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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 451 records · Page 25Linked to original sources
PubMed1981

Cultured human T-cell lines kill autologous solid tumours.

Lymphocytes from peripheral blood, lymph node, spleen and tumour of 7 patients with various carcinomas (2 lung, 3 colon, 1 gastric and 1 parotid tumour) were cultured for 15 days in conditioned media containing T-cell growth factor (TCGF; Interleukin 2) after which their cytotoxic activity against autologous tumour (and in some instances, autologous normal) cells and allogeneic tumour targets was evaluated in a short-term 51Cr-release assay. Significant cytotoxicity against autologous tumour targets was detected in at least one effector preparation from all of the patients, under conditions where, in some cases, other autologous cells (normal lung, PHA-transformed lymphocytes) were resistant. This cytotoxicity also generally extended to allogeneic tumour targets, but lysis of K562, a cell line sensitive to natural killing, occurred in only 3 of 19 effector cell preparations. The data are consistent with a polyclonal expansion of cytotoxic T-cells of tumour-bearing patients which includes the amplification of a population recognitive of antigens expressed on autologous neoplastic cells.

Cell Line↗
PubMed1981

Specific and non-specific lymphocyte cytotoxicity in colon carcinoma.

The cytotoxic activity of peripheral-blood (PBL), lymph-node (LNC) and tumour-infiltrating lymphocytes (TIL) from 47 patients undergoing surgery for colon carcinoma (Duke's Stage A, 1 patient; B, 24; C, 15 and C with metastases, 7) was examined in short-term 51Cr-release assays, against fresh autologous tumour cells, allogeneic colon cancer cells and the erythroleukaemia cell line, K562. Cytotoxicity against autologous cells was detected in at least one effector population in 23/47 patients (49%), with overall frequencies which did not differ for patients in different Duke's stages of disease. By contrast, lysis of allogeneic tumour cells was infrequent (11%) regardless of the effector population to which they were exposed. Cytotoxicity against K562, cells highly sensitive to NK activity, though variable, was detected in 93% of PBL of normal donors and 83% of patients, and among the latter showed no evidence of significant decline with advancing disease. However, LNC and TIL anti-K562 activity was infrequent (17%) in concordance with previous reports. There was no correlation between the ability of patients' PBL to lyse autologous tumour and K562 cells. The independence of these 2 cytotoxic actions was further explored in studies fractionating lymphocytes: autologous tumour killing was augmented in T-enriched PBL; whereas the greatest anti-K562 activity was found in the corresponding non-T fraction. Lymphocyte cytotoxicity in colonic neoplasia is thus manifest in 2 apparently independent lymphocyte populations; a relatively specific killer T-cell population, detectable in PBL, LNC and TIL, which is preferentially reactive with the autologous cells; and a non-specific killer population, largely limited to PBL, with the properties of NK cells. The activity of neither population reflects the clinical status of patients with this disease.

Adult↗
PubMed1981

Selective enhancement of human mononuclear leucocyte cytotoxic function by interferon.

The influence of type I interferon (IFN) on leucocyte-mediated antibody-dependent cellular cytotoxicity (ADCC) has been examined in a system in which differential alloantibody sensitization of human erythrocyte target cells allows discrimination between lymphocyte and monocyte effector function. ADCC mediated by unfractionated mononuclear leucocyte populations was regularly enhanced by interferon pretreatment over a range of concentrations of the sensitizing antibody. The capacity of IFN-augmented reactivity was, however, removed with adherent cell depletion, suggesting that lymphocyte (K-cell) effectors are not modulated by IFN, even though such populations demonstrate IFN-potentiated natural killer (NK) reactivity against K562. These results suggest that monocyte and NK cell function but not K-cell activity was influenced by interferon.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Lysis of alloantibody-sensitized human erythrocytes by peripheral blood mononuclear cells: heterogeneity of effector populations.

Cell-mediated haemolysis of human erythrocytes (HRBC) mediated by sensitizing alloantibodies of two specificities was studied using the 51Cr release assay. Peripheral blood mononuclear cells (PBMC) were found capable fo lysing HRBC of phenotype ARh(D) + ve sensitized with either anti-D or "natural" anti-A antibodies. The characteristics of the effector population, however, were dependent upon the sensitizing antibody. HRBC sensitized with anti-A were lysed by a radioresistant, silica- and carrageenan-sensitive population which could be selectively removed by adherence. Sensitization with rhesus antibody induced cytotoxicity by a population which was radiosensitive and relatively unaffected by removal of adherent cells or by treatment with silica or carrageenan. The results demonstrate that the antigen-antibody interaction, rather than the target cell type, determines which effector cells participate in antibody-dependent cellular cytotoxicity (ADCC) against human red cells.

ABO Blood-Group System↗
PubMed1981

Proliferative response of lymphocyte subpopulations differing in avidity for sheep red blood cells after stimulation with normal allogeneic and tumour cells.

Lymphocytes from normal donors were cultured with cell lines of erythroid (K562) and lymphoid (Bri8) origin, fresh cells derived from chronic myeloid leukaemia patients (FLC), T-depleted normal peripheral blood lymphocytes (PBL) and normal bone marrow cells (NBMC). The proliferative response to these stimulator cells was evaluated in both the total lymphocyte population and in subpopulations with different affinity receptors for sheep red blood cells (SRBC), on the second, fourth and sixth days of culture. No DNA synthesis was induced by the K562 cell line, while Bri8 cells induced a proliferative response greater than that observed against PBL. No differences in the DNA synthesis pattern were observed when NBMC and FLC were used as stimulators which was comparable with that for PBL. There was a correlation between the degree of activation of the culture and the changes in size of the responding SRBC binding cell population (ET+). A progressive increase with duration of the cultures in the number of SRBC high avidity cells (EH+) and a parallel contraction of the SRBC low avidity (EL+) and E- cell populations was generally observed, so that EH+ and ET+ fractions gave similar values at the later time points. The analysis of [3H]-thymidine uptake of E+ and E- fractions on days 3 and 6, in FLC and NBMC-stimulated lymphocytes showed a prevalent involvement of E- cells on day 3, while on day 6 the majority of dividing cells belonged to the E+ compartment. A higher recruitment of E- cells in the early phase of the response was observed in FLC-stimulated lymphocytes. The participation of non-T cell populations in the proliferative response against allogeneic normal and tumour antigens is discussed.

Animals↗
PubMed1981

C1q binding activity in the sera of patients with chronic lung diseases.

Sera from patients with chronic lung diseases were tested for the presence of immune complexes (ICs) by the 125I-C1q-binding assay. Contrary to earlier reports, modification of the test system by addition of heparin decreased rather than increased the ability of the test to discriminate between control and pathological sera. Using the unmodified system, elevated C1q-binding activity (C1qBA) was found in patients with asthma (18%), chronic bronchitis (18%), sarcoidosis (18%), fibrosing alveolitis (50%), bronchogenic carcinoma (52%) and bronchiectasis (67%). Studies with the reducing agent 2-mercaptoethanol (2-ME) suggested a role for IgM rheumatoid factor (RF) and/or IgG-containing complexes in the C1q-reactive material of sera from patients with bronchiectasis and bronchogenic carcinoma. In the latter two groups, C1qBA was found to correlate with serum levels of IgG and IgA but not with C3 and C4. A weak condition between levels of C-reactive protein (CRP) and C1qBA was found in the bronchogenic carcinoma group. Carcinoembryonic antigen (CEA) levels were elevated in all groups studied but no correlation with C1qBA was demonstrated, suggesting that CEA and CEA-ICs, if present, do not have an influence on the C1qBA of such sera. The results indicate that elevated serum C1qBA is a concomitant of both chronic inflammatory and neoplastic diseases of the lung but the extent of any similarity in the non-immunoglobulin components of the immune complexes in the respective conditions remains unknown.

Adolescent↗
PubMed1981

Alcohol intake, cigarette smoking and plasma lipids and lipoproteins in 12--19-year-old children. The Collaborative Lipid Research Clinics Prevalence Study.

The relationship of alcohol intake to plasma lipids and lipoproteins was assessed in 1603 white children, ages 12-19 years, from six Lipid Research Clinics as part of the Lipid Research Clinics Collaborative Population Studies. Of the 1603 children, 933 came from a randomly recalled group and 660 from a group recalled because of elevated cholesterol or triglyceride or both (the hyperlipidemic recall group). Using multiple regression analysis, the relationships of lipoproteins (as dependent variables) to alcohol, smoking, age and body mass (as explanatory variables) are assessed in both recall groups. In the random recall group, high-density lipoprotein (HDL) cholesterol was positively related to alcohol intake, independent of the other variables considered; for every ounce of alcohol intake, HDL cholesterol was 0.55 mg/dl higher in males and 1.04 mg/dl higher in females. HDL cholesterol was strongly and inversely related to smoking and body mass in both males and females and was inversely related to age in males. In females, plasma low-density lipoprotein (LDL) cholesterol, triglycerides and very low density lipoprotein (VLDL) cholesterol were all positively related to alcohol intake. In the hyperlipidemic recall group of children, alcohol intake had a weak positive relationship with HDL cholesterol in males; in the females, for every ounce of alcohol intake, HDL cholesterol was higher by 1.5 mg/dl. Alcohol intake was positively related to triglyceride levels in hypertriglyceridemic male children. In each recall group, alcohol intake had a small, significant, positive association with HDL cholesterol levels in 12--19-year-old children, and a less consistent positive association with triglyceride and VLDL cholesterol. If low HDL cholesterol concentrations in children are undesirable, attention should first be focused reduction of smoking (inversely associated with HDL cholesterol) and weight (inversely associated with HDL cholesterol, positively associated with LDL cholesterol, triglyceride and VLDL cholesterol), as measures that may modify HDL cholesterol levels.

Adolescent↗
PubMed1981

In vitro augmentation of human natural cytotoxic activity.

Stimulation of human blood lymphocyte preparations with mitomycin C-treated lymphoid cell lines produced increased levels of cytotoxicity against both NK-susceptible and NK-resistant target cell lines. The greatest effect was seen following stimulation by the B lymphocyte-derived lines, Bri8 and raji. K562 also stimulated high levels of activity while the T lymphocyte-derived lines, CCRF/CEM and MOLT 4, produced smaller increases activity was also found in PHA- and MLC-stimulated populations. Stimulation by lymphoid cell lines gave increased cytotoxic activity against all five cell lines when used as target cells and the pattern of target cell susceptibility was maintained, with K562, CCRF/CEM and MOLT 4 being more susceptible than Bri8 and Raji. No direct correlation was found between the level of cytotoxic activity and the level of 3H-thymidine uptake in stimulated effector cell populations. The B cell lines stimulated high levels of isotopic uptake, while the T cell lines gave no significant stimulation. Similarly, the level of 3H-thymidine incorporation following PHA and MLC stimulation showed no direct correlation with the level of cytotoxic activity. Stimulation of lymphocyte transformation did not appear to be necessary for the induction of cytotoxic activity, although the largest increases in cytotoxicity occurred in populations showing high isotope incorporation. No correlation was found between the target cell susceptibility of the different cell lines and their ability to stimulate cytotoxicity.

Cell Line↗
PubMed1980

Modulation of target cell susceptibility to human natural killer cells by interferon.

The spontaneous cytolytic activity of human peripheral blood lymphocytes in a short-term 51chromium release assay was markedly enhanced by pretreatment with partially purified "Namalva" lymphoblastoid (type I) interferon (IF), provided that the target cells, five lymphoblastoid cell lines of variable natural killer (NK) sensitivity (K562, Molt 4, CCRF/CEM, Raji and Bri8), were not similarly treated with IF. When the targets were pre-exposed to comparable concentrations of IF, their susceptibility to lysis by IF-stimulated or unstimulated effectors was diminished, while exposure of both effectors and targets to IF for the duration of the cytotoxicity assay produced levels of cytotoxicity intermediate between those obtained when either effectors or targets were pretreated. The results indicate that, depending on the experimental design. IF is capable of exerting a protective effect on certain targets, a conclusion supported by competition assays wherein IF-treated cold K562 cells competed less successfully than untreated cold K562 cells for lysis of their radiolabelled counterparts by both IF-stimulated and unstimulated effectors. The data suggest that certain lymphoblastoid targets, in common with effector lymphocytes, possess receptors for IF. Some possible biological implications of the protective interaction of IF with tumour targets, which is antagonistic to that on effector cells, are discussed.

Cell Line↗
PubMed1980

The association of depo-medroxyprogesterone acetate and breast cancer.

The use of depo-medroxyprogesterone acetate (DMPA) as an injectable contraceptive for women has continued to be controversial for over 10 years. The U.S. Food and Drug Administration has not approved it for contraceptive use but the World Health Organization has. We undertook a case-control study to clarify the possible association of breast cancer and DMPA use. Subjects were selected from women enrolled in the Grady Memorial Hospital Family Planning Clinic in Atlanta, Georgia, from 1967 to 1979. The risk of breast cancer in DMPA users compared to nonusers is identical. The small number of women with breast cancer, the short average exposure to DMPA, and the lack of detail about the subjects themselves caused us to interpret our results cautiously. However, it seems reasonable to conclude that short-term use of DMPA among black women is not associated with any increased risk of breast cancer.

Adult↗
PubMed1980

Enhancement of human natural cell-mediated cytotoxicity by interferon.

The effect of exogenous Namalva interferon (IF) on the natural killer (NK) cell activity of human blood lymphocytes was examined against 5 target cell lines (K562, CCRF/CEM, Molt 4, Raji and Bri8) using the 51Cr-release assay. Addition of IF to the test significantly increased the cytotoxicity, though not as much as when effector cells were treated with IF before the test. Augmentation of cytotoxicity was evident after only 1 h pretreatment and was maximal by 6 h. The rate of lysis of susceptible targets by IF-treated effectors markedly exceeded that by their untreated counterparts. Separation of lymphocyte subpopulations (by SRBC-rosette sedimentation and nylon-fibre column filtration) demonstrated that the activities of IF-stimulated and unstimulated cells were similarly distributed, suggesting that the major effect of IF is enhancement of the activity of pre-existing NK cells rather than generation of new populations of effectors. Target cell lines with high and low susceptibility to NK cells showed increased cytotoxicity by IF-treated effector cells. These findings may be relevant to the current discussion of the role of NK cells in immunosurveillance against neoplasia.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Congenital erythrocytosis: a new form associated with an erythropoietin-dependent mechanism.

Three patients with probable congenital erythrocytosis were studied to determine the role of erythropoietin (ESF) in their disease. In addition, haemoglobin function was measured and ESF excretion determined in response to reduction in the haemoglobin concentration. In two cases ESF excretion was clearly elevated above normal, and in the third excretion was normal even at an elevated PCV. In all, phlebotomy of 15--20% of the blood volume led tomore than doubling in ESF excretion. This occurred in the presence of normal molecular haemoglobin function. Studies of the renal vasculature were normal. These results suggest a new form of congenital erythrocytosis associated with increased ESF production which is reciprocally related to the oxygen carrying capacity of the blood, but in the absence of any demonstrable abnormality in oxygen transport. These findings suggest an inherited defect, likely residing in the renal sensor responsible for the production of ESF. This defect is possible due to impaired recognition of available oxygen or else a decrease in oxygen supply at the subcellular level.

Adolescent↗
PubMed1980

Membrane alterations in acute myocardial ischemia.

The molecular consequences of acute myocardial ischemia induced in rabbit hearts by ligation of the left circumflex branch of the coronary artery were assessed in terms of the biochemical properties of subcellular organelles. Mitochondrial alteration, as reflected in progressive decrease in the activity of azide-sensitive ATPase, was apparent as early as 5 min postligation, but the activity of another mitochondrial enzyme, cytochrome c oxidase, was unchanged, even following 60 min of coronary ligation. Sarcolemmal Na+K+-ATPase exhibited a time course of inactivation similar to that of the mitochondrial ATPase, but differed from the latter in that the impairment was not reversed on reperfusion. Cellular levels of ATP, which decreased in parallel with the loss of ATPase activities, also remained depressed following reperfusion. Decreases in lysosomal enzyme latency were noted, but these occurred somewhat later than the sarcolemmal and mitochondrial alterations. Attempts to demonstrate the production of a population of labile lysosomal structures during ischemia were unsuccessful. Similarly, no alterations in the gel electrophoretic profiles of proteins or in the P phosphatidylcholine/P phosphatidylethanolamine ratio of isolated mitochondrial or sarcolemmal membranes from hearts subjected to ischemia and (or) subsequent reperfusion could be found. It is suggested that sarcolemmal Na+,K+-ATPase may serve as a sensitive and readily quantifiable index of irreversible cellular necrosis and, therefore, be of value in assessing the possible beneficial effects of pharmacological interventions.

Acetylglucosaminidase↗
PubMed1980

Natural cytotoxicity in humans: susceptibility of freshly isolatd tumor cells to lysis.

The cytotoxic potential of blood lymphocyters from healthy donors was tested against freshly isolated lung cancer cells and the erythroleukemia K562 cell line in short-term 51Cr release assays conducted at an effector:target ratio of 50:1. Most donors exhibited significant activity against K6-562 cells. By contrast, fresh tumor cells were refractory, only 6 of 30 showing significant cytotoxicity. The low susceptibility of these tumor cells was confirmed in third-party cold inhibition assays in which they interfered minimally with killing of K562 targets under conditions in which unlabeled K562 cells efficiently blocked cytotoxicity. Cells prepared from normal lung tissue and Raji cells also failed to inhibit killing. Although in comparison to the K562 cell line freshly isolated tumor cells were resistant, their susceptibility may not be so low as to be biologically irrelevant, inasmuch as boosting of natural killing activity by interferon induced levels of cytotoxicity against both types of target cell that were unattainable by unstimulated effectors. Interferon-boosted killers were lytic for "normal" lung cells and the Raji cell line.

Cell Line↗
PubMed1980

An evaluation of hexamethylmelamine, cis-diamminedichloroplatinum, and mitomycin-C in advanced breast cancer. A pilot study of the Southeastern Cancer Study Group.

Eleven patients with metastatic breast cancer refractory to conventional therapy were treated with a combination of hexamethylmelamine 250 mg/m2 p.o. days 1-14, repeated at 4-week intervals; cis-platinum 30 mg/m2 I.V. q 28 days; and mitomycin-C 7.5-10 mg/m2 I.V. q 56 days. There were no complete responders and three partial responders for a response rate of 27%. Two patients (18%) had stabilization of disease for brief periods. The gastrointestinal toxicity of hexamethylmelamine was unacceptable. Recent reports that cis-platinum and hexamethylmelamine lack activity in breast cancer suggest that the activity of the combination was due to mitomycin-C alone.

Altretamine↗