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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 433 records · Page 24Linked to original sources
PubMed1982

Small-scale isolation and characterisation of human peripheral blood monocytes.

A technique is described for the isolation and characterisation of monocytes from 15 ml of human peripheral blood. After density gradient centrifugation over Ficoll-Hypaque, monocytes are purified further by substrate adherence under carefully defined conditions. The use of a simple microwell slide system permits the production of multiple small-scale monolayer populations which can be characterised further in terms of their histochemical reactivity (combined stain for chloroacetate and non-specific esterases); endocytic capacity (latex particles); Fc (sensitised ox erythrocytes) and C3 (serum-coated yeast) receptor expression; and precursor maturation potential (7-day cultures). Evidence of considerable cellular heterogeneity is presented.

Cell Separation↗
PubMed1982

Susceptibility of human leukaemias to cell-mediated cytotoxicity by interferon-treated allogeneic lymphocytes.

Twenty-two human leukaemias, comprising acute phase leucocytes from 13 acute myeloid and nine lymphoid leukaemias, were tested for susceptibility to spontaneous cell-mediated cytotoxicity (CMC) by untreated lymphocytes and lymphocytes treated for 18 h with 250 IU lymphoblastoid (Namalva) interferon (IFN-alpha). IFN-amplified killing (IAK) by lymphocytes from 24 normal lymphocyte donors was checked on the K562 erythroleukaemia cell line, for comparison with IAK on fresh leukaemias. Nine leukaemias were tested with lymphocytes from three donors, nine with lymphocytes from six donors, three with lymphocytes from nine donors, and one with lymphocytes from 11 donors. Some degree of susceptibility to IAK was found in five acute myeloid and five lymphoid leukaemias, which was markedly dependent upon the source of the effector lymphocytes and did not correlate with the degree of IAK on K562. The 12 other leukaemias were virtually resistant to IAK. The results emphasize the variability in the capacity of IFN-treated lymphocytes to lyse leukaemias that have not been adapted to tissue culture. The basis of effector recognition of cell line and fresh tumour targets is discussed.

Cell Line↗
PubMed1982

Mitogen responsiveness and inhibitory activity of mesenteric lymph node cells. Conditioned medium containing T cell growth factor reverses suppressor function.

Blood-, lymph node-, and tumour-infiltrating lymphocytes (PBL, LNC, and TIL, respectively) from patients with colonic neoplasms were tested for responsiveness to phytohaemagglutinin (PHA). All populations responded, with LNC and PBL showing comparable reactivities while TIL were less reactive as assessed by incorporation of 3H-thymidine. Increased mitogen responsiveness was observed for T cells enriched by SRBC rosette formation or passage through nylon columns. Mitomycin C-treated LNC and TIL inhibited PHA induced 3H-thymidine incorporation of admixed autologous PBL, suggesting the presence of suppressor cells. Suppressor activity resided primarily in the SRBC rosetting population and was dose-dependent, with increasing numbers of LNC giving greater diminution of PHA response. Suppression by LNC was apparent only when they were added to PBL responders within 6 h of the initiation of stimulation assays, in common with the effects of Concanavalin A (Con A)-induced suppressors on PBL phytomitogen responsiveness. Con A-induced and LNC-suppressor activity could be reversed by addition of lymphocyte-conditioned medium (CM) containing T cell growth factor (TCGF; interleukin IL-2). These data provide further evidence that the suppressor phenomena observed in this system are a function of activated T cells present both in drainage lymph nodes and at the tumour site.

Cells, Cultured↗
PubMed1982

Biochemical correlation of glycogen content and activity of some enzymes of carbohydrate metabolism in rat liver during early stages of carcinogenesis.

The livers of rats treated for 12 weeks with N-nitrosomorpholine (80 mg/1 drinking water) were investigated on the day of carcinogen withdrawal (12 + 0 weeks) and 8 weeks after cessation of treatment (12 + 8 weeks). The glycogen content in relation to the DNA and protein content of the liver and the activities of glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, and glucose-6-phosphate dehydrogenase were determined in the liver homogenates. The glycogen content of the livers was slightly elevated at both times investigated. Phosphorylase and synthetase activities showed no clear alterations in livers of treated animals as compared with controls. Glucose-6-phosphatase activity was significantly reduced at 12 + 0 weeks and returned to normal values at 12 + 8 weeks. The activity of glucose-6-phosphate dehydrogenase was unchanged at 12 + 0 weeks, but exhibited a significant increase at 12 + 8 weeks. Polyacrylamide gel electrophoresis with staining of the gels by an assay specific for the glucose-6-phosphate-dehydrogenase-catalysed reaction revealed the same pattern of active bands in treated and untreated animals but with higher activities in two bands originating from extracts of nitrosomorpholine-treated livers.

Animals↗
PubMed1982

Human bronchoalveolar macrophage cytotoxicity for cultured human lung-tumour cells.

Human bronchoalveolar macrophages were separated from other free lung cells by density sedimentation on Percoll gradients. They were then tested for cytotoxicity against the human lung adenocarcinoma cell line A549, using a Selenomethionine-75 post-labelling assay. The cytotoxicity of the macrophages increased as the effector:target cell ratio was increased, approaching 100% at 20:1. There was no significant difference in the cytotoxicity of macrophages isolated from the lungs of bronchial-carcinoma or non-carcinoma patients. The highly cytotoxic nature of the macrophages was not due to selection of a more potent cytotoxic subpopulation of macrophages on the Percoll gradient, nor to a generally elevated activation of the macrophages due to the pathological conditions in the patients' lungs. An attempt to determine whether low concentrations of macrophages could potentiate target-cell growth proved negative. Cytotoxicity of macrophages for cultured lung target cells was not restricted to A549 cells and is not in accordance with the view that defective bronchoalveolar macrophage cytotoxicity contributes to the emergence of bronchial neoplasia.

Adenocarcinoma↗
PubMed1982

Monoclonal antibodies against two human lung carcinoma cell lines.

Monoclonal antibodies against 2 human lung carcinoma cell lines (E14 and BEN) were prepared by production and cloning of somatic cell hybrids between the murine myeloma NS1, and spleens from E14- and BEN-immune BALB/c mice. Approximately 2000 hybrid culture supernatants were screened for antibody simultaneously against the immunizing cell line and lung fibroblasts (573 Lu) using a radiolabelled Protein A binding assay. Although the vast majority secreted antibodies which recognized species-specific antigens, a few supernatants showed marked differential reactivity against E14 or BEN. These were cloned and subsequently tested against a panel of up to 25 human cell lines originating from different neoplastic and non-neoplastic tissues. Two anti-E14 clones (3E19.8 and 4EAB3.7) displayed preferential activity against lung cancer cell lines, but a low level of reactivity was also detectable with cell lines of different tissue provenance. The antibodies of 3 anti-BEN clones (7B3.5, 7B5.4, 7B17.7) likewise recognized antigens present to a higher density on lung cancer cell lines but were also reactive (to a variable extent for the different clones) with a diversity of other tumour cell lines. The antibodies of 2 further clones were exceptional in so far as one (7BC9.1) reacted only with BEN and WIDR (colorectal cancer) cells, while another (7B24.4) reacted, with apparent exclusivity, against BEN cells. With the exception of the latter, the distinction in antigen expression between many of the cell lines was quantitative rather than qualitative and the emergent picture is one of random expression of individual determinants on several disparate types of cancer cells, rather than restriction to cells of a given morphological type or histogenic derivation.

Antibodies, Monoclonal↗
PubMed1982

Role of autologous lymphocyte cytotoxicity in colonic neoplasia.

The T-lymphocyte mediated killing of autologous carcinoma colon cells was investigated. There was no change in the incidence of activity with advanced disease, age, or nutritional status of the patient and no difference could be demonstrated in lymphocytes extracted from blood, draining lymph nodes, or the tumour itself. Nevertheless. T-lymphocyte activity did appear to be specific for the patients's own tumour, as it was rarely observed with allogeneic tumours. There was also no correlation with lymphocyte natural killer activity. The in vitro studies demonstrated patient specific T-lymphocyte activity in 23 of 47 patients with carcinoma of the colon, but the results do not correlate with clinical and pathological findings.

Adult↗
PubMed1982

Heterogeneity of circulating immune complexes in chronic lung diseases.

Circulating immune complex (IC) levels in sera from 58 healthy controls and a total of 212 patients with various chronic lung diseases were measured using 3 assays. Two complement-dependent assays (C1q fluid phase and Raji) and a complement-independent assay (L1210) were employed. The 3 assays generally revealed similar patterns of reactivity when control and pathological groups were compared, with the L1210 assay invariably demonstrating the lowest incidence of positive values in each group. The most significant elevations in IC levels were exhibited in bronchiectasis and bronchogenic carcinoma. However, within these two groups correlations between IC assays performed on individual sera were poor. Significant but weak correlations (p less than 0.01) were only observed for C1q vs Raji in bronchiectasis and C1q vs L1210 in bronchogenic carcinoma. Complement-binding ICs were present to a similar extent in both conditions. However, non-complement binding ICs were found to be more common in bronchiectasis. The relative sensitivity of the tests and the contribution of interfering factors to the disparity between the assays is discussed. However, the interpretation favoured is that the lack of correlation is primarily a reflection of the intrinsic heterogeneity of immune complexes formed under similar and dissimilar pathological conditions.

Animals↗
PubMed1982

Alterations in activities of anaphylatoxin inactivator and chemotactic factor inactivator during hemodialysis.

The systemic infusion of complement-derived anaphylatoxin ane chemotaxins during hemodialysis results in profound transient neutropenia and may be associated with subtle pulmonary dysfunction. The fact that these potent inflammatory peptides do not usually produce serious ill effects may be due in part to their rapid inactivation by the serum regulatory proteins anaphylatoxin inactivator (AI) and chemotactic factor inactivator (CFI). Accordingly, the authors investigated the effect of hemodialysis on circulating neutrophil counts and serum levels of AI and CFI activity in 10 patients. In all patients, circulating neutrophil counts plummeted by more than 50% within 5 minutes of the onset of dialysis and rose beyond control levels by 1 hour. AI activity significantly fell from 65 +/- 16 mU/ml before dialysis to 18.7 +/- 7.8 mU/ml within 5 minutes of its initiation; levels remained depressed throughout the procedure. In contrast, CFI gradually increased, achieving a level significantly different from the predialysis value by 15 minutes. These events contrasted with the observation that activation of the complement system in vitro results in a significant decline in both CFI and AI activities. We suggest that the maintenance of or increase in CFI activity in patients undergoing hemodialysis enhances the clearance of circulating chemotactins, preventing the persistent activation of neutrophils during the procedure and subsequent organ dysfunction.

Adult↗
PubMed1981

Extravascular natural cytotoxicity in man: Anti-K562 activity of lymph-node and tumour-infiltrating lymphocytes.

A major distinction is reported between the cytolytic activity of peripheral blood lymphocytes (PBL) and that of lymph-node and tumour-infiltrating lymphocytes (TIL) against targets of the NK-sensitive K562 cell line in short-term 51Cr release assays. In the PBL of normal donors and lung cancer patients in whom disease was advanced anti-K562 reactivity, though variable, was consistently detectable and this activity could be augmented to a similar extent in patients and controls by treatment of effectors with exogenous interferon (IF). By contrast anti-K562 activity in lymph-node cells (LNC) and TIL was virtually absent and significant levels could not be induced by exposure to IF. This activity was not attributable to coexistent suppressor cells for NK function since admixture of LNC and TIL with normal PBL failed to modulate K562 killing by the latter. The results imply that K562-reactive NK cells and their precursors may frequently be present at sub-threshold levels in the lymph nodes of tumour-bearing patients and a similar explanation could account for the inactivity of TIL. However, in the latter situation, actively-induced NK dysfunction in situ incapable of regeneration by IF, and attributable to as yet undefined tumour-associated factors, may also be involved.

Animals↗
PubMed1981

Cytogenetic analysis of the L5178Y/TK+/- leads to TK-/- mouse lymphoma mutagenesis assay system.

The L5178Y/TK+/- leads to TK-/- mouse lymphoma mutagen assay, which allows selection of forward mutations at the autosomal thymidine kinase (TK) locus, uses a TK+/- heterozygous cell line, TK+/- 3.7.2C. Quantitation of colonies of mutant TK-/- cells in the assay forms the basis for calculations of mutagenic potential of test compounds. We have evaluated the banded karyotypes of the parent TK+/- heterozygous cell line, as well as homozygous TK-/- mutants, in order to relate the genetic and morphological properties of mutant colonies. The parent cell line displays karyotype homogeneity, all cells containing normal mouse chromosomes, readily identifiable chromosome rearrangements, and cell line specific marker chromosomes. Mutant TK-/- colonies of the TK+/- 3.7.2C cell line form a bimodal frequency distribution of colony sizes for most mutagenic or carcinogenic test substances. Large-colony (lambda) TK-/- mutants with normal growth kinetics appear karyotypically identical within and among clones and with the TK+/- parental cell line. In contrast, most slow-growing small-colony (sigma) TK-/- mutants have readily recognizable chromosome rearrangements involving chromosome 11, which contains the thymidine kinase gene locus. It is possible that the heritable differences in growth kinetics and resultant colony morphology in lambda and sigma mutants are related to the type of chromosomal damage sustained. Large-colony mutants receive minimal damage, possibly in the form of point mutations at the TK locus, while small-colony mutants receive damage to other genetic functions coordinately with loss of TK activity, implying gross insult to chromosomal material. It seems likely that lambda and sigma mutants result from 2 different mutational mechanisms that may be distinguished on the basis of mutant colony morphology.

Animals↗