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C Gunn

Publications and source records attributed to C Gunn.

13 recordsLinked to original sources
PubMed1994

On the pH-dependent yield of hydroxyl radical products from peroxynitrite.

Nitric oxide reacts rapidly with superoxide to give the strongly oxidizing peroxynitrite anion (ONOO-), which undergoes spontaneous first-order decomposition when protonated. The oxidative chemistry of peroxynitrite (ONOO-) is highly pH-dependent. At acidic pH, peroxynitrous acid (ONOOH) oxidizes dimethylsulfoxide to formaldehyde and 2,2'-azino-bis-(3-ethyl-1,2- dihydrobenzothiazoline 6-sulfonate) (ABTS) to the greenish-colored ABTS+ radical cation. The product yield from dimethylsulfoxide and ABTS decreased at more alkaline pH with apparent pK(a)s of 7.9 and 8.2, respectively. Decreasing yield with increasing pH could not be explained by the oxidation of either formaldehyde or ABTS+ by peroxynitrite. In the presence of 50 mM dimethylsulfoxide, nitrogen dioxide was formed in approximately equimolar amounts to the other reaction product, formaldehyde. The yield of nitrogen dioxide also decreased with an apparent pK(a) of 8.0. We propose that the complex oxidative chemistry of peroxynitrite is controlled by the pH-dependent isomerization of the relatively stable cis-configuration (predominant at high pH) to the trans-configuration. Trans-peroxynitrous acid can form a vibrationally excited intermediate capable of reacting like hydroxyl radical. The vibrationally excited intermediate can also directly rearrange to nitric acid, reducing the apparent hydroxyl radical yield to less than 30%. The loss of hydroxyl radical-like reactivity can be explained on the basis of ionization of trans-peroxynitrous acid to the trans-anion, which in turn undergoes internal rearrangement to nitrate without forming a strong oxidant.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzothiazoles↗
PubMed1992

Bactericidal activity of peroxynitrite.

Peroxynitrite is a strong oxidant formed by macrophages and potentially by other cells that produce nitric oxide and superoxide. Peroxynitrite was highly bactericidal, killing Escherichia coli in direct proportion to its concentration with an LD50 of 250 microM at 37 degrees C in potassium phosphate, pH 7.4. The apparent bactericidal activity of a given concentration peroxynitrite at acidic pH was less than that at neutral and alkaline pH. However, after taking the rapid pH-dependent decomposition of peroxynitrite into account, the rate of the killing was not significantly different at pH 5 compared to pH 7.4. Metal chelators did not decrease peroxynitrite-mediated killing, indicating that exogenous transition metals were not required for toxicity. The hydroxyl radical scavengers mannitol, ethanol, and benzoate did not significantly affect toxicity while dimethyl sulfoxide enhanced peroxynitrite-mediated killing. Dimethyl sulfoxide is a more efficient hydroxyl radical scavenger than the other three scavengers and increased the formation of nitrogen dioxide from peroxynitrite. In the presence of 100 mM dimethyl sulfoxide, 60.0 +/- 0.3 microM nitrogen dioxide was formed from 250 microM peroxynitrite as compared to 2.0 +/- 0.1 microM in buffer alone. Thus, formation of nitrogen dioxide may have enhanced the toxicity of peroxynitrite decomposing in the presence of dimethyl sulfoxide.

Anti-Bacterial Agents↗
PubMed1989

Identification of a common idiotype on myelin oligodendrocyte glycoprotein-specific autoantibodies in chronic relapsing experimental allergic encephalomyelitis.

The myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for autoantibody-mediated demyelination in chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Strain 13 guinea pig. Anti-idiotypic antibodies directed against a demyelinating MOG-specific monoclonal antibody (8-18C5) have identified a cross-reactive idiotype in 10/10 CREAE sera. In nine of these sera inhibition studies demonstrated that this idiotype was at or in close proximity to the combination site of guinea pig anti-MOG autoantibodies. This cross-reactive anti-MOG idiotype may represent an important target for the anti-idiotypic regulation of demyelinating antibody responses in CREAE.

Animals↗
PubMed1986

Hepatic dearterialization in the dog.

Hepatic dearterialization was performed in 9 adult dogs. Evaluation of the technique was based on clinical and laboratory assessment of physiologic and pathologic changes related to the procedure. All dogs had hematologic and histopathologic evidence of transient hepatic ischemia that was reflected by minimal post-operative morbidity.

Animals↗
PubMed1985

The absence of any effect of methimazole on in vitro cell-mediated cytotoxicity.

Two recent studies have reported that antithyroid drugs inhibit killer (K) and natural killer (NK) cell function in vitro, which could be relevant to the changes in these cell populations during treatment of Graves' disease. In contrast to these reports we have found no in vitro effect of pharmacologically relevant concentrations of methimazole (MMI) (100 mumol/l) on (i) NK cell function using K562 cells or MOLT-4 cells as targets, (ii) K cell function using antibody-dependent cytotoxicity assays with L929 cells or thyroid-antigen-coated chick red cells, or (iii) monocyte-dependent cytotoxin-mediated killing of L929 cells. Enhanced cytotoxicity was found with 1 mmol/l MMI in some of these assays but this was not consistent since it occurred only in certain individual cultures. Since we have shown previously that 100 mumol/l MMI inhibits oxygen radical generation, the present results add to the evidence that these radicals are not directly involved in cell-mediated cytotoxicity and do not support the concept that antithyroid drugs have a significant effect on antibody-dependent cell-mediated cytotoxicity in Graves' disease.

Adult↗
PubMed1985

The effects of hyperthyroidism on experimental autoimmune thyroiditis in the rat.

The effects of hyperthyroidism on experimental autoimmune thyroiditis were investigated in the rat. Rats were given T4 twice daily by sc injection in amounts sufficient to raise circulating hormone levels 10-fold 4 h after administration. Thyroiditis was induced by immunization with rat thyroglobulin (Tg) in complete Freund's adjuvant, and the severity of the disease was assessed by comparison with saline-treated controls. Thymic and splenic hypertrophy were found in T4-treated animals, whereas lymph node wt decreased. The levels of Tg antibodies did not differ between animals given saline and those given T4, but the expected sustained rise in control animals was not seen in those treated with T4; in addition, there was a significant decrease in the amount of Tg antibody produced by in vitro culture of lymph node lymphocytes from T4-treated rats. Continuous T4 administration lowered the number of T cells in the circulation, but the number of phenotypically identified helper cells remained the same. The most striking effects of T4 were to ameliorate the intensity of histologically defined thyroiditis and lower the response of lymph node T cells to the nonspecific mitogen, phytohemagglutinin. These results show that excessive T4 does not, as previously suggested, enhance the immune response in autoimmune thyroid disease: on the contrary, suppression is found with the dose and model we have used. In view of the magnitude of this effect, it is now important to identify the site of T4 action and investigate how this effect contributes to the autoimmune response in Graves' disease.

Animals↗
PubMed1985

Thyroid autoantigen-induced lymphocyte proliferation in Graves' disease and Hashimoto's thyroiditis.

Further progress in understanding T-cell interactions in autoimmune thyroid disease would be possible if T-cell lines and clones could be established. We have therefore examined peripheral blood lymphocyte proliferation in response to a variety of thyroid antigens in Graves' disease and Hashimoto's thyroiditis. A number of different culture conditions were used but in all cases the frequency and magnitude of positive responses were low, the maximum stimulation found for any individual culture with antigen being less than 4-fold above background proliferation. In addition we have examined the blastogenic response of Graves' lymphocytes from thyroid, cervical lymph node and thymus. Positive responses were again found but the stimulation produced by antigen was only 3-fold above background. These results are compatible with recent findings in experimental autoimmune thyroiditis and suggest either that very few antigen-specific T cells are involved in the autoimmune process or that antigen-specific cells exist which can suppress the proliferative response in vitro. It therefore seems unlikely that randomly collected peripheral blood T cells from patients with autoimmune thyroid disease can be sufficiently stimulated by thyroid autoantigens to establish lines or clones without additional manoeuvres such as fractionation into subsets.

Antigens↗
PubMed1984

The accumulation of [35S]methimazole by monocytes and macrophages.

We have used an automatic cell harvester and micro culture techniques to examine the accumulation of [35S]methimazole by monocytes, macrophages and lymphocytes. Significant temperature-dependent accumulation of the drug was found in resting monocytes and macrophages; this was increased up to 4-fold by phagocytosis. Lymphocytes accumulated little or no drug and myeloma and leukaemic cell lines accumulated none. These results show that two interrelated cells with endogenous peroxidatic activity take up the antithyroid drug methimazole providing further support for the concept that immunosuppression by this drug in Graves' disease is mediated via an action on antigen-presenting cells.

Animals↗