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1.
Mol Psychiatry ; 19(11): 1227-34, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24419041

ABSTRACT

Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/complications , Anemia/blood , Anemia/complications , Cognitive Dysfunction/blood , Cognitive Dysfunction/complications , Aged , Aged, 80 and over , Australia/epidemiology , Cross-Sectional Studies , Female , Folic Acid/blood , Hemoglobins/metabolism , Humans , Iron/blood , Male , Middle Aged , Prospective Studies , Risk Factors , Transferrin/metabolism
2.
Mol Vis ; 15: 1390-7, 2009 Jul 17.
Article in English | MEDLINE | ID: mdl-19626135

ABSTRACT

PURPOSE: The Retinoic Acid Receptor Alpha (RARA) gene is a potential candidate gene for myopia due to its differential expression in animal models during experimentally induced myopia. To test for whether RARA is associated with myopia we have undertaken a case-control study assessing for associations between RARA and myopia, hypermetropia, and ocular biometric measures. METHODS: A total of 802 Anglo-Celtic individuals were genotyped. Five tag single nucleotide polymorphisms (tSNPs) in RARA with an r(2) of 0.8 and a minor allele frequency greater than 5% were selected for genotyping. Genotype frequencies of these 5 tSNPs were compared between individuals with emmetropia and those with myopia or hypermetropia. A quantitative analysis was also performed to assess associations with ocular biometric measures including axial length, corneal curvature and anterior chamber depth. RESULTS: We did not identify any significant association between tSNPs in RARA with either myopia or hypermetropia as qualitative traits. Neither did we identify any significant associations of these tSNPs with the quantitative traits of axial length, corneal curvature and anterior chamber depth. CONCLUSIONS: This is the first study to assess for associations between RARA and myopia, hypermetropia, and ocular biometric measures. Our findings suggest that variations in the nucleotide sequence of RARA are not associated with myopia, hypermetropia, or ocular biometric measures in our population.


Subject(s)
Biometry , Eye/pathology , Genetic Predisposition to Disease , Hyperopia/genetics , Myopia/genetics , Receptors, Retinoic Acid/genetics , Demography , Female , Humans , Hyperopia/physiopathology , Linkage Disequilibrium/genetics , Male , Middle Aged , Myopia/physiopathology , Polymorphism, Single Nucleotide/genetics , Refraction, Ocular , Retinoic Acid Receptor alpha
3.
Antimicrob Agents Chemother ; 49(5): 1688-94, 2005 May.
Article in English | MEDLINE | ID: mdl-15855482

ABSTRACT

Previously, we reported the isolation of 10 vancomycin-resistant gram-positive anaerobic bacilli carrying the vanB ligase gene from nine hemodialysis patients (S. A. Ballard et al., Antimicrob. Agents Chemother. 49:77-81, 2005; T. P. Stinear et al., Lancet 357:855-856, 2001). In the present study, the molecular and evolutionary relationship of the vanB resistance element within these 10 anaerobes and two vancomycin-resistant Enterococcus faecium strains were examined. PCR analysis and nucleotide sequencing demonstrated that all 12 isolates carried the vanB operon associated with an element identical to Tn1549 and Tn5382 of Enterococcus. Restriction fragment length polymorphism analysis of the vanB operon in these isolates revealed two distinct patterns, and sequencing showed that minor base differences existed. PCR amplification of the joint region of a circular intermediate was demonstrated in nine of these organisms, a finding indicative of an ability to excise and circularize, an intermediate step in transposition and conjugative transfer. Southern hybridization with a vanB-vanX(B) probe suggests that there is one insert of the transposon in all isolates. Sequence analysis of the integration site revealed distinct sequences: the Tn1549/5382 element within E. faecium was inserted within the host chromosome, whereas nucleotide sequences surrounding the Tn1549/5382 element in the 10 anaerobes showed no significant homology to sequences in the GenBank database. We demonstrate considerable similarity between the Tn1549/5382 element identified in 10 anaerobe isolates with that found in enterococci. The homology and potential to transpose suggest a recent horizontal transfer event may have occurred. However, the original direction of transposition and the mechanism involved remains unknown.


Subject(s)
Bacteria, Anaerobic/genetics , Bacterial Proteins/genetics , Digestive System/microbiology , Anti-Bacterial Agents/pharmacology , Blotting, Southern , DNA Transposable Elements/genetics , DNA, Bacterial/genetics , Drug Resistance, Bacterial , Electrophoresis, Gel, Pulsed-Field , Enterococcus faecium/drug effects , Enterococcus faecium/genetics , Genome , Microbial Sensitivity Tests , Molecular Sequence Data , Operon/genetics , Polymorphism, Restriction Fragment Length , Reverse Transcriptase Polymerase Chain Reaction , Ribotyping , Vancomycin/pharmacology
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