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Biomedical subjects

R D Murdoch

Publications and source records attributed to R D Murdoch.

27 records · Page 2Linked to original sources

Platinum group metal sensitivity: reactivity to platinum group metal salts in platinum halide salt-sensitive workers.

The ability of closely related platinum group metal salts (PGMS) to cross-react with the principal sensitising agent ammonium hexachloroplatinate IV was investigated in refinery workers. Selected subjects were screened by skin prick test, specific RAST, RAST inhibition, and primate PCA tests. These showed--but only in platinum-sensitive subjects--a low prevalence of skin and RAST sensitivity to the other PGMS and limited evidence of hapten specific cross-reactivity.

Animals↗

IgE antibody responses to platinum group metals: a large scale refinery survey.

All 306 South African platinum refinery workers (116 white, 190 coloured) accepted for employment on grounds of absence of evidence of atopy were investigated using the skin prick test and RAST to detect sensitivity to platinum, palladium, and rhodium salts. RAST studies were made for these, together with HSA and DNP-HSA RAST. Of the 306 workers, 38 had a positive skin prick test to the platinum halide salts; of these, one gave a positive reaction to the palladium salt and six to the rhodium salt. There were no isolated positives to the rhodium and palladium halide salts. Total IgE levels were raised in 24 of the 38 (63%) platinum salt prick test positive workers compared with only 43 of the 268 (16%) prick test negative group (p less than 0.001). Positive RASTs were obtained in 62% of those with positive skin tests to the platinum salts. Four of the six giving positive rhodium salt skin tests gave a positive RAST to rhodium salt. Of these, two gave positive RASTS to HSA and all four to DNP-HSA. The palladium salt RAST was negative in the single skin test reactor. In the platinum salt skin test positive group a raised HSA RAST was obtained in 10.5% compared with only 2.5% in the skin negative group. Twenty one per cent of the platinum salt skin positive group had a raised RAST score to DNP-HSA with only 3.5% (4/116) in the skin test negative group, of whom three also had a raised HSA RAST. The latter findings are suggestive of IgE antibody production to new antigenic determinants in HSA produced by conjugation with the platinum salts.

Dermatitis, Occupational↗

Enhancement of antibody production by mercury and platinum group metal halide salts. Kinetics of total and ovalbumin-specific IgE synthesis.

The effects of halide salts of mercury, platinum and palladium on the synthesis of total and specific serum IgE and of total IgG were studied in groups of Hooded Lister rats immunised with antigen (ovalbumin) in the presence and absence of an adjuvant (Bordetella pertussis vaccine or aluminium hydroxide). Repeated intraperitoneal injections of mercuric chloride alone rapidly enhanced total IgE levels in control rats, independent of adjuvant. Injections of the platinum salt, however, elevated total IgE levels more slowly and then only in the B. pertussis-treated group. The halide salt of palladium was ineffective. In rats immunised with antigen and adjuvant, mercury treatment rapidly produced enhancement of the titre-specific IgE antibodies, whereas treatment with platinum again raised these levels more slowly. The palladium salt had no such effect.

Adjuvants, Immunologic↗

Cross reactivity studies with platinum group metal salts in platinum-sensitised rats.

Hooded Lister rats were sensitised to the halide salt of platinum ammonium tetrachloroplatinate(II)[(NH4)2PtCl4] in its conjugated form with ovalbumin. Sensitisation was achieved by intraperitoneal injection with Bordetella pertussis vaccine as adjuvant, followed 21 days later by a further injection in saline. The presence of specific anti-platinum IgE antibody was determined by passive cutaneous anaphylaxis (PCA) and radioallergosorbent test (RAST) using the platinum halide salt conjugated to a heterologous carrier. Sera exhibiting positive reactions were pooled and PCA tests performed on the titrated pooled sera with 3 conjugated platinum group metal salts, 5 platinum group metals in their free salt form and 6 platinum salts with differing ligands. PCA challenges with these compounds resulted in significant cross reactivity between ammonium tetrachloroplatinate(II), ammonium hexachloroplatinate(IV) and the conjugated tetrachloroplatinate. There was very limited cross reactivity with other platinum or platinum group metal salts in either free or conjugated forms. Furthermore, these results were confirmed by RAST inhibition studies.

Animals↗

Immunological responses to complex salts of platinum. II. Enhanced IgE antibody responses to ovalbumin with concurrent administration of platinum salts in the rat.

The effect of platinum group metal salts on IgE antibody synthesis in an animal model was studied with respect to the magnitude and kinetics of the response. In outbred Hooded Lister Rats immunized with 10 micrograms ovalbumin with B. pertussis as adjuvant and boosted with 1 microgram in saline an enhanced secondary response to ovalbumin was obtained when certain halide platinum salts were given concurrently with primary immunization. This phenomenon was limited to ammonium tetrachloroplatinate II, ammonium hexachloroplatinate IV and to a lesser extent the cesium trichloronitroplatinate II. Platinum group metal salts not possessing this characteristic were cis-dichlorodiammine plantinum II, tetra-ammineplatinum II chloride, ammonium aquopentachlororhodate III and ammonium tetrachloropalladate II. Kinetic studies show that the time courses of the primary and secondary responses were not altered in the presence of the platinum salts. In rats immunized with ovalbumin without adjuvant there was no detectable antibody and concurrent administration of platinum salts also had no effects. Thus platinum salts whilst acting synergistically with adjuvant to enhance antibody synthesis do not act as adjuvants in their own right.

Adjuvants, Immunologic↗

Immunological responses to complex salts of platinum. I. Specific IgE antibody production in the rat.

Ammonium tetrachloroplatinate II ([NH4]2 PtCl4) was used in free and conjugated forms with ovalbumin in an attempt to elicit specific antibody directed against either the free platinum (Pt) salt or the platinum moiety of ovalbumin-Pt conjugates in the hooded Lister rat. Immunization with free Pt salt via intraperitoneal, intramuscular, intradermal, subcutaneous, intratracheal and footpad routes over a wide range of doses (1 microgram-1 mg) employing both B. pertussis and/or aluminium hydroxide gel as adjuvants failed to induce specific IgE antibody, either primary or secondary, as shown by direct skin, PCA test or RAST. Conjugation of (NH4)2 PtCl4 with ovalbumin produced conjugates, with between two and 10 haptenic Pt groups per ovalbumin molecule, capable of inducing IgE antibody directed against the Pt moiety as determined by heterologous PCA challenge, where carrier cross-reactivity was excluded, and by specific RAST, confirmed by RAST inhibition.

Adjuvants, Immunologic↗

Rectal mucosal histamine release in ulcerative colitis.

1. Rectal dialysis in vivo was used to assess rectal mucosal release of histamine in patients with ulcerative colitis and in control subjects. 2. Rectal mucosal histamine release was significantly increased in ulcerative colitis, whether the patients were in remission or relapse. The highest values were found in active colitis, but in several such patients histamine release was within the control range. Measurement of rectal mucosal electrical potential difference suggested that increased mucosal histamine release in this group of patients was not due to enhanced epithelial permeability. 3. Rectal dialysis appears to be a useful method for assessing mucosal histamine production and the results obtained are consistent with the hypothesis that immediate hypersensitivity reactions could be of importance in some patients with ulcerative colitis.

Colitis, Ulcerative↗