• Birth defects and anti–heat shock protein 70 antibodies in early pregnancy

      Child, David F.; Hudson, Peter R.; Hunter-Lavin, Claire; Mukhergee, Sagarika; China, Susnata; Williams, Clive P.; Williams, John H. H.; University of Chester (Hunter-Lavin & Williams) (Springer-Verlag, 2006-03)
    • Folate supplementation reduces serum Hsp70 levels in patients with type 2 diabetes

      Hunter-Lavin, Claire; Hudson, Peter R.; Mukhergee, Sagarika; Davies, Gareth K.; Williams, Clive P.; Harvey, John N.; Child, David F.; Williams, John H. H.; University College Chester ; Wrexham Maelor Hospital, North East Wales NHS Trust ; Wrexham Maelor Hospital, North East Wales NHS Trust ; Wrexham Maelor Hospital, North East Wales NHS Trust ; Wrexham Maelor Hospital, North East Wales NHS Trust ; Wrexham Maelor Hospital, North East Wales NHS Trust ; Wrexham Maelor Hospital, North East Wales NHS Trust ; University College Chester (Cell Stress Society International, 2004-10)
      Type 2 diabetes patients are subject to oxidative stress as a result of hyperglycemia. The aim of this study was to determine whether administration of the antioxidant folic acid, previously shown to reduce homocysteine levels, would reduce circulating levels of Hsp70 while improving the condition of type 2 diabetes patients with microalbuminuria. Plasma homocysteine fell from pretreatment values of 12.9 to 10.3 μM (P < 0.0001). The urine albumin-creatinine ratio fell from 12.4 to 10.4 mg/mM (P = 0.38). Pretreatment Hsp70 levels were higher in patients not taking insulin (5.32 ng/mL) compared with those on insulin (2.44 ng/mL) (P = 0.012). Folic acid supplementation resulted in a significant fall in Hsp70 (5.32 to 2.05 ng/mL) (P = 0.004). There was no change in Hsp70 in those receiving insulin. Folic acid supplementation in non–insulin-treated type 2 diabetes patients, therefore, resulted in a fall in Hsp70, reflecting an improvement in oxidative stress. The data shows that improvement in homocysteine status can lead to a reduction in Hsp70, indicating the possibility of its use as a marker for severity of disease.
    • Homocysteine and cognitive decline in healthy elderly

      McCaddon, Andrew; Hudson, Peter R.; Davies, Gareth K.; Hughes, Alan; Williams, John H. H.; Wilkinson, Clare; University of Wales College of Medicine ; Wrexham Maelor Hospital ; Wrexham Maelor Hospital ; Royal Alexandra Hospital, Paisley ; Chester College ; University of Wales College of Medicine (Karger, 2001-09)
      Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer's disease (AD), vascular dementia and "age-associated memory impairment". Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period.
    • Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease

      McCaddon, Andrew; Bleenow, Kaj; Hudson, Peter R.; Hughes, Alan; Barber, Joan; Gray, Rob; Davies, Gareth K.; Williams, John H. H.; Duguid, Jennifer; Lloyd, Alwyn; et al. (S. Karger AG, 2004)
      Isoforms of the vitamin B<12< carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer's disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox's F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox's F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.