Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia: a case-control study

BACKGROUND: Deposition of beta-amyloid in the brains of patients with Alzheimer's disease is thought to precede a chain of events that leads to an inflammatory response by the brain. We postulated that genetic variation in the regulatory region of the gene for the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) leads to increased risk of Alzheimer's disease and vascular dementia. METHODS: A polymorphism in the regulatory region of the TNF-alpha gene was analysed in a case-control study. The polymorphism (C-850T) was typed in 242 patients with sporadic Alzheimer's disease, 81 patients with vascular dementia, 61 stroke patients without dementia, and 235 normal controls. These groups of individuals were also genotyped for the apolipoprotein E polymorphism, and the vascular dementia and stroke groups were typed at the HLA-DR locus. FINDINGS: The distribution of TNF-alpha genotypes in the vascular dementia group differed significantly from that in the stroke and normal control groups, giving an odds ratio of 2.51 (95% CI 1.49-4.21) for the development of vascular dementia for individuals with a CT or TT genotype. Logistic regression analysis indicated that the possession of the T allele significantly increased the risk of Alzheimer's disease associated with carriage of the apolipoprotein E epsilon4 allele (odds ratio 2.73 [1.68-4.44] for those with apolipoprotein E epsilon4 but no TNF-alpha T, vs 4.62 [2.38-8.96] for those with apolipoprotein E epsilon4 and TNF-alpha T; p=0.03). INTERPRETATION: Possession of the TNF-alpha T allele significantly increases the risk of vascular dementia, and increases the risk of Alzheimer's disease associated with apolipoprotein E. Although further research is needed, these findings suggest a potential role for anti-inflammatory therapy in vascular dementia and Alzheimer's disease, and perhaps especially in patients who have had a stroke.

Maleimide spacers as versatile linkers in the synthesis of bioconjugates of anthracyclines

This review covers the structural design and versatile use of maleimide spacers in the preparation of bioconjugates of the anthracyclines doxorubicin and daunorubicin. It underpins the research conducted in our group on the preparation of conjugates of daunorubicin and transferrin.

Strömgren uvby photometry of B-type stars from the Palomar-Green Survey

We present Strömgren uvby photometry for a sample of 31 high Galactic latitude stars selected from the Palomar-Green Survey. The data include photometric magnitudes accurate to

Electron and laser interactions with positive ions

Recent progress in laboratory-based electron-ion scattering is reviewed, and the sensitivity of observed interference structure as a probe of collision dynamics is discussed. The extension of our use of positive ions as scattering targets to photon-ion interactions is demonstrated with the first ion-beam measurements for the fragmentation of a molecular ion, H-2(+), using intense femtosecond laser pulses.

Self-perception in overweight and obese children: a cross-sectional study

Aim The aim of this study was to examine the relationship between obesity and self-esteem in children in relation to specific domains of their self-perception, and further to explore the extent to which this may vary by gender and economic circumstances. Method A total of 211 children aged 8–9 years drawn from both advantaged and disadvantaged areas of Belfast completed the Harter Self-Perception Profile for Children and measures of body mass index were obtained. Results Overweight, impoverished children had significantly reduced social acceptance and physical competence scores. Boys had significantly lower scores than girls in the behavioural conduct domain. Girls had significantly lower scores than boys for the athletic competence. Conclusion These results suggest that risk factors of increased weight and impoverished backgrounds have a combined negative effect, placing some children at increased risk of having lower self-perceptions in some, but not all domains. Health interventions for childhood obesity should consider the likelihood of specific relationships between physical and psychosocial factors.

Coordination and movement pathology: models of structure and function

Here we consider the role of abstract models in advancing our understanding of movement pathology. Models of movement coordination and control provide the frameworks necessary for the design and interpretation of studies of acquired and developmental disorders. These models do not however provide the resolution necessary to reveal the nature of the functional impairments that characterise specific movement pathologies. In addition, they do not provide a mapping between the structural bases of various pathologies and the associated disorders of movement. Current and prospective approaches to the study and treatment of movement disorders are discussed. It is argued that the appreciation of structure-function relationships, to which these approaches give rise, represents a challenge to current models of interlimb coordination, and a stimulus for their continued development. (C) 2002 Elsevier Science B.V. All rights reserved.

The component masses of the cataclysmic variable V347 Puppis

We present time-resolved spectroscopy and photometry of the double-lined eclipsing cataclysmic variable V347 Pup ( = LB 1800). There is evidence of irradiation on the inner hemisphere of the secondary star, which we correct for using a model to give a secondary-star radial velocity of K R = 198 +/- 5 km s(-1). The rotational velocity of the secondary star in V347 Pup is found to be v sin i = 131 +/- 5 km s(-1) and the system inclination is i = 84degrees.0 +/- 2degrees.3. From these parameters we obtain masses of M-1 = 0.63 +/- 0.04 M for the white dwarf primary and M-2 = 0.52 +/- 0.06 M for the M0.5V secondary star, giving a mass ratio of q = 0.83 +/- 0.05. On the basis of the component masses, and the spectral type and radius of the secondary star in V347 Pup, we find tentative evidence for an evolved companion. V347 Pup shows many of the characteristics of the SW Sex stars, exhibiting single-peaked emission lines, high-velocity S-wave components and phase-offsets in the radial velocity curve. We find spiral arms in the accretion disc of V347 Pup and measure the disc radius to be close to the maximum allowed in a pressureless disc.

SCUBA imaging of high mass star formation regions

We present 450 and 850 mu m images of five ultracompact HII regions (G10.47, G12.21, G13.87, G31.41 and G43.89) taken at 9