Microsatellite instability, Epstein-Barr virus, mutation of type II transforming growth factor receptor and BAX in gastric carcinomas in Hong Kong Chinese

Conference Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

Situs inversus totalis in a fetus with a deletion at 7q36.2 detected on microarray analysis

Laterality disorders are a heterogeneous group of disorders associated with maternal diseases (maternal IDDM), maternal exposures to teratogens (retinoic acid), chromosome abnormalities and single gene disorders (ZIC3 mutation). We report on a fetus with a submicroscopic deletion at 7q36.2 with right atrial isomerism (RAI). CASE: The mother was a 30y G4P1SA2L1 and the father was 35y. Both were healthy and non-consanguineous and their family history was non-contributory. They had a healthy son and daughter and had two miscarriages. MSS was negative. Detailed fetal U/S and echocardiography at 20w showed: RAI with ...postprin

Establishment of HKU lung cancer lines in Hong Kong - an ongoing conjoint effort and progress report

published_or_final_versio

Structural subnetwork evolution across the life-span: rich-club, feeder, seeder

The impact of developmental and aging processes on brain connectivity and the connectome has been widely studied. Network theoretical measures and certain topological principles are computed from the entire brain, however there is a need to separate and understand the underlying subnetworks which contribute towards these observed holistic connectomic alterations. One organizational principle is the rich-club - a core subnetwork of brain regions that are strongly connected, forming a high-cost, high-capacity backbone that is critical for effective communication in the network. Investigations primarily focus on its alterations with disease and age. Here, we present a systematic analysis of not only the rich-club, but also other subnetworks derived from this backbone - namely feeder and seeder subnetworks. Our analysis is applied to structural connectomes in a normal cohort from a large, publicly available lifespan study. We demonstrate changes in rich-club membership with age alongside a shift in importance from 'peripheral' seeder to feeder subnetworks. Our results show a refinement within the rich-club structure (increase in transitivity and betweenness centrality), as well as increased efficiency in the feeder subnetwork and decreased measures of network integration and segregation in the seeder subnetwork. These results demonstrate the different developmental patterns when analyzing the connectome stratified according to its rich-club and the potential of utilizing this subnetwork analysis to reveal the evolution of brain architectural alterations across the life-span

Promotor hypermethylation of the CpG Islands of human Ras Association Domain Family 1A gene (RASSF1A) in adenocarcinoma of lung in Hong Kong Chinese - a comparison between smokers and non-smokers

published_or_final_versio

Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.

BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic

Modulation of human macrophage responses to mycobacterium tuberculosis by silver nanoparticles of different size and surface modification

Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Fractional quantum Hall effect in a quantum point contact at filling fraction 5/2

Recent theories suggest that the excitations of certain quantum Hall states may have exotic braiding statistics which could be used to build topological quantum gates. This has prompted an experimental push to study such states using confined geometries where the statistics can be tested. We study the transport properties of quantum point contacts (QPCs) fabricated on a GaAs/AlGaAs two dimensional electron gas that exhibits well-developed fractional quantum Hall effect, including at bulk filling fraction 5/2. We find that a plateau at effective QPC filling factor 5/2 is identifiable in point contacts with lithographic widths of 1.2 microns and 0.8 microns, but not 0.5 microns. We study the temperature and dc-current-bias dependence of the 5/2 plateau in the QPC, as well as neighboring fractional and integer plateaus in the QPC while keeping the bulk at filling factor 3. Transport near QPC filling factor 5/2 is consistent with a picture of chiral Luttinger liquid edge-states with inter-edge tunneling, suggesting that an incompressible state at 5/2 forms in this confined geometry