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P Brett

Publications and source records attributed to P Brett.

18 recordsLinked to original sources
PubMed2006

NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study.

INTRODUCTION: Neutrophils (PMN) in aggressive periodontitis (AgP) patients have been reported to be hyperactive especially with regards to superoxide production. Polymorphisms in genes influencing PMN function have been proposed as candidate risk factors for AgP. The aim of this study was to test the association of specific gene polymorphisms affecting PMN functions with AgP. MATERIALS AND METHODS: Two hundred and twenty-four patients with confirmed diagnosis of AgP and 231 subjects with healthy periodontium took part in the study. A blood sample was collected from subjects and genotypes for p22phox (CYBA) NADPH oxidase, FP, Fcalpha and Fcgamma receptors were analysed in a blind fashion. RESULTS: The C242T p22phox NADPH oxidase T allele was significantly associated with AgP in a multiple logistic regression model adjusting for confounders, and this was observed for all subjects [p = 0.002, odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.27-2.83] and Caucasians (p = 0.009, OR=2.07, 95% CI = 1.20-3.59). Concomitant presence of C242T p22phox NADPH oxidase T allele and FcgammaRIIIb NA1 homozygosity was associated with the generalized AgP phenotype in Caucasians (p = 0.001, OR = 30.35, 95% CI = 3.81-241.97). CONCLUSIONS: C242T p22phox NADPH oxidase and FcgammaR polymorphisms may predispose to AgP through a modulation of neutrophil superoxide production.

Adult↗
PubMed2004

Gene expression profiling of bone cells on smooth and rough titanium surfaces.

Titanium (Ti) and Ti alloys are widely used as dental and orthopaedic implants, but the effects of the surface characteristics of these materials on the response of cells and target tissues is not well understood. The present study has therefore examined the effects of a rough Ti (RT) and a smooth Ti (ST) surface on human bone cells in vitro. Scanning electron microscopy showed attachment and spreading of cells on both surfaces. Expression profiling using ATLAS gene arrays showed marked differences in gene responses after 3 h of culture. A number of osteoblast genes were identified as "roughness response" genes on the basis of changes in expression on the RT compared with the ST surfaces. The surface roughness of Ti was thus found to have a profound effect on the profile of genes expressed by the bone cells, and suggests that improvements in the biological activity and possibly the clinical efficacy of these materials could be achieved by selective regulation of gene expression mediated by controlled modification of Ti surface.

Adult↗
PubMed2004

Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13.

OBJECTIVES: To localize genes influencing the susceptibility to Gilles de la Tourette syndrome (GTS) and associated chronic multiple tics (CMT). METHOD: A single, large, multiple affected pedigree containing 35 subjects diagnosed with GTS and a further 14 with CMT was genotyped for markers spanning the autosomes. Linkage analysis was carried out using classical lod score analysis and model-free lod score analysis. All markers were subjected to two-point analysis, and markers producing a two-point result significant at P<0.005 were subjected to three-point analysis using adjacent markers. RESULTS: The following markers produced at least one result significant at 0.005 using two-point analysis: D5S1981, D5S2050, D10S591, D10S189, D13S217, and D14S288. Three-point analysis with D5S2050 and D5S400 produced a lod of 2.9 with CMT. Three-point analysis of D10S591 and D10S189 produced lods of 1.9 with GTS and CMT. Three-point analysis of D13S217 and D13S171 produced a lod of 2.7 with GTS. No single haplotype appeared to account for the majority of cases within the pedigree. CONCLUSIONS: It seems likely that more than one susceptibility allele is present in the pedigree. Although none of the three positive regions is conclusively implicated, it seems probable that at least one contains a susceptibility locus. We recommend that association-based studies be carried out in these three regions to produce further evidence for a localization and to carry out fine-mapping.

Chromosome Mapping↗
PubMed2001

Identification of the acid phosphatase (acpA) gene homologues in pathogenic and non-pathogenic Burkholderia spp. facilitates TnphoA mutagenesis.

Burkholderia pseudomallei and Burkholderia mallei are pathogens responsible for disease in both humans and animals. Burkholderia thailandensis, while phylogenetically similar, is considered avirulent in comparison. These three species exhibit phosphatase activity when grown on media containing chromogenic substrates such as 5-bromo-4-chloro-3-indolyl phosphate (XP). Tn5-OT182 mutagenesis has been utilized to isolate mutants of B. pseudomallei and B. thailandensis unable to hydrolyse XP. Sequence analysis of these mutants revealed an ORF of 1734 nucleotides demonstrating a high degree of homology to the acpA gene product of Francisella tularensis. PCR primers were designed based on the B. pseudomallei acpA gene sequence and were used to amplify an acpA homologue from B. mallei. The predicted amino acid sequence of B. pseudomallei AcpA differed from those of the predicted B. thailandensis AcpA and B. mallei AcpA by 15 and 3 amino acids, respectively. Allelic exchange was used to construct DeltaacpA mutants in each of these Burkholderia spp. These mutants were shown to be devoid of phosphatase activity and have subsequently allowed for the implementation of phoA fusion transposon mutagenesis systems. Two such systems have been successfully utilized in Burkholderia spp. for the identification of several genes encoding exported proteins.

Acid Phosphatase↗
PubMed1998

Roles and influence of people who accompany patients on visits to the doctor.

OBJECTIVES: To determine the proportion of patients who are accompanied by another person (ie, partner, child, relative, friend) during visits to their doctors; to describe the demographic characteristics and role(s) assumed by the main accompanying person and the nature of the presenting dyads; and to describe the influence of the main accompanying person on the patient-doctor interaction. DESIGN: Prospective observational survey. SETTING: Family practices in London, Ont, and surrounding area. PARTICIPANTS: Eight family physicians completed surveys on 100 consecutive patients attending for both regularly scheduled and emergency visits. MAIN OUTCOME MEASURES: Roles and influence of the main accompanying person. RESULTS: Approximately one third (30.4%) of patients were accompanied during visits to their doctors. Children and patients older than 75 years most frequently had another person with them. Most patients (74.1%) were accompanied by one person who most often was female (72.6%) and between the ages of 21 and 40 years (53.6%). The accompanying person's role was most frequently described by doctors as an advocate for the patient (n = 235, 68.5%). If the accompanying person was a child, however, the role was most often described as a silent observer (n = 36, 68.6%). The influence of the main accompanying person on the patient-doctor encounter was usually described as positive (95.1%). CONCLUSIONS: Physicians report that people accompanying patients usually have a positive influence on medical encounters. Future studies need to include patients' and accompanying persons' perspectives.

Adolescent↗
PubMed1996

TIMP-3 is expressed in the human retinal pigment epithelium.

TIMP-3 is the most recent member of the tissue inhibitor of metalloproteinases (TIMP) family. In the present study, we describe the expression of TIMP-3 messenger RNA (mRNA) by the retinal pigment epithelium of the normal human eye (hRPE). In addition to the three predominant transcripts of approximately 5.1, 2.8, and 2.4 Kbp found in several other human tissues at adult and fetal stages. The hRPE also expresses two RNA species of 1.2 and 1.0 Kbp. Based on the sequence analysis of cDNA clones isolated from a hRPE cDNA library, the use of alternate polyadenylation signals could account for the expression of these smaller transcripts. The possibility of an alternative mechanism of regulation of the expression of TIMP-3 by the RPE is not discarded. The number of RNA transcripts specific for TIMP-3 per nanogram of poly A+ RNA was quantified by RT-PCR. 9.6 x 10(5) transcripts per nanogram of polyA +RNA were found at the adult stage and 1.2 x 10(6) transcripts per nanogram of polyA +RNA were detected at the fetal stage. These findings were supported by the predominant labeling in the RPE layer of retinal tissue sections in in situ hybridization experiments. All of these data support the hypothesis that the production of TIMP-3 by the RPE may be crucial for the maintenance of Bruch's membrane, the complex layer of extracellular matrix that provides a structural substrate for the RPE in the healthy retina and is perturbed during the ageing process and in Sorby's Fundus Dystrophy a inherited disease.

Adult↗
PubMed1996

A genetic linkage study of the D2 dopamine receptor locus in heavy drinking and alcoholism.

BACKGROUND: Reports of an association between restriction fragment length polymorphisms (RFLPs) at the dopamine D2 receptor (DRD2) locus and alcoholism have suggested involvement of that locus in the aetiology of alcoholism. METHOD: Sib pair linkage analyses were conducted in families multiply affected by alcoholism, using both the Taql 'A' RFLP and a microsatellite repeat polymorphism at the DRD2 locus. RESULTS: The 'Identical By Descent' analysis provided significant evidence of an effect of the DRD2 locus on the liability to develop heavy drinking (P < 0.0016) and Research Diagnostic Criteria alcoholism (P < 0.0003) in the first sample of families studied. However, this result was explicable by the segregation of alleles in a single large sibship, and it was not replicated in a second sample of families. CONCLUSIONS: The results do not support linkage between the DRD2 locus and alcoholism in most of the families studied. It remains possible that this locus influences the predisposition to alcoholism in some families.

Alcoholism↗
PubMed1993

Segregation and linkage analysis in five manic depression pedigrees excludes the 5HT1a receptor gene (HTR1A).

Five kindreds selected through probands attending an Icelandic hospital were recruited for linkage studies of manic depression. The rates of affection were equal for males and females and the age of onset appeared to be predominantly in early adult life, since prevalence did not rise appreciably with age. A complex segregation analysis was performed using the computer program POINTER to obtain maximum likelihood estimates of the contributions to liability from multifactorial transmission and a single major locus. Likelihood ratios between models supported a role for a single major locus which was dominant and had moderately high penetrance with, in the case of unipolar illness, additional multifactorial transmission. The best-fitting parameters were used to devise a transmission model for linkage analysis. Three markers on chromosome 5 were studied, at D5S76, D5S6 and D5S39. Strongly negative lod scores were obtained which were less than -2 over a distance of 40 cM, which included the region to which the gene for the 5HT1a receptor has been mapped.

Bipolar Disorder↗
PubMed1993

Genetic linkage analysis of manic depression in Iceland.

Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression.

Algorithms↗
PubMed1991

No evidence for a susceptibility locus predisposing to manic depression in the region of the dopamine (D2) receptor gene.

Recent reports of cytogenetic abnormalities linked to psychiatric illness and the localisations of the genes for the dopamine (D2) receptor and tyrosinase on the long arm of chromosome 11 have suggested that susceptibility loci for schizophrenia and manic depression might be situated in this region. We could find no evidence for linkage in five Icelandic pedigrees between manic depression and markers in this region, and we have excluded candidate genes coding for the D2 receptor and tyrosinase. We conclude that mutations at loci in this region are not a common cause of manic depression in the population studied.

Adult↗
PubMed1982

The effects of diltiazem and reduced serum ionized calcium on ischemic ventricular fibrillation in the dog.

Calcium influx blockers reportedly suppress ventricular arrhythmias during acute ischemia. We therefore studied the effects of diltiazem and reduced serum ionized calcium on ventricular fibrillation (VF) in a reversible ligation model. VF was produced at 15-minute intervals by simultaneous occlusion of the left anterior descending and circumflex arteries of 31 dogs. Time from coronary occlusion to onset of VF showed no significant variation during 15 consecutive trials in six dogs that received saline alone. Intravenous infusion of diltiazem (0.02 mg/kg per min) markedly delayed the onset of VF in each of 10 dogs (P less than 0.0001). Mean VF latency increased from 138 to 295 seconds during a 45-minute diltiazem infusion, declined exponentially when the infusion ceased, and was strongly correlated with serum diltiazem concentration (r = 0.96, P less than 10(-6)). In five dogs, hemodynamic measurements, including coronary venous blood flow, were performed during each occlusion. The increase in VF latency by diltiazem was not due to increased coronary flow during occlusion or to reduction of left ventricular (LV) mechanical work. In six dogs, mean serum ionized calcium, [Ca++], was reduced from 1.11 to 0.59 mM by infusion of sodium citrate. Citrate infusion increased mean VF latency from 155 to 243 seconds, and the increase observed in each dog was correlated (r = 0.84, P less than 10(-6)) with the reduction in [Ca++]. VF latency was unaffected by lidocaine in nine dogs. The antifibrillatory effect of diltiazem during global LV ischemia may be an electrophysiological phenomenon related to reduction of cellular calcium influx.

Animals↗
PubMedDate not supplied

Addictive behavior of older adults.

Very little is known about addictive alcohol use by older people. In the present paper personal effects reasons for drinking (i.e. drinking for the effects of alcohol) and concerns about drinking were used as indicators of addictive drinking behavior among a sample of 826 people aged 65 and older who participated in survey interviews in their homes. The relationship of addictive drinking behavior to frequency of drinking, quantity of drinks per occasion, and depressant drug use was examined. Alcohol use was higher among males and young-old (aged 65-74), while depressant medication use was higher among females and old-old (aged 75+). However, with the exception of use of over-the-counter medications containing codeine (which was significantly higher among current drinkers), no relationship existed between alcohol use and use of depressant medications. Personal effects reasons for drinking and concerns about drinking were related both to alcohol and depressant medication use. Frequency of drinking was associated with higher endorsement of both personal effects and social reasons, whereas volume of alcohol consumption (drinks per drinking day) was associated only with personal effects drinking. In addition, use of depressant medications by drinkers was significantly related to consuming alcohol for personal effects reasons (but unrelated to consuming for social reasons) and with having concerns about one's own drinking. These results suggest that even within the generally low levels of alcohol consumption of older people, addictive-use patterns emerge. In addition, the results confirm the importance of including depressant medication use in evaluating the drinking behavior of older people.

Age Factors↗