Search PubMed⌕ Search

Biomedical subjects

V Chan

Publications and source records attributed to V Chan.

At least 19 recordsLinked to original sources
PubMed2006

A new strategy for prenatal diagnosis of homozygous alpha(0)-thalassemia.

OBJECTIVES: We have shown previously that ultrasound examination performed by one experienced operator can be useful to exclude homozygous alpha(0)-thalassemia in a tertiary referral center. This study aimed to determine whether the technique was still applicable when performed by several operators and in different centers. METHODS: At the Maternal and Neonatal Hospital of Guangzhou (MNH) and Tsan Yuk Hospital of Hong Kong (TYH), women at risk of homozygous alpha(0)-thalassemia were given the option of a non-invasive approach (using serial ultrasound examinations at 12-15, 16-20 and 25-30 weeks' gestation) to exclude an affected pregnancy. The fetal cardiothoracic ratio (CTR) was measured at each of these examinations and the placental thickness was measured at 12-15 weeks' gestation. The operators of MNH received training on the ultrasound examination techniques at TYH and the quality of the subsequent ultrasound examinations was checked regularly. The final diagnosis of homozygous alpha(0)-thalassemia was confirmed using an invasive test. RESULTS: Of 832 at-risk pregnancies studied in the two hospitals, 168 (20.2%) were affected. The overall sensitivity and specificity of the non-invasive approach was 100% and 95.6%, respectively. At MNH, the need for an invasive test was reduced by 80.8%, and all the affected pregnancies were diagnosed before 24 weeks' gestation. The results achieved at MNH were comparable with those at TYH. The at-risk pregnancies including the affected ones presented at a more advanced gestational age at MNH. At each hospital, one affected pregnancy was missed at the 12-week scan but this was subsequently detected at the 15-18-week scan. CONCLUSIONS: This non-invasive approach to exclude homozygous alpha(0)-thalassemia can be applicable when it is performed by several operators and in different centers.

Cardiomegaly↗
PubMed2006

Novel biophysical techniques for investigating long-term cell adhesion dynamics on biomaterial surfaces.

Cell adhesion on biomaterial surface is crucial for the regeneration and function of clinically viable cell and tissues. In turn, the cellular phenotypes, following the mechanochemical transduction of adherent cells on biomaterials, are directly correlated to the biophysical responses of cells. However, the lack of an integrated bio-analytical system for probing the cell-substrate interface poses significant obstacles to understanding the behavior of cells on biomaterial surface. We have developed a novel method, based on the principle of confocal reflectance interference contrast microscopy (C-RICM) that has enabled us to study the biomechanical deformation of cells on biomaterial surfaces. In this article, we would like to describe our recent development of the C-RICM system that integrates a confocal fluorescence microscope, phase contrast microscope and GFP expression system. We shall demonstrate the system by determining the adhesion contact kinetics, initial deformation rate, cytoskeleton structures of adherent cells on extracellular matrices (e.g., collagen and fibronectin) and biodegradable polymer (e.g., poly(lactic acid)) during long-term culture. We shall demonstrate that this unique approach could provide valuable biophysical information necessary for designing optimized biomaterial surfaces for cell/tissue regeneration applications.

Animals↗
PubMed2006

Performance of bioprostheses and mechanical prostheses assessed by composites of valve-related complications to 15 years after aortic valve replacement.

OBJECTIVE: This study was conducted to compare the composites of valve-related complications, namely reoperation, morbidity (defined as permanent neurologic or other functional impairment), and mortality, between bioprostheses and mechanical prostheses for aortic valve replacement. METHODS: Between 1982 and 1998, 2195 bioprostheses were implanted in 2179 patients and 980 mechanical prostheses were implanted in 883 patients. Total follow-up was 16,442 years and 5740 years for bioprostheses and mechanical prostheses, respectively. Eight variables were considered as predictors of risk for the composites of valve-related complications. RESULTS: Linearized rates for valve-related reoperation were 1.3%/patient-year and 0.3%/patient-year for bioprostheses and mechanical prostheses (P < .001), respectively. All age groups were differentiated, except >70 years. Valve-related morbidity was differentiated for all age groups and overall, for bioprostheses and mechanical protheses, was 0.4 %/patient-year and 2.1%/patient-year, respectively (P < .001). Overall valve-related mortality was 1.0%/patient-year for bioprostheses and 0.7%/patient-year for mechanical prostheses (P = .018). Age and valve-type were predictive risk factors for reoperation and morbidity, whereas age alone was predictive of mortality. Actual freedom from valve-related reoperation favored mechanical prostheses for all age groups, except 61-70 years and >70 years. Actual freedom from valve-related morbidity favored bioprostheses in all age groups, except < or =40 years. Actual freedom from valve-related mortality was undifferentiated in patients 51-60, 61-70, and >70 years. CONCLUSION: No differences were observed in valve-related reoperation and mortality in patients >60 years. Comparative evaluation gives high priority for bioprostheses in patients >60 years based on improved morbidity profile. This evaluation extends this center's recommendation for bioprostheses in aortic valve replacement to include patients >60 years.

Adolescent↗
PubMed2006

Effect of environmental factors and gender on the heritability of bone mineral density and bone size.

Bone mineral density (BMD), a risk factor for osteoporosis, is believed to be under genetic control. The effect of environmental factors and gender on the heritability of BMD and bone size is ill-defined. In this study, heritability estimates (h2) were determined in 3,320 southern Chinese subjects from 1,019 families using the variance components model. The h2 for age, weight and height-adjusted BMD was 0.63-0.71 for females, and 0.74-0.79 for males; and for bone size, 0.44-0.64 for females and 0.32-0.86 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking and alcohol consumption altered the h2 differently in males and females. The proportion of variance in BMD and bone size explained by all covariates varied between skeletal sites, but was consistently greater in females than males. A significant gender difference was observed in the genetic variance of BMD and bone size at the hip but not the spine. In conclusion, a gender difference was observed in the degree of heritability of BMD and bone size at specific skeletal sites. Environmental influences contributed variably at different sites in the two sexes.

Adult↗
PubMed2003

Progress in silicon-based quantum computing.

We review progress at the Australian Centre for Quantum Computer Technology towards the fabrication and demonstration of spin qubits and charge qubits based on phosphorus donor atoms embedded in intrinsic silicon. Fabrication is being pursued via two complementary pathways: a 'top-down' approach for near-term production of few-qubit demonstration devices and a 'bottom-up' approach for large-scale qubit arrays with sub-nanometre precision. The 'top-down' approach employs a low-energy (keV) ion beam to implant the phosphorus atoms. Single-atom control during implantation is achieved by monitoring on-chip detector electrodes, integrated within the device structure. In contrast, the 'bottom-up' approach uses scanning tunnelling microscope lithography and epitaxial silicon overgrowth to construct devices at an atomic scale. In both cases, surface electrodes control the qubit using voltage pulses, and dual single-electron transistors operating near the quantum limit provide fast read-out with spurious-signal rejection.

Journal Article↗
PubMed2003

A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaïve patients with metastatic or locally advanced non-small cell lung cancer.

AIMS: To evaluate the efficacy and safety of docetaxel-cisplatin in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). METHODS: Chemotherapy-naïve patients with histologically confirmed TNM stage III or IV NSCLC were recruited from 12 Asian trial centers. Patients received docetaxel (75 mg/m2) and cisplatin (75 mg/m2) every 3 weeks for 6 cycles. RESULTS: 130 of 146 patients were evaluable for efficacy (60% stage IV). Three complete and 58 partial responses were observed (overall response rate: 46.9%; 95% CI: 38.3-55.5%). Median time to progression was 6.9 months and median survival was 14.0 months; 1-year survival was 59.5%. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 69.2%, 6.2% and 18.5% of patients, respectively. Grade 3/4 vomiting was observed in 13.7% and grade 3/4 neurosensory effects were observed in 2.7% of patients. There was one case of treatment-related death due to sepsis. CONCLUSION: Docetaxel-cisplatin is an effective and well-tolerated treatment in Asian patients with NSCLC.

Adult↗
PubMed2002

Mutations in the hepatocyte nuclear factor-1alpha gene in Chinese MODY families: prevalence and functional analysis.

AIMS/HYPOTHESIS: Maturity-onset diabetes of the young is an autosomal dominant form of diabetes characterised by an early age of onset (usually <25 years). We investigated the prevalence and trans-activating activity of hepatocyte nuclear factor (HNF) -1 alpha mutations in southern Chinese families with MODY. METHODS: We screened for mutations in the HNF-1 alpha gene in 50 unrelated southern Chinese families, which fulfilled the minimum criteria for MODY. Functional properties of the mutant proteins were investigated using site-directed mutagenesis and luciferase reporter assay. RESULTS: Five of the 50 (10%) families were found to have mutations in the coding region, including a new nonsense mutation Q176X and four reported mutations (frameshift mutation P379fsdelCT, nonsense mutation R171X, missense mutations G20R and P112L). These mutations had decreased trans-activating activity on the human insulin gene promoter. We also detected a new intronic sequence variation IVS7nt-6 G-->A, which co-segregated with diabetes. The intronic variation creates a potential splice acceptor site and might alter the splicing of the HNF-1 alpha mRNA. CONCLUSION/INTERPRETATION: Mutations in the HNF-1 alpha gene seem to be an important cause of MODY in southern Chinese. The mutations could affect normal islet function by altering the expression of target genes.

Amino Acid Substitution↗
PubMed2002

Capsule-substrate contact deformation: determination of adhesion energy.

A study is reported of a cellular entity (liquid-filled microcapsule) adhered on a flat glass substrate in response to changes in osmotic pressure and temperature. High-resolution reflection interference contrast microscopy (HR-RICM) and phase-contrast microscopy were developed for probing the adhesion contact area, capsule-substrate separation profile and adhesion energy of the adhering microcapsule. The new technique increased the detection limit of the measured capsule wall-substrate separation in the cohesive zone from 1 to 4.5 microm and improved the spatial resolution of the heterogeneous contact zones. A theoretical model was applied to correlate quantitatively the adhesion energy to the area of the contact zone. The work demonstrated the possibility of ascertaining the quantitative interfacial adhesion energy of a liquid-filled microcapsule using the present technique and represents the first step in extending this novel approach to study more complicated systems, such as cell-substrate interactions, in the future.

Animals↗
PubMed2001

Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta -catenin signaling is activated in human colon tumors.

Genetic studies have identified mutations in key regulators of the Wnt/beta-catenin pathway in a variety of cancers, most frequently in colon cancers. However, whether the pathway is activated in clinical cancer samples is not easily determined, and therefore it is useful to find markers that could be surrogates to show activation of the Wnt/beta-catenin pathway. Gene expression profiles were analyzed in SW620, a colon cancer cell line in which beta-catenin levels are stabilized as a consequence of truncated adenomatous polyposis coli and were compared with profiles of the same cells transfected with antisense oligodeoxynucleotides. Treatment of cells with beta-catenin antisense oligodeoxynucleotides resulted in a decrease in the levels of axin2 and human naked cuticle (hnkd) mRNAs. Interestingly, the proteins encoded by both of these mRNAs are known inhibitors of the beta-catenin pathway. In 30 human cell lines derived from different origins, axin2 and hnkd were expressed only in human colon cancer cell lines that are known to have activating mutations in the Wnt/beta-catenin pathway. Further, levels of both axin2 and hnkd mRNA were also found to be elevated in about 65% of laser microdissected cells from human colon tumors compared with laser microdissected cells of normal morphology from the same patient samples. The increased expression of axin2 and hnkd correlated with truncations in adenomatous polyposis coli in the same patient samples. These results reveal that it is possible to detect activation of a carcinogenic pathway in human cancer samples with specific markers.

Axin Protein↗
PubMed2001

Modeling complex disease with demographic and environmental covariates and a candidate gene marker.

We randomly chose replicates 28 and 29 of the simulated data sets of Genetic Analysis Workshop 12 to model the dependence of affection status on covariates, quantitative traits, and genes using all living pedigree members. First we explored the relationship of affection status to demographic and environmental factors using logistic regression and the Cox proportional hazards models. In the second stage of our analyses the generalized transmission disequilibrium test (GTDT) was applied to nuclear families with at least two affected siblings to select single markers and high-risk alleles, which were tested in the population association analyses including all pedigree members. Multiple logistic regression models were fitted to investigate the joint contributions of genetic and nongenetic factors and a block-recursive modeling approach was adopted to study inherent hierarchical dependence structure in the data. We found that allele 2 on marker 35 of chromosome 6 is associated with higher risk compared with the other 3 alleles of this marker. In addition to this significant genetic effect, age at exam and four of the five quantitative traits (QT1, QT2, QT4, and QT5) had a significant association with the disease. Our results were obtained without knowledge of the true disease generating models.

Adolescent↗
PubMed2001

Does simultaneous consideration of multiple regions improve disease gene localization?

Improvement in localization of disease susceptibility genes by simultaneous consideration of multiple interacting loci was assessed using the Genetic Analysis Workshop 12 simulated data. Evidence of linkage at primary loci was used to weight families for analyses at secondary loci. To identify regions linked to disease susceptibility genes, parametric and allele-sharing genome scans were performed in the extended pedigrees and nuclear families, respectively. The position of the peak allele-sharing lod was used as the estimate of a disease gene location. In weighted analyses, the positions where the greatest lod increases occurred were taken as alternative estimates of the gene locations. Variability of the location estimates of disease genes given by the unweighted and weighted analyses was compared. Similar analyses were carried out using true disease loci to determine weights. Weighted analyses did not in general improve the localization of disease genes in this data set, even with a large sample of 1,928 nuclear families, due to the features of the underlying additive liability threshold model.

Alleles↗
PubMed2001

A three-outcome design for phase II clinical trials.

The goal of a phase II trial is to make a preliminary determination regarding the activity and tolerability of a new treatment and thus to determine whether the treatment warrants further study in the phase III setting. Phase II clinical trials are typically designed in the hypothesis testing framework with two possible outcomes, either reject the null hypothesis H(0) or reject the alternative hypothesis H(a), based on the observed activity level. However, in cases where the observed activity is "borderline," the decision regarding the future of the agent is not as clear as the prespecified hypothesis test would indicate. In this paper we propose an alternative design that allows for three outcomes: reject H(0), reject H(a), or reject neither. We describe the theoretical properties of this design and illustrate it with several examples. We focus on the clinical implications of the three-outcome design. Control Clin Trials 2001;22:117-125

Clinical Trials, Phase II as Topic↗
PubMed2001

Interactions of phospholipid bilayer with chitosan: effect of molecular weight and pH.

Chitosan has demonstrated its potentials as a gene carrier and a membrane perturbant for subsequent drug delivery to cells. However, there is currently a lack of experimental correlation between the physiochemical properties of chitosan and the resulting degree of lipid bilayer destabilization. In this study, the effect of pH and chitosan molecular weight on the interaction between chitosan and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer was examined with cross-polarization microscopy, differential scanning calorimetry (DSC), and Fourier transform- (FT-) Raman spectroscopy. Cross-polarized images showed that the direct hydration of the DPPC/chitosan mixture led to the formation of larger DPPC multilamellar vesicles (MLV), and pure chitosan also induced fusions of individual MLV. Under the influence of chitosan, the calorimetric enthalpy of DPPC was reduced in a concentration-dependent manner, and a new phase appeared at 28 degrees C during sample cooling. Even the lowest chitosan mole fraction of 0.04% reduced the cooperative unit of the DPPC bilayer by more than 70%. In addition, the electrostatic effect between chitosan and DPPC tuned the degree of membrane bilayer perturbation. Reduction of pH increased the number of protonated amines on the chitosan backbone and caused further disruption on the membrane organization. Mixing DPPC with chitosan in an organic medium before hydration enhanced the hydrophobic interactions between the two molecules and greatly reduced the cooperative unit among individual lipids during the main phase transition. The increase of chitosan molecular weight also affected the cooperativity in the thermotropic transition of DPPC bilayer. FT-Raman spectroscopy provided additional evidence that chitosan directly perturbed the organizations of the hydrophobic inner core of the DPPC bilayer.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Successful mismatched sibling cord blood transplant in Hb Bart's disease.

A 20-month-old girl with Hb Bart's disease, who had survived neonatal complications, underwent HLA-DR antigen mismatched sibling cord blood transplantation successfully. Immune thrombocytopenia, which occurred around 2.5 months after transplant, responded to intravenous gamma-globulin. The fetal hemoglobin level rose to a peak of 52.3% on day +69 post transplant and declined gradually during the following year. Ten percent of hemoglobin Bart's was detected 2 months after transplant and this reflects the alpha-thalassemia trait of the donor.

Female↗
PubMed2001

Quantitative polymerase chain reaction for the rapid prenatal diagnosis of homozygous alpha-thalassaemia (Hb Barts hydrops fetalis).

A quantitative polymerase chain reaction (Q-PCR) method based on the TaqMan technology has been devised for the prenatal diagnosis of homozygous alpha*-thalassaemia (south-east Asian type deletion). Primers and TaqMan probes were designed to specifically amplify an alpha*-thal chromosomal fragment or a normal alpha-chromosomal fragment. Variations in input target DNA in individual sample wells were normalized by the simultaneous amplification of a beta-actin gene fragment and results expressed as a ratio to that of beta-actin. There was no overlap of the data between the homozygous alpha*-thal, alpha*-thal and normal subjects. Up to 5% maternal DNA (alpha*-thal) contamination did not affect the specificity of the result. In 31 prenatal diagnoses, the result using Q-PCR compared favourably with the gold standard of Southern hybridization of alpha-genes.

Actins↗