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Biomedical subjects

N Matthews

Publications and source records attributed to N Matthews.

At least 73 records · Page 4Linked to original sources
PubMed1987

Production of hemopoietic growth factors and gamma-interferon by large granular lymphocytes from patients with T gamma lymphocytosis.

Two patients with T gamma lymphocytosis in whom expanded large granular lymphocyte (LGL) populations were detected in peripheral blood and bone marrow are described. The surface antigen phenotypes of the LGL from these patients were similar with a major portion of cells carrying T3, T8, T11 and Leu7 markers. However, whereas fresh LGL from both patients demonstrated antibody-dependent cell cytotoxicity (ADCC), natural killer (NK) cell function was present in one case but absent in the other. Supernatants from enriched suspensions of the LGL unstimulated by exogenous antigen or mitogens were shown to contain significant amounts of hemopoietic growth factors colony-stimulating activity (CSA) and burst-promoting activity (BPA). In one case gamma-interferon was also detected. This study contributes to the accumulating evidence that LGL are able to generate factors which have the capacity to influence the proliferation of hemopoietic progenitor cells in vitro.

Colony-Forming Units Assay↗
PubMed1987

Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism.

Previous work on the mechanism of tumour-cell killing by the macrophage product tumour necrosis factor (TNF) is consistent with a free radical-induced process. In this study, free-radical involvement was sought by (i) investigating the effects on TNF cytolysis of anaerobic conditions, free-radical scavengers and inhibitors of two potential pathways of free-radical generation (oxidative phosphorylation and arachidonate metabolism) and (ii) looking for increased malonyldialdehyde (MDA) production in TNF-treated cells (MDA is a free radical-induced lipid peroxidation product). Although TNF cytolysis of L929 cells was inhibited by anaerobic conditions, only limited effects were seen with free-radical scavengers. Suppression of arachidonate metabolism by steroids effectively inhibited TNF cytolysis but the mitochondrial poison rotenone did not. There was a marked, but late, increase in MDA production in TNF-treated cells. Overall, these results indicate that if free radicals are involved it is at a late stage in the cytolytic process. However the most striking observation in this study is that arachidonate metabolism is an essential link in the cytolytic process.

Animals↗
PubMed1986

Antibody response to anaerobic coccoid rods in Crohn's disease.

The IgG and IgM specific antibodies against a panel of 23 anaerobic gut bacteria were examined in Crohn's disease, ulcerative colitis, and healthy controls. Four of the organisms, Bifidobacterium bifidum, Coprococcus comes (ME46), Coprococcus comes (Sp4), and Eubacterium limosum gave abnormal antibody titres in Crohn's disease compared with those of controls. In Crohn's disease specific IgG antibodies to three of the organisms were low and the IgM antibodies were higher than those of controls. IgM antibodies were also raised in ulcerative colitis. Antigenic cross reactivity could be shown between some of these organisms. The possible clinical importance of these abnormal antibody responses to specific organisms is unexplained.

Bacteria, Anaerobic↗
PubMed1986

Inherited thrombocytopenia, elevated serum IgA and renal disease: identification as a variant of the Wiskott-Aldrich syndrome.

A kindred with X-linked hereditary thrombocytopenia in association with elevated serum IgA and a mild nephropathy is described. Thirteen males with thrombocytopenia were identified in three generations amongst 49 family members who were available for screening. Serious infective sequelae were absent but five patients had suffered from severe eczema since infancy. The platelet volume as measured by an automated counter and electron microscopy was reduced compared with normal and in vitro tests demonstrated minor abnormalities of immune function in three patients. The disorder is identified as a novel variant of the Wiskott-Aldrich syndrome and comparisons are made with previously described kindreds showing different patterns of expression.

Adult↗
PubMed1985

Human monocyte cytotoxin is not identical with lymphoblastoid lymphotoxin.

Mononuclear phagocytes and lymphocytes can both synthesize cytotoxins which kill certain tumor cell lines and recent evidence suggests that these cytotoxins may be identical. In this study, human monocyte cytotoxin and lymphoblastoid lymphotoxin have been critically compared in terms of specificity, physicochemical characteristics and antigenicity. Despite their similar pattern of reactivity with a panel of cell lines, lymphotoxin was less readily adsorbed than monocyte cytotoxin by tumor cells. The cytotoxins could also be distinguished by their behavior on high performance liquid chromatography and by the failure of antibody to monocyte cytotoxin to react with lymphotoxin.

Antigens, Neoplasm↗
PubMed1985

Meningococcal endocarditis with profound acquired hypocomplementaemia.

A patient is described who presented with chronic endocarditis, due to Neisseria meningitidis, affecting a previously normal mitral valve. The illness was associated with glomerulonephritis that caused renal impairment and the nephrotic syndrome. Despite antibiotic treatment and replacement of the mitral valve, serum complement values remained very low, only returning to normal when immune complexes and a type III cryoglobulin disappeared from the circulation three months after resection of the valve vegetation. Such acquired hypocomplementaemia may have contributed to the chronicity of the disease process in this patient.

Adult↗
PubMed1985

A study of cell mediated and humoral immunity in haemophilia and related disorders.

Helper (OKT4) and suppressor (OKT8) T lymphocyte populations and functional assays of cellular immunity were studied in 37 patients with haemophilia and related disorders in parallel with age matched control subjects. The study included 26 patients with factor VIII (FVIII:C) deficiency, eight patients with factor IX deficiency and three patients with severe von Willebrand's disease (vWd). In patients with factor VIII deficiency low helper T lymphocyte counts, low T helper: suppressor ratios and a diminished response to the lymphocyte mitogen phytohaemagglutinin with decreased natural killer cell activity were observed. Individuals with factor IX deficiency had low absolute T lymphocyte (OKT3) counts and T helper cell counts. Patients with severe factor VIII deficiency (FVIII:C less than 1 u/dl) had lower T helper suppressor ratios and lower killer cell and natural killer cell activity in comparison to mildly affected individuals and all of the severely affected factor IX deficient cases. Studies of humoral immunity revealed a generalized increase in immunoglobulin levels in patients with coagulation disorders of any type. The total haemolytic complement activity was reduced in a significant proportion of haemophilic subjects. Levels of alpha-1-interferon were elevated in the groups of haemophilic subjects studied. The abnormalities of cellular and humoral immunity observed did not correlate with the amount or type of coagulation factor administered to individual patients in the preceding 2 years. The most marked abnormalities of immune function occurred in the one patient diagnosed as suffering from AIDS on clinical grounds.

Adolescent↗
PubMed1985

Mixed lymphocyte reaction supernatants exert varied effects upon gingival fibroblasts in vitro.

Supernatants from mixed lymphocyte cultures (MLRs) were tested for modulation of gingival fibroblast growth by both dye and 3H-thymidine uptake assays. Significant levels of inhibition of growth were observed with both assays with 24 and 72 hr MLR supernatants, but stimulation of growth was seen to occur, consistently, with 48 and 96 hr MLR supernatants as assessed by the dye uptake method. Fractionation of 24 hr supernatants by gel-filtration, on Ultrogel ACA 54 yielded fractions with enhanced growth inhibitory activity. The MLR supernatants would appear to contain mediators with opposing growth effects at different times during the culture.

Adult↗
PubMed1984

Agglutinins to anaerobic bacteria in Crohn's disease and in Indian patients with diarrhoea.

Agglutinins to certain species of Eubacterium and Peptostreptococcus have been reported in sera from a high proportion of patients with Crohn's disease. Because this might be a non-specific finding common to patients with diarrhoea associated with damaged intestinal mucosa, we have compared the incidence of such agglutinins in patients with Crohn's disease with that seen in patients in North-East India with acute or chronic diarrhoea. The incidence of agglutinins in Crohn's disease was 44%, compared with 11% in acute and 17% in chronic diarrhoea. These figures suggest that mucosal damage alone does not explain the high incidence of agglutinins in Crohn's disease.

Adult↗
PubMed1984

Antimicrobial effects of a macrophage-derived cytotoxin from the serum of BCG-primed rabbits (tumour necrosis serum).

Previous studies have shown that a macrophage-derived cytotoxin, found in high titre in the serum of BCG-primed rabbits, killed malarial parasites and certain tumour cells. In this study, the macrophage cytotoxin was tested for activity against microorganisms other than protozoa. No activity was seen against a range of gram-negative or gram-positive bacteria or against Candida albicans. It is concluded that the macrophage cytotoxin has limited anti-microbial activity, perhaps restricted to certain intra-cellular parasites.

Animals↗
PubMed1984

Malarial parasites and tumour cells are killed by the same component of tumour necrosis serum.

Tumour necrosis serum (TNS), from animals primed with macrophage activating agents and challenged with endotoxin, causes necrosis of some tumours and can kill certain tumour lines in vitro and malarial parasites in vitro and in vivo. We have tested the possibility that the same factor is responsible for killing both tumour cells and malarial parasites. In competitive inhibition experiments, parasitized erythrocytes, but not normal erythrocytes, inhibited the cytotoxicity of TNS against a tumour cell line. Conversely, the tumour cells inhibited the killing of Plasmodium yoelii in vitro by TNS. When rabbit TNS was fractionated by ion exchange chromatography followed by gel filtration and the fractions at each step were pooled according to their ability to kill the tumour cells, in vitro parasite killing activity was found to correlate with tumour cell cytotoxicity, to a final sample which was purified more than 600-fold. Our results suggest that in terms of function, at least, the same component of TNS is responsible for the killing of both tumour cells and malarial parasites.

Animals↗
PubMed1984

Anti-tumour cytotoxin from macrophages: no correlation between cytotoxin adsorption by tumour cell lines and their cytotoxin susceptibility.

Mononuclear phagocytes can synthesize a cytotoxin, similar to that in tumour necrosis serum, which is cytotoxic to certain tumour cell lines in vitro. This study has investigated whether susceptibility and resistance to the cytotoxin can be explained in terms of the amount of cytotoxin receptor expressed on the tumour cell surface. Binding of cytotoxin has been quantitated both by direct adsorption and competitive inhibition assays with cytotoxin-resistant or -susceptible tumour lines and with sublines of susceptible lines, selected for resistance to the cytotoxin. For both rabbit and human cytotoxin, there was no correlation between cytotoxin adsorption by tumour cell lines and their cytotoxin susceptibility, suggesting that resistance to the cytotoxin is expressed at a post-receptor stage. Preliminary studies on the cytotoxin receptor of K562 cells have shown that it is probably not the transferrin receptor, and that protein but not carbohydrate is essential for its function.

Adsorption↗
PubMed1983

Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action.

Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium and is cytotoxic at higher concentrations and cytostatic at lower concentrations. First signs of cell damage appear about 20 h after contact with the cytotoxin which must be present throughout this period. The cytotoxin probably acts on the cell surface and is more effective at 40 degrees C than at 37 degrees C. For a given amount of cytotoxin the effects are inversely proportional to the target cell concentration. Treatment of the cytotoxin with phenanthroline inhibits cytotoxicity while treatment of the target cells with actinomycin D, but not cycloheximide or puromycin, enhances cytotoxicity. After 24 h cytotoxin treatment the target cells exhibit reduced respiration rate but enhanced glycolysis and glucose uptake suggesting mitochondrial dysfunction. A possible interpretation of these data is that the monocyte cytotoxin is a metalloenzyme which inactivates a cell surface receptor for a nutrient essential for mitochondrial function.

Adsorption↗
PubMed1983

Antimicrobial properties of preterm breast milk cells.

The antimicrobial properties of preterm and term breast milk cells were compared. They were similar in cell numbers and in the capacity to phagocytose and kill staphylococci. Interferon production on endotoxin challenge appeared to be higher in preterm cells. The antibacterial activity of breast milk cells was retained after storage at 4 degrees C for 24-48 hours. Cell numbers were unaffected by passage through a standard oral paediatric feeding set.

Female↗
PubMed1983

Effect of human monocyte killing of tumour cells of antibody raised against an extracellular monocyte cytotoxin.

Human monocytes can kill or inhibit the growth of certain tumour cell lines. Amongst the possible mediators is a cytotoxin synthesized in readily detectable amounts by endotoxin-stimulated monocytes. A neutralizing antiserum to the cytotoxin has been used to assess the cytotoxin's contribution to monocyte killing of tumour cells. The antiserum was tested for possible inhibition of monocyte killing of three tumour cell lines--L929, K562 and A549. Inhibition was complete with L929, partial with K562 and insignificant with A549. Thus the contribution of the cytotoxin to monocyte killing of tumour cells depends upon the tumour line under test. Antibody against endotoxin-induced cytotoxin also neutralized cytotoxin induced in monocytes by other agents including BCG, Corynebacterium parvum, pokeweed mitogen and zymosan. Cytotoxin could be quantitatively removed from monocyte supernatants by Sepharose-bound, anticytotoxin antibody. Recovery of the cytotoxin from the immunoadsorbent was difficult because of its lability in the solutions commonly used for desorption. The best recovery has been achieved with 2 M urea, 2 M MgCl2 giving a 25% yield and a forty-fold increase in purity in a single step.

Adenocarcinoma↗