Page 1. INTRODUCTION During inflammation, many cell types release reactive oxygen species (ROS) v... more Page 1. INTRODUCTION During inflammation, many cell types release reactive oxygen species (ROS) via the respiratory burst.1 These ROS are potent oxidants of LDL and its major protein, apolipoprotein B. Whilst native LDL ...
Immunoglobulin G from rheumatoid patients is denatured around the hinge region. This has been pro... more Immunoglobulin G from rheumatoid patients is denatured around the hinge region. This has been proposed as an explanation for the presence of circulating autoantibodies to IgG in these patients. It has previously been suggested that oxygen radicals (OR) derived from activated polymorphs may play a role in denaturation in vivo. Using sera from rheumatoid patients and age-matched controls in a modified ELISA technique, we have investigated the potential for polyclonal rheumatoid factors (RF) to bind to OR denatured IgG. Three model systems were used to generate OR in vitro: (a) purified PMN s activated by the cell surface stimulant PMA, (b) radiolysis of IgG in solution to generate specifically the superoxide radical and, in a separate system, the hydroxyl radical, (OH.), (c) purified myeloperoxide in the presence of H2O2 and halide ions. 1. The binding of both IgA and IgM RF s to PMN denatured IgG increased dose dependently for seropositive sera only. 2. The OH. radical but not the superoxide radical significantly increased the binding of IgA and M RF, again only for seropositive sera. 3. The myeloperoxidase enzyme system did not increase RF binding. 4. IgG incubated with elastase was not found to be a better antigen than native IgG. These results indicate that IgG is denatured by OR released from activated PMN, thereby producing an antigen for polyclonal RF s.
The effect of chelators on free radical damage to deoxyribose induced by iron, on IgG by UV irrad... more The effect of chelators on free radical damage to deoxyribose induced by iron, on IgG by UV irradiation, and on mouse muscle by homogenisation has been studied using the Thiobarbituric acid method and the increase in fluorescence in IgG mixtures. Although there were some variations on the effects of the chelators in the three models, it was shown that most of the chelators could inhibit the noxious effects of the free radicals and some which are orally effective in increasing iron excretion in animals could be potentially useful in preventing iron toxicity in related pathogenic diseases.
Epidemiological studies strongly suggest associations between chronic exposure to endogenous oest... more Epidemiological studies strongly suggest associations between chronic exposure to endogenous oestrogens and the development of breast and gynaecological tumours. Two mechanisms by which 17 beta-oestradiol (E2) may enhance tumorigenesis are: (i) enhancement of cell proliferation and (ii) the production of reactive, genotoxic metabolites. Here we suggest an additional mechanism, inhibition of DNA repair. The removal of UV-induced thymine dimers from human keratinocytes, reflective of nucleotide excision repair, was significantly attenuated by treatment of cells with E2. In contrast, treatment with 17 alpha-oestradiol had no effect. Mechanisms are proposed for this effect of E2, which may contribute to its carcinogenic potential.
... proteins (Johnson et al., 2004; Moosmann and Behl, 2004). Oxidative stress has been implicate... more ... proteins (Johnson et al., 2004; Moosmann and Behl, 2004). Oxidative stress has been implicated in the pathogenesis of several muscle diseases (Olive et al., 2004). Myopathy during statin treatment has been associated with ...
Page 1. INTRODUCTION During inflammation, many cell types release reactive oxygen species (ROS) v... more Page 1. INTRODUCTION During inflammation, many cell types release reactive oxygen species (ROS) via the respiratory burst.1 These ROS are potent oxidants of LDL and its major protein, apolipoprotein B. Whilst native LDL ...
Immunoglobulin G from rheumatoid patients is denatured around the hinge region. This has been pro... more Immunoglobulin G from rheumatoid patients is denatured around the hinge region. This has been proposed as an explanation for the presence of circulating autoantibodies to IgG in these patients. It has previously been suggested that oxygen radicals (OR) derived from activated polymorphs may play a role in denaturation in vivo. Using sera from rheumatoid patients and age-matched controls in a modified ELISA technique, we have investigated the potential for polyclonal rheumatoid factors (RF) to bind to OR denatured IgG. Three model systems were used to generate OR in vitro: (a) purified PMN s activated by the cell surface stimulant PMA, (b) radiolysis of IgG in solution to generate specifically the superoxide radical and, in a separate system, the hydroxyl radical, (OH.), (c) purified myeloperoxide in the presence of H2O2 and halide ions. 1. The binding of both IgA and IgM RF s to PMN denatured IgG increased dose dependently for seropositive sera only. 2. The OH. radical but not the superoxide radical significantly increased the binding of IgA and M RF, again only for seropositive sera. 3. The myeloperoxidase enzyme system did not increase RF binding. 4. IgG incubated with elastase was not found to be a better antigen than native IgG. These results indicate that IgG is denatured by OR released from activated PMN, thereby producing an antigen for polyclonal RF s.
The effect of chelators on free radical damage to deoxyribose induced by iron, on IgG by UV irrad... more The effect of chelators on free radical damage to deoxyribose induced by iron, on IgG by UV irradiation, and on mouse muscle by homogenisation has been studied using the Thiobarbituric acid method and the increase in fluorescence in IgG mixtures. Although there were some variations on the effects of the chelators in the three models, it was shown that most of the chelators could inhibit the noxious effects of the free radicals and some which are orally effective in increasing iron excretion in animals could be potentially useful in preventing iron toxicity in related pathogenic diseases.
Epidemiological studies strongly suggest associations between chronic exposure to endogenous oest... more Epidemiological studies strongly suggest associations between chronic exposure to endogenous oestrogens and the development of breast and gynaecological tumours. Two mechanisms by which 17 beta-oestradiol (E2) may enhance tumorigenesis are: (i) enhancement of cell proliferation and (ii) the production of reactive, genotoxic metabolites. Here we suggest an additional mechanism, inhibition of DNA repair. The removal of UV-induced thymine dimers from human keratinocytes, reflective of nucleotide excision repair, was significantly attenuated by treatment of cells with E2. In contrast, treatment with 17 alpha-oestradiol had no effect. Mechanisms are proposed for this effect of E2, which may contribute to its carcinogenic potential.
... proteins (Johnson et al., 2004; Moosmann and Behl, 2004). Oxidative stress has been implicate... more ... proteins (Johnson et al., 2004; Moosmann and Behl, 2004). Oxidative stress has been implicated in the pathogenesis of several muscle diseases (Olive et al., 2004). Myopathy during statin treatment has been associated with ...
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Papers by Joseph Lunec