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Articles by S Smith
Total Records ( 5 ) for S Smith
  G Douaud , C Mackay , J Andersson , S James , D Quested , M. K Ray , J Connell , N Roberts , T. J Crow , P. M Matthews , S Smith and A. James
 

Early-onset schizophrenia appears to be clinically more severe than the adult-onset form of the disease. In a previous study, we showed that anatomically related grey and white matter abnormalities found in adolescents patients were larger and more widespread than what had been reported in the literature on adult schizophrenia. Particularly, we found novel structural abnormalities in the primary sensorimotor and premotor systems. Here, we tested alternative hypotheses: either this striking sensorimotor-related pattern is an artefact due to a better sensitivity of the methods, or apparent greater structural abnormalities in the early-onset population are specifically associated with earlier disease onset. Then, if we were to find such characteristic structural pattern, we would test whether these anatomical abnormalities would remain static or, conversely, show dynamic changes in the still developing brain. To address these questions, we combined a cross-sectional study of brain structure for adolescent-onset patients (n = 25) and adult-onset patients (n = 35) and respective matched healthy subjects with a longitudinal study of adolescent-onset patients (n = 12, representative subset of the cross-sectional group) and matched healthy controls for >2 years. Looking at differences between adolescent and adult patients’ grey matter volume and white matter microstructure abnormalities, we first confirmed the specificity (especially in motor-related areas) and the greater severity of structural abnormalities in the adolescent patients. Closer examination revealed, however, that such greater anomalies seemed to arise because adolescent patients fail to follow the same developmental time course as the healthy control group. Longitudinal analysis of a representative subset of the adolescent patient and matched healthy populations corroborated the delayed and altered maturation in both grey and white matters. Structural abnormalities specific to adolescent-onset schizophrenia in the sensori-motor cortices and corticospinal tract were less marked or even disappeared within the longitudinal period of observation, grey matter abnormalities in adolescent patients evolving towards the adult-onset pattern as defined by recent meta-analyses of adult schizophrenia. Combining cross-sectional adolescent and adult datasets with longitudinal adolescent dataset allowed us to find a unique, abnormal trajectory of grey matter maturation regardless of the age at onset of symptoms and of disease duration, with a lower and later peak than for healthy subjects. Taken together, these results suggest common aetiological mechanisms for adolescent- and adult-onset schizophrenia with an altered neurodevelopmental time course in the schizophrenic patients that is particularly salient in adolescence.

  S. L Zheng , V. L Stevens , F Wiklund , S. D Isaacs , J Sun , S Smith , K Pruett , K. E Wiley , S. T Kim , Y Zhu , Z Zhang , F. C Hsu , A. R Turner , J. E Johansson , W Liu , J. W Kim , B. L Chang , D Duggan , J Carpten , C Rodriguez , W Isaacs , H Gronberg and J. Xu
 

Single nucleotide polymorphisms (SNP) at 11q13 were recently implicated in prostate cancer risk by two genome-wide association studies and were consistently replicated in multiple study populations. To explore prostate cancer association in the regions flanking these SNPs, we genotyped 31 tagging SNPs in a ~110 kb region at 11q13 in a Swedish case-control study (Cancer of the Prostate in Sweden), including 2,899 cases and 1,722 controls. We found evidence of prostate cancer association for the previously implicated SNPs including rs10896449, which we termed locus 1. In addition, multiple SNPs on the centromeric side of the region, including rs12418451, were also significantly associated with prostate cancer risk (termed locus 2). The two groups of SNPs were separated by a recombination hotspot. We then evaluated these two representative SNPs in an additional ~4,000 cases and ~3,000 controls from three study populations and confirmed both loci at 11q13. In the combined allelic test of all four populations, P = 4.0 x 10–11 for rs10896449 at locus 1 and P = 1.2 x 10–6 for rs12418451 at locus 2, and both remained significant after adjusting for the other locus and study population. The prostate cancer association at these two 11q13 loci was unlikely confounded by prostate-specific antigen (PSA) detection bias because neither SNP was associated with PSA levels in controls. Unlike locus 1, in which no known gene is located, several putative mRNAs are in close proximity to locus 2. Additional confirmation studies at locus 2 and functional studies for both loci are needed to advance our knowledge on the etiology of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1815–20)

  S. P Duggan , F. M Behan , M Kirca , S Smith , J. V Reynolds , A Long and D. Kelleher
 

Reflux of gastroduodenal contents and consequent inflammatory responses are associated with the development of Barrett's oesophagus (BO) and the promotion of oesophageal adenocarcinoma (OAC). Deregulation of inflammatory processes is a hallmark of oesophageal cancer. In this study, we aimed to investigate (i) the transcriptional responses to deoxycholic acid (DCA) in cell lines representative of either end of the oesophageal cancer sequence, (ii) the expression of DCA-regulated genes in data charting oesophageal carcinogenesis and (iii) the impact of these genes on oesophageal inflammatory signalling. Gene expression microarrays were utilized to demonstrate differential transcriptional responses between squamous (HET-1A) and adenomatous (SKGT4) cell lines exposed to DCA. Differential basal and DCA-inducible expression of cytokines such as interleukin (IL) 8 was observed between both cell types. A cohort of DCA-regulated genes specific to each cell type was identified in microarray experimentation and subsequently validated. Cell type-specific genes included TRB3, CXCL14, GDF15 and LIF in HET-1A cells, with COX2-, ESM1-, URHF1- and IL1-and IL1β-specific expression in SKGT4 cells. Over 30% of the genes altered in BO and OAC were shown to be regulated by DCA utilizing an integrative genomic approach. One such gene, tribbles-homology-3 (TRB3) was induced specifically in HET-1A cells, absent in SKGT4 cells and decreased in BO samples in silico and in vivo. Inhibition and re-introduction of TRB3 in HET-1A and SKGT4 cells, respectively, demonstrated the ability of TRB3 to regulate inflammatory signalling through nuclear factor-kappaB. This study identifies mechanisms through which bile acids such as DCA, in conjunction with the loss of key signalling molecules, could regulate oesophageal metaplasticity.

  D Yumino , S Redolfi , P Ruttanaumpawan , M. C Su , S Smith , G. E Newton , S Mak and T. D. Bradley
 

Background— Obstructive sleep apnea (OSA) and central sleep apnea are common in patients with heart failure. We hypothesized that in such patients, severity of OSA is related to overnight rostral leg fluid displacement and increase in neck circumference, severity of central sleep apnea is related to overnight rostral fluid displacement and to sleep Pco2, and continuous positive airway pressure alleviates OSA in association with prevention of fluid accumulation in the neck.

Methods and Results— In 57 patients with heart failure (ejection fraction ≤45%), we measured change in leg fluid volume and neck circumference before and after polysomnography, and we measured transcutaneous Pco2 during polysomnography. Patients were divided into an obstructive-dominant group (≥50% of apneas and hypopneas obstructive) and a central-dominant group (>50% of events central). Patients with OSA received continuous positive airway pressure. In obstructive-dominant patients, there were inverse relationships between overnight change in leg fluid volume and both the overnight change in neck circumference (r=–0.780, P<0.001) and the apnea-hypopnea index (r=–0.881, P<0.001) but not transcutaneous Pco2. In central-dominant patients, the overnight reduction in leg fluid volume correlated inversely with the apnea-hypopnea index (r=–0.919, P<0.001) and the overnight change in neck circumference (r=–0.568, P=0.013) and directly with transcutaneous Pco2 (r=0.569, P=0.009). Continuous positive airway pressure alleviated OSA in association with prevention of the overnight increase in neck circumference (P<0.001).

Conclusions— Our findings suggest that nocturnal rostral fluid shift is a unifying concept contributing to the pathogenesis of both OSA and central sleep apnea in patients with heart failure.

  S Lindsay , S Smith , P Bellaby and R. Baker
 

The aim of this study was to assess whether our online closed community heart care support group and information resource could sustain changes in health behaviour after the moderators withdrew their support. Heart patients (n = 108) living in a deprived area of Greater Manchester were recruited from general practitioners’ coronary heart disease registries. The sample for this randomized controlled trial was divided in half at random where half of the participants received password-protected access to our health portal and the other half did not. At 6 months follow-up (based on the moderated phase), there was a significant difference between the experimental group and the controls in terms of self-reported diet (eating bad foods less often). This change in behaviour was not sustained during the 3-month unmoderated phase. During this unmoderated phase of the intervention, the experimental group had significantly more health care visits compared with the controls. There was no significant difference between the two phases for either group in terms of exercise, smoking or social support. This study offers insight into the potential implications for health changes of moderating arrangements for online health communities.

 
 
 
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