PubMed Health⌕ Search

Biomedical subjects

A Bushell

Publications and source records attributed to A Bushell.

At least 37 records · Page 2Linked to original sources

Restriction fragment analysis of the HLA class II region: application to tissue transplantation.

Southern blotting and hybridization with locus specific probes is a reliable method for the determination of HLA Class II specificities and in conjunction with several other techniques is providing valuable information on the nature of Class II polymorphisms in man. In terms of the identification of Class II specificities in transplantation however, the advanced nature of DR serology means that DR beta restriction fragment analysis is probably limited only to those situations where serological methods have been unsuccessful. Whether DQ and DP incompatibilities can evoke rejection responses in vivo remains to be fully ascertained although our preliminary data suggest that DQ mismatches probably have little effect upon graft outcome. Restriction fragment analysis is particularly attractive in that it enables reliable retrospective studies to be performed in conjunction with prolonged clinical follow up, and the technique will clearly continue to contribute significantly to our understanding of the importance of these molecules in transplantation.

Genes, MHC Class II↗

HLA-DQ mismatches between donor and recipient in the presence of HLA-DR compatibility do not influence the function or outcome of renal transplants.

Although matching of kidney donors and recipients for antigens of the HLA-DR series is considered to have a significant influence on graft outcome, the independent effects of incompatibilities for the closely linked HLA-DQ series of antigens are unknown largely because serological compatibility for HLA-DR usually ensures a corresponding compatibility for HLA-DQ. In a retrospective study using restriction fragment analysis we have identified clear HLA-DQ mismatches in 25 out of 62 recipients of HLA-DR-compatible kidney grafts. Though these incompatibilities correspond to differences at the cell surface and hence potential alloantigenic stimuli, none of the eight clinical parameters examined indicate that HLA-DQ mismatches in the presence of compatibility for HLA-DR have any significant effect on either graft function or outcome.

Adolescent↗

Genomic analysis identifies class II mismatches in serologically DR-compatible human renal allografts.

Many studies, including those from our own center, have shown that matching the donor and recipient for HLA-DR antigens has a beneficial effect on the outcome of cadaveric renal transplantation. However, cases of irreversible graft rejection are sometimes seen in patients who have received an HLA-DR-compatible kidney, suggesting that serologic compatibility for HLA-DR may not always ensure reduced alloreactivity toward the graft. We have examined a number of recipients and their serologically DR-compatible cadaveric donors by Southern blotting and hybridization with locus specific HLA class II probes in order to determine whether in these patients there were class II mismatches that had been undetected by serology. The results show that the analysis of DR beta restriction fragment patterns does little more than complement and confirm the serologic identification of HLA-DR. Hybridization with DQ alpha and DQ beta probes, however, significantly extends the number of DQ specificities that can be detected and suggests that DQ mismatches in DR-compatible donor-recipient pairs may be more common than previously supposed, although it is not possible to draw any conclusions on the influence of DQ incompatibilities in the presence of DR compatibility on graft outcome.

Cadaver↗

An interactive computer program for the analysis of HLA class II restriction fragment patterns.

There is considerable current interest in the application of Southern blotting and hybridization, with locus-specific HLA class II probes, to HLA typing. The work of several laboratories has shown that, under suitable conditions, restriction fragment patterns that correlate with DR and DQ serology and with DP cellular reactivities can be obtained from homozygous cell lines. Although the identification of class II specificities from restriction fragment patterns is relatively straightforward in homozygotes, the increased complexity of the patterns obtained from heterozygotes makes the interpretation considerably more difficult; this difficulty is compounded by even slight variation between and within gels. We have developed an interactive computer program that allows HLA-DR and DQ typing by the visual matching of restriction fragment pattern data with standard data derived from a panel of well-characterized homozygous cell lines. The program also uses a simple algorithm (after Southern) to estimate the fragment sizes in the unknown track. The screen display can be printed out to give a convenient record of the match; a numerical measure is also given of the goodness of fit of the new data.

Algorithms↗

Functional and biochemical subtypes of the haplotype HLA-DR3 in patients with celiac disease or idiopathic membranous nephropathy.

HLA class II beta-chain polymorphism was investigated in the haplotype HLA-DR3 to determine if patients with HLA-DR3-associated diseases express normal or variant class II polymorphisms. Analysis was carried out by two-dimensional gel electrophoresis of immunoprecipitated HLA class II molecules, DNA hybridization with DR beta and DQ beta gene probes on Taq 1, Bam H1, or Rsa 1 digests, and mixed lymphocyte culture. Two subtypes of HLA-DR3 were identified in normal homozygous DR3 individuals on the basis of polymorphism in one of two DR beta chains detected, corresponding to differences in DR beta restriction fragment patterns. These polymorphisms exhibited significant linkage disequilibrium with the A1,B8,DR3 and B18,DR3 haplotypes, respectively. In proliferative experiments, cells with the B18,DR3-associated polymorphism strongly stimulated cells from donors with the B8,DR3-related polymorphism, suggesting that a T-cell epitope recognized by B8,DR3 cells lies on the B18,DR3-associated DR beta chain. In seven HLA-DR3 homozygous patients with celiac disease and three HLA-DR3-homozygous patients with idiopathic membranous nephropathy, only the normal patterns of HLA class II molecules were displayed, the B8,DR3 type occurring in all patients and the B18,DR3 type in one patient. These data suggest that celiac disease and idiopathic membranous nephropathy are not related to disease-specific HLA-DR beta or -DQ beta gene variants within the DR3 population that are revealed by these methods.

Adult↗

A histopathologic, histobacteriologic, and radiographic study of periapical endodontic surgical specimens.

Data available on 230 periapical endodontic surgical specimens were studied. It was found that bacteria occurred in the periapical tissue very infrequently. In addition, there was no correlation between the presence of acute inflammatory cells and the presence or absence of pain. Granulomas with epithelium occurred in 61 out of 230 cases, while 14 of these were cysts. Of the 110 cases with radiographic follow-up data, 67 were classified as successful, 40 were uncertain, and 3 were unsuccessful according to a modification of Strindberg's criteria, whereas 107 would have been successes according to the criteria of Bender and Seltzer and their associates. No valid biologic or clinical basis for endodontic therapy as suggested by Bhaskar was found in this material.

Connective Tissue↗