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Biomedical subjects

D Middleton

Publications and source records attributed to D Middleton.

At least 19 recordsLinked to original sources
PubMed2004

Risk factors for Salmonella typhimurium DT104 and non-DT104 infection: a Canadian multi-provincial case-control study.

To identify risk factors for sporadic Salmonella Typhimurium definitive phage-type 104 (DT104) and non-DT104 diarrhoeal illness in Canada, we conducted a matched case-control study between 1999 and 2000. Cases were matched 1:1 on age and province of residence. Multivariate analysis suggested that recent antibiotic use [odds ratio (OR) 5.2, 95% confidence interval (CI) 1.8-15.3], living on a livestock farm (OR 4.9, 95% CI 1.9-18.9), and recent travel outside Canada (OR 4.1, 95% CI 1.2-13.8) are independent risk factors for DT104 illness. Similar analyses suggested that recent travel outside North America is a sizable risk factor for non-DT104 illness (OR 66.8, 95% CI 6.7-665.3). No food exposure was a risk factor in either analysis. Educating health-care providers and the public about appropriate antibiotic use and antimicrobial resistance is important. Appropriate administration of antibiotics to livestock, particularly cattle, and hygienic measures such as handwashing after contact with farm animals may reduce risk. Travel represents an important and probably underestimated risk factor for sporadic illness with S. Typhimurium. Improved national surveillance and detailed investigation of travel-related illness are required.

Adolescent↗
PubMed2004

HLA class I allele distribution of a Hong Kong Chinese population based on high-resolution PCR-SSOP typing.

A stem cell registry population from Hong Kong, of Chinese ethnicity, was examined for HLA-A and HLA-B alleles using a two-stage sequence-specific oligonucleotide probe system. Comparison of the HLA-A and HLA-B frequencies with different populations showed a close relationship with a Chinese population from Singapore, although there were several differences in the presence/absence of alleles at the HLA-B locus. Having the data available on these registry donors will influence the search strategy and the ongoing compilation of new donors to the registry. In addition, knowing which alleles do/do not occur in this population will aid in the distinction of ambiguities which result from the use of many of the typing kits available.

Alleles↗
PubMed2004

Investigation of killer cell immunoglobulin-like receptor gene diversity III. KIR2DL3.

The allelic variation of one of the chromosome 19 KIR genes, KIR2DL3, has been investigated using a polymerase chain reaction sequence-specific oligonucleotide probe-based methodology. The procedure has been applied to a healthy Northern Irish control group in order to establish phenotype and genotype frequencies in this Caucasian population. In addition, cell line DNA and Centre d'Etude du Humaine (CEPH) families, both from the 13th International Histocompatibility Workshop have been investigated, establishing control data for this gene.

Alleles↗
PubMed2003

Distribution of HLA-A alleles in eight ethnic groups from Pakistan.

The extreme polymorphism found at some loci of the HLA system has made it an invaluable tool for population genetic analyses. In this study eight diverse ethnic groups from Pakistan were analyzed at the HLA-A locus using sequence specific primers for polymerase chain reaction (PCR-SSP) and then further typed to the allele level using a two-stage sequence specific oligonucleotide probe (SSOP) strategy. Four of these ethnic groups (Burusho, Hazara, Kalash, Pathan) were from the north and four (Baloch, Brahui, Sindhi and Parsi) were from the south of Pakistan. Nine alleles were identified as unique to a particular ethnic group within Pakistan. Maximum variation was seen in the HLA-A*02 allele family for which 11 alleles were detected in the eight Pakistani ethnic groups. The alleles that showed significant variation between the Pakistani ethnic groups include A*0101, A*0206, A*0209, A*0207, A*0217, A*1101, A*2402/09 N/11 N, A*2902, A*3301 and A*3001. A phylogenetic tree based on DA distances for HLA-A allele frequencies separated the Pakistani populations from other world populations and also separated the only Dravidian speaking population of Pakistan, the Brahui, from the remaining Indo-European speaking ethnic groups of Pakistan.

Alleles↗
PubMed2003

New allele frequency database: http://www.allelefrequencies.net.

A new website (http://www.allelefrequencies.net) has been compiled to execute the frequency of alleles at various polymorphic regions of different populations in the field of histocompatibility and immunogenetics. Data for HLA alleles has been added but this will be extended to include frequency data of polymorphisms in other immunogenetic regions, e.g. cytokines, KIR receptors, MIC.

Alleles↗
PubMed2003

Are human platelet alloantigens (HPA) minor transplantation antigens in clinical bone marrow transplantation?

The role of human platelet alloantigens (HPA) in clinical bone marrow allotransplantation was investigated. The leading hypothesis was that HPA alloepitopes act as minor histocompatibility antigens and aggravate graft-versus-host disease (GVHD). To exclude the effect of MHC disparity, only HLA identical donor-recipient pairs were entered into the study. The influence of HPA compatibility on overall survival, occurrence of relapses and haematopoietic recovery was also investigated. A total of 223 patients who received a graft from an HLA-identical sibling, genotyped for HPA -1, -2, -3, -4 and -5, were observed over a post-transplant period of 24 months following the protocol recommended by EBMT. The data from patients having received grafts from HPA compatible donors were compared to data from patients having received grafts that were mismatched in HPA allotypes in the GVH direction. Analysis of the incidence of acute and chronic (GVHD), overall survival, relapse incidence, haematopoietic recovery and some other clinical parameters did not reveal any significant difference between the HPA-matched and -mismatched groups of patients, regardless of their age. Our results give no evidence that HPA-1, -2, -3 and -5 alloantigens should be considered minor transplantation antigens in clinical bone marrow transplantation.

Adult↗
PubMed2002

Distribution of HLA alleles in Portugal and Cabo Verde. Relationships with the slave trade route.

HLA-A, -B, and -DR frequencies were analysed in populations from Portugal and the Madeira and Cabo Verde Archipelagos, aiming to characterize their genetic composition. Portuguese settlers colonized both Archipelagos in the 15th and 16th centuries. Madeira received many sub-Saharan slaves to work in the sugar plantations, and Cabo Verde served as a pivotal market in the Atlantic slave trade and was populated by individuals coming from the Senegambia region of the West African coast. The population of Madeira shows the highest genetic diversity and the presence of alleles and haplotypes usually linked to sub-Saharan populations, the haplotypes accounting for 3.5% of the total. Cabo Verde presents typical markers acknowledged to be of European or Ibero-Mediterranean origin, thus revealing the admixture of European settlers with Sub-Saharan slaves. Altogether the number of European haplotypes reaches 15% of the total. The Portuguese population shows a perceivable and significant heterogeneity both in allele and haplotype frequencies, unveiling a differential input of peoples from different origins. A PCA of the populations studied, plus other relevant ones, clearly shows gene heterogeneity in mainland Portugal as well as the differences and relationships between these populations and Madeira and Cabo Verde.

Africa, Western↗
PubMed2002

A common KIR2DS4 deletion variant in the human that predicts a soluble KIR molecule analogous to the KIR1D molecule observed in the rhesus monkey.

A KIR2DS4 deletion variant allele, previously identified through KIR PCR-SSOP typing studies, was characterized, alongside a normal KIR2DS4 allele, by cDNA cloning and sequencing and its prevalence in the population determined using a deletion specific probe. The KIR2DS4 deletion variant was found in 72 of the 90 individuals screened and differed from the normal KIR2DS4 sequence by a single 22 bp deletion in exon 5. The deletion causes a frameshift predicting a truncated KIR2DS4 protein with a significantly altered D2 domain that would be secreted due to the loss of the transmembrane/cytoplasmic domains. Parallels with a recent study in the rhesus monkey highlighting access to the same open reading frame as the deletion variant, also predicting a soluble KIR molecule, are drawn.

Amino Acid Sequence↗
PubMed2002

The IL12B 3' untranslated region DNA polymorphism is not associated with early-onset type 1 diabetes.

A recent study employing Australian and UK type 1 diabetes families has demonstrated significant transmission bias to affected offspring of a polymorphism (1188A allele; termed allele 1) in the 3' untranslated region (3'UTR) of the interleukin 12B (IL12B) gene which encodes the IL-12p40 subunit of the pro-inflammatory cytokine IL-12. However, results from replication studies in other populations have been controversial. We performed both case-control (n=120 cases; n=330 controls) and family-based (n=307 families) association studies, using the transmission disequilibrium test, to investigate if allele 1 is associated with early-onset type 1 diabetes in Northern Ireland. No association was observed between allele 1 and type 1 diabetes in either case-control (80.8% vs 80.8%; P=0.98) or family-based (49.7% transmissions; P=0.94) studies. Our results do not support earlier reports of an association between allele 1 in the 3'UTR of the IL12B gene and type 1 diabetes.

3' Untranslated Regions↗
PubMed2002

Pathogenesis studies with Australian bat lyssavirus in grey-headed flying foxes (Pteropus poliocephalus).

OBJECTIVE: To examine the susceptibility of the grey-headed flying fox (Pteropus poliocephalus) to Australian bat lyssavirus (ABL), and to provide preliminary observations on the pathogenesis of the disease in flying foxes. PROCEDURE: Ten flying foxes were inoculated intramuscularly with ABL, and four with a bat-associated rabies virus. Inoculated animals were observed daily, and clinical samples collected every 9 to 14 days. Animals with abnormal clinical signs were euthanased, and samples collected for histological, serological, virological and immunohistological examinations. At 3 months post inoculation (PI), all survivors were euthanased, and each submitted to a similar examination. RESULTS: Three ABL-inoculated flying foxes, and two rabies-inoculated animals developed abnormal clinical signs between 15 and 24 days PI. All three ABL-inoculated animals had histological lesions consistent with a lyssavirus infection, and lyssaviral antigen was identified in the central nervous system (CNS) of each. Virus was isolated from the brain of two affected animals. Of the rabies-inoculated flying foxes, both had histological lesions and viral antigen in the CNS. Virus was recovered from the brain of only one. None of the five affected flying foxes developed anti-lyssavirus antibodies, but, by 3 months PI, five of the seven ABL-inoculated survivors, and one of the two rabies virus-inoculated survivors, had seroconverted. The dynamics of the immune responses were quite variable. CONCLUSIONS: The response of flying foxes to ABL, administered by a peripheral route of inoculation, was similar to that of bats inoculated peripherally with bat-derived rabies viruses.

Animals↗
PubMed2002

First identification of a ranavirus from green pythons (Chondropython viridis).

Ten juvenile green pythons (Chondropython viridis) died or were euthanized shortly after having been illegally imported into Australia from Indonesia in 1998. Histologic examination of two of the three snakes that died revealed moderately severe chronic ulceration of the nasal mucosa and focal or periacinar degeneration and necrosis of the liver. In addition there was severe necrotizing inflammation of the pharyngeal submucosa accompanied by numerous macrophages, heterophils, and edema. An iridovirus was isolated in culture from several tissues and characterized by immunohistochemistry, electron microscopy, enzyme-linked immunosorbent Assay, polyacrylamide gel electrophoresis, polymerase chain reaction and sequence analysis, restriction endonuclease digestion, and DNA hybridization. This is the first report of a systemic ranavirus infection in any species of snake and is a new member of the genus, Ranavirus.

Amino Acid Sequence↗
PubMed2001

Mismatched human leukocyte antigen alleles protect against heterosexual HIV transmission.

Genetic variation at the human leukocyte antigen (HLA) loci has been shown to be an important risk factor for progression to HIV disease, but its significance in infection is less well understood. We have investigated its role in HIV transmission in a cohort of individuals at risk for heterosexual infection. Analysis of over 80 individuals revealed that that the degree of concordance at HLA A, B, and DR loci differs significantly between transmitting and nontransmitting couples at risk for heterosexual HIV transmission (p <.02), suggesting that allogeneic immune responses may confer a degree of protection against HIV infection. Analysis of the frequencies of specific alleles at the A, B, and DR loci revealed a significantly higher frequency of HLA DR5 among exposed uninfected individuals, relative to population controls.

Alleles↗
PubMed2001

Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia: a case-control study.

BACKGROUND: Deposition of beta-amyloid in the brains of patients with Alzheimer's disease is thought to precede a chain of events that leads to an inflammatory response by the brain. We postulated that genetic variation in the regulatory region of the gene for the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) leads to increased risk of Alzheimer's disease and vascular dementia. METHODS: A polymorphism in the regulatory region of the TNF-alpha gene was analysed in a case-control study. The polymorphism (C-850T) was typed in 242 patients with sporadic Alzheimer's disease, 81 patients with vascular dementia, 61 stroke patients without dementia, and 235 normal controls. These groups of individuals were also genotyped for the apolipoprotein E polymorphism, and the vascular dementia and stroke groups were typed at the HLA-DR locus. FINDINGS: The distribution of TNF-alpha genotypes in the vascular dementia group differed significantly from that in the stroke and normal control groups, giving an odds ratio of 2.51 (95% CI 1.49-4.21) for the development of vascular dementia for individuals with a CT or TT genotype. Logistic regression analysis indicated that the possession of the T allele significantly increased the risk of Alzheimer's disease associated with carriage of the apolipoprotein E epsilon4 allele (odds ratio 2.73 [1.68-4.44] for those with apolipoprotein E epsilon4 but no TNF-alpha T, vs 4.62 [2.38-8.96] for those with apolipoprotein E epsilon4 and TNF-alpha T; p=0.03). INTERPRETATION: Possession of the TNF-alpha T allele significantly increases the risk of vascular dementia, and increases the risk of Alzheimer's disease associated with apolipoprotein E. Although further research is needed, these findings suggest a potential role for anti-inflammatory therapy in vascular dementia and Alzheimer's disease, and perhaps especially in patients who have had a stroke.

Aged↗