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C D Pusey

Publications and source records attributed to C D Pusey.

151 records · Page 9Linked to original sources
PubMed1979

Acute renal failure in burns.

We present the combined experience of a burns unit and a renal dialysis unit in treating acute renal failure in burn injury patients. A total of 28 cases have been treated of whom 4 regained normal renal function. We would like to emphasize the following points which may improve the usually very poor prognosis: early diagnosis, early daily haemodialysis, adequate feeding and the early amputation of non viable limbs. A search of the literature reveals that only 11 previously reported cases of burns injury patients being successfully dialysed for acute renal failure.

Acute Kidney Injury↗
PubMedDate not supplied

Identification of the Goodpasture antigen, alpha 3(IV) NC1, and four other NC1 domains of type IV collagen, by amino-terminal sequence analysis of human glomerular basement membrane separated by two-dimensional electrophoresis.

Two-dimensional (2-D) electrophoresis of collagenase-digested human glomerular basement membrane (GBM), containing the Goodpasture antigen, revealed a range of monomeric (24-30 kD) and dimeric (43-56 kD) subunits present across a pI range of 3-10. Five distinct alpha(IV)-chains were identified by amino-terminal sequence analysis of 18 of these components transferred to polyvinylidene difluoride membrane. The positions of the well-characterised 26-kD alpha 1(IV)-chain and 24-kD alpha 2(IV)-chain were confirmed. A highly cationic 28-kD monomer was identified as the alpha 3(IV)-chain, while more neutral 28-kD monomers were found to contain the alpha 4(IV)-chain. Sequences from neutral 26-kD monomers corresponded to the known cDNA sequence of the alpha 5(IV)-chain. The presence of charge isoforms of the alpha 1(IV)- and alpha 4(IV)-chains was confirmed by identification of several monomers with different pI but the same sequence. Sequence analysis of dimeric components demonstrated homodimers of alpha 1(IV), alpha 2(IV) and alpha 4(IV), and suggested the presence of heterodimers of alpha 3/alpha 5 and alpha 1/alpha 5. 2-D Western blots of human GBM, with anti-GBM autoantibodies, a monoclonal antibody (P1) to the Goodpasture antigen and a monoclonal antibody to the alpha 3(IV)-chain, demonstrated that the major autoantigenic epitope was localised to the alpha 3(IV)-chain, but that there was also reactivity with the alpha 4(IV)-chain.

Amino Acid Sequence↗
PubMedDate not supplied

Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens.

Anti-neutrophil cytoplasm antibodies (ANCA) are strongly associated with the development of systemic vasculitis. Myeloperoxidase and proteinase-3 have been identified as targets for P-ANCA and C-ANCA, respectively. Both enzymes are released from neutrophil azurophil granules following neutrophil activation and both are highly cationic. Purified myeloperoxidase is demonstrated to bind non-convalently to endothelial cell membranes, to retain its enzymic function following binding, and to retain its antigenicity for P-ANCA. Endothelial cell-bound myeloperoxidase enhances complement-dependent cytotoxicity of some P-ANCA sere that also contain anti-endothelial cell antibodies. Studies using purified proteinase-3 show that it also can bind to endothelial cells and be recognized by C-ANCA. The interactions of myeloperoxidase and proteinase-3 with endothelial cells and ANCA may thus contribute to the development of vascular injury in patients with systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMedDate not supplied

The functional affinity and specificity of autoantibodies in animal models of anti-glomerular basement membrane disease.

We studied characteristics of the anti-glomerular basement membrane (GBM) antibody response in three animal models of Goodpasture's disease: treatment of Brown Norway (BN) rats with the polyclonal activator mercuric chloride (HgCl2), and immunization of BN and Wistar Kyoto (WKY) rats with rat GBM. Serial serum samples were obtained over the time course of the models, and anti-GBM antibodies eluted from the kidneys. Functional affinity of the anti-GBM antibodies was measured in a solid-phase ELISA incorporating the mild chaotropic agent diethylamine. Evidence for shared epitope specificity with human anti-GBM antibodies was sought using competition ELISA. As with recent studies in human anti-GBM disease, there was no evidence for affinity maturation of the anti-GBM response in the serum of any of the animal models. Antibodies eluted from the kidneys were of higher functional affinity than serum antibodies only in the HgCl2-treated BN rat. There was no obvious correlation between the functional affinity of the antibodies and the severity of nephritis in the three models. Competition studies between eluted anti-GBM antibodies from the rat models and human anti-GBM antibodies did not provide any evidence for shared epitope recognition. This study provides further information on the extent to which these models reflect the human disease.

Animals↗
PubMedDate not supplied

Still a role for plasma exchange in rapidly progressive glomerulonephritis?

Plasmapheresis combined with immunosuppression dramatically improved the survival of patients with Goodpasture's disease in the late 1970's. The presence of circulating pathogenic autoantibodies in this disease provided a logical rationale for the use of plasma exchange therapy. Careful analysis of the response to treatment has suggested that patients presenting with a serum creatinine < 600 mumol/I have the most benefit from plasma exchange. Subsequently plasmapheresis has been tried in a variety of other nephritides, predominantly those causing rapidly progressive glomerulonephritis, with variable success. Initial studies failed adequately to distinguish patients with a number of quite distinct causes of crescentic nephritis. However it has become clear that plasma exchange significantly improves the outcome of patients with pauci-immune crescentic glomerulonephritis who present with severe renal failure requiring dialysis, but not those with less severe renal disease.

Anti-Glomerular Basement Membrane Disease↗