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Biomedical subjects

H Dunckley

Publications and source records attributed to H Dunckley.

At least 55 records · Page 3Linked to original sources
PubMed1993

Systemic lupus erythematosus in Australian aborigines: high prevalence, morbidity and mortality.

BACKGROUND: Racial differences occur in the incidence of systemic lupus erythematosus (SLE). It has been suggested that SLE occurs at a higher prevalence and with greater severity in Aboriginal Australians, but because of the small, widely distributed population base, this has not been well documented. AIMS: To confirm and document the clinical impression of an increased prevalence and severity of systemic lupus erythematosus (SLE) in Aboriginal Australians, and to identify prognostic indicators. METHODS: Top End Northern Territory (NT) Aborigines with SLE on 1 January 1984 or diagnosed thereafter were followed until 1 January 1991. Epidemiological, clinical and serological data were collected. RESULTS: Prevalence on 1 January 1991 estimated at 1:1900, at least twice the estimated prevalence in non-Aboriginal Australians. High frequencies of renal disease (62% with proteinuria > 0.5 g/day) and autoantibodies to the Sm antigen (29%) were identified, contributing to the high mortality. Five year survival rate was 60%, with 67% of deaths resulting from infection. CONCLUSIONS: There is a high prevalence of SLE in NT Aborigines. In view of probable under-recognition of mild cases the true prevalence is likely to be even higher. Although morbidity and mortality may have been overestimated for the same reason, both were found to be high. Improved living conditions and health care delivery may improve prognosis.

Adolescent↗
PubMed1993

Analysis of HLA-DR matching in DNA-typed cadaver kidney transplants.

The effect of matching for HLA-DR antigens was analyzed retrospectively in 3455 cadaver kidney transplants that were typed by the DNA-RFLP method. HLA-DR matching improved the one-year graft survival rate significantly (P < 0.01). Importantly, in 718 first transplants in which the number of mismatches assigned by serological typing was different from that assigned by DNA typing, only the DNA results showed a significant impact of matching on graft outcome (P = 0.03). These results demonstrate that DNA typing is clinically relevant. We were unable to confirm that the HLA-DR6 specificity or the DR6-split DRB1*1302 are associated with poor graft survival.

Cadaver↗
PubMed1992

DNA typing: an important step forward? Collaborative Transplant Study.

In a collaborative project which was supported by 96 transplant centers, DNA typing of HLA-DR antigens was carried out on over 7,000 transplant donors and recipients at 8 participating laboratories. Approximately 25% of the individuals were found to have been typed incorrectly by serological means. An analysis of over 2,500 first cadaver kidney transplants showed a significant correlation of matching for the HLA-DR antigens in transplants where the serological typing was confirmed by DNA typing. In transplants where the serological typing was found to be incorrect, the analysis of serological HLA-DR mismatches resulted in no correlation with graft outcome whereas a significant correlation was found when the corrected DNA typed HLA-DR antigens were analyzed. Transplants which had been reported to the Collaborative Transplant Study based on serological typing as matched for HLA-A, -B, -DR or HLA-B, -DR were found to have a superior graft survival rate only if HLA-DR compatibility was confirmed by DNA typing.

DNA Fingerprinting↗
PubMed1992

Analysis of HLA class II allogenotyping in Australian aborigines and Papua New Guinea populations.

Human leukocyte antigen (HLA) class II allogenotyping has been applied to investigate the polymorphism of the DRB, DQB1, DQB2, DQA1, and DQA2 genes in Aborigines from the East Coast of Australia and in Melanesians from the Papua New Guinea North-East Coast and Highlands. Three new DR/DQ arrangements were observed, DRw14/DQB1-2b/DQA1-1a and DRw5Nauru/DQB1-3a/DQA1-2 (n Australian Aborigines), and DRw5Nauru/DQB1-1a/DQA1-1b (in Madang). DQA2 and DQB2 allogenotyping with TaqI and PstI digested genomic DNA revealed little polymorphism among the Papua New Guineans, with DQA2-Xa1 and DQB2-Xb1 the most common alleles in all the groups. However, the presence of DQA2-Xa2 in Papuans and Australian Aborigines reflects the degree of admixture with Caucasoids while the DQA2-Xa4 allele in Madang is probably a marker of Mongoloid origin.

Asian People↗
PubMed1991

Role of single amino acids in the recognition of a T cell epitope.

T cell epitopes can be defined by the use of synthetic peptides, which when added to APC efficiently mimic naturally processed Ag. Free peptide is thought to bind to cell-surface MHC glycoproteins and the TCR then recognizes the resulting complex. The specificity of a tetanus toxin-specific human Th cell clone was investigated using a complete replacement set of peptides in which every amino acid within the minimal T cell epitope was replaced by each of the 19 alternative genetically coded amino acids. Within the minimal epitope, found to be YSYFPSVI (tetanus toxin 593-600), a small number of substitutions could be made without significant loss of activity, defined as substitutions giving peptides whose activity fell within +/- 3 SD of the mean parent response. Y593 could be substituted with F, W, M, L, V, and I; S594 with G and T; Y595, F596, and P597 with no other amino acids; S598 with A; V599 with S, and I600 with L. Rank ordering of the substitutions allowed a precise description to be made of MHC and/or TCR interaction with each amino acid side chain within the epitope. Simplified theoretic calculations based on this study indicate that class II T cell recognition has a specificity greater than 1 in 10(8). Competition experiments indicate that Y595, F596, P597, and I600 are critical for binding of this epitope to its restricting element, HLA DR4Dw14.

Amino Acid Sequence↗
PubMed1991

Survival of DNA HLA-DR typed and matched cadaver kidney transplants. The Collaborative Transplant Study.

The clinical value of serological HLA matching for cadaver kidney transplantation remains uncertain because the success rate for HLA-matched cadaver transplants is lower than that of HLA-matched sibling grafts. Up to 25% of serological HLA-DR typings may be incorrect when compared with a more accurate DNA-RFLP method, and we have now examined whether incorrect HLA-DR typings account for the lower than expected success rates of HLA-matched cadaver transplants. 58 transplant centres took part in this study and DNA was extracted from over 4000 samples of frozen tissue at the study centre. 8 laboratories then completed blind RFLP typing for HLA-DR. Serological typing data were reported by individual transplant laboratories. 29 of 107 transplants (27%) that were reported as HLA A, B, DR compatible and 76 of 273 (28%) transplants that were reported as HLA B, DR compatible according to serological typing were found to be HLA-DR mismatched by DNA typing. The one-year transplant success rate for DNA-matched HLA, A, B, DR grafts was 87% compared with 69% for mismatched grafts (p less than 0.02); the corresponding success rate for DNA-matched HLA B, DR grafts was 85% compared with 72% for mismatched grafts (p less than 0.01). Many transplants that were previously thought to be HLA matched are mismatched, and this finding may account for previously unexplained graft failures.

Cadaver↗
PubMed1989

Gm allogenotype distribution and lack of HLA-DR, Gm interaction in SLE and CREST/PSS.

The distribution of Gm allogenotypes (Gm allotypes identified by IgCH restriction fragment length polymorphism (RFLP) analysis) was compared in 66 systemic lupus erythematosus (SLE) patients, 38 CREST/PSS group (P less than 0.05) but not in the SLE group. HLA-DR5 is significantly increased in frequency in this series of CREST/PSS patients compared to controls (P less than 0.001), and log linear regression analysis showed that although both DR5 and Gm homozygosity were significant factors determining disease susceptibility, there was no evidence of an interactive effect between these two groups of genes increasing the predisposition to CREST/PSS.

Autoimmune Diseases↗
PubMed1988

HLA-DR and -DQ DNA genotyping in seven populations of Asia-Oceania and Australia.

Haplotype patterns of HLA-DR and -DQ restriction fragment length polymorphisms (RFLPs) were compared in seven populations in the region of Asia-Oceania: Australian Caucasoids, Melanesians, micronesians, Polynesians, Chinese, Koreans, and Japanese. Several DR beta RFLP patterns, including those correlating with DR2, 4,5, w6, 7 and w8 in Caucasoids, were associated with multiple DQ alpha/DQ beta RFLP haplotypes, of which only two occurred universally - one associated with DR4 and one with DR5. RFLPs revealed new population or group specific characteristics, which had not been previously discovered using serological or cellular HLA typing techniques. The populations of Asia-Oceania have some features of the class II RFLPs in common, which are distinctly different from Caucasoids. On the other hand, a number of characteristics distinguish between the various Asian and Pacific groups. This study demonstrates the power of RFLP analysis of closely linked genes in population genetics, and shows the value of ethnic comparisons in further characterizing the polymorphisms of the HLA class II genes.

Asia↗
PubMed1988

Gm typing by immunoglobulin heavy-chain gene RFLP analysis.

This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now possible to define common Gm haplotypes in Caucasians by RFLP analysis. This method provides a useful adjunct to serological allotyping and indeed has several important advantages over traditional serology: it allows confident Gm assignment and the definition of homozygous and heterozygous Gm arrangements, is highly reproducible, and is readily executed in any molecular genetic laboratory.

Cloning, Molecular↗
PubMed1987

A high frequency of inherited deficiency of complement component C4 in Darwin Aborigines.

A high frequency of serum complement component C4A deficiency may explain the higher prevalence and greater severity of systemic lupus erythematosus reported in Australian Aborigines. Inherited deficiencies of serum complement components C4A, C4B, and C2 were examined in two Australian Aboriginal populations from Darwin and Alice Springs and compared with the prevalence of complement deficiencies in white Australian blood donors. The frequency of C4A deficiency alleles was 29% in Darwin Aborigines compared with 12% in Alice Springs and 17% in Canberra blood donors. Partial C4B deficiency was also higher in Darwin Aborigines than in the other populations. Inherited deficiency of serum complement component C2 was not observed.

Alleles↗
PubMed1987

Strong association between the major histocompatibility complex and systemic lupus erythematosus in southern Chinese.

The distribution of HLA-A, B, and DR alleles has been studied in 100 Chinese patients with systemic lupus erythematosus and in 100 healthy Chinese controls. Complement components factor B, C4A and C4B were studied in 72 patients and 61 controls. There was no significant difference between patients and controls in the distribution of HLA-A, HLA-B, factor B and C4B alleles, but there was a significant excess of HLA-DR2 and C4A null in the patients. An unusual variant of C4B was found in 6 patients and 1 control. The possible role of haplotypes is considered in interpreting these results and relating them to previous findings in Chinese.

Adolescent↗