Biomedical subjects

Chi Pui Pang

Publications and source records attributed to Chi Pui Pang.

41 records · Page 3Linked to original sources

PubMed2002

TIGR/MYOC gene sequence alterations in individuals with and without primary open-angle glaucoma.

PURPOSE: To discover sequence alterations in the TIGR/MYOC gene associated with primary open-angle glaucoma (POAG) in Chinese subjects. METHODS: Two hundred one unrelated Chinese patients with POAG and 291 unrelated individuals without glaucoma, aged 50 years or more, were screened for sequence alterations in the TIGR/MYOC gene by polymerase chain reaction, conformation sensitive gel electrophoresis, and DNA sequencing. Up to 111 more control subjects were screened for some of the alterations. RESULTS: Fourteen sequence variants that lead to amino acid changes were identified. Seven were novel: Pro16Leu, Ala17Ser, Leu95Pro, Leu215Pro, Glu300Lys, Glu414Lys, and Tyr471Cys. Of these, Glu300Lys and Tyr471Cys were found only in POAG. Arg46Stop was found in 4 patients with POAG (2.0%) and 9 of 402 control subjects (2.2%); one control subject was homozygous. IOP showed a trend (P = 0.11) toward a decrease of 1.5 mm Hg among the control subjects, with Arg46Stop compared with matched control subjects without Arg46Stop. Gly12Arg occurred four times as frequently in control subjects as in patients, but the difference was not statistically significant. CONCLUSIONS: Gly12Arg might be negatively associated with POAG, suggesting a protective effect. Three patients with POAG had a sequence change not found in control subjects, for a frequency of possible disease-causing TIGR/MYOC mutations of 1.5% (95% confidence interval [CI] = 0.3%-4.3%). Arg46Stop occurred with similar frequency in patients with POAG and control subjects, suggesting that the reduced amount of TIGR/MYOC predicted to result from this truncation does not dramatically increase or decrease risk of glaucoma.

Aged↗

PubMed2002

EYE on bioinformatics: dissecting complex disease traits in silico.

Bioinformatics has provided an unprecedented power and resource for us to decipher the enigma of complex diseases. It can reveal otherwise promiscuous information from the tremendous amount of data generated by the new, powerful and high-throughput technologies of genomics and proteomics. In this paper, we review the cutting edge developments in complex disease trait mapping, databases, computational gene recognition, gene function prediction, pathway reconstruction and disease classification by expression profiling, and computational modelling of living systems. Integration of all this knowledge and the different technologies, alongside cooperation between experts from different fields, will enhance our understanding of the molecular and mechanistic abnormalities in disease state, and greatly assist the rational development of effective therapies.

Chromosome Mapping↗

PubMedDate not supplied

Cytotoxicity of triamcinolone on cultured human retinal pigment epithelial cells: comparison with dexamethasone and hydrocortisone.

PURPOSE: Triamcinolone acetonide (TA) is a corticosteroid that can be used in the treatment of cystoid macular edema (CME) and other ocular inflammatory conditions. This study aims to investigate the degree of cytotoxic effect of TA on human retinal pigment epithelium (ARPE19 cell line) and to compare the relative toxicity of TA with two other corticosteroids, hydrocortisone (HC) and dexamethasone (DEX), over a range of concentrations and durations of exposure. METHODS: The ARPE19 cell line was cultured and maintained in a 1 : 1 mixture of Dulbecco's modified Eagle's medium and HAMS F12 medium containing 3 mM l-glutamine supplemented with 10% fetal bovine serum, penicillin G, and streptomycin sulfate. Following an initial overnight incubation, corticosteroids (0.01-1 mg/ml) or vehicle (benzyl alcohol, 0.025%), diluted in culture medium, was added to the ARPE19 culture (5000 cells/well) on Day 0. Subsequently the culture medium containing corticosteroid or vehicle was refreshed daily. After 1, 3, and 5 days, the proliferated amount of cells with and without corticosteroid treatment was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All samples were read in triplicate, with n = 4 in all cases. The final results were analyzed using analysis of variance. RESULTS: TA, DEX, and HC caused a significant reduction in cell numbers throughout the whole range of concentrations when cells were exposed to them for more than one day. The action of the corticosteroids, apart from TA, was biphasic. There was an initial rise in cell proliferation in the presence of DEX and HC at 0.01-0.1 mg/ml on Day 1. Log-linear plots of DEX and HC concentrations against percent viability (mean % +/- SD) showed a significantly higher total viable cell percentage versus TA: 120.5 +/- 1.8% and 134.9 +/- 4.1% in the presence of DEX, and 110.0 +/- 15.3% and 118.3 +/- 9.0% in the presence of HC. The LD(50) values of the three corticosteroids show that, regardless of the duration of exposure, TA was the most toxic, with relative toxicity of TA > DEX > HC, equivalent to a ratio of 1.0 : 1.6 : 1.8, after one day of incubation. The vehicle alone had no effect. CONCLUSIONS: The present study demonstrated the degree of cytotoxicity of TA compared with DEX and HC. The results provide a profile of this drug relative to other common corticosteroids. Further studies are planned to characterize its effects and the degree of influence on cells of different ocular regions in order to show the full cytotoxicity of TA.

Cell Division↗

PubMedDate not supplied

ABCA4 sequence variants in Chinese patients with age-related macular degeneration or Stargardt's disease.

ABCA4 gene sequence alterations cause Stargardt's disease (STGD) and may cause some age-related macular degeneration (AMD). We sought to shed light on these associations among Hong Kong Chinese by genotyping 140 AMD, 18 STGD and 95 normal control subjects for 15 ABCA4 exons which were reported to often contain AMD- or STGD-associated mutations. Sequence alterations R212H, T1428M, V1433I, T1572M, I2166M, IVS6-5T>G and IVS33+1G>T were found in AMD patients. T1428M and R2040X occurred in STGD patients. Control subjects displayed all the above missense alterations but no splicing or nonsense changes. Therefore, ABCA4 splicing mutations may be associated with a small proportion of AMD cases.

ATP-Binding Cassette Transporters↗

PubMedDate not supplied

Familial high myopia linkage to chromosome 18p.

A locus for autosomal dominant high myopia was reported on chromosome 18p. We sought to confirm this finding and narrow the reported interval by analyzing high myopia among families of Hong Kong Chinese, in whom myopia is common. In 15 families with a possibly autosomal dominant inheritance of high myopia (>or=-6 dpt) in at least 2 generations, 10 chromosome 18p markers were analyzed for linkage with high myopia. Two-point linkage analysis showed trends toward linkage of markers D18S476 and D18S62 with high myopia, with maximum logarithm of odds (LOD) scores of at least 1.1 and 1.7, respectively. Multipoint analysis of those 2 markers gave a maximum LOD score of at least 2.1. To attempt to account for likely genetic heterogeneity, 5 families showing evidence of linkage of the 2 markers with high myopia were selected for further multipoint linkage analysis, resulting in a maximum LOD score of 2.4 at D18S476. While multiple genetic and environmental factors likely contribute to myopia, these data are consistent with the possibility of a locus on chromosome 18p.

Asian People↗