PubMed Health⌕ Search

Biomedical subjects

H Dunckley

Publications and source records attributed to H Dunckley.

At least 19 recordsLinked to original sources
PubMed2005

Immune response genes in the post-Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever.

BACKGROUND: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear. AIM: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups. DESIGN: Genetic association study. METHODS: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population. RESULTS: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels. DISCUSSION: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.

Coxiella burnetii↗
PubMed2004

New HLA-B alleles detected by polymerase chain reaction-sequence-specific oligonucleotide typing: HLA-B*0725, B*0728, and B*3808.

Three novel alleles, human leukocyte antigen (HLA)-B*0725, B*0728, and B*3808, were discovered during routine genotyping of samples for the Australian Bone Marrow Donor Registry and Australian Cord Blood Bank. The new alleles contain amino acid changes in the antigen-binding site of the expressed HLA protein, which may alter the antigen-binding properties of the functional protein.

Base Sequence↗
PubMed2004

Detection of a novel HLA-A allele by polymerase chain reaction-sequence-specific oligonucleotide typing: HLA-A*0252.

Anew human leukocyte antigen (HLA) class I allele, HLA-A*0252, has been found during routine typing of samples for the Australian Bone Marrow Donor Registry. A*0252 differs from A*020101 at four codon positions, with all the new polymorphisms resulting in an amino acid change. The amino acids involved are located in the antigen-binding region of the HLA protein.

Base Sequence↗
PubMed2004

A new HLA-B allele, B*1565, identified in three unrelated samples.

Anew human leukocyte antigen-B allele, B*1565, has been identified during routine typing of cord blood samples. Subsequently, two individuals from the same family as the first cord blood sample plus two unrelated Australian Bone Marrow Donor Registry samples have been found to carry this novel allele.

Amino Acid Sequence↗
PubMed2004

Identification of two novel HLA class II alleles, DQB1*030503 and DRB1*0447.

Two novel human leukocyte antigen (HLA) class II alleles have been identified in routine typing of bone marrow donors for the Australian Bone Marrow Donor Registry in Sydney, Australia. Sequence analysis of exon 2 of both the DQB1 and DRB1 genes revealed the novel polymorphism. A silent substitution of G to A at nucleotide position 210 has been identified for the DQB1*030503 allele when compared to the closest matched allele, DQB1*030501. There is no associated amino acid difference between the translated products of the two alleles. The second new allele is a variant of the DRB1 gene. The DRB1*0447 allele was identified with three nucleotide substitutions compared to the closest matched allele DRB1*0436. There is a silent mutation at nucleotide position 303, G to C and two substitutions at adjacent nucleotide positions 344 and 345, T to G and G to T, respectively. The latter two substitutions result in an amino acid change from valine to glycine at position 86, implicating a different specificity and affinity of antigen binding.

Alleles↗
PubMed2004

Identification of three novel HLA class I alleles: HLA-B*3928, HLA-B*400104 and HLA-B*4437.

Three new human leukocyte antigen (HLA) class I alleles have been identified in the Tissue Typing Laboratory in Sydney, Australia. Sequence analysis of exon 2 and exon 3 of the HLA-B gene revealed the novel polymorphism. A silent substitution of C to T at nucleotide position 369 has been identified for the HLA-B*400104 allele when compared to the closest matched allele, HLA-B*400101. The HLA-B*3928 allele was identified with a nucleotide substitution of G to C at position 362 when compared to the closest matched allele, HLA-B*390101, resulting in an amino acid substitution of Arginine to Threonine. A nucleotide substitution of C to G at position 572 resulting in the amino acid change Serine to Tryptophan was identified in the new allele HLA-B*4437, when compared to the closest matched allele HLA-B*440301. Both amino acid substitutions implicate a different specificity and affinity of antigen binding for the alleles HLA-B*3928 and HLA-B*4437.

Alleles↗
PubMed2004

Identification of new HLA-C alleles by polymerase chain reaction-sequence specific oligonucleotide typing: Cw*0314 and Cw*1511*.

In this article, we report two new human leukocyte antigen-C (HLA-C) alleles, HLA-Cw*0314 and Cw*1511, which were identified during routine tissue typing of donors for the Australian Bone Marrow Donor Registry and Australian Cord Blood Bank. HLA-Cw*0314 shows six codon changes in exon 3 compared to Cw*030401 and shares some sequence homology with Cw*07 alleles. Cw*1511 has two nucleotide changes compared with Cw*150201 in exon 2, both resulting in amino acid changes in the protein sequence.

Alleles↗
PubMed2004

Identification of two novel HLA class II alleles, DQB1*0311 and DQB1*0620.

Two novel HLA class II alleles have been identified in routine typing of a kidney transplant patient and a cord blood unit from the Australian Cord Blood Bank in Sydney. Sequence analysis of exon 2 of the DQB1 genes revealed the novel polymorphism. A substitution of A to C at nucleotide position 136 has been identified for the DQB1*0311 allele when compared to the closest-matched allele, DQB1*030201. An identical substitution has also been identified for the DQB1*0620 allele when compared to the closest-matched allele, DQB1*0602. The substitution results in an amino acid change from methionine to leucine at position 46 implicating different specificity and affinity of antigen binding.

Alleles↗
PubMed2002

Identification of sequence errors in HLA-DRB1*0801 and HLA-DRB1*12011.

We report the identification of previously unrecognised errors in the nucleotide sequences of two long established HLA-DRB1 alleles, DRB1*0801 and DRB1*12011. The errors were detected during development of sequencing based typing (SBT) methods for the HLA-DRB1 locus and were confirmed by sequencing cell lines from the 10th International Histocompatibility Workshop (IHW).

Alleles↗
PubMed2002

Six new HLA class I alleles detected by PCR-SSO genotyping.

This paper describes six new alleles; A*0240, A*2614, B*3924, B*4425, Cw*0807 and Cw*12023, which were discovered during routine genotyping with sequence specific oligonucleotides (SSO's). Five of the new alleles have changes in residues which belong to the antigen binding site of the HLA protein. These new variants may have altered antigen binding properties and may cause differential immunological responses that could affect transplantation outcome1.

Base Sequence↗
PubMed2002

Novel HLA-DRB1 alleles revealed by sequencing based typing, DRB1*04053 and DRB1*1143.

We report the discovery of two HLA-DRB1 alleles by sequencing based typing (SBT). DRB1*04053 differs from previously reported DRB1 alleles by a single synonymous nucleotide substitution, resulting in a unique polymorphism at codon 93. DRB1*1143 differs from previously identified DRB1 alleles by a single non-synonymous nucleotide substitution, resulting in a polymorphism observed in other DRB1 and DRB3 alleles1.

Alleles↗
PubMed2001

PCR-RFLP typing detects new HLA-DRB1 alleles: DRB1*13022, DRB1*1336 and DRB1*1435.

It is difficult to resolve all heterozygous combinations of the HLA-DRB1*03, *08, *11, *12, *13 and *14 allele group in a one-step generic HLA-DRB1 typing system. Therefore, it is common to employ a secondary technique utilizing group-specific primers to amplify this group of alleles separately from the other HLA-DRB1, -DRB3, -DRB4 and -DRB5 alleles. This paper describes a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for broad typing of the HLA-DRB1*03, *08, *11, *12, *13 and *14 alleles which, as well as being time-efficient and cost-effective, has so far allowed the detection of 10 new alleles. The new alleles were identified after following up unusual or novel PCR-RFLP patterns. Of the 10 novel alleles found so far with this method, seven have been described previously while three, DRB1*13022, DRB1*1336 and DRB1*1435, are presented here.

Alleles↗
PubMed2000

Monophosphoryl lipid A and QS21 increase CD8 T lymphocyte cytotoxicity to herpes simplex virus-2 infected cell proteins 4 and 27 through IFN-gamma and IL-12 production.

We have shown previously that IFN-gamma pretreatment of human epidermal cells (ECs) cultured in vitro partially reverses down-regulation of surface MHC class I by HSV infection, allowing recognition by CD8 CTLs, and that HSV immediate early (IE)/early (E) proteins are the predominant targets for CD8 CTLs. In this study of 25 subjects, CD8 CTLs recognized the HSV-2 IE infected cell protein 27 (ICP27) (expressed in autologous IFN-gamma-pretreated, Vaccinia virus recombinant-infected ECs) in all subjects studied, ICP4 in 89%, and ICP0 in 11%. The main hierarchy of recognition was ICP27 > ICP4. ICP27 was the dominant target in 89% of subjects but showed great individual variability in the degree of cytotoxicity. CD8 cytotoxicity specific for HSV-2 IE proteins was enhanced by 48-67% when CD8 CTLs were coincubated with the combination of monophosphoryl lipid A and QS21 adjuvants at the time of Ag presentation. These adjuvants also significantly enhanced IL-12 and IFN-gamma production from nonadherent mononuclear cells stimulated by HSV-2-infected ECs. Addition of IL-12 and IFN-gamma at the time of initial Ag presentation enhanced CD8 cytotoxicity to levels comparable with those stimulated by the adjuvants. Addition of neutralizing Abs to IL-12 or IFN-gamma inhibited CD8 T cell cytotoxicity up to 95% when a combination of the Abs were added at the time of initial Ag presentation. Therefore, the mechanism for the enhancement of CD8 T cell cytotoxicity by adjuvants in this system appears to be via increased levels of IL-12 and IFN-gamma.

Adjuvants, Immunologic↗
PubMed2000

New DRB1* alleles (HLA-DRB1*1135, DRB1*1430 and DRB1*1433) and a confirmatory sequence (DRB1*1133).

Three new DRB1 alleles (DRB1*1135, DRB1*1430 and DRB1*1433) and a confirmatory sequence (DRB1*1133) have been identified after following up unusual or novel polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) patterns during routine typing of the DRB1*03,*08,*11,*12,*13 and *14 allele groups. Of the new alleles found and described in this paper, two alleles were initially detected by the PCR-RFLP method which produced unexpected restriction polymorphism (DRB1*1133 and DRB1*1135) while the remaining two were found after following up rare allele typings from this technique (DRB1*1430 and DRB1*1433).

Alleles↗
PubMed2000

A new HLA-A*02 allele, A*0234, detected by polymerase chain reaction using sequence-specific primers (PCR-SSP).

A novel HLA-A*02 allele, A*0234, was identified in a potential unrelated bone marrow donor typed by polymerase chain reaction using sequence-specific primers (PCR-SSP). Positive reactions obtained upon testing with PCR-SSP did not fit any known combination of alleles indicating the possible presence of a novel allele. Sequencing of clones from this individual revealed the presence of a novel allele, HLA-A*0234. The sequence of exons 2, 3 and part of exon 4 showed that A*0234 differed from A*02011 by a single nucleotide in exon 2 at position 282 (C to G). The nucleotide substitution results in an amino acid change at residue 70 (Histidine to Glutamine) in the alpha1 domain.

Alleles↗
PubMed2000

Routine HLA-B genotyping with PCR-sequence-specific oligonucleotides (PCR-SSO) detects eight new alleles: B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508.

This paper describes eight new alleles (B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508) that have been found by routine HLA-B genotyping with sequence-specific oligonucleotides (SSOs). All of the new alleles have variations which cause changes in residues that occur within antigen binding pockets and T-cell recognition sites of the antigen. The new polymorphisms within these new alleles may affect the nature and specificity of peptide binding and cause differential T-cell activation, which may have an affect in transplantation.

Alleles↗