these three agents. These results are discussed in the context of the mode of action of macrophage aggregating factor (MAgF).

Animals↗
PubMed1982

Macrophage aggregation factor: some properties.

The lymphokine activity, macrophage aggregation factor (MAgF) has been investigated further. Activity was consistently found in 24 hr test, but not control, spleen cell culture supernatants. This was higher after dialysis against water, than in the original culture supernatants. MAgF was heat-stable, inactivated by alpha-chymotrypsin, partially inactivated by trypsin and not affected by neuraminidase. Activity was recovered from the supernatant after protein precipitation with 1 M perchloric acid, leading to a modest purification. Activity was only marginally reduced after treatment with periodate, and was not absorbed by Concanavalin A-Sepharose. Polyacrylamide gel electrophoresis showed that MAgF migrated cathodally to albumin. Aggregation, as measured in a batch centrifugation assay, was an expression both of cell-substrate and cell--cell adhesion.

Animals↗
PubMed1982

Lymphokine-induced neutrophil aggregation.

Lymphokine (LK) preparations, containing macrophage aggregating activity, also aggregated purified neutrophils, but not blood mononuclear cells or erythrocytes. Additionally, aggregation of blood leucocytes (containing 50%-70% neutrophils), from sensitized guinea-pigs, could be induced by culture of these cells with antigen, in a direct aggregation assay. Optimal measurement of direct aggregation was at 6 hr, whereas soluble neutrophil aggregating activity was produced by blood mononuclear cell cultures continuously for at least 24 hr. Sephadex fractionation showed that although macrophage and neutrophil aggregating activity was associated with molecules of mean mol. wt 50,000, neutrophils were also aggregated by material in the 90,000-225,000 mol. wt range. LK-induced neutrophil aggregation, like macrophage aggregation, was inhibited by colchicine, prostaglandin E2, chlorpromazine and the glycolytic inhibitors 2-deoxyglucose and iodoacetate.

Animals↗