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Biomedical subjects

R A Fox

Publications and source records attributed to R A Fox.

At least 163 records · Page 9Linked to original sources
PubMed1978

The role of suppressor cells in the production of macrophage migration inhibition factor.

The production of migration inhibition factor (MIF) by human peripheral blood lymphocytes and guinea pig lymph node lymphocytes, in response to mitogen, concanavalin A, or antigen, tuberculin, has been studied. Suppressor cells have been depleted by in vitro ageing of cultures for 24 hours, and this has resulted in a significant increase in MIF activity. Reconstitution of the aged lymphocyte population by the addition of fresh lymphocytes results in a suppression of MIF production. When lymphocytes, which have been cultured for 24 hours in the presence of antigen or mitogen to generate suppressor cells, are added to aged cultures MIF production is inhibited. These results suggest that suppressor cells play a regulatory role in the production of MIF.

Animals↗
PubMed1977

A pulse-radiolysis study of the manganese-containing superoxide dismutase from Bacillus stearothermophilus. A kinetic model for the enzyme action.

The enzymic reaction mechanism of a manganese-containing superoxide dismutase from Bacillus stearothermophilus was studied by using pulse radiolysis. During catalysis (pH 8.9; 25 degrees C), changes occurring in the kinetics of substrate disappearance and in the visible absorption of the enzyme at 480 nm established that the simple two-step mechanism found for copper- and iron-containing superoxide dismutases is not involved. At a low ratio (less than 15) of substrate concentration to enzyme concentration the decay of O2--is close to exponetial, whereas at much higher ratios (greater than 100) the observed decay is predominantly zero-order. The simplest interpretation of the results invokes a rapid one-electron oxidation-reduction cycle ('the fast cycle') and, concurrently, a slower reaction giving a form of the enzyme that is essentially unreactive towards O2-- but which undergoes a first-order decay to yield fully active native enzyme ('the slow cycle'). The fast cycle involves the native enzyme EA and a form of the enzyme EB which can be obtained also by treating the form EA with H2O2. Computer calculations made with such a simple model predict behaviour in excellent agreement with the observed results.

Catalysis↗
PubMed1977

A pulse-radiolysis study of the manganese-containing superoxide dismutase from Bacillus stearothermophilus.

In the preceding paper the mechanism of catalysis of the manganese-containing superoxide dismutase from Bacillus stearothermophilus was shown to involve a 'fast cycle' and a 'slow cycle' [McAdam, Fox, Lavelle & Fielden, 1977 (Biochem. J. 165, 71-79)]. Further properties of the enzyme was considered in the present paper. Pulse-radiolysis studies, under conditions of low substrate concentration to (i.e. when the fast cycle predominates), showed that enzyme activity decreases as pH increases (6.5-10.2). Activity was unaffected by the addition of H2O2 or NaN3 but slightly decreased by KCN. Both H2O2 and the reducing radical anion CO2-- caused a decrease in A480 of the native enzyme. The rate of the fast catalytic cycle was independent of temperature (5-55 degrees C), and as temperature increases the slow cycle becomes relatively more important. Arrhenius parameters of the rate contants were estimated. The possible identity of the various forms of the enzyme is considered.

Carbon Dioxide↗
PubMed1977

Migration inhibition produced by sodium periodate oxidation of the macrophage membrane, and reversal by sodium borohydride.

Guinea pig peritoneal exudate cells were harvested 3 to 4 days after the intraperitoneal injection of Marcol oil. The washed cells were exposed to various concentrations of sodium periodate in phosphate-buffered saline (PBS) at pH 7.4 for 10 min at +4 degrees C. The cells were then used in the in vitro migration assay, and migration was consistently inhibited at concentrations from 10(-3) to 10(-5) M. The viability of the macrophages was not affected by this treatment. Sodium borohydride (10(-3) to 10(-5) M) in PBS for 10 min at pH 7.4 reversed the periodate effect. Experiments with purified macrophages showed that sodium periodate has a direct effect on macrophage function rather than an indirect effect via the potentiation of migration inhibition factor. In support of this, the in vitro spreading of macrophages on glass substrate for 1 h has been shown to be inhibited. This spreading inhibition can also be reversed by treatment with sodium borohydride. These results provide a new approach to understanding the biological significance and role of macrophage migration inhibition.

Animals↗
PubMed1976

Cytotoxic lymphocytes in infectious mononucleosis.

Seven patients with a clinical diagnosis of infectious mononucleosis (IM) and detectable heterophil antibodies were found to have peripheral blood lymphocytes that were cytotoxic for lymphoid cells containing Epstein-Barr virus from a patient with Burkitt's lymphoma. The cytotoxic lymphocytes persisted in the peripheral circulation for up to 45 days. Patients who had had IM 1 to 5 years previously lacked such cytotoxic lymphocytes. Patients who had signs and symptoms of IM but no detectable heterophil antibodies lacked cytotoxic lymphocytes. The lymphocytes of one patient with IM showed progressive diminution of cytotoxic ability after prednisone treatment.

Adult↗
PubMed1976

The analysis of single-strand breaks in E. coli using a curve-fitting procedure.

A curve-fitting technique has been used to analyse the activity profiles occurring when the tritium labelled DNA of irradiated E. coli is sedimented in an alkaline sucrose gradient. The fitted curve is a modification of an expression derived elsewhere, which assumes that DNA of unit length undergoes scissions at random positions on the DNA strand. The theoretical curves fit the data well, even after considerable repair or excision of the radiation damage has been effected by cellular enzymes. The profile resulting from sedimentation of unirradiated DNA may be fitted with the same theoretical expression provided that the velocity of centrifugation is not too high. The number of single-strand breaks derived from the analysis is almost unaffected by the presence of extraneous activity at the top or bottom of the sucrose gradient. The method is therefore more reliable than many other methods used to analyse sedimentation data.

Centrifugation, Density Gradient↗
PubMed1976

Potentiation of the macrophage response to migration inhibition factor from fetal calf serum by blood group substances with human H activity.

Soluble blood group substances, with human H and A activity, have previously been shown to block the interaction between guinea pig peritoneal macrophages and migration inhibition factor from fetal calf serum (FCS-MIF). Conversely, incubation of macrophages at 37 degrees C for 1 h in the presence of 0.1% blood group substance, followed by thorough washing, potentiates the action of FCS-MIF. The sensitivity of the macrophages is markedly increased, allowing detection of subthreshold levels of FCS-MIF. Blood group substances (BGS) labeled with radioidine are taken up by macrophages, and a proportion remains on the surface. This radiolabeled BGS is lost from the surface spontaneously, and the rate of loss is increased by treatment with trypsin. It is suggested that the BGS mimic the natural macrophage receptor for FCS-MIF and potentiate its effect by incorporating new receptors into the macrophage membrane.

ABO Blood-Group System↗
PubMed1975

Carcinoembryonic antigen: characterization of binding with insoluble lectins.

Insoluble conanavalin A and wheat germ agglutinin (WGA) were found to bind to carbohydrates on radio-labelled carcinoembryonic antigen (CEA). Binding by WGA was inhibited both by N-acetyl D-glucosamine and fragments of antibody to CEA, but was increased by intact antibody to CEA. This suggests that WGA binds to exposed N-acetyl D-glucosamine determinants on 125I CEA and also on antibody molecules. It also suggests that 125I CEA contains binding sites for anti-CEA which contain N-acetyl D-glucosamine as well as others which do not. Molecules of 125I CEA which bound to the insoluble lectins were more antigenic for anti-CEA than unbound molecules. These results suggest that the principal antigenic site on CEA contains N-acetyl D-glucosamine and may help to explain the agglutination of tumour cells by lectins.

Acetylglucosamine↗
PubMed1973

Lymphocyte transformation in response to phytohaemagglutinin in primary biliary cirrhosis: the search for a plasma inhibitory factor.

The aim of this study was to determine the importance of plasma inhibitory factors in producing the impaired phytohaemagglutinin (PHA)-induced lymphocyte transformation that is seen in some patients with primary biliary cirrhosis. Twenty-six normal subjects and 12 patients with primary biliary cirrhosis were studied. The lymphocytes from each subject were cultured in the presence of autologous plasma and also in the presence of homologous plasma from a normal subject or from a patient with primary biliary cirrhosis. The results confirm that a proportion of patients with primary biliary cirrhosis are anergic and that the impaired lymphocyte transformation to PHA in vitro can be partially accounted for by the presence of inhibitory factors in the plasma. However, these factors are unlikely to account completely for the impaired transformation, it being probable that there are also abnormalities of the T lymphocytes themselves.

Adult↗