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Nicola Jones

Publications and source records attributed to Nicola Jones.

At least 19 recordsLinked to original sources
PubMed2011

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

ATP-Binding Cassette Transporters↗
PubMed2006

Enhanced invasiveness of bovine-derived neonatal sequence type 17 group B streptococcus is independent of capsular serotype.

BACKGROUND: A defined geographical area (Oxford, United Kingdom) was investigated for the role of group B Streptococcus (GBS) as a human pathogen. METHODS: GBS carriage in pregnant women and invasive disease in neonates and adults >60 years of age was studied over a 3-year period. Multilocus sequence typing and capsular serotyping were used to study 369 isolates of GBS from carriage in pregnant women (n=190) and invasive disease in neonates (n=109) and adults >60 years of age (n=70). RESULTS: A total of 20.3% of pregnant women carried GBS. Invasive GBS disease occurred at a rate of 0.9 cases per 1000 live births and 11 cases per 100,000 population >60 years of age per annum. Four sequence types (STs) (ST-17, ST-19, ST-23, and ST-1) that were identified with use of multilocus sequence typing accounted for >50% of carried and invasive strains. A single sequence type (ST-17), previously shown to be phylogenetically of bovine origin, was significantly associated with increased invasiveness in neonates (P=.00002), and this was independent of capsular serotype III. In contrast, among adults >60 years of age, no STs exhibited increased invasiveness, compared with STs carried in pregnant women. CONCLUSIONS: Enhanced invasiveness associated with ST-17 is specific to neonates and is independent of capsular serotype.

Adult↗
PubMed2005

Genetic islands of Streptococcus agalactiae strains NEM316 and 2603VR and their presence in other Group B streptococcal strains.

BACKGROUND: Streptococcus agalactiae (Group B Streptococcus; GBS) is a major contributor to obstetric and neonatal bacterial sepsis. Serotype III strains cause the majority of late-onset sepsis and meningitis in babies, and thus appear to have an enhanced invasive capacity compared with the other serotypes that cause disease predominantly in immunocompromised pregnant women. We compared the serotype III and V whole genome sequences, strains NEM316 and 2603VR respectively, in an attempt to identify genetic attributes of strain NEM316 that might explain the propensity of strain NEM316 to cause late-onset disease in babies. Fourteen putative pathogenicity islands were described in the strain NEM316 whole genome sequence. Using PCR- and targeted microarray- strategies, the presence of these islands were assessed in a diverse strain collection including 18 colonizing isolates from healthy pregnant women, and 13 and 8 invasive isolates from infants with early- and late-onset sepsis, respectively. RESULTS: Side-by-side comparison of the strain NEM316 and strain 2603VR genomes revealed that they are extremely similar, with the only major difference being the capsulation loci and mobile genetic elements. PCR and Comparative Genome Hybridization (CGH) were used to define the presence of each island in 39 GBS isolates. Only islands I, VI, XII, and possibly X, met criteria of a true pathogenicity island, but no significant correlation was found between the presence of any of the fourteen islands and whether the strains were invasive or colonizing. Possible associations were seen between the presence of island VI and late-onset sepsis, and island X and early-onset sepsis, which warrant further investigation. CONCLUSION: The NEM316 and 2603VR strains are remarkable in that their whole genome sequences are so similar, suggesting that the capsulation loci or other genetic differences, such as pathogenicity islands, are the main determinants of the propensity of serotype III strains to cause late-onset disease. This study supports the notion that GBS strain NEM316 has four putative pathogenicity islands, but none is absolutely necessary for disease causation, whether early- or late-onset sepsis. Mobile genetic elements are a common feature of GBS isolates, with each strain having its own peculiar burden of transposons, phages, integrases and integrated plasmids. The majority of these are unlikely to influence the disease capacity of an isolate. Serotype associated disease phenotypes may thus be solely related to differences in the capsulation loci.

Genome, Bacterial↗
PubMed2005

Population structure of group B streptococcus from a low-incidence region for invasive neonatal disease.

The population structure of group B streptococcus (GBS) from a low-incidence region for invasive neonatal disease (Israel) was investigated using multilocus genotype data. The strain collection consisted of isolates from maternal carriage (n=104) and invasive neonatal disease (n=50), resolving into 46 sequence types. The most prevalent sequence types were ST-1 (17.5 %), ST-19 (10.4 %), ST-17 (9.7 %), ST-22 (8.4 %) and ST-23 (6.5 %). Serotype III was the most common, accounting for 29.2 % of the isolates. None of the serotypes was significantly associated with invasive neonatal disease. burst analysis resolved the 46 sequence types into seven lineages (clonal complexes), from which only lineage ST-17, expressing serotype III only, was significantly associated with invasive neonatal disease. Lineage ST-22 expressed mainly serotype II, and was significantly associated with carriage. The distribution of the various sequence types and lineages, and the association of lineage ST-17 with invasive disease, are consistent with the results of analyses from a global GBS isolate collection. These findings could imply that the global variation in disease incidence is independent of the circulating GBS populations, and may be more affected by other risk factors for invasive GBS disease, or by different prevention strategies.

Carrier State↗
PubMed2005

Caspase inhibition improves ischemia-reperfusion injury after lung transplantation.

Ischemia-reperfusion injury is associated with cell death in many organ systems. The role of programmed cell death (PCD) pathways and the ultimate clinical relevance of PCD in the context of lung transplantation (LTx) are unknown. In randomized and blinded studies, rat single LTx was performed in the presence of caspase inhibitors after 'short' (6 h) and 'long' (18 h) periods of cold ischemic storage. Lung function, electron microscopic morphology, caspase 3, 8 and 9 activities and TUNEL assays were evaluated. Endothelial cells and lymphocytes were observed undergoing apoptotic cell death with electron microscopy. Caspase activities were significantly up-regulated immediately after the initial flush and increased further during short periods of cold ischemic storage. A significant amount of apoptotic cell death was observed after LTx and reperfusion. Caspase inhibition virtually eliminated apoptotic cell death and led to improved lung function after LTx and reperfusion. Activation of caspases during cold ischemia contributes significantly to cell death in LTx. Suppression of caspase activity appears to decrease apoptosis and improve lung function. Clearly, this needs to be investigated further with more experiments to validate the potential role of caspase inhibition as a therapeutic modality in ischemia-reperfusion-induced lung injury.

Animals↗
PubMed2004

Health status ten years after pediatric liver transplantation--looking beyond the graft.

BACKGROUND: Little is known about long-term health after pediatric orthotopic liver transplantation (OLT). This study aimed to characterize the health status of recipients 10 years after OLT, with an emphasis on transplant-related morbidity and quality of life. METHODS: We performed a retrospective database review of 32 children who underwent OLT before October 1992 at one center and were alive after 10 years. Outcome measures were assessed 10 years after OLT. Cantril's self-anchoring scale was used for global quality of life assessment. RESULTS: Synthetic liver function at 10 years was preserved in all patients. The annual rate of episodes of acute rejection dropped markedly after the first year (1.4 at year 1 to 0.19 rejections/patient/year at year 10). Histologically confirmed chronic rejection developed in eight (25%) patients. At 10 years, long-term complications included mild to severe chronic renal failure (77%), mild chronic anemia (59%), and hypertension (25%). Significant growth retardation (z-score < -2), hyperlipidemia, and diabetes were uncommon. Infection requiring hospitalization occurred in 81% of the patients, with varicella zoster virus as the most common pathogen. Epstein-Barr virus-related malignancies affected 22% of patients. Ten-year survivors perceived quality of life as very good. Self-reporting of drug nonadherence by seven (22%) adolescents may have contributed to development of late onset rejection in this subgroup. Conclusions. Children who are 10-year survivors of OLT have excellent graft function and, despite chronic extrahepatic morbidities, a self-reported high quality of life.

Adolescent↗
PubMed2004

Multilocus sequence typing of serotype III group B streptococcus and correlation with pathogenic potential.

Serotype III group B streptococcus (GBS) causes more invasive disease in infants than do other serotypes in North America. We used multilocus sequence typing to identify clones within 28 invasive serotype III GBS isolates identified from a population-based study and 55 serotype III GBS colonizing isolates from a cohort of women from the same population. Ten allelic sequence types (STs) were identified and primarily involved 2 profiles: ST-19 (57.1% of invasive isolates and 58.2% of colonizing isolates) and ST-17 (32.1% of invasive isolates and 29.1% of colonizing isolates). On concatenation, the 10 allelic profiles converged into 3 groups. Group 1 consisted of ST-19 complex, ST-36, and ST-1, and was closely related to reference genome 2603V/R (serotype V). Group 2 consisted of ST-17 complex. Group 3 consisted of ST-23 complex and was closely related to the serotype III genome strain NEM 316. Neither of the major sequence types or groups was more commonly associated with invasion (P=.61) or with lower levels of maternal capsular polysaccharide-specific IgG (0.89 microg/mL and 0.39 microg/mL, respectively) for ST-19 and ST-17 (P=.86). The close association of genomic strain 2603V/R (serotype V) with ST-19 suggests that the phenomenon of capsule switching may have occurred.

Alleles↗
PubMed2004

Sirolimus for pediatric liver transplant recipients with post-transplant lymphoproliferative disease and hepatoblastoma.

Sirolimus is a promising immune suppressive agent, with the potential to reduce calcineurin inhibitor associated nephrotoxicity, halt progression of chronic rejection and prevent tumor proliferation. The aim of this study was to review the experience using sirolimus in pediatric liver transplant recipients at a single center. Database and medical charts of all pediatric liver transplant recipients receiving sirolimus at the Hospital for Sick Children in Toronto were reviewed. Eight patients received sirolimus between October, 2000 and September, 2002. Indications for using sirolimus were post-transplant lymphoproliferative disease (PTLD) (n = 6) and hepatoblastoma (n = 2). Two patients with PTLD concurrently had renal impairment and chronic rejection. Sirolimus dosages ranged between 1.5 and 5 mg once daily. Median duration of follow-up was 17 months. Persistently elevated liver transaminase levels in the two children with chronic rejection decreased during sirolimus therapy. Recurrence of PTLD occurred in one patient. Two patients were diagnosed with acute cellular rejection after transition to maintenance sirolimus monotherapy. Resolution of adverse effects including mouth sores (n = 3), leg swelling (n = 2) and hyperlipidemia (n = 3) occurred either spontaneously or with dose reduction. Sirolimus was discontinued in four patients because of persisting bone marrow suppression, interstitial pneumonitis, life-threatening sepsis and refractory diarrhea. Children with PTLD or hepatoblastoma may benefit from immune suppression with sirolimus after liver transplantation. Further multi-center, prospective, randomized controlled trials will be instrumental to further the knowledge of long-term efficacy, safety and tolerability of sirolimus for selected children following liver transplantation.

Adolescent↗
PubMed2004

Hyperinvasive neonatal group B streptococcus has arisen from a bovine ancestor.

The genetic relatedness and evolutionary relationships between group B streptococcus (GBS) isolates from humans and those from bovines were investigated by phylogenetic analysis of multilocus sequence typing data. The collection of isolates consisted of 111 GBS isolates from cows with mastitis and a diverse global collection of GBS isolates from patients with invasive disease (n = 83) and carriers (n = 69). Cluster analysis showed that the majority of the bovine isolates (93%) grouped into one phylogenetic cluster. The human isolates showed greater diversity and clustered separately from the bovine population. However, the homogeneous human sequence type 17 (ST-17) complex, known to be significantly associated with invasive neonatal disease, was the only human lineage found to be clustered within the bovine population and was distinct from all the other human lineages. Split decomposition analysis revealed that the human isolate ST-17 complex, the major hyperinvasive neonatal clone, has recently arisen from a bovine lineage.

Animals↗
PubMed2004

Helicobacter pylori and the prevention of gastric cancer.

BACKGROUND: Helicobacter pylori is an important cause of stomach cancer that infects a substantial proportion of the Canadian adult population. H pylori can be detected by noninvasive tests and effectively eradicated by medical treatment. Screening for and treatment of H pylori may represent a significant opportunity for preventive oncology. METHODS: Cancer Care Ontario organized a workshop held in Toronto, Ontario, on October 24 and 25, 2002, to: review the current state of knowledge regarding H pylori treatment and cancer prevention; determine if there is currently sufficient evidence to consider the promotion of H pylori treatment for the purpose of cancer prevention; identify critical areas for research; and advise Cancer Care Ontario on H pylori and cancer prevention. RESULTS: Workshop participants developed a number of recommendations for research into the relationship between H pylori and stomach cancer, including determining the prevalence of infection in different regions of Canada, the pathogenetic sequence of carcinogenesis from H pylori infection, and the implementation of a prospective observational study. INTERPRETATION: Although the rate of H pylori infection is declining in Canada and the treatment of H pylori is generally accepted to be safe, the evidence to date may not warrant the implementation of population screening for H pylori infection to prevent gastric carcinoma in average-risk populations. Rather, a demonstration project is needed to estimate prevalence, evaluate the merits of screening, measure patient compliance and physician participation, develop education materials, establish a registry for monitoring and evaluation, and develop a quality assurance framework.

Canada↗
PubMed2004

Serotype III Streptococcus agalactiae from bovine milk and human neonatal infections.

Streptococcus agalactiae (group B streptococcus [GBS]) causes invasive human infections and bovine mastitis. This study examined the genetic relationship between bovine and human serotype III GBS by using molecular techniques that classify human serotype III GBS into four distinct phylogenetic lineages. Bovine serotype III GBS were largely contained in two lineages, which are distinct from the two major lineages (restriction digest types III-2 and III-3) that infect human neonates. One of the bovine lineages closely resembles the human III-1 lineage, whose members occasionally cause human neonatal infections. The bovine strains in the other lineage characteristically have an initiation factor IF2 gene (infB) H allele and multilocus sequence types that are not found in human GBS strains. Evidence suggests that this "H allele" lineage is related to the human III-3 lineage. These results support the assertion that human and bovine GBS are largely unrelated and provide further insight into the genetic relation between human and bovine GBS.

Alleles↗
PubMed2003

Preoccupation, food, and failure: an investigation of cognitive performance deficits in dieters.

OBJECTIVE: This study tested two explanations of the cognitive performance deficits of dieters. First, these deficits are due to the metabolic consequences of food deprivation. Second, they are psychological in origin (i.e., preoccupation with dieting-related thoughts during dieting depletes the cognitive resources available for nondieting tasks). METHOD: Dieters and nondieters performed a battery of cognitive tasks before and after consumption of a high-energy chocolate bar. Eating the chocolate bar was expected to reverse the effects of food deprivation but, as a "diet-threatening" food, it could increase dieting-related preoccupation. RESULTS AND CONCLUSIONS: The results supported the latter prediction. Performance on a memory task was further impaired, rather than improved, after food consumption in dieters. In addition, dieters experienced a significant increase in the number of food and dieting-related thoughts. Some dieters attributed their poorer performance to distraction by these thoughts. Marked individual differences in thought content accounted for some of the variability in the effects on performance.

Adolescent↗
PubMed2003

Outcome of pediatric live-donor liver transplantation-the Toronto experience.

BACKGROUND/PURPOSE: Live-donor liver transplantation (LDLT) has developed to address the critical shortage of cadaveric organs that accounts for 20% of children who die while awaiting for a liver transplant in Ontario each year. This report reviews the outcome of the pediatric recipients of LDLT at the authors' center. METHODS: The charts of all children who received a LDLT between June 1996 and March 2002 were reviewed retrospectively. RESULTS: Thirteen children (mean age, 3.6 years) underwent LDLT. All donors were parents except for one cousin. Ten grafts were left-lateral segments, 2 were right lobes, and 1 was a left lobe. Three patients required a SILASTIC((R)) (Dow Corning, Midland, MI) patch for delayed abdominal wall closure. Patient and graft survival rate was 100% with a median follow-up of 376 days. Major postoperative complications included biliary leaks (n = 2), biliary strictures (n = 1), portal vein thrombosis (n = 1), and hepatic venous complications (n = 1). There were no cases of hepatic artery thrombosis. Ten of 12 children became Positive for Epstein-Barr virus (EBV), and 3 of these patients had readily treatable post-transplant lymphoproliferative disorder. CONCLUSIONS: LDLT is an acceptable alternative to cadaveric transplantation for children with end-stage liver disease.

Adolescent↗