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Biomedical subjects

J R Chapman

Publications and source records attributed to J R Chapman.

At least 127 records · Page 7Linked to original sources

Immunoglobulin class and specificity of lymphocytotoxic antibodies after kidney transplantation.

The immunoglobulin class and specificity of the cytotoxic antibodies were investigated in sera collected during the first weeks following transplantation from 35 patients with functioning and 20 patients with failed grafts. No patient had had cytotoxic antibodies before the transplant, but 71.5% (25 of 35) of patients with functioning and 75% (15 of 20) of patients with failed graft subsequently developed them. The addition of dithiothreitol, which digests IgM antibodies, resulted in the disappearance of cytotoxicity in all positive sera from patients with a functioning graft. However, in the patients with failed grafts, the immunoglobulin class of the antibody varied; seven patients had only IgM antibodies, and seven had both IgM and IgG. After graft nephrectomy, IgG antibodies appeared in another six patients. In five of six patients with functioning grafts, mouse monoclonal antibodies blocked the cytotoxic activity; four with HLA-DQ monoclonal antibodies (Leu 10), one with HLA Class I (GD5). In the patients with failed grafts, blocking was seen in all nine patients studied; eight by GD5, six by Leu 10, and two by a monoclonal antibody to a monomorphic determinant of HLA-DR (100/77). Although the frequency of antibody-positive patients was similar in the successful and failed groups, the immunoglobulin class of the antibodies developed was IgM in the former group, whereas in the latter group some were IgM and others were IgG. Characterisation of the antibodies could be useful in the interpretation of a positive cross-match, since IgG antibodies are damaging to the graft whereas IgM antibodies are not.

Adult↗

Continuous-flow fast atom bombardment mass spectrometry.

The continuous-flow fast atom bombardment probe performs equally well with or without a high-performance liquid chromatography column producing clean spectra containing little or no background noise. Its function as a liquid chromatography-mass spectrometry interface for labile and involatile samples has been illustrated with reference to dansylated amino acids. The versatility of the new probe has been exemplified by on-line enzymatic peptide sequencing.

Amino Acids↗

Thermospray liquid chromatography-mass spectrometry in food and agricultural research.

A thermospray liquid chromatography-mass spectrometry interface connected to a double-focusing magnetic sector instrument has been applied successfully to the solution of a number of analytical problems in food and agricultural research. Examples of the qualitative analysis of some anti-nutrients, plant growth control hormones, biotechnology products and a plant polyphenol are presented and discussed.

Agriculture↗

Improvements in instrumentation for thermospray operation on a magnetic sector mass spectrometer.

Changes in the design of a thermospray liquid chromatography-mass spectrometry ion source can be made to improve the sensitivity towards solute related ions and therefore extend the practical utility of the complete system. The addition of a discharge ionization facility provides much greater scope for gradient elution analyses and forms the basis of a method which offers increased structural information. All of these changes are illustrated by practical examples.

Chromatography, High Pressure Liquid↗

Cyclosporin conversion versus conventional immunosuppression: long-term follow-up and histological evaluation.

129 patients who received a cadaver renal transplant entered a randomised prospective trial of cyclosporin for 3 months with conversion to azathioprine and prednisolone compared with conventional therapy of azathioprine and prednisolone. In the 64 patients who received cyclosporin, actuarial patient survival was 92%, and actuarial graft survival was 72% and 67% at 1 and 4 years after transplantation. Graft survival was significantly better (p less than 0.03) than in the 65 patients who received conventional therapy, in whom actuarial patient survival was 94%, and actuarial graft survival was 59% and 47% at 1 and 4 years. Renal function and other side-effects improved quickly after conversion with the better renal function maintained throughout follow-up. Renal biopsies at 90 days and 1 year in all patients did not show consistent improvement after conversion from cyclosporin in the histological features that might be attributable to cyclosporin toxicity. After conversion, 32% of the patients had acute rejection, generally within 30 days. 1 graft was lost to early acute rejection after conversion and another was lost 3 months later from acute-on-chronic rejection. A total of 8 grafts were lost to chronic rejection in the cyclosporin-treated group and 6 in the conventional group. The improvement in renal function obtained with this protocol of short-term cyclosporin with conversion to azathioprine and prednisolone has to be balanced against the risk of acute rejection and even loss of the graft after conversion.

Administration, Oral↗

A positive B cell crossmatch due to IgG anti-HLA-DQ antibody present at the time of transplantation in a successful renal allograft.

The role of a positive B cell crossmatch in renal transplantation is uncertain, partly because of the difficulty in determining the true specificity of the various antibodies that may cause a positive crossmatch. We have used monoclonal antibodies against HLA class I, HLA-DR and HLA-DQ antigens to inhibit cytotoxicity of sera from renal patients, in order to define the specificity of a positive B cell crossmatch. We have used reduction with dithiothreitol (DTT) to identify the immunoglobulin class. These methods were used to identify the specificity and immunoglobulin class of the antibody causing a positive B cell crossmatch in a highly sensitised patient. The results show that the antibody was IgG anti HLA-DQ and the graft was functioning 1 year after transplantation. Immunoperoxidase techniques demonstrated a normal expression of HLA-DQ antigen in biopsies of the transplanted kidney. The successful outcome of the transplant raises questions about the role of anti-HLA class II antibodies in renal transplantation.

B-Lymphocytes↗