Search PubMed⌕ Search

Biomedical subjects

D Duffy

Publications and source records attributed to D Duffy.

At least 19 recordsLinked to original sources
PubMed2006

The phenotype and survival of antigen-stimulated transgenic CD4 T cells in vivo: the influence of persisting antigen.

Naive and primed/memory CD4 T cells are distinguished by changes in the expression of activation/adhesion molecules that correspond with an altered function. Adoptively transferred TCR transgenic (tg) CD4 T cells specific for ovalbumin peptide (OVA-pep) were analysed for changing phenotype and the speed of change in vivo following antigen challenge with alum-precipitated (ap) OVA-pep, a conjugate that stimulated a Th2-type cytokine response. The change of CD45RB in relation to number of divisions showed that the transition from CD45RB(hi) (naive) to CD45RB(low) (primed/memory) was incremental; with each cell cycle the number of CD45RB(hi) molecules on the cell surface was diluted by approximately half and replaced by the low-weight isoform. Similarly, the change to CD44(hi) expression increased gradually during four rounds of proliferation. The loss of CD62L expression occurred early and was independent of cell division. CD69 was up-regulated quickly within 1-2 cycles, but down-regulated after about seven divisions. The expression of CD49d was not altered during the early rounds of division, although it was up-regulated on 30-60% of tg T cells dividing repeatedly (>or=8 cycles). When analysed on day 3 following stimulation, CD25 was no longer up-regulated. The intra-peritoneal injection of ap-OVA-pep stimulated tg T cells in the spleen and mesenteric lymph node one day in advance of those in more distant peripheral lymph nodes. Evidence indicated that residual antigen persisted for at least 4 weeks and was able to stimulate naive tg T cells. However, residual antigen had no net effect on extending or reducing survival of the transferred population.

Animals↗
PubMed2005

Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population.

BACKGROUND: The cysteinyl-leukotrienes (cys-LTs) are important pro-inflammatory mediators in asthma, and have been shown to have a role in specific disease subtypes, including asthma severity. Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5-lipoxygenase activating protein (FLAP), and asthma. We hypothesized that polymorphisms in this gene are associated with asthma and in particular, with asthma severity, in an Australian population. OBJECTIVE: To screen the coding region of the ALOX5AP gene for polymorphisms and to determine the association between previously described polymorphisms and asthma and asthma severity in an Australian population. METHODS: We used PCR-SSCP and PCR-RFLP analysis to examine a previously described promoter polyA variable repeat polymorphism and two intronic polymorphisms (IVS2+12C>A, IVS2+105T>C), and to screen all five exons of the gene for new polymorphisms, in a large Australian population of randomly selected, non-asthmatic controls (n=457), mild asthmatics (n=274), moderate asthmatics (n=231) and severe asthmatics (n=79). RESULTS: We confirmed the presence of two polymorphisms in intron 2 and found no association between these polymorphisms and asthma or asthma severity, nor between a promoter polymorphism in the ALOX5AP gene and asthma or asthma severity. Gene fragment analysis of the promoter polymorphism revealed novel, conserved repeat numbers in our population, and no new polymorphisms were found in the coding region of the gene. CONCLUSION: These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys-LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.

5-Lipoxygenase-Activating Proteins↗
PubMed2005

A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women.

BACKGROUND: Airway remodelling is a characteristic feature of chronic asthma and there is evidence that an airway imbalance between levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) is associated with airway remodelling. On this basis, we hypothesised that polymorphisms in the MMP-9 and TIMP-1 genes were associated with the disease process. METHODS: A number of MMP-9 and TIMP-1 gene polymorphisms were examined in an adult white Australian population of mild (n = 259), moderate (n = 213) and severe (n = 71) asthmatics and non-asthmatic controls (n = 406) using PCR-RFLP and PCR-SSCP analyses. RESULTS: MMP-9 -1562C>T and 836G>A (Arg279Gln) were not associated with asthma (p> or =0.15) or asthma severity (p> or =0.13), and TIMP-1 434T>C (Phe124Phe) was not associated with asthma in women (p = 0.094) or men (p = 0.207). In this population, MMP-9 -861C>T and TIMP-1 323C>T (Pro87Pro) were not informative (with minor allele frequencies of <1%), and MMP-9 -1702T>A and TIMP-1 595C>T (Ser178Phe) were not detectable. However, a novel polymorphism was detected in the TIMP-1 gene 536C>T (Ile158Ile) which was significantly associated with asthma in women (p = 0.011; OR = 5.54, 95% CI 1.66 to 34.4) but not in men (p = 1.0). 536C>T was found to be in linkage disequilibrium with 434T>C, and haplotype analysis supported an association with asthma (p = 0.014). CONCLUSIONS: This is the first reported association between a polymorphism in the TIMP-1 gene and asthma, and supports the hypothesis that the protease/antiprotease balance has an important role in this common disease.

Adolescent↗
PubMed2005

The CD14 C-159T polymorphism is not associated with asthma or asthma severity in an Australian adult population.

BACKGROUND: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to play a role in the polarisation of T lymphocytes into Th1 and Th2 subsets, thereby influencing the cytokine profile and subsequent IgE production in response to antigen/allergen contact in allergic phenotypes. A functional C-159T polymorphism has been described in the promoter region of the gene and has been associated with increased gene expression, atopy, and non-atopic asthma in different ethnic populations. A study was undertaken to examine the association between the C-159T polymorphism and asthma, asthma severity, and atopy in a large Australian white population. METHODS: PCR-RFLP analysis was used to characterise the C-159T polymorphism in mild (n = 264), moderate (n = 225) and severe (n = 79) asthmatic patients and non-asthmatic controls (n = 443), including atopic (n = 688) and non-atopic (n = 323) individuals. Association analyses were performed using chi(2) tests. RESULTS: There was no association between the polymorphism and asthma (p = 0.468) or asthma severity (p = 0.727), and only a very weak association with atopy (p = 0.084). A meta-analysis of all studies conducted to date revealed similar genotypic frequencies in white ethnic populations and confirmed that there was no overall association with atopy (p = 0.52) or asthma (p = 0.23), although there was significant between study heterogeneity (p = 0.01). CONCLUSIONS: This study confirms that there is no association between the CD14 C-159T polymorphism and asthma or asthma severity and a weak association between this polymorphism and atopy in an adult population.

Asthma↗
PubMed2004

CCR5-Delta32 mutation is strongly associated with primary sclerosing cholangitis.

CCR5 plays a key role in the distribution of CD45RO+ T cells and contributes to generation of a T helper 1 immune response. CCR5-Delta32 is a 32-bp deletion associated with significant reduction in cell surface expression of the receptor. We investigated the role of CCR5-Delta32 on susceptibility to ulcerative colitis (UC), Crohn's disease (CD) and primary sclerosing cholangitis (PSC). Genotype and allelic association analyses were performed in 162 patients with UC, 131 with CD, 71 with PSC and 419 matched controls. There was a significant difference in CCR5 genotype (OR 2.27, P=0.003) between patients with sclerosing cholangitis and controls. Similarly, CCR5-Delta32 allele frequency was significantly higher in sclerosing cholangitis (17.6%) compared to controls (9.9%, OR 2.47, P=0.007) and inflammatory bowel disease patients without sclerosing cholangitis (11.3%, OR 1.9, P=0.027). There were no significant differences in CCR5 genotype or allele frequency between those with either UC or CD and controls. Genotypes with the CCR5-Delta32 variant were increased in patients with severe liver disease defined by portal hypertension and/or transplantation (45%) compared to those with mild liver disease (21%, OR 3.17, P=0.03). The CCR5-Delta32 mutation may influence disease susceptibility and severity in patients with PSC.

Adult↗
PubMed2001

Response biases in auditory forebrain regions of female songbirds following exposure to sexually relevant variation in male song.

In many species of songbirds, individual variation between the songs of competing males is correlated with female behavioral preferences. The neural mechanisms of song based female preference in songbirds are not known. Working with female European starlings (Sturnus vulgaris), we used immunocytochemistry for ZENK protein to localize forebrain regions that respond to sexually relevant variation in conspecific male song. The number of ZENK-ir cells in ventral caudo-medial neostriatum [NCMv] was significantly higher in females exposed to longer songs than in those exposed to shorter songs, whereas variation in the total duration of song exposure yielded no significant differences in ZENK expression. ZENK expression in caudo-medial ventral hyperstriatum [cmHV] was uniformly high in all subjects, and did not vary significantly among the three groups. These results suggest that subregions of NCM in female starlings are tuned to variation in male song length, or to song features correlated therewith. Female starlings exhibit robust behavioral preferences for longer over shorter male songs (Gentner and Hulse; Anim Behav 59:443-458, 2000). Therefore, the results of this study strongly implicate NCM in at least a portion of the perceptual processes underlying the complex natural behavior of female choice.

Acoustic Stimulation↗
PubMed2001

Familial Paget's disease of bone: nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree.

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees. We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log10 of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42. These data confirm the genetic heterogeneity of Paget's disease of bone. Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.

Adult↗
PubMed2000

Suicide and self-harm in inpatient psychiatric units: a national survey of observation policies.

There is little empirical literature on observation as a psychiatric nursing procedure to prevent patients from harming themselves or others. National guidelines for this practice do not exist, with a consequence that local policies might be variable in content and quality. This paper reports a national survey of observation policies and usage based upon a stratified random sample of 27 psychiatric inpatient service providers in England and Wales. Extreme variation in terminology and practice was encountered. The terminological confusion is likely to reduce nurses' clarity about their responsibilities and increase risks to patients. Further variation exists from place to place as to whether, and to what extent, student nurses and family members should be entrusted with the responsibility to observe patients. More than one in 10 services of the sample still have no written observation policy, and four in 10 have no clinical recording system of the procedure in place. Nurses commonly amend the procedure and terminology on an ad hoc basis. The results of this survey confirm that the Department of Health should set national standards for the policies and procedures for patient observation and that as an interim step practice guidance should be issued to all nurses (and other mental health workers) involved in this procedure.

Documentation↗
PubMed1999

CDKN2A variants in a population-based sample of Queensland families with melanoma.

BACKGROUND: Mutations in the CDKN2A gene confer susceptibility to cutaneous malignant melanoma (CMM); however, the population incidence of such mutations is unknown. Polymorphisms in CDKN2A have also been described, but it is not known whether they influence melanoma risk. We investigated the association of CDKN2A mutations and polymorphisms with melanoma risk in a population-based sample of families ascertained through probands with melanoma. METHODS: The 482 Queensland, Australia, families in our sample were characterized previously as having high, intermediate, or low family risk of CMM. Unrelated individuals (n = 200 families/individuals) drawn from the Australian Twin Registry served as control subjects. For individuals in the high-risk group, the entire CDKN2A gene coding region was screened for mutations by use of the polymerase chain reaction, agarose gel electrophoresis, allele-specific oligonucleotide (ASO) hybridization, and single-strand conformation polymorphism analysis. The intermediate- and low-risk families and control subjects were analyzed by ASO hybridization for a total of six recurring mutations as well as for polymorphisms at nucleotides (Nts) 442, 500, and 540. RESULTS: CDKN2A mutations were found only in the high-risk families (nine [10.3%] of 87). The prevalence of the Nt500G (guanosine) polymorphism increased linearly with increasing familial risk (two-sided P = .02) and was highest in the nine (primarily Celtic) families with CDKN2A mutations. After adjustment for ethnic origin, the relationship between risk group and the frequency of the Nt500G allele was weakened (P = .25); however, there was no relationship between ethnic origin and Nt500-polymorphism frequency among the control subjects. CONCLUSIONS: CDKN2A mutations are rare in this population (approximately 0.2% of all melanoma cases in Queensland) and appear to be associated with melanoma in only the most affected families. The Nt500G allele appears to be associated with familial risk, but this association probably reflects Celtic ancestry.

Autoradiography↗
PubMed1999

Clinical benefits of lightweight compression: reduction of venous-related symptoms by ready-to-wear lightweight gradient compression hosiery.

BACKGROUND: Medical-grade compression of class I (20-30 mmHg) and class II (30-40 mmHg) have been shown to be beneficial against venous hypertension or congestion. Relatively few studies address the effects of ready-to-wear (RTW) lightweight gradient compression pantyhose on venous symptoms. OBJECTIVE: To perform a study comparing the effects of two different compression RTW lightweight gradient compression stockings (8-15 mmHg and 15-20 mmHg) on the venous symptoms of flight attendants. METHOD: A prospective crossover trial of symptom evaluation in 19 flight attendants was performed in which participants rated their symptoms on a visual analog scale. During the initial phase, participants wore no compression for 2 weeks. They then wore 8-15 mmHg and 15-20 mmHg gradient compression support hose while flying over a 4-week period. Symptoms before and after wearing the gradient compression stockings were compared and statistically analyzed. RESULTS: Wearing of 8-15 mmHg gradient hose resulted in statistically significant improvement of discomfort (P < 0.01). Swelling, fatigue, aching, and tightness of the leg were all improved to a statistically significant degree (P < 0.01). For 15-20 mmHg gradient hosiery, symptoms were improved to a statistically significant or almost significant level. The difference between the 8-15 mmHg and 15-20 mmHg compression was not statistically significant. CONCLUSIONS: Use of lightweight (low compression) RTW gradient compression hosiery is very effective in improving symptoms of discomfort (P < 0.01), swelling (almost P < 0. 05), fatigue (P < 0.05), aching (P < 0.01), as well as leg tightness. Improvement of symptoms is statistically significant compared to no compression when hosiery was worn regularly during waking hours for 4 weeks.

Adult↗
PubMed1998

Microbial growth in a steady-state model of ethylene glycol-contaminated soil.

Biodegradation of ethylene glycol was tested in a laboratory-scale, steady-state infiltration system of two arid region soil types by monitoring indigenous microbial growth after the infiltration of three concentrations of ethylene glycol. Microorganisms in the soils were able to adapt to the ethylene glycol in several cases, resulting in higher numbers of microorganisms and lower pHs in the effluents. These microorganisms were identified and were able to use ethylene glycol as a sole carbon source. The adaptation was seen best with high-moisture-content soils when the ethylene glycol concentrations were 1% or 10%. However, acclimation to 0.1% and 10% ethylene glycol did not occur in low-moisture-content clay soil, but did occur in low-moisture-content silt soil, indicating that soil type and moisture content are important factors. In all cases, microbial diversity decreased over time.

Bacteria↗
PubMed1998

Measurement of how well a paediatric training programme prepares graduates for their chosen career paths.

To provide a sound basis for modification of our paediatric residency education programme, we surveyed graduates from the past 16 years. The questionnaire was designed to determine the adequacy of training rotations in preparing graduates for their career paths. Questionnaires were mailed to 81 graduates; 73 (90%) replied. A modified version was completed by 27 of 29 current residents (93%). For most rotations, responses were normally distributed. However, 10 or more respondents identified exposure in one area as 'excessive' and in 6 as 'inadequate'. Current residents scored many rotations as 'inadequate', likely indicative of their limited exposure to actual practice. Recommendations were consistent for subjects needing more instruction. All major issues raised by graduates had been identified by faculty, but the substantiation enabled changes to be made with widespread support. We recommend periodic survey of graduates to evaluate how well education is preparing residents for their ultimate career paths.

Career Choice↗
PubMed1998

Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes.

The CCR5-Delta32 deletion obliterates the CCR5 chemokine and the human immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to strong resistance against HIV-1 infection and AIDS. A genotype survey of 4,166 individuals revealed a cline of CCR5-Delta32 allele frequencies of 0%-14% across Eurasia, whereas the variant is absent among native African, American Indian, and East Asian ethnic groups. Haplotype analysis of 192 Caucasian chromosomes revealed strong linkage disequilibrium between CCR5 and two microsatellite loci. By use of coalescence theory to interpret modern haplotype genealogy, we estimate the origin of the CCR5-Delta32-containing ancestral haplotype to be approximately 700 years ago, with an estimated range of 275-1,875 years. The geographic cline of CCR5-Delta32 frequencies and its recent emergence are consistent with a historic strong selective event (e.g. , an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving its frequency upward in ancestral Caucasian populations.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Novel susceptibility gene for late-onset NIDDM is localized to human chromosome 12q.

NIDDM has a substantial genetic component, but the nature of the genetic susceptibility is largely unknown. Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of NIDDM characterized by an early age of onset and autosomal dominant inheritance, and linkage studies have identified genes that are mutated in different MODY pedigrees on chromosome 20 (MODY1 locus, hepatocyte nuclear factor-4alpha [HNF-4alpha] gene), chromosome 7 (MODY2 locus, glucokinase gene), and chromosome 12 (MODY3 locus, HNF-1alpha gene). We studied an extended pedigree in which multiple members are affected by late-onset NIDDM associated with insulin resistance and performed linkage analysis with four microsatellite markers in the MODY3 region of chromosome 12q. We found significant evidence for linkage between NIDDM and the MODY3 locus (logarithm of odds score 3.65 at theta = 0.008 telomeric to marker D12S321), but sequencing of the 10 exons and promoter of HNF-1alpha did not identify any causative mutation in this gene. Our results indicate that the region of chromosome 12q close to MODY3 harbors a novel susceptibility gene or genes for NIDDM.

Adult↗