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1.  Identification and Characterization of Putative Virulence Genes and Gene Clusters in Aeromonas hydrophila PPD134/91 
Aeromonas hydrophila is a gram-negative opportunistic pathogen of animals and humans. The pathogenesis of A. hydrophila is multifactorial. Genomic subtraction and markers of genomic islands (GIs) were used to identify putative virulence genes in A. hydrophila PPD134/91. Two rounds of genomic subtraction led to the identification of 22 unique DNA fragments encoding 19 putative virulence factors and seven new open reading frames, which are commonly present in the eight virulence strains examined. In addition, four GIs were found, including O-antigen, capsule, phage-associated, and type III secretion system (TTSS) gene clusters. These putative virulence genes and gene clusters were positioned on a physical map of A. hydrophila PPD134/91 to determine their genetic organization in this bacterium. Further in vivo study of insertion and deletion mutants showed that the TTSS may be one of the important virulence factors in A. hydrophila pathogenesis. Furthermore, deletions of multiple virulence factors such as S-layer, serine protease, and metalloprotease also increased the 50% lethal dose to the same level as the TTSS mutation (about 1 log) in a blue gourami infection model. This observation sheds light on the multifactorial and concerted nature of pathogenicity in A. hydrophila. The large number of putative virulence genes identified in this study will form the basis for further investigation of this emerging pathogen and help to develop effective vaccines, diagnostics, and novel therapeutics.
doi:10.1128/AEM.71.8.4469-4477.2005
PMCID: PMC1183340  PMID: 16085838
2.  Field-Based Flow Cytometry for Ex Vivo Characterization of Plasmodium vivax and P. falciparum Antimalarial Sensitivity 
Antimicrobial Agents and Chemotherapy  2013;57(10):5170-5174.
Ex vivo antimalarial sensitivity testing in human malaria parasites has largely depended on microscopic determination of schizont maturation. While this microscopic method is sensitive, it suffers from poor precision and is laborious. The recent development of portable, low-cost cytometers has allowed us to develop and validate a simple, field-optimized protocol using SYBR green and dihydroethidium for the accurate and objective determination of antimalarial drug sensitivity in freshly isolated Plasmodium vivax and Plasmodium falciparum.
doi:10.1128/AAC.00682-13
PMCID: PMC3811473  PMID: 23877705
3.  Foetal Exposure to Maternal Passive Smoking Is Associated with Childhood Asthma, Allergic Rhinitis, and Eczema 
The Scientific World Journal  2012;2012:542983.
Objective. We examined the hypothesis that foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema. Methods. The study was a population-based cross-sectional survey of Hong Kong Chinese children aged ≤14 years carried out in 2005 to 2006. Results. Foetal exposure to maternal passive smoking was significantly associated with wheeze ever (OR 2.05; 95% CI 1.58–2.67), current wheeze (OR 2.06; 95% CI 1.48–2.86), allergic rhinitis ever (OR 1.22; 95% CI 1.09–1.37), and eczema ever (OR 1.61; 95% CI 1.38–1.87). Foetal exposure to maternal active smoking was significantly associated with asthma ever (OR 2.10; 95% CI 1.14–3.84), wheeze ever (OR 2.46; 95% CI 1.27–4.78), and current wheeze (OR 2.74; 95% CI 1.24–6.01) but not with allergic rhinitis ever (OR 1.01; 95% CI 0.70–1.46) or eczema ever (OR 1.38; 95% CI 0.87–2.18). The dose response relationship between wheeze ever and current wheeze with increasing exposure, from no exposure to maternal passive smoking and then to maternal active smoking, further supports causality. Conclusion. There is significant association between foetal exposure to maternal passive smoking and maternal active smoking with childhood asthma and related atopic illnesses. Further studies are warranted to explore the potential causal relationship.
doi:10.1100/2012/542983
PMCID: PMC3425811  PMID: 22927783
4.  Chronic health problems and health-related quality of life in Chinese children and adolescents: a population-based study in Hong Kong 
BMJ Open  2013;3(1):e001183.
Objective
We examined the association of different chronic physical and mental conditions, individually or comorbidly on health-related quality of life (QoL) in Chinese children aged ≤14 years in Hong Kong.
Design
Population-based cross-sectional survey.
Participants
Approximately 7500 Chinese children aged <14 years in Hong Kong.
Interventions
Nil.
Primary and secondary outcome measures
Various health concepts of validated Chinese version of Child Health Questionnaire (CHQ), a health-related QoL questionnaire in children.
Result
There was significant association of physical and mental health conditions, either individually or comorbidly, on the various concepts of CHQ. Children with mental health problems were apparently more affected than those with physical health problems. Chronic renal disease and congenital malformation were the physical health conditions associated with the lowest scores in CHQ concepts in children aged 5–10 years and aged 10–14 years, respectively. Behavioural problem was the mental health condition associated with the lowest score in CHQ concepts in both age groups.
Conclusions
Our study shows important information concerning the prevalence of different health conditions and its association, either individually or comorbidly on the QoL in a representative sample of Chinese children in HK.
doi:10.1136/bmjopen-2012-001183
PMCID: PMC3549227  PMID: 23293240
PUBLIC HEALTH
5.  Association between air pollution and asthma admission among children in Hong Kong 
Clinical and Experimental Allergy   2006;36(9):1138-1146.
Objective
To examine the association of air pollutants with hospital admission for childhood asthma in Hong Kong.
Methods
Data on hospital admissions for asthma, influenza and total hospital admissions in children aged ≤18 years at all Hospital Authority hospitals during 1997–2002 were obtained. Data on daily mean concentrations of particles with aerodynamic diameter <10 μm (i. e. PM10) and <2.5 μm (i. e. PM2.5), nitrogen dioxide (NO2), sulphur dioxide (SO2), and ozone (O3) and data on meteorological variables were associated with asthma hospital admissions using Poisson's regression with generalized additive models for correction of yearly trend, temperature, humidity, day-of-week effect, holiday, influenza admissions and total hospital admission. The possibility of a lag effect of each pollutant and the interaction of different pollutants were also examined.
Results
The association between asthma admission with change of NO2, PM10, PM2.5 and O3 levels remained significant after adjustment for multi-pollutants effect and confounding variables, with increase in asthma admission rate of 5.64% (3.21–8.14) at lag 3 for NO2, 3.67% (1.52–5.86) at lag 4 for PM10, 3.24% (0.93–5.60) at lag 4 for PM2.5 and 2.63% (0.64–4.67) at lag 2 for O3. Effect of SO2 was lost after adjustment.
Conclusion
Ambient levels of PM10, PM2.5, NO2 and O3 are associated with childhood asthma hospital admission in Hong Kong.
doi:10.1111/j.1365-2222.2006.02555.x
PMCID: PMC1618810  PMID: 16961713
air pollution; asthma; children; Hong Kong; hospital admission
6.  Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese 
Genes and Immunity  2009;10(5):414-420.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 × 10−9; TNFSF4, rs844648, OR=1.22, P=2.47 × 10−3; TNFSF4, rs2205960, OR=1.30, P=2.41 × 10−4). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 × 10−3). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 × 10−8, respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 × 10−3), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.
doi:10.1038/gene.2009.16
PMCID: PMC2834352  PMID: 19357697
SLE; BANK1; TNFSF4; Chinese; genetic association
7.  Monitoring of leukocyte cytomegalovirus DNA in bone marrow transplant recipients by nested PCR. 
Journal of Clinical Microbiology  1995;33(10):2530-2534.
A nested PCR assay for the detection of human cytomegalovirus (CMV) DNA was evaluated by weekly monitoring of blood samples taken from 101 bone marrow transplant (BMT) recipients. When peripheral blood leukocytes were used as the source of CMV DNA, even a modified assay with stringent temperature-cycling conditions was as sensitive as the standard assay. The sensitivity, specificity, and positive predictive value of two consecutively positive leukocytic PCR results with this modified assay in predicting CMV disease of 101 patients submitting 1,441 peripheral blood leukocyte samples were found to be 92.1, 63.5, and 60.3%, respectively. The positive predictive value of patients' seropositivity for CMV was 40%, while that of viremia was 72%. However, viremia followed CMV disease by a median of 1.5 days, while the first leukocytic positive PCR assay preceded disease by a median of 14 days. By use of the criteria of two consecutively positive PCR results instead of recipient CMV seropositivity for starting preemptive ganciclovir treatment, 38 of the 43 recipients with isolated single positive or negative assays (groups I and II) would be spared unnecessary ganciclovir treatment. Moreover, two other findings support the use of antiviral prophylaxis before engraftment in high-risk cases and subsequent preemptive treatment of patients with two consecutively positive PCR assays. First, for 7.9% of 76 patients with positive assays (groups II and III), the first positive PCR assay occurred before engraftment, which implied the presence of viral DNA in the blood (DNAemia) soon after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC228523  PMID: 8567878
9.  A case of middle lobe pulmonary sequestration. 
Thorax  1986;41(10):810-811.
Images
PMCID: PMC460495  PMID: 3787515
11.  Surgical treatment of adder bite. 
Two cases of children who suffered adder bites and who developed severe local complications are reported. One required a split skin graft and the other a decompression fasciotomy.
Images
PMCID: PMC1290058  PMID: 4067976
12.  Clustering of childhood leukaemia in Hong Kong: association with the childhood peak and common acute lymphoblastic leukaemia and with population mixing. 
British Journal of Cancer  1997;75(3):457-463.
Incidence data of childhood leukaemia (CL) in Hong Kong (1984-90) have been analysed for evidence of variation between small areas. All cases (n=261) were classified by morphological cell type, with the majority (n=205) being acute lymphoblastic leukaemia (ALL), and haematological review has permitted immunophenotypic classification for 73% of these. The data have been examined for evidence of spatial clustering within small census areas (TPUs) and for association with population mixing, with attention focused on those subgroups (especially the childhood peak of ALL--taken here to be diagnoses in children from 24 months up to the seventh birthday--and common ALL) which, it has been hypothesized, may be caused by unusual patterns of exposure and response to common infections. For the whole of Hong Kong, there was evidence of spatial clustering of ALL at ages 0-4 years (P = 0.09) and in the childhood peak (P<0.05). When these analyses were restricted to TPUs where extreme population mixing may have occurred, overall incidence was elevated and significant evidence of clustering was found for ALL (P<0.007) at these ages and for the common ALL in the childhood peak (P = 0.032). Replication of the analyses for subsets of leukaemia that were not dominated by the childhood peak of ALL found no evidence of clustering. This is the first investigation of an association between population mixing and childhood leukaemia in Asia and the first to include clustering and to consider particular subsets. The results are supportive of the 'infectious' aetiology hypothesis for subsets of childhood leukaemia, specifically common ALL in the childhood peak.
PMCID: PMC2063384  PMID: 9020498

Results 1-12 (12)